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Selected Abstracts from Artery 22

Selected Abstracts from Artery 22 Artery Research Artery Research https://doi.org/10.1007/s44200-022-00028-8 Open Access ABSTR AC T S Wednesday 19 – Saturday 22 October 2022, Centre de Congrès Prouvé, Nancy, France Oral presentations deterioration of elastic fibers and mechano-sensing appear to be pri- mary drivers of aberrant tissue remodeling and associated dilatation in the Marfan aorta, which is characterized by progressive stiffening. O.1 Microstructural deterioration drives progressive functional loss in Marfan syndrome aneurysms 1 1 2 3 Cristina Cavinato , David Lee , Marcos Latorre , Minghao Chen , 1 4 3,5 Dar Weiss , María Jesús Ruiz‑Rodríguez , Martin A. Schwartz , 1,5 Jay D. Humphrey Department of Biomedical Engineering, Yale University, New Haven, USA, Center for Research & Innovation in Bioengineering, Valencia Polytechnic University, Valencia, Spain, Cardiovascular Research Center, Yale School of Medicine, New Haven, USA, Centro Nacional de Investigaciones Car‑ diovasculares Carlos III, Madrid, Spain, Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, USA Background: Marfan Syndrome is a primary cause of thoracic aortic aneurysms; it arises from dysfunctional fibrillin-1, which normally sta- bilizes elastic fibers and promotes smooth muscle mechano-sensing of the matrix. Despite significant advancements, clear correlations between microstructural integrity and aortic functionality remain wanting. Biaxial stress-stretch curves (A) and circumferential stiffness vs. elastin Methods: Age-matched wild-type, Fbn1C1041G/ + [1], and Fbn1mgR/ porosity (B) for the ascending thoracic aorta of the analyzed Marfan mgR [2] mice represented three stages of disease severity. Experi- mice. Dilatation and circumferential stiffness from the G&R model (C). ments quantified specimen-specific thoracic aortopathy in terms of: (1) mechanical metrics from ex vivo biaxial testing that were described References by a four-fiber family hyperelastic model [3]; (2) microstructural met - [1] Milewicz DM, et al. Marfan syndrome. Nat Rev Dis Primers. 2021;7(1):64. rics[4] from ex  vivo multiphoton microscopy including elastin poros- [2] Pereira L, et al. Pathogenetic sequence for aneurysm revealed in mice ity, density, and engagement of collagen fibers and cells; (3) cardiac underexpressing fibrillin‑1. PNAS. 1999;96(7):3819–23. function from in  vivo ultrasound and µCT imaging. Material proper- [3] Judge DP, et al. Evidence for a critical contribution of haploinsufficiency ties were incorporated within a mechanobiologically equilibrated in the complex pathogenesis of Marfan syndrome. J Clin Invest. constrained mixture model of arterial growth and remodeling (G&R) 2004;114(2):172–81. [5]. The analysis assessed long-term impacts of locally compromised [4] Cavinato C, Chen M, Weiss D, Ruiz‑Rodríguez MJ, Schwartz MA, Humphrey elastin integrity, cellular mechanosensing and mechanoregulation, JD. Progressive Microstructural deterioration dictates evolving biome‑ collagen turnover, and endothelial function on disease progression chanical dysfunction in the Marfan aorta. Front Cardiovascular Medicine. through perturbations to the initial homeostatic state. 2021;8:1904. Results: Aortic dilatation correlated strongly with key mechanical met- [5] Latorre M, Humphrey JD. Numerical knockouts–In silico assessment of rics of compromised aortic functionality as well as with elastin defects, factors predisposing to thoracic aortic aneurysms. PLoS Comput Biol. collagen remodeling, and altered cellular function. Variable dilatations 2020;16(10). at a given age reflected a “pseudo-time” of progressive deterioration consistent with a progressive anoikis. The G&R model reproduces the Keywords: Marfan syndrome, Biaxial mechanics, Microstructure, same trends in aortic dilatation, stored energy, and circumferential Growth and remodeling, Aneurysms stiffness with increasing losses of elastic fiber integrity. The progressive © The Author(s) 2022. 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Artery Research O.2 Methods: To address this need, we applied mechanical stimulations Impaired β2‑adrenergic endothelium‑dependent vasodilation on human aortic SMC in culture at passage 6–7, by using the Flex- is reversed by phosphodiesterase inhibition in patients previously cell tension system (Fig.  1A). We tried different durations of stimu- hospitalized with COVID‑19 lation (24  h, 48  h, 72  h, and 100  h) versus unstimulated control. We chose 7 genes, coding for contractile proteins of the cytoskeleton 1 1 1 1 Dr. Luca Faconti , Ms Bushra Farikh , Dr. Ryan J McNally , Dr Sally Brett , (Fbn1, ACTA2), extracellular matrix components (Coll1A1, LAMA5), or Prof. Philip J Chowienczyk involved in activation/regulation of traction forces (TGFBR1, MYLK), King’s College London, London, United Kingdom and in cell differentiation (TAGLN). The expression of these genes was quantified with qPCR analysis, relatively to a reference gene (HPRT) Background: Endothelial dysfunction may underlie many of the com- (Fig. 1B). plications of COVID-19 [1]. The pulse wave response to salbutamol Results: We observed that: 1. From 72 h of stimulation, the difference (PWRS)—change in the augmentation index, AIx- provides a means between stimulated and control groups is the most significant; 2. For to assess endothelial vasodilator function mediated through the nitric the majority of the genes, their expression decreases with the stimula- oxide-cyclic guanosine monophosphate pathway (NO-cGMP) [2,3]. tion; 3. The basal medium enhances α-SMA production. Nevertheless, Here we aim to determine whether PWRS is abnormal in patients due to the low quantity of RNA available, we had to repeat cell stimu- recovered from COVID-19. lation, and reach n = 3 repetitions for each group during the qPCR Methods: We examined PWRS in subjects previously hospitalized analysis for more accurate results. with COVID-19, those recovered from mild symptoms and seronega- Conclusions: We were able to quantify SMC mechanosensitivity and tive controls (absence of SARS-CoV-2-antibodies) with similar risk fac- mechanotransduction. AoSMC seem to modulate their gene expres- tors for cardiovascular disease. In a sub-sample, we also assessed the sion after 72 h of stimulation. As future work, we would like to investi- response in the presence and absence of the phosphodiesterase type gate the influence of intercellular signaling under stimulation. 5 inhibitor sildenafil which inhibits the breakdown of cGMP. Results: 101 subjects (60 men) aged 47.8 ± 14.1 (mean ± SD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Inhaled salbutamol reduced AIx in controls (n = 34) and those recov- ered from mild symptoms of COVID-19 (n = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] − 2.85 [− 5.52, − 0.188] %, − 2.32 [− 5.17, 0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symp- toms and those previously hospitalised respectively (P = 0.001). In a sub-sample (n = 22), sildenafil enhanced the response to salbutamol (change in AIx 0.05 [− 2.15, 2.24] vs. − 3.96 [− 7.01, − 2.18], P = 0.006) with no significant difference between hospitalized (n = 12) and non- hospitalized subjects (n = 10). Conclusions: In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function which can be ame- liorated by sildenafil. (A) Control group and stimulated group with Flexcell tension system. (B) Results of the qPCR analysis on all groups for 7 genes (cDNA quan- References tity, relatively to a reference gene (HPRT )). [1] Libby P, Lüscher T. COVID-19 is, in the end, an endothelial disease. Eur. Heart J. 2020;41:3038–3044. References [2] Chowienczyk PJ, Kelly RP, MacCallum H, Millasseau SC, Anders- 1. Michel J‑B, Jondeau G, Milewicz DM. From genetics to response to injury: son TLG, Gosling RG, Ritter JM, Änggård EE. Photoplethysmographic vascular smooth muscle cells in aneurysms and dissections of the assessment of pulse wave reflection: Blunted response to endothe - ascending aorta. Cardiovasc Res. 2018;114(4):578–89. lium-dependent beta2-adrenergic vasodilation in type II diabetes mel- 2. Milewicz DM, Trybus KM, Guo D, Sweeney HL, et al. Altered Smooth litus. J. Am. Coll. Cardiol. 1999;34:2007–2014. Muscle Cell Force Generation as a Driver of Thoracic Aortic Aneurysms [3] Wilkinson IB, Hall IR, Maccallum H, Mackenzie IS, Mceniery CM, and Dissections. Arteriosclerosis, Thrombosis, and Vascular Biology. Arend BJ Van Der, Shu Y, Mackay LS, Webb DJ, Cockcroft JR. Clinical 2016;116:303229. Evaluation of a Noninvasive, Widely Applicable Method for Assessing 3. Liu M, Gomez D. Smooth Muscle Cell Phenotypic Diversity. Arterioscler Endothelial Function. 2002; Thromb Vasc Biol. 2019;39(9):1715–1723. 4. Humphrey JD, Schwartz MA, Tellides G, Milewicz DM. Role of Mechanotrans‑ Keywords: COVID-19, Endothelium, AIx duction in Vascular Biology: Focus on Thoracic Aortic Aneurysms and Dissections. Circulation Research. 2015;116(8):1448–61. O.3 Keywords: Cell biomechanics, Epigenetics, Mechanical stimulation, How does mechanical stress affect gene expression in human qPC aortic smooth muscle cells? 1 1 2 Mme Claudie Petit , Amira Ben Hassine, Mireille Thomas , 2 1 Alain Guignandon , Pr. Stéphane Avril O.4 Pentosan polysulfate, an aggrecanase inhibitor modulates Mines Saint‑Etienne, Université de Lyon, INSERM, U 1059 SAINBIOSE, arterial stiffness in spontaneously hypertensive rats Saint‑Etienne, France, Université Jean Monnet, Université de Lyon, 1 2 3 INSERM, U 1059 SAINBIOSE, Saint‑Etienne, France Miss Aleksandra Klosinska , Dr Keith Siew , Mr Tao L uo , 4 1 5 5 Mrs Nichola Figg , Mrs Sarah Cleary , Dr Isam Sharif , Mr Colin Williams , Background: SMC modulate their phenotype in response to envi- 1 3 Professor Ian Wilkinson , Professor Michael Sutcliffe , Professor Kevin ronmental conditions, as in for instance ascending thoracic aortic 1 1 O’Shaughnessy , Dr Y Yasmin aneurysms (ATAA) (1–3). It was previously shown that missensing of University of Cambridge, Department of Medicine, EMIT Division, mechanical stimuli plays a major role in ATAA (2,4). Nevertheless, there Cambridge, United Kingdom, University College London, Department is a pressing need to better quantify the mechanobiological behaviour of Renal Medicine, London, United Kingdom, University of Cambridge, of SMCs. A rtery Research Department of Engineering, Cambridge, United Kingdom, University whether healthy adults (controls, n = 36) or patients with moderate of Cambridge, Department of Medicine, Cardiovascular Division, Cam‑ chronic kidney disease (CKD, n = 30) were analyzed respectively with bridge, United Kingdom, Covance CRS Limited, Huntingdon, United paired or independent samples t-tests. Kingdom Results: Despite similar cd-PWV and cr-PWV, rd-PWV at baseline was significantly lower in CKD than in controls (3.6 ± 1.4  m/s vs. Background: Arterial stiffness is an independent predictor of all-cause 4.5 ± 1.8  m/s, p = 0.024), but this difference faded (p = 0.145) after and cardiovascular mortality in many populations. Our recent research adjustment for age. Post NTG, brachial blood pressure decreased and showed that loss of aggrecan integrity associates with age-related heart rate increased similarly between groups. Rd-PWV increased in arterial stiffening (ARAS) in humans1, and others have shown that inhi- controls (from 4.62 ± 1.49 m/s to 5.94 ± 2.29 m/s, p < 0.001) and in CKD bition of ADAMTS/aggrecanase enzymes, which degrade aggrecan, (from 3.71 ± 1.60  m/s to 5.18 ± 2.12  m/s, p < 0.001), in a similar extent improves cardiac function 2. Currently, there are no drugs that specifi- (interaction p = 0.111). However, cd-PWV significantly increased post- cally target arterial stiffening in humans. We hypothesise that ADAMTS NTG only in the CKD group (p = 0.009). inhibitor, Pentosan Polysulfate (PPS), represents an attractive molecule Conclusions: This technique, adapted by our team for small conduit that can be repurposed as a first-in-class drug treatment for ARAS. arteries, may broaden our understanding of the consequences of the inversion of the stiffness gradient. Methods: We performed an in vivo pharmacological experiment using 15wk-old spontaneous hypertensive male rats (SHR) that were admin- References istered either PPS or vehicle control (n = 7 per group) subcutaneously 1. Obeid H, Fortier C, Garneau CA, Pare M, Boutouyrie P, Bruno RM, et al. 3 times per week for 4 weeks. Animals were sacrificed and fully intact Radial‑ digital pulse wave velocity: a noninvasive method for assess‑ aortae including blood, cartilage, etc. were harvested and stored at ing stiffness of small conduit arteries. Am J Physiol Heart Circ Physiol. − 800  °C. Arterial wall thickness, stress-strain and failures stress were 2021;320(4):H1361‑H9. measured, and tensile elasticity calculated ex vivo. 2. Fortier C, Garneau CA, Pare M, Obeid H, Cote N, Duval K, et al. Modulation of Results: Preliminary analysis showed that PPS significantly reduced Arterial Stiffness Gradient by Acute Administration of Nitroglycerin. Front aortic wall thickening normally associated with arterial stiffening in Physiol. 2021;12:774056. hypertension (Vehicle 225 ± 6 µm vs 204 ± 6  µm, p = 0.0143). PPS also decreased aortic stiffening significantly at supraphysiological pres- Keywords: Chronic kidney disease, Nitroglycerin, Arterial stiffness gra- sures in treated rats, and treated rats had a higher failure stress relative dient, Small conduit arteries to vehicle controls. Conclusions: This proof-of-principle study demonstrated that an O.6 aggrecanase inhibitor can modulate aortic stiffness markers in SHR, Characterization of internal jugular vein region‑specific but the short treatment period may not be adequate to reveal clini- distension during progressive volume loading cally significant differences. Further longitudinal studies are therefore, 1 1,2 2 needed to establish if longer exposure to PPS can reduce aortic stiff- Mr Jeremy N. Cohen , Mr Eric T. Hedge , Dr Danielle K. Greaves , 1,2 3 1 ness at clinically significant levels in older animals. Dr Andrew D. Robertson , Dr Lonnie G. Petersen , Dr Jason S. Au Department of Kinesiology and Health Sciences, University Of Waterloo, References Waterloo, Canada, Schlegel‑University of Waterloo Research Institute [1] Yasmin et al. The matrix proteins aggrecan and fibulin‑1 play a key role in for Aging, University of Waterloo, Waterloo, Canada, Department determining aortic stiffness. Sci Rep. 2018 Jun 4;8(1):8550. https:// doi. org/ of Aeronautics and Astronautics, Massachusetts Institute of Technology, 10. 1038/ s41598‑ 018‑ 25851‑5. Cambridge, United States of America [2] Vistnes M. et al. Penstisan polysulfate decreases myocardial expression of the extracellular matrixenzyme ADAMTS4 and improves cardiac function Background: The internal jugular vein (IJV) is highly compliant with in vivo rates subjected to pressure overload by aortoc banding. PLOS One roles in intracranial blood flow and pressure regulation. The dynamic and 2014: 9, e8923. https:// doi. org/ 10. 1371/ journ al. pone. 00896 21. variable nature of venous flow, especially during changes in gravitational stress, leads to non-linear geometry. However, the impact of this irregu- Keywords: Arterial stiffness, Aggrecan, Pentosan polysulfate, Sponta- lar anatomy on IJV distension during progressive volume loading is not neous hypertensive rats understood and may contribute to adverse flow profiles, a component of Virchow’s triad for thrombotic risk. We characterized IJV 3D shape and volume expansion during progressive head-down tilt (HDT), a micro- O.5 gravity analogue. Radial‑digital pulse wave velocity: stiffness of small conduit Methods: We recruited 5 healthy, young adults (2 females, 25 ± 4 year, arteries increases after nitroglycerin administration 168 ± 8  cm, 68 ± 15  kg). Using an ultrasound probe tracked in 3D 1,2 1 1 space, we captured right IJV cross-sectional area (CSA) from clavicle to Dr Catherine Fortier , Charles‑Antoine Garneau , Mathilde Paré , 1 1 1 2 mandible. Progressive cephalad fluid shift was achieved by HDT at 0°, Dr Hasan Obeid , Nadège Côté , Karine Duval , Dr Rémi Goupil , − 6°, − 15°, and − 30°, each held for 5 min. CSA were traced at 0.3 cm Dr Mohsen Agharazii intervals from caudal to cranial and vein volume calculated by cylindri- Chu De Québec Research Center ‑ Université Laval, Québec, Canada, cal CSA. CIUSSS NIM‑ Sacré Coeur de Montréal, Montréal, Canada Results: Progressive HDT significantly altered IJV distension, demon- 2 2 strating stepwise effects on average CSA (0.89 ± 0.4cm , 1.26 ± 0.6cm , Background: The alteration of the physiological stiffness gradient 2 2 2 1.68 ± 0.7cm , 2.02 ± 1cm ; P = 0.003, η = 0.67) and total volume within larger vessels would increase the transmission of greater pul- (4.0 ± 1.5  mL, 5.8 ± 3.3  mL, 7.6 ± 4.2  mL, 9.3 ± 5.4  mL; P = 0.007, satility to the microcirculation, thus explaining the damage to the η = 0.63) through HDT conditions 0°, − 6°, − 15°, − 30°, respectively. pressure-sensitive organs. We aimed to describe the response of small Caudal regions displayed greater distension capacity compared to cra- conduit arteries of the hand (radial-digital PWV, rd-PWV) (1) following nial across conditions (P < 0.001). the pharmacological alteration of the stiffness gradient using nitro - Conclusion: Our precise 3D volume measures demonstrate the IJV can glycerin. (2). accommodate significant fluid shifts through a large range in disten- Methods: Simultaneous application of piezoelectric sensors (Com- sion ability, beyond stimuli mimicking microgravity. Irregular expan- plior) at the level of the carotid (c), the radial artery (r) and the tip sion patterns in the caudal regions may lend to flow abnormalities and of the index finger (d) was used to calculate the rd-PWV, before and requires investigation to ascertain prognostic value of IJV geometry on 4  min after a sublingual administration of 0.4  mg of NTG. Changes in thrombotic risk. arterial stiffness pre-post NTG and comparisons between two groups Artery Research Reference Fayon A, Menu P & El Omar, R. Cellularized small‑ caliber tissue‑ engineered vascular grafts: looking for the ultimate gold standard. npj Regen Med. 2021 Aug (6), 46 Keywords: Tissue-engineered vascular graft, Human umbilical cord, Inside-out, Artery bypass models, Vascular Tissue Engineering O.8 Inhibition of atherosclerotic plaque calcification by Omega‑3 polyunsaturated fatty acids through the resolvin E1 receptor ChemR23 1 1 PhD Gonzalo Ar tiach , PhD Andres Laguna‑Fernandez , 1 1 1,2 PhD Miguel Carracedo , PhD Hildur Arnardottir , Prof. Magnus Bäck Department of Medicine, Karolinska Institutet, Stockholm, Sweden, Theme Heart and Vessels, Karolinska University Hospital, Stockholm, Sweden Fig. 1 Internal jugular vein cross‑sectional area from caudal to cranial Background: The immune cell response in atherosclerotic plaques is regions normalized to individual neck length (A) and total cylindrical vein characterized by an impaired resolution of inflammation (1). Resolvin E1 (RvE1), a specialized pro-resolving lipid mediator derived from volume during progressive head‑ down tilt (B) omega-3 polyunsaturated fatty acids (PUFA) has been shown to play Keywords: Microgravity, Venous, 3D a critical role in atherosclerosis by promoting the resolution of the inflammation (2). The aim of the present study was to unravel the role of omega-3 PUFA, RvE1 and the RvE1 receptor ChemR23 in the process O.7 of atherosclerotic plaque calcification. New approach in the design of a human tissue engineered Methods: Fat-1 transgene (Fat-1tg), which enables the endogenous pro- vascular graft and preliminary studies in arterial bypass models duction of n-3 PUFA, was inserted in apolipoprotein E (ApoE)-deficient in the pig mice, in combination or not with genetic deletion of ChemR23. Calcifi- 1 1 2 Dr Adrien Fayon , Mrs Deborah Helle , Dr Véronique R egnault , cation was assessed by Alizarin Red staining and macrophage markers 3 3 2,4 Dr Marc Ponçot , Pr Isabelle R oyaud , Pr Jean‑Pablo Maureira , were assessed by immunohistochemistry in aortic root sections. 4 5 1 1 Dr Dan Pan , Dr Caroline Gaucher , Pr Patrick M enu , Dr Reine El Omar Results: Our results show that 72  week old Fat-1tg × Apoe -/- mice 1 2 Université de Lorraine, CNRS, IMoPA, F‑54000 Nancy, France, Uni‑ developed less atherosclerotic plaque calcification compared with versité de Lorraine, Inserm, DCAC, F‑54000 Nancy, France, Université Apoe-/- mice (0–3% vs 4–8%, p < 0.001). Moreover, deletion of de Lorraine, CNRS, IJL, F‑54000 Nancy, France, Université de Lorraine, ChemR23 enhanced atherosclerotic plaque calcification (4–13% CHRU‑Nancy, Service de Chirurgie Cardiovasculaire, F‑54000 Nancy, vs. 4–8%, p < 0.001), and this effect was not reversed by the pres- France, Université de Lorraine, CITHEFOR, F‑54000 Nancy, France ence of Fat-1tg (4–14% vs. 4–8%, p < 0.001). Furthermore, the Fat- 1tg × Apoe-/- mice had significantly higher expression of the M2 Background: Arterial bypass surgery of small-caliber vessels using macrophage marker Arg1 compared with Apoe-/- mice (17.4 ± 2.5% synthetic vascular prostheses remains inefficient as they promote vs 5.1 ± 1.5%; p < 0.0001), which was reversed by genetic dele- thrombosis probably due to a low or non-functionalization of their tion of ChemR23 (5.0 ± 1.1% vs. 17.4 ± 2.5%; p < 0.0001 vs internal surface(1). As a potential therapeutic alternative, we have Fat-1tg × Apoe -/- mice). developed a human cellularized TEVG (tissue-engineered vascular Conclusion: These results suggest that the beneficial effects of Fat- graft) whose components are all derived from the umbilical cord. 1tg were mediated through ChemR23. Hence, omega-3 PUFA may Methods: Decellularized umbilical arteries were coated at their lumi- have a therapeutic potential for reducing atherosclerotic plaque cal- nal surface with an extracellular matrix extracted from Wharton’s cification through RvE1-signaling by means of ChemR23. jelly and then cellularized by mesenchymal stromal cells derived also from WJ. The luminal coating and cellularization were optimized by References an innovative "inside-out" method allowing easy access to the lumi- 1. Bäck M, Yurdagul A, Tabas I, Öörni K and Kovanen PT. Inflammation and its nal surface. TEVG hemocompatibility (Thrombin Generation Assay) resolution in atherosclerosis: mediators and therapeutic opportunities. and mechanical properties (burst pressure test, stress rupture test, Nat Rev Cardiol. 2019 Jul;16(7):389–406. dynamic mechanical analysis) were evaluated. Preliminary in  vivo 2. Carracedo M, Artiach G, Arnardottir H and Bäck M. The resolution of inflam‑ implantations were conducted in pigs for coronary or femoral arterial mation through omega‑3 fatty acids in atherosclerosis, intimal hyperpla‑ bypass. sia, and vascular calcification. Semin Immunopathol. 2019;41:757–766. Results: The “inside-out” method, which did not impact mechanical properties of the TEVG, allowed a homogeneous cellularization of Keywords: Atherosclerosis, Calcification, Omega-3, Resolvin arteries luminal surface confirming its adaptability to a vascular con- text. Hemocompatibility assays showed that the TEVG behaves as a native blood vessel due to full cell covering of the luminal surface. The TEVG was successfully implanted in a coronary artery bypass O.9 model (n = 1), and was well tolerated, colonized and remain pat- Reduced Micromechanical Stiffness of Large Diameter Abdominal ent for 2  weeks post-implantation in a femoral replacement model Aortic Aneurysm (AAA) Wall Tissue (n = 1). 2 2 2 1 Martin Hossack , Robert Fisher, Francesco Torella , Jillian Madine , Conclusion: Our TEVG is an allogeneic therapeutic solution offering Riaz Akhtar a ready-to-use graft that may supply a tissue bank and which can be 1 2 grafted by minimally invasive robotic techniques avoiding an invasive University of Liverpool, United Kingdom, Liverpool University Hospitals surgery, having beneficial societal and economic impacts. NHS Foundation Trust, United Kingdom A rtery Research Introduction: Use of a maximum diameter threshold as the sole O.10 indicator for aneurysm repair risks rupture during surveillance in Reservoir‑wave parameters and cardiovascular prediction: higher-risk cases, and unnecessary repair in others [1]. Here, we Analysis of the population‑based CARTaGENE cohort characterised the micromechanical properties of aneurysmal aortic 1,4 2,3 Dr Louis‑Charles Desbiens , Dr Catherine Fortier , Dr Annie‑Claire tissues with the aim of identifying high-risk cases and directing spe- 1,4 2,4 5 Nadeau‑Fredette , Dr François Madore , Dr Bernhard Hametner , cific management. 5 3,6 2,4 Dr Siegfried Wassertheurer , Dr Mohsen Agharazii , Dr Rémi Goupil Methods: Full thickness anterior aortic wall tissue samples were 1 2 Hôpital Maisonneuve‑Rosemont, Montréal, Canada, Hôpital du harvested from 16 patients undergoing repair of degenerative AAA. Sacré‑Coeur de Montréal, Montréal, Canada, CHU de Québec—Univer‑ Nanoindentation was used to determine the shear storage modulus sité Laval, Québec, Canada, Université de Montréal, Montréal, Canada, (G′). We performed indentations on tissue cross-sections in 3 lay- 5 6 AIT Austrian Institute of Technology, Vienna, Austria, Université Laval, ers (inner, middle, outer). At least 4 samples were tested from each Québec, Canada patient. In total, there were 102 samples (1269 indentations). We stratified micromechanical findings according to maximum trans- Background: The reservoir-wave concept hypothesizes that blood verse diameter (MTD), established through interrogation of pre- pressure is the sum of a reservoir and an excess pressure. Nevertheless, operative contrast-enhanced CT scans. the clinical association of reservoir-wave parameters with cardiovascu- Results & Discussion: Aortic wall tissue demonstrated a pattern lar outcomes remains controversial. of reducing stiffness from the inner to middle (median 31.5  kPa vs Methods: We studied individuals aged between 40 and 69 from the 24.4  kPa, P < 0.05) and middle to outer layers (24.4  kPa vs 13.1  kPa, CARTaGENE cohort (Canada). Radial waveforms were measured with P < 0.05). Wall stiffness increased as MTD increased from 50–59  mm aplanation tonometry (SphygmoCor). They were transformed to cen- to 60–69  mm (median 20.7  kPa vs 29.5  kPa, P < 0.05). At 70-79  mm, tral waveforms using generalized transfer functions and used to gen- wall stiffness reduced (median 22  kPa, NS), and reduced further erate reservoir parameters (Reservoir pressure [RP], Reservoir pressure as MTD exceeded 80  mm (median 19.6  kPa, P < 0.05) (Fig.  1). The integral [RPI], Excess pressure [XSP], Excess pressure integral [XSPI], mechanical properties of vascular tissues depend largely on the Systolic rate constant [SC], Diastolic rate constant [DC], Optimized extracellular matrix. A reduced G′, observed in larger diameter aneu- asymptotic pressure [PInf]). Major adverse atherosclerotic events rysms may indicate a failure in the collagen network, predisposing (MACE: cardiovascular death, stroke, myocardial infarction) during a to rupture. 10-year follow-up were obtained using medico-administrative data- Conclusion: At higher MTD, AAA wall loses stiffness at larger diam- bases. Associations of reservoir parameters with MACE were derived eters. The work can be translated to identify individuals with high- using crude and fully adjusted Cox models. Incremental predictive risk AAA. performance over the ASCVD score (atherosclerotic cardiovascular dis- ease score; using revised pooled cohort equations) for each reservoir parameter was displayed using c-statistic improvement and continu- ous net reclassification indexes (NRI). Results: From 17,629 individuals, 2327 had a MACE during the fol- low-up. All reservoir parameters were significantly higher in patients who experienced a MACE. After full adjustment, RP, XSPI and DC were associated with increased MACE incidence ( Table). Spline anal- ysis did not reveal any non-linear relationships between reservoir parameters and MACEs. When added to the ASCVD prediction score, XSP and DC significantly improved c-statistics while RP, XSPI, DC and PInf led to a significant net reclassification improvement. Conclusion: Reservoir parameters, especially the diastolic rate con- stant, improve cardiovascular prediction in a population-based cohort. Table Fig. 1 Shear storage modulus shown as a function of maximum trans‑ verse diameter Reference 1.Polzer, S., Gasser, T.C., Vlachovský, R., Kubíček, L., Lambert, L., Man, V., Novák, K., Slažanský, M., Burša, J. and Staffa, R., 2020. Biomechanical indices are more sensitive than diameter in predicting rupture of asympto‑ O.11 matic abdominal aortic aneurysms. Journal of vascular surgery, 71(2), Histomorphometric analysis of cell and matrix components pp.617–626. of ascending thoracic aortic aneurysm 1,2 3 4 2 Berta Ganizada , Shaiv Parikh , Mitch Ramaekers , Armand Jaminon , Keywords: abdominal aortic aneurysms, maximum diameter, biome- 2 1 5 Asim Cengiz Akbulut , Ehsan Natour , Ryan Accord , Joachim Ernst chanics, vascular Artery Research 4 1 1 3 1 Wildberger , Simon Schalla , Jos M aessen, Reesink , Elham Bidar , Age and weight are represented as mean ± SD and other values as Leon Schurgers. median with IQR [Q1-Q3]. Department of Cardiothoracic Surgery, Maastricht University Medical 2 References Centre + , Maastricht, The Netherlands, Department of Biochemistry, 1. Erbel R, Aboyans V, Boileau C, et al. 2014 ESC Guidelines on the diagnosis Cardiovascular Research Institute Maastricht, Maastricht University, 3 and treatment of aortic diseases: Document covering acute and chronic Maastricht, The Netherlands, Department of Biomedical Engineer‑ 4 aortic diseases of the thoracic and abdominal aorta of the adult. The Task ing, Maastricht University, Maastricht, The Netherlands, Department Force for the Diagnosis and Treatment of Aortic Diseases of the European of Radiology and Nuclear Medicine Cardiology, Maastricht University 5 Society of Cardiology (ESC) [published correction appears in Eur Heart J. Medical Centre + , Maastricht, The Netherlands, Department of Pediatric 2015 Nov 1;36(41):2779]. Eur Heart J. 2014;35(41):2873–2926. and Congenital Cardiothoracic Surgery, University Medical Center Gronin‑ 2. Cebull HL, Rayz VL, Goergen CJ. Recent Advances in Biomechanical Charac‑ gen, Groningen, The Netherlands. terization of Thoracic Aortic Aneurysms. Front Cardiovasc Med. 2020;7:75 Background: Current indication for ascending thoracic aortic aneu- Keywords: Ascending aorta, Aneurysms, ECM-VSMC, Arterial rysm (aTAA) surgery is based on aortic diameter of 5–5.5  cm or a remodeling growth rate of > 0.5 cm/year [1]. However, current screening surveil- lance and risk estimation simplifies the complexity of aTAA disease, which might lead to a high-risk open-chest cardiac surgery [2]. Our O.12 aim was to examine ex vivo histological features of aTAA specimens, C–C chemokine ligand 5 from subcutaneous adipose tissue to assess changes in extracellular matrix (ECM) content and vascular has a central role in vascular aging smooth muscle cell ( VSMC) properties. Laura Le Pelletier Methods: Surgical samples of the ventral aspect of the ascending UMRS938 Inserm Saint Antoine Research Center, Paris, France aorta were collected from patients suffering from aTAA (n = 20) and patients with non-aneurysmal coronary bypass or stenotic valve sur- Background: Adipose tissue (AT) has a critical role in cardiovascular gery which served as controls (n = 10). Medial cross-sectional thick- diseases – particularly through its secretory activity. Aging is associ- ness, collagen/elastin content, and VSMC number were determined ated with AT redistribution, senescence, and changes in the secretome by quantitative histomorphometry. In addition, immunohistochemi- (1,2). We have previously shown that human adipose stromal cells cal markers of VSMC phenotype, α-smooth muscle actin (α-SMA), (ASCs) from the subcutaneous AT (SCAT) of aged women display calponin-1 (CNN1), and S100 calcium binding protein A4 (S100A4) senescence and oxidative stress (3). We hypothesized that the ASC were assessed. Image quantification analysis was performed using secretome contributes to the onset of endothelial dysfunction, an QuPath. early stage in vascular aging. Results: Aneurysmal aortas showed increased elastin fragmentation Methods: Conditioned media were prepared from ASCs isolated and regionally more dense collagen I/III confirming medial degenera- from SCAT of healthy young (< 25y) or aged (> 60y) women. ASCs’ tion. This resulted in a marked rise in collagen-to-elastin ratio (Table 1). secretome were added to human coronary artery endothelial cells. Medial cross-sectional thickness and number of VSMCs were increased C–C-chemokine-ligand-5 (CCL5) was identified by an adipokine array. in aneurysmal aortas (Table  1). Expression of α-SMA and CNN1 The expression of CCL5 in SCAT from men with coronary disease was decreased significantly, whilst S100A4 expression was not different evaluated. The effect of a CCL5 receptor antagonist, maraviroc, was between the groups (Table 1). investigate in peripheral blood mononuclear cells (PBMCs) in HIV- Conclusions: Our preliminary results support the notion of an infected individuals from two studies. imbalanced interaction between ECM-VSMCs that may play a cru- Results: The secretome of aged-donor ASCs induced endothelial cial role in arterial remodeling cascade, leading to aTAA formation. cell dysfunction and senescence. We showed that CCL5 was respon- Further research is needed with the ultimate aim to guide clinical sible for these effects and corroborate in experiments with recom- management. binant protein and maraviroc. We observed that CCL5 expression in SCAT of patients with coronary heart disease was strongly associated with blood pressure. Moreover, maraviroc prevented endothelial cell dysfunction in  vitro and reverted PBMC senescence in HIV-infected individuals. Conclusions: Our results highlighted the ability of the CCL5 secreted by aged ASCs from SCAT to induce endothelial dysfunction and senes- cence—both of which are early steps in vascular aging—and a poten- tial link between these phenomena and hypertension. References 1.Stout MB, Justice JN, Nicklas BJ, Kirkland JL. Physiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty. Physiol Bethesda Md. janv 2017;32(1):9‑19. 2.Liu Z, Wu KKL, Jiang X, Xu A, Cheng KKY. The role of adipose tissue senes‑ cence in obesity‑ and ageing‑related metabolic disorders. Clin Sci Lond Engl 1979. 31 janv 2020;134(2):315‑30. 3.Le Pelletier L, Mantecon M, Gorwood J, Auclair M, Foresti R, Motterlini R, et al. Metformin alleviates stress‑induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction. eLife. 21 sept 2021;10:e62635. Keywords: Aging, adipose tissue, endothelial dysfunction, adipose stromal cells A rtery Research O.13 (PeriCam PSI NR System, Perimed). Post-occlusive reactive hyper- Cardiovascular risk in adolescents translates into lower carotid emia (PORH) was assessed following a standardized protocol and intima‑media thickness and better distensibility in young data were analyzed with a signal processing software (PIMSoft, Per- adults—The KiGGS2‑cohort imed). The amplitude of PORH responses was expressed as a per- 1,2,3 2,3 1 centage increase between peak and baseline perfusion (%). Karsten Königstein , Julia Büschges , Arno SchmidtT ‑ rucksäss , 2,3 Results: Twenty-nine individuals (14 patients with prediabetes and Hannelore Neuhauser 15 controls) were studied. There wasn’t any statistically significant 1 2 University of Basel, Basel, Switzerland, Robert‑Koch Institute, Berlin, difference regarding age, sex, body mass index and blood pres- Germany, DZHK (German Centre for Cardiovascular Research), Berlin, sure levels between the two groups. At baseline, skin microvascu- Germany lar perfusion was significantly higher in patients with prediabetes compared to controls (50.9 ± 11.5 vs. 39.2 ± 8.7, p = 0.006) while Background: Lifestyle-associated cardiovascular risk may be elevated during occlusion, perfusion was similarly reduced in both groups. already during adolescence translating into an increased disease Post occlusion reperfusion was significantly lower in the prediabetes burden in adulthood. The KiGGS cohort characterizes cardiovascular group as compared to the controls (145.0 ± 42.8 vs. 195.2 ± 47.3% aging from childhood until young adulthood in the German general respectively, p = 0.007). population. This study analyzes the effects of increased cardiovascular Conclusions: We showed, for the first time, that individuals with risk during adolescence on carotid properties in young adults. prediabetes demonstrated skin microvascular dysfunction, that may Methods: 1,545 participants of the representative healthy popula- reflect a more generalized microvascular damage. tion sample of the national KiGGS-0 cohort (10–17  years of age) had carotid ultrasound-assessment 10 years later at the KiGGS-2 follow-up References (20–28 years of age). A cardiovascular risk score (CV-R) was calculated 1. Lamparter J, Raum P, Pfeiffer N, Peto T, Höhn R, et al. Prevalence and associa‑ at KiGGS-0 including variables of arterial hypertension, obesity, dyslipi- tions of diabetic retinopathy in a large cohort of prediabetic subjects: The demia and smoking. Carotid intima-media thickness (CIMT) and dis- Gutenberg Health Study. J Diabetes Complications. 2014;28(4):482–7. tensibility (DC) at KiGGS-2 were associated with CV-R. 2. Friedman A, Marrero D, Ma Y, Ackermann R, Narayan KMV, et al. Value of Results: Unfavorable alterations of all components of CV-R were urinary albumin‑to ‑ creatinine ratio as a predictor of type 2 diabetes in associated with higher CIMT and/or reduced DC. Relative risks for pre‑ diabetic individuals. Diabetes Care. 2008;31(12):2344–8. pathologically elevated CIMT ≥ 90th percentile and/or decreased 3. de Matheus AS, Clemente ELS, de Lourdes RM, Torres VDC, Gomes MB, et al. DC ≤ 10th percentile were elevated in participants with ‘intermedi- Assessment of microvascular endothelial function in type 1 diabetes ate’ (RRCIMT = 1.89 [1.23–2.91], p < 0.05; RRDC = 1.27 [0.79–2.06]) or using laser speckle contrast imaging. J Diabetes Complications. 2017, ‘high’ risk (RRCIMT = 1.83 [0.95–3.52], p < 0.1; RRDC = 1.76 [0.93–3.32], 31(4):753–7. p < 0.1) according to CV-R. Conclusions: If an intermediate or high cardiovascular risk according Keywords: prediabetes, microcirculation dysfunction, LASCA to CV-R is apparent in adolescence, signs of early vascular aging may occur at a very young age. The promotion of a favorable lifestyle to reduce risk factor burden even in the overall healthy general popula- tion at a young age seems to be crucial for primary prevention of car- O.15 diovascular diseases. Arterial Stiffness Assessment by Pulse Arrival Time: An In Silico Proof of Concept. Keywords: carotid intima-media thickness (cIMT ), primary prevention, 1 2 1 Jingyuan Hong , Manasi Nandi , Jordi Alastruey. cardiovascular risk, adolescents School of Biomedical Engineering & Imaging Sciences, King’s College London, London, UK, School of Cancer & Pharmaceutical Sciences, King’s O.14 College London, London, UK Evaluation of skin microvascular dysfunction with Laser Speckle Contrast Analysis in prediabetes Arterial stiffness (AS) is one of the primary symptoms of vascu- 1 1 2 lar ageing (1). Stiffer arteries lead to increased pulse wave velocity Stamatina Lamprou , Nikolaos Koletsos , Ioanna Zografou , 3 1 (PWV ) and decreased pulse transit time (PTT ). PWV is considered the Gesthimani Mintziori , Konstantinos Mastrogiannis , 2 1 1 clinical gold standard for the diagnosis of AS, but direct measure- Michael Doumas , Eugenia Gkaliagkousi , Areti Triantafyllou. ment in daily life is challenging (2). Pulse arrival time (PAT), which Third Department of Internal Medicine, Papageorgiou General Hospital, consists of the pre-ejection period (PEP) and PTT, is defined as the Aristotle University of Thessaloniki, Thessaloniki, Greece, Second Prope‑ time interval between the R-peak of electrocardiogram (ECG) and deutic Department of Internal Medicine, Hippokration General Hospital, a characteristic point of photoplethysmogram (PPG) (3,4). Since Aristotle University of Thessaloniki, Thessaloniki, Greece, Unit of Repro‑ most standard wearable devices can capture PPG and ECG signals, ductive Endocrinology, 1st Department of Obstetrics and Gynecology, and PAT correlates highly with vascular properties, such as vascu- Papageorgiou General Hospital, Aristotle University of Thessaloniki, lar tone, PAT extracted from wearable signals has the potential to Thessaloniki, Greece indicate cardiovascular health (5). The study used a database of in silico pulse wave signals for 4,374 virtual subjects to calculate aor- Objectives: Prediabetes is recognized as a significant metabolic tic PWV (aPWV), aortic-radial PTT (arPTT ), and PEP (6). The strength status, being a key factor in the occurrence of diabetes mellitus of the correlation between PAT and aPWV was assessed using the (DM). There is increasing evidence concerning microvascular com- correlation coefficient (R2). Relative sensitivity analysis was used to plications in prediabetes most commonly in skin, kidneys and ret- investigate the effects of cardiac and vascular properties on PAT. The ina (1,2). Laser speckle contrast analysis (LASCA) is a non-invasive R2 value between PAT and aPWV was 0.84. The inverse relationship technique that can be used to evaluate skin microvascular func- between PAT and aPWV illustrates that stiffer arteries resulted in tion. Previous studies have shown skin microvascular dysfunction in decreased PAT, even when considering specific age groups. Accord- patients with DM (3). However, to our knowledge, no previous study ing to the relative sensitivity analysis, PAT is mainly affected by has evaluated skin microcirculation, using LASCA, in patients with stroke volume and PWV. Our in silico study suggests that PAT has the prediabetes. potential to be used as a marker for assessing the arterial stiffening Methods: In all subjects, forearm skin blood flow was recorded component of vascular ageing. under standardized conditions using a laser speckle contrast imager Artery Research Results: In the overall population (n = 7924, 54.2% women, age 18–82  years), the prevalence of HVA/NVA/EVA was 7.8/68.1/24.1%, respectively, with EVA prevalence increasing in older age. NVA and EVA, as compared to HVA, were independently associated with anthropometric (BMI), metabolic (HbA1c), psychosocial (family sta- tus) and lifestyle (pack years, alcohol intake) factors, on top of age, gender, and blood pressure (Figure). Additional associations with VA categories were found in younger and older age (level of education), in middle age (income), and in older age (lack of physical activity). Conclusions: In this large population-based study we found a high percentage of early vascular aging, with a significant increase with increasing age. Psychosocial and lifestyle factors seem to play an independent role. Schematic representation of the definition of pulse arrival time (Back - ground), the extraction method of pulse transit time and pre-ejection period (Methodology), and arterial stiffness analysis of pulse arrival time (Result). References 1. Olsen MH, Angell SY, Asma S, Boutouyrie P, et al. The Lancet. 2016 Nov;388(10060):2665–712. 2. Willum Hansen T, Staessen JA, Torp‑Pedersen C, Rasmussen S, et al. Circula‑ Keywords: Vascular aging tion. 2006 Feb;113(5):664–70. 3. Zhang G, Gao M, Xu D, Olivier NB, Mukkamala R. Journal of Applied Physiol‑ ogy. 2011 Dec;111(6):1681–6. 4. Zheng YL, Ding XR, Poon CCY, Lo BPL, et al. IEEE Trans Biomed Eng. 2014 O.17 May;61(5):1538–54. Hydrochlorothiazide, but not chlortalidone nor furosemide, 5. Zheng YL, Yan BP, Zhang Y T, Poon CCY. Ann Biomed Eng. 2015 enhances vascular calcification in CKD rats with mineral bone Sep;43(9):2242–52. disorder 6. Charlton PH, Mariscal Harana J, Vennin S, Li Y, Chowienczyk P, Alastruey J. 1 1 1 1 Mohsen Agharazii , Richard Larivière , Roth‑Visal Ung , Sylvain Picard , Am. J. Physiol.‑Heart Circ. Physiol. 2019 Nov;H1062–85. 1 1 1 Dailson N. de Souza , Darren E. Richard , Fabrice Mac‑Way Chu De Québec‑université Laval, Québec, Canada Keywords: Vascular ageing, Arterial stiffness, Pulse arrival time, Pulse wave velocity, Wearable signals Background: Previously, we reported that hydrochlorothiazide (HCTZ)-based regimen aggravated arterial calcification and stiff- O.16 ness in a rat model of chronic kidney disease (CKD) with mineral and Prevalence and determinants of vascular aging: the LEAD study. bone disorder (MBD). In this study, we investigated if all diuretic- 1 2 2 based treatments aggravate of arterial stiffness and calcification in Kathrin Danninger , Otto Burghuber , Marie‑Kathrin Breyer , 2 2 2 CKD-MBD rats. Patricia Puchhammer , Alina Ofenheimer , Robab Breyer‑Kohansal , 3 2 1 Methods: In rats with renal mass ablation-induced CKD, MBD Christoph Kaufmann , Sylvia Hartl, Thomas Weber was generated by a Ca/P-rich diet and calcitriol. The animals were Klinikum Wels‑Grieskirchen, Department of Cardiology, Linz, Austria, divided into four groups; (1) CKD-MBD control; (2) CKD-MBD + HC TZ 2 3 Ludwig‑Boltzmann‑Institute for Lung Diseases, Vienna, Austria, Klinikum (thiazide diuretic, 5  mg/kg/d); (3) CKD-MBD + Chlor thalidone (thi- Ottakring, Department of Cardiology, Vienna, Vienna azide-like diuretic, 5  mg/kg/d), and; (4) CKD-MBD + Furosemide (loop diuretics, 10  mg/kg/d). At week 6, systolic and mean blood Background: Vascular aging (VA) is an important and prognostically pressure (SBP and MBP), pulse pressure (PP) and pulse wave velocity relevant aspect of biological aging. Its determinants are incompletely (PWV) were determined invaisively. Thoracic aorta calcification was understood, and a holistic view is missing. assessed by von Kossa staining. Methods: The LEAD (Lung, Heart, Social, Body) study is an ongoing, Results: SBP was reduced by all types of diuretics. Contrary to chlo- longitudinal, population-based observational study, which started rtalidone and furosemide, HCTZ treatment led to a reduction of in 2011 in Vienna and six villages from Lower Austria. As part of the MBP, but an increase in PP and PWV in CKD-MBD rats (p < 0.05). As study, cfPWV was measured non-invasively using applanation tonom- expected from these hemodynamic changes, medial calcification in etry (SphygmoCor device, Atcor medical). In a predefined healthy nor - the thoracic aorta was significantly greater in CKD-MBD rats treated mal population (non-smokers without known hypertension, diabetes, with HCTZ as compared to all the other groups of rats (p < 0.05). hyperlipidemia, or cardiovascular disease, free from antihypertensive Conclusions: In rats with CKD-MBD, HCTZ, but not other types of and lipid-lowering medication, blood pressure of < 130/85  mmHg), diuretic, exacerbated arterial stiffness and vascular calcification age-specific Z-scores for cfPWV were calculated. Healthy VA (HVA), nor - despite a reduction in SBP. The deleterious effect of HCTZ in CKD- mal (NVA) and early (EVA) VA was defined as cfPWV value < 10th, 10th- MBD rats may have major clinical impact as this diuretic is widely 90th, and > 90th percentile, respectively. use in patients with CKD that often develop MBD. A rtery Research The figures shows blood pressure (systolic, mean, diastolic, pulse pres- sure), and aortic stiffness by pulse wave velocity (PWV), and aortic calcifi- cation by von Kossa staining. Keywords: Chronic kidney disease, mineral bone disease, vascular calcification O.18 Results are adjusted for age, race-study center, body mass index, dia- Relationships between excessive daytime sleepiness, arterial betes, heart rate, mean arterial pressure, and blood-pressure medica- stiffness, and physical activity. The Atherosclerosis Risk tion use. AHA: American Heart Association: T: tertile. in Communities (ARIC) Study References Michael A Newton, Rachael Hamm, Emma Barinas‑Mitchell, Pamela L 1. Blachier M, Dauvilliers Y, Jaussent I et al. Excessive daytime sleepiness and Lutsey, Hirofumi Tanaka, Kapuaola Gellert, Lee Stoner, Michelle Meyer vascular events: the Three City Study. Ann Neurol. 2012;71(5):661–7. University of North Carolina at Chapel Hill, Chapel Hill, United States, 2. Lee CH, Ng WY, Hau W et al. Excessive daytime sleepiness is associated with University of North Carolina at Chapel Hill, Chapel Hill, United States, longer culprit lesion and adverse outcomes in patients with coronary 3 4 University of Pittsburgh, Pittsburgh, United States, University of Minne‑ artery disease. J Clin Sleep Med. 2013;9(12):1267–72. sota Twin Cities, Minneapolis, United States, University of Texas at Austin, 3. Li J, Covassin N, Bock JM et al. Excessive Daytime Sleepiness and Cardiovas‑ Austin, United States, University of Hawaii, Honolulu, United States, cular Mortality in US Adults: A NHANES 2005–2008 Follow‑Up Study. Nat University of North Carolina at Chapel Hill, Chapel Hill, United States, Sci Sleep. 2021;13:1049–59. University of North Carolina at Chapel Hill, Chapel Hill, United States Keywords: Arterial stiffness, sleep, physical activity, older adults Background: Excessive Daytime Sleepiness (EDS) is associated with higher risk of cardiovascular disease (CVD) events (1,2) and mortal- ity (3). However, the association between EDS and subclinical CVD, O.19 such as arterial stiffness, is not fully understood nor is the role of Greater intrinsic arterial wall stiffness and its unfavourable physical activity (PA) in this association. We examined the relation- trajectory over time in type 2 diabetes ship between EDS and arterial stiffness, measured using carotid- 1 1 1 Kunihiko Aizawa , Phillip E Gates , David M Mawson , femoral pulse wave velocity (cfPWV), with PA as a potential effect 1 1 1 2,3 Francesco Casanova , Kim M Gooding , Suzy V Hope , Isabel Goncalves , modifier. 2 4 5 6 Jan Nilsson , Faisel Kahn , Helen M Colhoun , Andrea Natali , Carlo Methods: A cross-sectional analysis of ARIC Study participants 7 1 Palombo , Angela C Shore (n = 2349, mean age: 79.6, 57.2% female, 19.2% black adults) who underwent cfPWV measures (VP-1000 Plus, Omron Co., Kyoto, 1 NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Japan) and completed the Epworth Sleep Scale (ESS) and Baecke 2 Exeter, United Kingdom, Department of Clinical Sciences, Lund Univer‑ questionnaires in 2016–2019. EDS was defined as ESS ≥ 11. We 3 sity, Malmö, Sweden, Department of Cardiology, Skåne University Hospi‑ calculated moderate-vigorous PA (min/week) and categorized PA 4 tal, Malmö, Sweden, Division of Systems Medicine, University of Dundee, based on the distribution and guidelines. We used multivariable 5 Dundee, UK, Centre for Genomic and Experimental Medicine, University linear regression to estimate the association between ESS, EDS, 6 of Edinburgh, Edinburgh, UK, Department of Clinical and Experimental and cfPWV, and evaluated effect modification by PA. Results are 7 Medicine, University of Pisa, Pisa, Italy, Department of Surgical, Medical, presented as beta coefficients (β) and 95% confidence intervals Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy (CI). Results: A total of 14.4% participants reported EDS. The association Background: A greater central artery stiffness is observed in people of ESS and EDS with cfPWV differed by PA level. The association of ESS with type 2 diabetes (T2DM). However, it is unclear about intrinsic arte- (Figure A) and EDS (Figure B) with cfPWV became more negative with rial wall stiffness in these patients. We aimed to determine the utility higher PA levels, although the associations with EDS were not statistically of β cross-sectionally and longitudinally in T2DM. METHODS: We stud- significant. ied 753 adults with T2DM (DM+: 67.5 ± 8.3 years, 227F) and 436 adults Conclusion: A negative association was observed between ESS without T2DM (DM−: 67.0 ± 9.2 years, 159F) cross-sectionally (Phase 1), and cfPWV at the most intense level of PA in older adults. In and subsequently studied 310 adults in DM + (68.6 ± 7.6 years, 104F) those not meeting PA guidelines, other adverse life and partici- and 210 adults in DM− (67.6 ± 8.5 years, 83F) over three years longitu- pant characteristics could outweigh the effects of ESS and EDS on dinally (Phase 2). Carotid-femoral pulse wave velocity was measured, cfPWV. and its data were used to calculate β as previously described . o Artery Research 1 1 1 1 Results: In Phase 1, β was significantly greater in DM+ than DM− Garcia‑Peña , Amaya Fernández‑Celis , Alicia Gainza , Virginia Álvarez , 1 1 1 after adjusting for age and sex [27.5 (26.6–28.3) vs 23.6 (22.4–24.8) Rafael Sádaba , Natalia López‑Andrés , Eva Jover García au, p < 0.001]. Partial correlation analyses after adjusting for age and 1 Cardiovascular Translational Research, Navarrabiomed, Hospital Univer‑ sex found that β was significantly associated with HbA1c (r = 0.15 sitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, p < 0.001) and heart rate (r = 0.23 p < 0.001) in DM+. I Phase 2, percent- Pamplona, Spain, Pamplona, Spain age changes in β were significantly greater in DM + than DM− [19.5 (14.9–24.0) vs 5.0 (− 0.6–10.6) %, p < 0.001] after adjusting for age, sex Background: The pathophysiological role of angiogenesis and lym- and baseline β . Multivariable linear regression analyses revealed that phangiogenesis in aortic stenosis (AS) remains unknown. Valve the percentage changes in β were independently associated with avascularity is seemly abrogated in AS and neovascularization is well- percentage changes in heart rate in DM + (overall R = 0.19). correlated with the disease(1,2). We study sex-related differences in Conclusion: β was greater in DM + than DM−. Furthermore, β angiogenesis and lymphangiogenesis in aortic valves (AVs) and valve o o changed over three years with ageing but it changed much more in interstitial cells (VICs) from AS patients. DM + than DM−. These data suggest that intrinsic arterial wall stiff- Methods: 226 patients recruited (60.6% men) with severe AS undergo- ness may be a useful target for therapeutic intervention. ing surgical valve replacement. Results: The density of total neovessels was higher in AVs from men Reference versus women’s. Small and medium neovessels were more abundant Spronck et al. J Hypertens 2017;35:98–104. in men’s AVs. Male AVs exhibited enhanced CD31 and VE-cadherin expressions. Levels of the pro-angiogenic markers [vascular endothe- Keywords: Ageing, Aorta, Blood pressure, Heart rate lial growth factor (VEGF)-A, VEGF receptor (VEGFR)1, VEGFR2, insu- lin-like growth factor-binding protein-2 (IGFBP-2), interleukin (IL)-8, chemerin and fibroblast growth factor (FGF)-7] were increased in O.20 men’s AVs. Transforming growth factor-β expression was higher in The bidirectional longitudinal relationships between arterial male AVs. Expression of antiangiogenic molecules [thrombospondin stiffness and hypertension and those between arterial stiffness (Tsp)-1, endostatin and CD36] was upregulated in male AVs, although and diabetes mellitus the levels of Tsp-2, IL-4, IL-12p70 and chondromodulin-1 were similar Professor Hirofumi Tomiyama between sexes. The number of lymphatic vessels and the expression of the lymphangiogenic markers Lyve-1 and D2-40 was enhanced in Japan, Suginami, Japabn men’s AV also VEGF-C, VEGF-D and VEGFR3. VICs isolated from men’s Background: Hypertension and diabetes mellitus frequently coex- AVs secreted higher amounts of pro-angiogenic (VEGF-A, VEGFR1, ist; however, it has not yet been clarified if the bidirectional longi- IGFBP-2 and FGF-7) and pro-lymphangiogenic factors (VEGF-C, VEGF- tudinal relationships between arterial stiffness and hypertension D and VEGFR3) than women’s without changes in antiangiogenic are independent of those between arterial stiffness and diabetes markers. mellitus. Conclusions: We show that aberrant angiogenic and lymphangio- Methods: In this 16-year prospective observational study, 3960 genic cues are over-represented in male AVs. VICs are a relevant source middle-aged employees of a Japanese construction company with- of multiple morphogens involved in angiogenesis and lymphangi- out hypertension/diabetes mellitus at the study baseline underwent ogenesis likely endowing the AV of men with the predominant calcific annual repeated measurements of the blood pressure, serum glyco- AS phenotypes (3,4). sylated hemoglobin A1c level (HbA1c), and brachial-ankle pulse wave velocity (baPWV ). References Results: By the end of the study period, 664, 779, 154, and 406 1. Collett GD, Canfield AE. Angiogenesis and pericytes in the initiation of subjects developed hypertension, prehypertension, diabetes ectopic calcification. Circ Res. 2005;96(9):930–8. mellitus, and prediabetes, respectively. Increased baPWV at the 2.Rajamannan NM, et al. Calcified rheumatic valve neoangiogenesis is associ‑ baseline was associated with a significant odds ratio (per 1 stand- ated with vascular endothelial growth factor expression and osteoblast‑ ard deviation increase) for new onset of prehypertension/hyper- like bone formation. Circulation. 2005;111(24):3296–301. tension with (2.45/3.28, P < 0.01) or without (2.49/2.76, P < 0.01) 3.Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N. VEGF couples coexisting prediabetes/diabetes mellitus, but not for new onset hypertrophic cartilage remodeling, ossification and angiogenesis during of prediabetes/diabetes mellitus without coexisting hypertension. endochondral bone formation. Nat Med. 1999;5(6):623–8. Analyses using the latent growth curve model confirmed the bi- 4.Nelson V, Patil V, Simon LR, Schmidt K, McCoy CM, Masters KS. Angiogenic directional relationships between baPWV and hypertension, but Secretion Profile of Valvular Interstitial Cells Varies With Cellular Sex and no such relationship was observed between baPWV and abnormal Phenotype. Front Cardiovasc Med. 2021;8:736303. glucose metabolism. Conclusions: In middle-aged Japanese subjects in contrast to the Keywords: Aortic-stenosis, sex, angiogenesis, lymphangiogenesis bi-directional relationships that exist between arterial stiffness and hypertension, increased arterial stiffness preceding the development of diabetes mellitus may represent that associated with the develop- O.22 ment of hypertension, as it is observed only in cases of diabetes mel- Arterial stiffness predicts sustained hypertension in patients litus coexisting with hypertension. Therefore, arterial stiffness may be with high normal blood pressure/grade 1 hypertension associated to a greater degree with the development of hypertension 1,2 1 1 Dr. Enrique Rodilla , Dr. Andrea Mendizábal , Dr. Iratxe Jiménez , than with the development of diabetes mellitus. 1 1 1 Dr. Leticia Pérez , Dr. Sergio Canales , Dr. Alicia Roldán , Dr. Santiago Keywords: arterial stiffness; hypertension 1 1 1 2 Pintos , Dr. Marta Catalán , Dr. María‑Carmen Sáez , Dr. José Chordá , Dr. José‑Antonio Costa O.21 1 2 Hospital Universitario de Sagunto, Puerto De Sagunto, Spain, Universi‑ Characterization of the sex‑specific pattern of angiogenesis dad Cardenal Herrera‑CEU, CEU Universities, Moncada, Spain and lymphangiogenesis in aortic stenosis 1 1 Background: 2018 ESC-ESH Guidelines for the Management of Arte- Lara Matilla Cuenca , Ernesto Martín‑Núñez , Mattie Garaikoetxea 1 1 1 1 rial Hypertension recommend pharmacological treatment if patients Zubillaga , Adela Navarro , Julieta Anabela Vico, Vanessa Arrieta , Amaia A rtery Research with grade 1 HTN at low-moderate risk remain hypertensive after a period of lifestyle intervention. Our objective was to assess the pre- dictive value of early vascular aging (EVA) to identifying patients who developed sustained HTN after baseline diagnosis. Methods: Retrospective, descriptive, longitudinal study including all consecutive patients referred to a HTN Unit with suspected naïve HTN without prior pharmacological treatment. EVA was defined accord- ing to estimated pulse wave velocity (brachial oscillometry, Mobil- O-Graph (IEM ) in seven age-groups(1). Standard clinical tests were performed at baseline and after 12 months. Results: Since 2010, 335 consecutive patients entered the study, with 201 women (60%), a mean age of 46,4 years (± 13), mean office BP of 130/76 (± 12/9), and ambulatory BP of 122/78 (± 8/7) mmHg. Distri- bution of BP was 155 (46.3%) patients with high-normal BP, 28 (8,4%) with white-coat HTN, 108 (32.2%) with masked HTN and 44 (13.1%) with established HTN. At baseline, 57% of patients showed EVA, after a mean time of 1.1 year, 65% of participants presented elevated ABPM. A selection of Survey Results In univariate analysis, baseline stiffness (EVA) was associated with ele - vated ABPM-values in the follow-up visit (OR: 2.0; IC 1.3–3.1; p = 0.003). Keywords: Survey, Knowledge, Awareness, Vascular age After adjustment for age, gender and pulse pressure, baseline EVA kept its significant predictive value (OR:2.6; IC 1.6–4.2; p = 0.001). O.25 Conclusions: Arterial damage characterized as EVA according to esti- Early vascular aging associated with sympathetic hyperactivity mated PWV by brachial oscillometry doubles the probability of sustained in obese hypertensive individuals with moderate to severe HTN one year after initial assessment in naïve patients with high-normal obstructive sleep apnea BP/grade 1 HTN at low-moderate risk. 1 1 1 Samanta Mattos , Michelle Rabello Cunha , Marcia Regina Simas Klein , Reference Mario Neves Nunan D, Fleming S, Hametner B, Wassertheurer S. Performance of pulse wave State University of Rio de Janeiro, Rio de Janeiro, Brazil velocity measured using a brachial cuff in a community setting. Blood Press Monit. 2014;19:315–9. Background: Obstructive sleep apnea (OSA) is an independent cardi- ovascular risk (CVR) factor. The objective was to evaluate sympathetic Keywords: Early vascular aging (EVA), risk stratification, pulse wave tone and vascular disease in obese hypertensive with moderate and velocity, high-normal blood pressure severe OSA. Methods: Individuals of both sexes, aged 40–70  years and body mass index (BMI) ≥ 30 and < 40  kg/m2, submitted to assessment of O.23 heart rate variability (HRV), central parameters by Mobil-O-Graph and Awareness and perceptions of health care providers carotid ultrasound. Sleep study was performed through a portable and researchers on vascular ageing: Quantitative Survey Results. home sleep test device (WatchPAT ). 1 2 5 4 Chloe Park , Andrie Panayiotou, Thomas Weber , Christopher Mayer , Results: Patients (n = 49) were divided into two groups based on 3 6 Areti Triantafyllou , Rachel Climie the apnea–hypopnea index (AHI): absent-mild (AM) group (AHI < 15 MRC Unit for lifelong Health and Ageing at UCL, London, United King‑ events/h, n = 17) and moderate-severe (MS) group (AHI ≥ 15 dom, Cyprus International Institute for Environmental and Public Health, events/h, n = 32). The mean BMI was similar (35 ± 3 vs 34 ± 2  kg/ Cyprus University of Technology, Limassol, Cyprus, Medical School, m2, p = 0.248). Systolic blood pressure (120 ± 15 vs 131 ± 14  mmHg, Aristoteleio University Thessaloniki, Thessaloniki, Greece, AIT Austrian p = 0.003), pulse pressure (43 ± 9 vs 49 ± 8  mmHg, p = 0.011), CVR Institute of Technology GmbH, Vienna, Austria, Cardiology Department, (6.8 ± 4.1 vs 14.4 ± 10.7%, p = 0.003) and cardiometabolic age Klinikum Wels‑Grieskirchen, Wels, Austria, Menzies Institute for Medical (48 ± 6 vs 52 ± 8  years, p = 0.034) were higher in the MS group. The Research, University of Tasmania, Hobart, Australia same group presented higher low frequency/high frequency (LF/ HF) ratio (0.83 ± 0.56 vs 1.91 ± 1.98, p = 0.017), pulse wave veloc- Introduction: Vascular Age (VA) can assess cardiovascular disease risk, ity (PWV) (7.1 ± 0.7 vs 8.0 ± 1.2  m/s, p = 0.003), vascular age (50 ± 6 independently of chronological age, however it is not yet widely applied vs 56 ± 8  years, p = 0.014) and carotid intima-media thickness in routine clinical practice. A quantitative questionnaire was developed (0.58 ± 0.09 vs 0.70 ± 0.12  mm, p = 0.001). PWV was significantly cor - to assess current knowledge gaps related to VA and barriers to imple- related with LF/HF ratio (r = 0.609, p < 0.001) only in the MS group. mentation in routine practice in both research and clinical settings. Conclusion: In this sample of obese hypertensive patients, moderate Methods: Using a stepwise mixed-methods approach, a quantitative to severe OSA was associated with sympathetic hyperactivity and evi- questionnaire was constructed. The 22-item anonymous survey was dence of early vascular aging with increased arterial stiffness and sub - based on a previous qualitative analysis including 80 participants with clinical atherosclerosis. multiple scientific backgrounds, and included questions on perceptions/ beliefs, knowledge, and implementation of VA. The survey was dissemi- Reference nated to clinicians and researchers world-wide, via social media and tar- Bironneau V, Tamisier R, Trzepizur W, et al. Sleep apnoea and endothelial dys‑ geted emails from well-known societies (including Artery, ESH, ISH, ESC). function: An individual patient data meta‑analysis. Sleep Med Rev. 2020 Results: 276 (50% female) completed the questionnaire, 46% were clini- Aug;52:101–309. cians, 33% researchers, 10% students. Clinical specialties included cardi- ology (36%), internal medicine (22%) and General Practice (10%). While Keywords: Hypertension; Sleep apnea; Obesity; Arterial stiffness 84% of clinicians and researchers rate VA importance as high or very high (Table), only 11% of clinicians measure VA in clinical settings. Limiting factors include cost, lack of guidelines and lack of knowledge. Discussion: These results show that implementation of VA is very low in clinical settings and awareness of VA needs to be improved via planned targeted awareness strategies and educational material. Artery Research O.26 pressure-diameter tests were performed at 95/100/105% of Acute vasopressin neutralization with the aptamer NOX‑F37 the < i > in vivo < /i > axial stretch and axial force –length tests at improves immediately cardiac but not peripheral endothelial 10/60/100/140  mmHg. Data were fit using a nonlinear constitutive dysfunction in rats with chronic heart failure model [1]. 1 1 1 1 Results: Figure (bar char ts, < i > n < /i > = 4–8 per group) shows pas- Yohan Stephan , Marina Hamrouche , Lise Charrier , Lionel Nicol , 2 2 1 1 sive metrics calculated at < i > in vivo < /i > axial stretch and group- Marie‑Laure Ozoux , Philip Janiak , Jeremy Bellien , Paul Mulder specific systolic blood pressures [2]. AngII caused larger increases in 1 2 Inserm U1096, Rouen, France, Corteria Pharmaceuticals, Paris, France wall thickness than NE. Both NE and AngII led to significant struc - tural arterial stiffening, driven by a combination of wall thickening Background: Vasopressin is one of the leading pathophysiologi- and stiffening of the wall material. Figure also shows correlation of cal drivers of chronic heart failure (CHF) acting via V1a-, V1b- and V2 wall thickness with contractility (scatter plots, < i > n < /i > = 4–7 per receptors. Selective V2 and dual V1a-V2 receptor antagonists amelio- group; symbols represent individual aortas). The stronger an individ- rate plasma sodium levels, but fail to reduce mortality in clinical stud- ual aorta was able to contract (larger absolute stress change; to the ies. Vasopressin neutralization is an original alterative for receptor left on < i > x < /i > -axis), the weaker its remodelling response. blockers but its effect in CHF is unknown. For this purpose, we sought Conclusions: NE- and AngII-induced hypertension elicit distinct investigated the short-term cardiac and vascular effects of the vaso - aortic remodelling responses. However, independent of the hyper- pressin neutralizing aptamer NOX-F37. tensive stimulus, aortic contractile capacity emerged as protective Methods: Left ventricular (LV) function (hemodynamics by LV cath- against hypertensive arterial remodelling. erization) and LV tissue perfusion (MRI) as well as mesenteric artery endothelium function (flow mediated dilation by arteriograph) were determined 2  h after NOX-F37 administration (80  nM/kg; IP) to rats with well-established CHF induced by coronary artery ligation. Results: Two hours after administration, NOX-F37 significantly improved LV systolic function, illustrated by the significant increase in LV end-systolic pressure volume relation (CHF: 20.2 ± 0.0.7; CHF + NOX: 23.3 ± 1.0  mmHg/RVU) and diastolic function, illustrated by the sig- nificant decrease in LV end-diastolic pressure volume relation (CHF: 4.03 ± 0.48; CHF + NOX: 2.06 ± 0.21  mmHg/RVU), which were associ- ated with a significant increase in LV tissue perfusion (CHF: 6.12 ± 0.24; CHF + NOX: 10.10 ± 0.26  ml/min/g LV tissue). However, mesenteric artery flow-induced dilatation was not modified and remained impaired (% dilatation at 150 µl/min; CHF: 10 ± 7; CHF + NOX: 9 ± 8). Conclusions: These results illustrate the immediate protective effects on cardiovascular function of vasopressin neutralization in chronic heart failure confirming the existence of a deleterious vaso - pressinergic tone in chronic heart failure. Whether these beneficial cardiac effects persist with chronic vasopressin neutralization needs to be confirmed. Keywords: Heart failure; pharmacology; vasopressin O.27 Hypertensive aortic remodelling as induced by adrenergic receptor activation vrsus renin–angiotensin–aldosterone system activation in mice 1,2,3 2 2 Bart Spronck , Alexander W. Caulk , Abhay B. Ramachandra , Sae‑Il 2 2,4 Murtada , Jay D. Humphrey Dept. of Biomedical Engineering, Maastricht University, Maastricht, The Netherlands, Dept. of Biomedical Engineering, Yale University, New Haven, United States, Macquarie Medical School, Macquarie University, Sydney, Australia, Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, United States Background: Hypertension causes the aorta to remodel and poten- tially stiffen. We aimed to compare the aortic remodelling response to hypertension as induced by adrenergic receptor activation versus renin–angiotensin–aldosterone system activation. Methods: Adult male C57BL/6 J mice were studied under seven con- ditions: untreated, and after 7/14/28-day subcutaneous infusion of 3880  ng/kg/min norepinephrine (NE) or 1000  ng/kg/min angioten- sin II (AngII). After euthanasia, ascending/descending thoracic (ATA/ Whiskers: standard errors, overbars: < i > p < /i > < 0.05 (Bonferroni). Sys- DTA) and infrarenal abdominal (IAA) aortas were dissected, placed tolic/diastolic blood pressures: 120/80 mmHg (WT); 154/103, 162/108, within a computer-controlled biaxial testing device, and subjected 154/103  mmHg (7/14/28d NE); 150/100, 159/106, 177/118  mmHg to isobaric (90 mmHg) vasoreactivity experiments to, among others, (7/14/28d AngII). Lines/grey areas: multilevel regressions/95% confi- 1  µM phenylephrine + 1  mM L-NAME [1]. Under passive conditions, dence intervals. A rtery Research References Basic [1] Spronck B, Latorre M, Wang M, Mehta S, Caulk AW, Ren P, et al. Excessive adventitial stress drives inflammation‑mediated fibrosis in hyperten‑ P.001 sive aortic remodelling in mice. J R Soc Interface 2021; 18:20,210,336. Variability of invasive aortic pulse wave velocity measured [2] Owens AP, 3rd, Subramanian V, Moorleghen JJ, Guo Z, McNamara CA, Cassis by catheter pull‑back method and implications for pulse wave LA, Daugherty A. Angiotensin II induces a region‑specific hyperplasia of velocity device validation the ascending aorta through regulation of inhibitor of differentiation 3. 1 2,7 2,8 Alexander Stäuber , Bart Spronck , Alessandro Giudici , Cornelia Circ Res 2010; 106:611–619. 3 3 4 5 Piper , Siegfried Eckert , Stefan Richter , Marc‑Alexander Ohlow , Johannes Baulmann Keywords: Angiotensin II; arterial mechanics; norepinephrine; vasoconstriction Professorship of Sports Medicine / Sports Biology, Chemnitz University of Technology, Chemnitz, Germany, Department of Biomedical Engineer‑ O.28 ing, CARIM School for Cardiovascular Diseases, Maastricht University, Raised arterial stiffness at 24–26 weeks of gestation is associated Maastricht, The Netherlands, Klinik für Allgemeine und Interventionelle with the development of hypertension in pregnancy Kardiologie/Angiologie, Herz‑ und Diabeteszentrum NRW, Univer ‑ sitätsklink der Ruhr‑Universität Bochum, Bad Oeynhausen, Germany, 1 1 1 1 Pritika Dutta, Tarang Gupta , Rajesh Kumari, Vidushi Kulshrestha , Department of Cardiology, Zentralklinik Bad Berka GmbH, Herzzentrum, 1 1 1 Ashok Kumar Jaryal , Kishore Kumar Deepak , Garima Kachhawa. Department of Cardiology, Bad Berka, Germany, Department of Cardiol‑ 1 6 All India Institute of Medical Sciences, New Delhi, India ogy, SRH Wald‑Klinikum, Gera, Germany, Praxis Dres. Gille/Baulmann, Rheinbach, Germany, Macquarie Medical School, Faculty of Medicine, Background: Increase in arterial stiffness in third trimester is pro - 8 Health and Human Sciences, Macquarie University, Australia, GROW posed to be involved in the pathogenesis of hypertensive disorders School for Oncology and Reproduction, Maastricht, The Netherlands of pregnancy. The present study was conducted to evaluate arte- rial stiffness in pregnant women at 24–26 + 6  weeks of gestation. Background: The invasive method of catheter pullback from ascending They were grouped into healthy pregnancy (HP), preeclampsia aorta (asc) to iliac bifurcation (bifu) is gold standard for aortic pulse wave (PE) or gestational hypertension (GHTN) depending upon maternal velocity (aPWV) and the reference standard for validation of non-invasive outcome. devices that estimate aPWV [1]. In this work, we examine aPWV variability Methods: Arterial stiffness was measured using applanation tonom- in invasive recordings of patients undergoing cardiac catheterization. etry. Central arterial stiffness was quantified by augmentation index Methods: Invasive measurements were performed in 56 patients (57% normalized to heart rate 75 beats/minutes (AIx@75) and carotid- male, 67 ± 13  years, mean ± standard deviation (SD)) with a femoral femoral pulse wave velocity (cfPWV), peripheral arterial stiffness catheter access. Catheter pullback method was used to measure aortic was quantified by carotid-radial pulse wave velocity (crPWV) using pulse transit time (aPTT ) from asc to bifu. Pulse wave analysis using the SphgmoCor CVMS CPVH device. intersecting tangent method (Sirius, Redwave Medical GmbH, Jena, Results: Out of 313 women, PE developed in 3.51% (n = 11), GHTN Germany) provided the diastolic foot points for each recording site in 5.11% (n = 16) and 22.04% (n = 69) remained healthy preg- (asc, bifu) and recorded heartbeat (number of beats, asc: 86 ± 42, bifu: nant without any obstetrical or medical factors. The mean age in 82 ± 43). From the respective time difference with the R-wave of the years, BMI in kilograms/metre2 and MAP in mmHg between the time-synchronised electrocardiogram, the pulse transit time for the groups were [(30.0 ± 1.6 vs 28.81 ± 4.8 vs 27.70 ± 4.0, p = 0.094), corresponding recording site (PTTasc, PTTbifu) was derived for each {27.41(25.10–33.09) vs 28.51(24.29–31.84) vs 27.01(25.39–28.40), heartbeat. aPTT was then determined from the difference of the aver - p = 0.529}, (99.09 ± 7.58 vs 95.88 ± 9.09 vs 85.99 ± 9.64, p < 0.0001)] aged PTTbifu and PTTasc. Based on aPTT, the known catheter pullback respectively. AIx@75 was found to be increased (PE:22.82 ± 14.65%, length and the estimated SD of aPTT, SD_aPTT = √(SD_PTTasc + SD_ GHTN:19.47 ± 10.60%, HP:10.35 ± 12.14%, p = 0.001) in women devel- PTTbifu ), the SD of the corresponding aPWV was calculated as SD_ oping hypertension in pregnancy than normotensive healthy preg- aPWV = aPWV × SD_aPTT/aPTT for each patient. nancy. Similarly cfPWV (PE:7.21 ± 1.24  m/s, GHTN:6.64 ± 1.22  m/s, HP: Results: aPTT was 44.01 ± 12.89 ms; aPWV was 9.7 ± 3.1 m/s. SD_aPT T 6.19 ± 1.06  m/s, p = 0.013) was also significantly higher in pregnant was 3.72 ± 1.73 ms, resulting in an SD_aPWV of 1.0 ± 0.8 m/s. women with PE and GHTN. The crPWV were comparable among PE, Conclusions: Our data indicate a substantial beat-to-beat SD in inva- GHTN and healthy pregnant. sively determined aPWV by catheter pull-back method. The issue of Conclusion: Raised central arterial stiffness is observed before the aPWV variability in the invasive reference needs to be addressed in clinical onset of disease in women destined to develop PE later in validation protocols for non-invasive estimation of aPWV. pregnancy. AIx@75 and cfPWV could be used as a putative prognos- tic marker of hypertensive disorders of pregnancy. Reference [1] Wilkinson IB, McEniery CM, Schillaci G, Boutouyrie P, Segers P, Donald A, References Chowienczyk PJ (2010). ARTERY Society guidelines for validation of non‑ 1.Garg P, Jaryal AK, Kachhawa G, Kriplani A, Deepak KK. Sequential profile of invasive haemodynamic measurement devices: Part 1, arterial pulse wave endothelial functions and arterial stiffness in preeclampsia during the velocity. Artery Research, 4(2), 34–40. course of pregnancy. Pregnancy Hypertens. 2019; 18: 88–95. 2.Franzi MB, Burgmann M, Neubauer A, Zeisleri H, Sanani R, Gottsauner‑ Wolf Keywords: PWV, PTT, variability M et al. Augmentation index and pulse wave velocity in normotensive and pre‑ eclamptic pregnancies. Acta. Obstet. Gynecol. Scand. 2013; 92: 960–66. P.002 3. Tomiyama H, Yamashina A. Non‑invasive vascular function tests: Their patho ‑ Multiple linear regression analysis of age, gender, anthropometric physiological background and clinical application. Circ. J. 2010; 74: 24–33. and haemodynamic factors to predict variability in aortic pulse transit time determined by the catheter pull‑back method Keywords: Arterial stiffness, augmentation index, pulse wave velocity, 1 2,7 2,8 Alexander Stäuber , Bart Spronck , Alessandro Giudici , Cornelia hypertensive disorders of pregnancy 3 3 4 5 Piper , Siegfried Eckert , Stefan Richter , Marc‑Alexander Ohlow , Posters Johannes Baulmann. Artery Research Professorship of Sports Medicine/Sports Biology, Chemnitz University mice survival. qPCR analysis indicated the altered expression of cir- of Technology, Chemnitz, Germany, Department of Biomedical Engineer‑ cadian-related genes such as genes of Bmal and ciart. ing, CARIM School for Cardiovascular Diseases, Maastricht University, Conclusions: Our data indicate the primary effect of Bcl11b inacti- Maastricht, The Netherlands, Klinik für Allgemeine und Interventionelle vation on cell death, probably by necroptosis. Kardiologie/Angiologie, Herz‑ und Diabeteszentrum NRW, Univer ‑ sitätsklink der Ruhr‑Universität Bochum, Bad Oeynhausen, Germany, Department of Cardiology, Zentralklinik Bad Berka GmbH, Herzzentrum, Department of Cardiology, Bad Berka, Germany, Department of Cardiol‑ ogy, SRH Wald‑Klinikum, Gera, Germany, Praxis Dres. Gille/Baulmann, Rheinbach, Germany, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Australia, GROW School for Oncology and Reproduction, Maastricht, The Netherlands Background: Aortic pulse transit time (aPTT) is not constant but fluc - tuates, which affects the accurate determination of aortic pulse wave velocity (aPWV). In this work, we investigate the influence of age, gen- der, anthropometric and haemodynamic parameters on aPTT variabil- ity determined by the catheter pull-back method. Methods: aPTT could be analysed in 69 patients (61% male, 68 ± 13 years) with femoral catheter access. A stepwise multiple linear regression analysis was performed with aPTT variability as dependent variable and age, gender, BMI, heart rate, aortic systolic blood pressure (aSBP), aortic diastolic blood pressure (aDBP) and variability of aSBP (aSBPV ) and aDBP (aDBPV ) as predictors. For the dependent haemody- namic variables, only data from the ascending aorta were used. Results: The regression model with the factors heart rate, aSBP, aSBPV, aDBPV achieved the highest goodness of fit of 0.49 (adjusted R-squared). aSBPV and heart rate proved to be the strongest factors (standardised regression coefficient beta 0.397 and 0.301, respec - tively) followed by 0.258 for aDBPV and -0.199 for aSBP (all p < 0.05). Photos showing thoracic aorta from control (A) and mutant mice (B) at The unstandardised regression coefficients B were 0.489 for aSBPV, 7 days after the injection of tamoxifen to 3 month-old mice. 0.322 for aDBPV, -0.020 for aSBP and 0.047 for heart rate. Conclusions: Our data show the influence of aortic systolic and diastolic References blood pressure variations, heart rate and aSBP on aPTT variability whereas Mitchell GF, Verwoert GC, Tarasov KV et al., Common genetic variation in the age, gender, and BMI had no significant influence. However, the adjusted 3’‑BCL11B gene desert is associated with carotid‑femoral pulse wave R-squared of the model suggests that a considerable part of aPTT variability velocity and excess cardiovascular disease risk: the AortaGen Consortium. cannot be explained by the independent variables included in the model. Circ Cardiovasc Genet. 2012;5(1):81–90. Valisno JAC, May J, Singh K, Helm EY, Venegas L, Budbazar E, Goodman JB, Keywords: PTT variability, PWV variability Nicholson CJ, Avram D, Cohen RA, Mitchell GF, Morgan KG, Seta F. BCL11B Regulates Arterial Stiffness and Related Target Organ Damage. Circ Res. 2021;128(6):755–768. P.003 Keywords: Cell death, CTIP2/Bcl11b, hemorrhage Smooth muscle cell‑specific knock‑out of CTIP2 gene results in aortic hemorrhage 1,2,3 1,2,3 1,2,3 P.004 Ara Parlakian , Jocelyne Blanc , Jacqueline GAO‑Li , Véronique 4 1,2,3 4 1,2,3 Smooth muscle integrin αv contributes to the regulation of cell Regnault , Onnik A gbulut , Patrick Lacolle y , Zhenlin Li stiffness 1 2 Sorbonne Universite, Paris, France, CNRS UMR8256, Paris, France, 1 2 3 3 4Alexandre Raoul , Ekaterina Belozertseva, Lei Tian , Xiao Liu , INSERM ERL U1164, Paris, France, INSERM—U1116, Nancy, France 3 2 2 4 Caterina Maria Tone , Jocelyne Blanc , Dario Coletti , Daniel Henrion , 1 1 3 Background: Ctip2/Bcl11b is a transcription factor with dual action Véronique Regnault , Patrick Lacolley , Emmanuelle Lacaze , Pascal 5 2 (repression/activation) that couples epigenetic regulation to gene Challande , Dr Zhenlin Li transcription in a variety of physiological responses under healthy 1 2 INSERM1116, Vandoeuvre‑lès‑nancy, France, CNRS8256, Paris, France, and pathological conditions of various tissues. Single nucleotide 3 4 CNRS7588, Paris, France, INSERM1083 – CNRS6214, Angers, France, polymorphisms of Ctip2/Bcl11b gene are associated with a higher CNRS7190, Paris, France susceptibility for aortic stiffness (1). although Ctip2/Bcl11b has been proposed as a crucial regulator of aortic smooth muscle func- Background: Integrin αv is a receptor for adhesion proteins expressed tion (2), its mechanism of action in smooth muscle cells is still to be at high density in vascular smooth muscle cells (VSMC) whose pheno- uncovered. typic modulation plays a crucial role in arterial ageing. Methods: Morphological, cellular and molecular analysis were car- Objectives: To define the arterial phenotype in mice conditionally ried out on the arteries of smooth muscle cell-specific Ctip2-knock - inactivated for the integrin αv subunit in VSMC and the role of this out (KO) mice at 3, 7, 28 days after tamoxifen injections. integrin in angiotensin II (Ang II)-induced arterial and VSMC stiffness. Results: There is no difference between control and mutant mice Methods and results: We used a VSMC specific knock-out αv mouse at the macroscopic level 3  days after Ctip2 KO induction, however, model induced in adult mice by injection of tamoxifen. Trangenic 7 day after Bcl11b inactivation, 65% of the Ctip2-SMKO mice showed mice (αvSMKO) and control littermates (Ctrl) were infused with Ang II signs of hemorrhage in the distal part of the thoracic aorta near the (1.5 mg/kg/day) for 4 weeks. The pressure effect of Ang II was similar in abdominal aorta. The histological examination of thoracic aorta at 7 Ctrl and αvSMKO mice. The carotid distensibility/pressure and elastic indicated the presence of “bumpy region” in the mutant aorta. These modulus/wall stress curves were similar in control and αvSMKO mice, areas is covered by a thicker layer of extracellular matrix and the indicating comparable arterial stiffness. Ang II treatment resulted in presence of IgG positive cells, indicating that cell death is occurring. increased carotid stiffness in both groups without changes in vascu- However, the hemorrhages is contained over time, do not impact lar reactivity and myogenic tone. Electronic microscopy revealed less A rtery Research vesicles containing fiber-like materials in the SMCs of Ang II-treated cardiovascular pathologies [2]. In the current project, we explore the αvSMKO carotids Elastic modulus of cultured VSMCs determined using impact of an AT biased agonist (TRV027) on the regulation of the cer- atomic force microscopy was higher after Ang II treatment in cells from ebral circulation. both groups. At baseline and after treatment, elastic modulus was Methods: We evaluated the TRV027 signaling on HEK293-cells higher in cells from αvSMKO mice than in cells from Ctrl mice.overexpressing AT using bioluminescence resonance energy Conclusion: Inactivation of αv-containing integrins on VSMCs transfer (NanoBRET) and calcium mobilization assays. In parallel, con- increases cell stiffness. The general mechanism involves a cross-talk centration–response curves to TRV027 were built on an ex vivo model between extracellular matrix, αv integrins and cytoskeletal complex. of isolated and perfused middle cerebral arteries (MCA) by measuring The lack of distensibility changes suggests additional changes at the changes in internal diameter. level of αv-mediated dynamics of focal adhesion. Results: BRET results show that TRV027 induces an activation of the β-arrestin pathway with a maximal increase of BRET ratio of 0.08 while Keywords: Integrin αv, vascular smooth muscle cells, cell stiffness inactivating the Gq pathway. Calcium mobilization assays confirm this Gq inactivation. As expected, results obtained in MCA show no effect of TRV027 on arterial diameter. P.005 Discussion: Tracking the A T receptor using specific fluorescent tools Estrogen modulates phenotypic state of male vascular smooth to follow its internalization (confocal microscopy) is currently under muscle cells exposed to flow conditions development. 1 1 1 1 The next step will be to assess in vivo the potential beneficial and pro - Enzo Lecoq , Nathan Wisniewski , Leo Jannot , Eva Feigerlova tective effects of TRV027 in cerebrovascular pathologies, in collabora- INSERM UMR_S 1116—DCAC Université de Lorraine, Nancy, France tion with Maastricht University. Although an estrogen-mediated vasculoprotective effect is widely References accepted in premenopausal women, literature data indicate that 1. Violin JD, Lefkowitz RJ. β‑Arrestin‑biased ligands at seven‑transmembrane estrogen therapy in transgender women confer an increased risk of receptors. Trends Pharmacol Sci. août 2007;28(8):416‑22. cardiovascular events. Vascular smooth muscle cell (VSMC) reside in a 2. Boerrigter G, Soergel DG, Lark MW, Burnett JC. TRV120027, a Novel Beta‑ 3-dimensional environment and are not normally exposed directly to Arrestin Biased Ligand at the Angiotensin II Type I Receptor, Unloads the shear stresses of flowing blood in the vascular system, because the the Heart and Maintains Renal Function When Added to Furosemide in endothelial cell layer provides the contacting surface for blood flow. Experimental Heart Failure. J Card Fail. août 2011;17(8):S63‑4. However, in cases of endothelial injury, the superficial layer of SMCs is exposed directly to blood flow shear stresses. We hypothesized that Keywords: AT receptor; cerebral circulation; β-arrestin; biased agonist treatment of male VSMCs with estrogens alters cell behavior. Our aim was to study the effect of shear stress on male VSMCs in a 2D Imaging technologies environment under flow model. Cells were treated with 17-β-estradiol and cultured in the Ibidi chamber under laminar flow and shear stress −2 of 1–2 dyn.cm . The cell orientation and morphology and phenotypic P.011 changes were analyzed. Non‑contact Method for Fast Localization of Perforator Arteries Results: We observed an increased expression of MYH10 exposed to 1,2 1 3,4 Valentina Vassilenko , Anna Poplavska , Diogo Casal , Edivaldo shear stress. The expression of MYH10 seems to be correlated with the 1,4 Junior orientation of VSMCs. The orientation of VSMCs treated with estrogens is parallel to the culture medium flow. Our preliminary results further Nova School Of Science And Technology—Nova University Of Lisbon, suggest an increased expression of the MMP-2 under estrogen treat- Campus FCT UNL, Portugal, Iberian Network on Arterial Structure, ment under flow conditions in the 2D model. Central Hemodynamics and Neurocognition,, Portugal, Plastic Conclusion: The differential effects of laminar flow and shear stress and Reconstructive Surgery Department and Burn Unit, Centro Hospitalar flow may be due to the different phenotypic state of the VSMCs. de Lisboa Central, Lisbon, Portugal, Anatomy Department, Nova Medical School—Nova University of Lisbon, Lisbon, Portugal Keywords: Sex hormones, Laminar flow and shear stress flow, Vascular Recently an extensive clinical experience in flap surgery has con- smooth muscle cell firmed that its success depends on the correct identification of vital perforator vessels [1]. Unfortunately, the perforator vessels frequently have a variable location. So, the knowledge about perforator anatomy Brain during preoperative planning is one of the most critical factors. In this work, we present the method and experimental results for non- P.006 contact and fast localization of the cutaneous perforators using Infra- Physiological effects of a biased angiotensin II type 1 receptor red Thermography (IRT ). This imaging technique can provide real-time agonist on cerebral circulation information on skin perfusion by measuring body surface tempera- 1,4 1 2 3 Mélissa Colin , Céline D elaitre , Sandra L ecat , Samir Acherar , ture. Validation of the method was performed against the ultrasound 4 1 1 Sébastien Foulquier , Isabelle Lartaud , François Dupuis. technology realized in the hand-held Doppler flowmeter, which is 1 2 widely used in most hospitals and is an essential tool where a rapid Université de Lorraine, CITHEFOR, Vandoeuvre‑lès‑Nancy, France, Uni‑ analysis of the vascular status of a patient is routine. versité de Strasbourg, CNRS, Biotechnologie et Signalisation Cellulaire, 3 Both technics were applied in this work for the identification of forearm Illkirch‑Graffenstaden, France, Université de Lorraine, CNRS, LCPM, Nancy, 4 cutaneous perforator vessels. The reflection of sound waves, predomi- France, Maastricht University, School for Mental Health and Neurosci‑ nantly from intravascular blood flow of the forearm, was registered by a ence, Maastricht, The Netherlands hand-held BT-200  V Vascular Doppler pan. The infrared images were Background: The angiotensin II type 1 (AT ) receptor has a relevant obtained by two cameras: FLIR E6 with temperature sensitivity < 0.06 °C role in the physiology and pathophysiology of the cerebrovascular and (320 × 240)-pixel display resolution, and Thermal Expert with sensitiv- system. Its vasoconstrictor effect, consecutive to Gq protein activa- ity < 0.05  °C and array format 640 × 480. Perforator mapping of the fore- tion, reduces cerebral perfusion during stroke. In addition, A T recep- arm area ware compared for accuracy, timing, and the operator’s skills. tor activity is directly regulated by the β-arrestin pathway, involved Obtained results show that IRT images provide valuable real-time in receptor internalization [1]. Recently, the development of biased information on the hemodynamic quality of perforators and their agonists, able to selectively activate the β-arrestin pathway without accurate location. Its potential to reveal underlying perforator vessels Gq activation appears to be a promising new therapeutic strategy in may also be used for postoperative monitoring of flap perfusion [2]. Artery Research References Methods: 49 runners (A) trained for 8.5 ± 8.9  years, 3.9 ± 1.4  days/ [1] D. Casal et al., “A Model of Free Tissue Transfer: The Rat Epigastric Free Flap,” week and 15 sedentary (S) subjects matched by sex, age, BMI, baseline J. Vis. Exp., no. 119, pp. 14–16, 2017. brachial pressures and heart rate underwent ultrasound semi-auto- [2] T. Sjøberg, J. B. Mercer, S. Weum, and L. de Weerd, “The Value of Dynamic matic assessment of the vascular system (arterial mean diameters, MD, Infrared Thermography in Pedicled Thoracodorsal Artery Perforator Flap and distensibility, DC, of abdominal aorta, common carotid, common Surgery,” Plast. Reconstr. Surg. – Glob. Open, vol. 8, no. 7, 2020. femoral, brachial artery) and of cardiac parameters. Central pressure- based (applanation tonometry) hemodynamic properties according to Keywords: Cutaneous Perforator Vessels (CPVs), Infrared Thermogra- the reservoir theory were derived. phy (IRT ), hand-held Doppler devices (HHDD), perforator mapping Results: Cardiac parameters related to dimensions, mass and vol- umes showed significantly higher values in A compared to S (A/S: Left Ventricular Internal diameter, 29 ± 3  mm/27 ± 3  mm; Left Ventricular P.013 Mass, 161 ± 31  g/141 ± 25  g; Aortic root size 30 ± 3  mm/27 ± 2  mm; Radial artery phenotyping in systemic sclerosis Stroke Volume, 76 ± 13  mL/69 ± 16  mL; Arterial Elastance, 7 ± 1  mm through ultra‑high frequency ultrasound: a radiomic approach –1 –1 HgmL /6 ± 1 mm HgmL ). 1 2 3 1,3 Federica Poli , Goncalo Boleto , Hakim Khettab , Pierre Bout ouyrie , MD was greater in each large arterial site in A than in S reporting a 2 1,3 Yannick Allanore , Rosa Maria Bruno trend in the carotid and significant differences in aorta and femoral artery (aorta: 16 ± 2  mm/13 ± 1  mm; femoral: 10 ± 1  mm/9 ± 1  mm). Paris Cardiovascular Research Center (PARCC)‑INSERM UMR‑970, Paris, DC evidenced a lowering trend in A for each arterial site except for the France, Department of Rheumatology, Université de Paris, Cochin Hospi‑ brachial artery. Hemodynamic parameters showed higher reservoir tal, Paris, France, AP‑HP, Hopital Européen Georges Pompidou, Université pressure in A compared to S (Pressure reservoir integral, 14 ± 4/11 ± 3). de Paris, Paris, France Conclusions: Strenuous exercise induced a well-known cardiac Background: Systemic sclerosis (SSc) is a disorder characterized by a remodeling which can be hypothesized to be slower in the arte- massive vascular involvement. Imaging biomarkers of vascular involve- rial tree because of highly differentiated and complex mechanism ment in SSc may have potential clinical implications for prediction of aiming to heart protection. Accordingly, the increased reservoir the pathogenesis of vascular complications [1]. This study is aimed at pressure in runners could be interpreted as sentinel parameter of identifying possible patterns of vascular wall disarray and remodeling vascular “fatigue”. in radial arteries of SSc patients, by means of ultrahigh frequency ultra- sound (UHFUS). References Methods: 5 end-diastolic frames of the right radial arteries of 41 1. Heffernan KS, Yoon ES, Sharman JE, Davies JE, Shih Y T, Chen CH, et al. patients with SSc and 41 healthy controls were obtained by VevoMD Resistance exercise training reduces arterial reservoir pressure in (70  MHz probe, FUJIFILM, VisualSonics, Toronto, Canada). 74 radiomic older adults with prehypertension and hypertension. Hypertens Res. features and 4 engineered parameters were extracted: inner and outer 2013;36(5):422–7. layer thickness, and presence of adjunctive acoustic interfaces (triple 2. Ramos JS, Ramos M V., Dalleck LC, Borrani F, Walker KB, Fassett RG, et al. signal). A feature selection algorithm was applied to reduce the num- Fitness Is Independently Associated with Central Hemodynamics in ber of features. The selected features were used to train classification Metabolic Syndrome. Med Sci Sports Exerc. 2016;48(8):1539–47. model, using Linear Support Vector Machine (SVM). 3. Ujka K, Bruno RM, Bastiani L, Bernardi E, Sdringola P, Dikic N, et al. Results: The SVM classification model showed good performance Relationship between occupational physical activity and subclinical (sensitivity = 0.63, specificity = 0.88, accuracy = 0.75, AUC = 0.75) to vascular damage in moderate‑altitude dwellers. High Alt Med Biol. discriminate SSc patients from controls using sixteen selected fea- 2017;18(3):249–57. tures. Inner layer (208 ± 61 vs 179 ± 47  µm, p = 0.04) and outer layer thickness (104 ± 22 vs 120 ± 36  µm, p = 0.03) were significantly higher Keywords: Cardiovascular adaptation, exercise, ultrasound in SSc than in controls, triple signal pattern more frequent in patients (p = 0.002). Conclusions: Wall ultrastructure of radial arteries of SSc patients is P.015 altered: inner and outer layer thickened, showing frequently a triple Sex‑related differences in skin microvascular function of healthy signal pattern. Radiomic approach allow to distinguish between radial normotensive individuals as assessed with laser speckle contrast images from SSc patients and controls with a 75% accuracy. imaging 1 1 1 Reference Antonios Lazaridis , Konstantinos Mastrogiannis , Anastasia Malliora , 1 1 1 1. Allanore Y, Distler O, Matucci‑ Cerinic M, Denton CP. Review: Defining a Stamatina Lamprou , Nikolaos Koletsos , Barbara Nikolaidou , Panagiotis 1 1 1 Unified Vascular Phenotype in Systemic Sclerosis. Arthritis Rheumatol Dolgyras, Areti Triantafyllou , Eugenia Gkaliagkousi Hoboken NJ. febbraio 2018;70(2):162–70. 3rd Department of Internal Medicine, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Keywords: UHFUS, radial arteries, radiomic analysis, machine learning Background: Skin microcirculation is considered a window to assess generalized microvascular function. Changes in skin micro- P.014 Cardiovascular adaptation to strenuous exercise: exploring vascular function (SMF) have been identified in several cardiovas- the complexity of the arterial protective role for the heart cular disease states. However, scarce data exists regarding SMF in 1 1 1 Maria Raffaella Martina , Elisabetta Bianchini , Marco Scalese , Nicole healthy adults and the impact of gender on it [1,2]. In this study, we 1 2 1 Di Lascio , Rosa Maria Bruno , Lorenza Pratali. assessed SMF in healthy individuals with the dynamic technique Lase Speckle Contrast Imaging (LSCI). Institute of Clinical Physiology—Italian National Research Council Methods: Healthy normotensives were included in the study. Office (CNR‑IFC), Pisa, Italy, Université Paris Cité, Inserm, PARCC, F‑75015, Paris, blood pressure (BP) was measured according to standard guidelines. France SMF was assessed with LSCI (PeriCam PSI NR, Perimed, Sweden) cou- pled with post-occlusive reactive hyperemia (PORH). Results were Background: The intense exercise effect evaluation on the cardiovas- expressed as perfusion during baseline, occlusion and peak period cular system can help to profile and reduce the risks (1–3). This work (arbitrary Perfusion Units,PUs), time until maximal perfusion (sec), the aims at assessing cardiovascular adaptation in runners by a multi-site percentage increase of perfusion between baseline and peak period non-invasive approach. A rtery Research (%) and PORH amplitude calculated as peak cutaneous vascular con- ductance (CVC) – baseline CVC. CVC was calculated as mean perfu- sion during each PORH period divided by mean BP (LSPUs/mmHg). Results: We studied 86 healthy normotensives including 50 women and 36 age-matched men. Body mass index, creatinine, office sys- tolic BP (SBP) and diastolic BP (DBP) were significantly higher in men compared to women. Regarding SMF, perfusion during baseline and occlusion, baseline CVC, peak CVC and PORH amplitude (0.89 ± 0.21 vs 0.75 ± 0.19, p < 0.01) were significantly higher in females compared to males. In addition, PORH was negatively associated with office SBP (r = − 0.258, p < 0.05). Conclusions: Healthy females present significantly higher SMF param- eters compared to age-matched males. Further research is needed to clarify the impact of gender on microvascular function and its further implications. References (a): AA longitudinal (white) and radial (red) strain from sagittal MRI [1] Stupin A, Stupin M, Baric L, Matic A, Kolar L and Drenjancevic I. Sex‑related (b): Dist-axial (left), DistR-sagittal (middle) and DistL-sagittal (right) differences in forearm skin microvascular reactivity of young healthy according to subject group: HV < 40  years, HV ≥ 40  years and AVS subjects. Clin Hemorheol Microcirc. 2019;72(4):339–351. patients. [2] Hodges G, Sharp L, Clements R, Goldspink R, George K, and Cable N. Influ‑ ence of age, sex, and aerobic capacity on forearm and skin blood flow References and vascular conductance. Eur J Appl Physiol. 2010;109(6):1009–15. [1] Lamy J, Soulat G, Evin M, Huber A, de Cesare A, Giron A, et al. Scan‑rescan reproducibility of ventricular and atrial MRI feature tracking strain. Com‑ Keywords: Microcirculation, laser speckle contrast imaging, perfusion, put Biol Med. 2018; 92:197–203. https:// doi. org/ 10. 1016/j. compb iomed. skin microvascular function 2017. 11. 015. [2] Redheuil A, Yu WC, Wu CO, Mousseaux E, de Cesare A, Yan R, Kachenoura P.021 N, Bluemke D, Lima JA. Reduced ascending aortic strain and distensibil‑ Longitudinal and radial distensibility of the ascending aorta ity: earliest manifestations of vascular aging in humans. Hypertension. in aging and aortic valve stenosis using MRI feature tracking 2010 Feb;55(2):319–26. https:// doi. org/ 10. 1161/ HYPER TENSI ONAHA. 109. 1,2 3 1 141275. Marie Shannon Soulez , Jérôme Lam y, Vincent Nguyen , Umit 4 4 4 1 Gencer , Gilles Soulat , Elie Mousseaux , Emilie Bollache , Nadjia 1 Keywords: MRI, Aortic strain, Aging, Aortic valve stenosis Kachenoura Sorbonne Université, CNRS, INSERM, Laboratoire d’Imagerie Biomédicale, Hypertension 2 3 LIB, Paris, France, Université Paris‑Est Créteil, Creteil, France, Department of Radiology and Biomedical Imaging, Yale University, New Haven, USA, P.022 PARCC, Université de Paris, Inserm/AP‑HP, Hôpital Européen Georges Exploring strain‑dependent collagen degradation as a driver Pompidou, Paris, France of hypertension‑induced arterial remodelling in lean ZSF1 rats: Background: We aimed to test the feasibility of MRI-based feature a pilot study tracking (FT) to measure longitudinal strain and radial motion frac- 1,2 1,2 3,4 Koen van der Laan , Koen Reesink , Sara Lambrichts , Laura van der tion of the proximal ascending aorta (AA) and to investigate how these 1,3 1 1,2 1,3,4 Taelen , Nicole Bitsch, Tammo Delhaas , Sebastien Foulquier , Bart measures are affected by aging and by the presence of calcified aortic 1,2,5 Spronck valve stenosis (AVS). 1 2 Methods: Twenty healthy volunteers (HV ) < 40 years (29 ± 1.6 years, 10 Carim, University Maastricht, Maastricht, Netherlands, Department males), 20 HV ≥ 40 years (58 ± 1.5 years, 10 males) and 31 patients with of Biomedical Engineering, Maastricht University medical centre, AVS (73 ± 1.6 years, 20 males) underwent 2D cine thoracic aortic MRI in Maastricht, Netherlands, Department of Pharmacology & Toxicology, sagittal and axial views immediately followed by carotid artery appla- Maastricht University, Maastricht, Netherlands, MHENS School for Mental nation tonometry. AA anterior wall (Figure a) was semi-automatically Health and Neuroscience, Maastricht University, Maastricht, Netherlands, tracked on sagittal images throughout the cardiac cycle to estimate Macquarie Medical School, Faculty of Medicine, Health and Human Sci‑ longitudinal strain and radial motion fraction peaks, while using cus- ences, Macquarie University, Sydney, Australia. tom FT software [1], which was previously dedicated to multi-chamber Background: Hypertension-induced arterial remodelling involves e.g., strain evaluation in the heart. Conventional global AA strain was also increased wall thickness, changes in collagen structure and increased measured on axial views based on cross-sectional area [2]. Finally, dis- collagen content [1]. Normally, collagen is degraded and deposited in tensibility was derived as strain/central pulse pressure. 8–10 week turn-over cycles [2]. Collagen fibre strain significantly influ- Results: Axial (Dist-axial: R = − 0.82, p < 0.0001) and sagittal (radial ences enzymatic degradation efficiency, where straightened but not DistR-sagittal: R = − 0.54, p = 0.0004, longitudinal DistL-sagittal: overstretched fibres experience minimum degradation (Fig. A) [3]. In R = − 0.37, p = 0.02) distensibility measures decreased significantly a homeostatic situation where collagen experiences minimum deg- with age and even more in the presence of AVS (Figure b). When inves- radation at mean arterial pressure, fibres would be optimally strained tigating the ability of distensibility measures to discriminate HV from [4]. The onset of hypertension overstretches collagen (1 in Fig. B), patients, newly proposed DistR-sagittal (0.84) and DistL-sagittal (0.92) demonstrated higher area under the ROC curve than Dist-axial (0.81). Conclusions: MRI FT revealed that age has a stronger impact on AA axial distensibility, while longitudinal distensibility could be more sen- sitive to the effect of AVS probably because of valvular calcifications that limit this longitudinal motion specifically. Artery Research accelerating collagen degradation [4]. We hypothesise that optimally P.024 strained fibres will gradually make up the bulk of collagen during Eec ff ts of Nitroglycerin Induced Vasodilation on Elastic hypertension, as overstrained collagen degrades faster. This implies versus Muscular Artery Stiffness in Older Veterans that, as collagen returns to the optimal level of strain, increased colla- 1 1 2 1 Ryan Pewowaruk , Amy Hein , Claudiq Korcarz , Adam Gepner. gen content is required to maintain luminal diameter and avoid dilata- William S. Middleton Memorial Veterans Hospital, Madison, United tion (2 in Fig. B). We evaluated this hypothesis, expecting hypertensive States, University of Wisconsin School of Medicine and Public Health, rat aorta to exhibit less collagen strain under normotensive conditions Madison, United States compared to normotensive control (3 in Fig. B). Methods: One normotensive (NT, Wistar) and one hypertensive (HT, Background: Vascular smooth muscle tone may play an important ZSF1 lean [5]) 22-week-old rat abdominal aorta were stretched to role in the physiology of increased arterial stiffness that occurs with in  vivo-like length and pressurised to 100  mmHg. Three-dimensional aging. This study evaluated the impact of smooth muscle tone on collagen structure was then imaged by second harmonic generation arterial stiffness in older individuals following nitroglycerin induced using a two-photon microscope. vasodilation in elastic and muscular arteries. Results: At 100 mmHg, the HT artery visibly displayed a thicker colla- Methods: 40 older Veterans (> 60 years old), without known cardio- gen layer and curlier collagen fibres than the NT artery (Fig. C-F), sug- vascular disease, were included in this study. 20 were hypertensive gesting lower collagen fibre strain at normotensive pressures (3 in Fig. (70.8 ± 6.6  years, 10 female) and 20 were normotensive controls B). (72.0 ± 9.3  years, 8 female). Nitroglycerin (NTG) induced changes in Conclusions: Strain-dependent collagen degradation may be a key arterial stiffness were measured locally with vascular ultrasound in process driving hypertension-induced arterial remodelling. the carotid and brachial arteries, and regionally by carotid-femoral pulse wave velocity (cfPWV ) by tonometry. Results: With NTG, both hypertensive and normotensive control Vet- erans showed increased carotid PWV (6.4 ± 1.3 m/s to 7.2 ± 1.4  m/s, Δ 0.8 ± 1.1  m/s, p = 0.007) and cfPWV (8.6 ± 1.9 m/s to 9.5 ± 2.4  m/s, Δ 0.9 ± 2.3  m/s, p = 0.020) but did not change brachial PWV (11.2 ± 2.4  m/s to 11.1 ± 2.2  m/s, Δ − 0.2 ± 2.5  m/s, p = 0.72). The carotid artery dilated more in control participants than hypertensive Veterans (Δ 0.54 ± 0.19  mm vs 0.42 ± 0.12  mm, p = 0.022). Brachial artery dilation was similar, (Δ 0.55 ± 0.26  mm vs 0.51 ± 0.20  mm, p = 0.46). Conclusion: In older Veterans, without known cardiovascular dis- ease, NTG induced vasodilation increased elastic artery stiffness and did not change muscular artery stiffness. Increased central arterial stiffness and reduction in the arterial stiffness gradient could offset some of the benefits of lowering blood pressure in older patients who are prescribed vasodilators as an antihypertensive therapy. Elastic artery stiffening with vasodilation warrants further investiga- tion as it may be important for antihypertensive medication selec- tion and influence CVD development. A: Straight-but-not-overstretched collagen experiences minimal degradation [3]. B: Diameter maintenance in hypertension requires additional collagen at minimum-degradation strain. More and curlier collagen in hypertension (E–F) than normotension (C-D). References 1. Intengan and Schiffrin. Vascular remodeling in hypertension. Hypertension. 2001;38:581–587. 2. Nissen et al. Increased turnover of arterial collagen in hypertensive rats. Proc Natl Acad Sci USA. 1978;75:451–453. 3. Gaul et al. Strain mediated enzymatic degradation of arterial tissue. Acta Biomater. 2018;77:301–310. 4. Gaul et al. Pressure‑induced collagen degradation in arterial tissue as a potential mechanism for degenerative arterial disease progression. J Mech Behav Biomed Mater. 2020;109:103,771. Graphic abstract overviewing 1. research question, 2. methods, 3. 5. Hamdani et al. Myocardial titin hypophosphorylation importantly contrib‑ results, and 4. clinical implications of findings utes to heart failure with preserved ejection fraction in a rat metabolic risk model. Circ Heart Fail. 2013;6:1239–1249. Reference Pewowaruk RJ, Gepner AD. Smooth muscle tone alters arterial stiffness: the Keywords: Remoddeling strain collagen degradation importance of the extracellular matrix to vascular smooth muscle stiff‑ ness ratio. J Hypertens. 2022 Mar 1;40(3):512–519. Keywords: Vascular stiffness, hypertension, vasodilation, smooth muscle A rtery Research P.025 arterial elastance, Ea, and end-systolic elastance, Ees were computed ® ® Performance of  pOpmetre versus  SphygmoCor to detect central during rest, exercise, and recovery. arterial stiffness using central aortic pressures Results: At rest, subjects with Ipc-PH or No PH tended to have lower 1 2 2 3 ZC and Ea than those with PAH (Fig.  1A&C); all Ees values were simi- Mathilde Laime , Hasan Obeid , Imad Abi‑Nasr , Hakim Khettab , Magid 2 3 4,5 lar (Fig.  1b). During exercise, Zc decreased in the subject with No PH, Hallab , Pierre Bout ouyrie , Loukman Omarjee whereas it increased in those with Ipc-PH and did not change in those University Bretagne Occidentale, Laboratoire ORPHY, Brest, France, with PAH. During exercise, both Ees and Ea increased for all subjects 2 3 Clinique Bizet, Cardiology unit, Paris, France, Pharmacology department, but the increase in Ea was larger than the increase in Ees for both the European Georges Pompidou Hospital and Assistance Publique Hôpitaux PAH and Ipc-PH groups, suggesting RV:PA uncoupling. Interestingly, de Paris, Paris Cardiovascular Research Center (PARCC), Paris, France, Univ the changes in ZC and Ees/Ea were inversely related in Ipc-PH during Rennes, CHU Rennes, INSERM CIC1414, Vascular Medicine Department, exercise. Rennes, France, Vascular Medicine Department, Redon Hospital, 35600, Conclusions: With the limitation that the sample size is small, our find- Redon, Redon, France ings suggest that analysis of pulsatile pulmonary hemodynamics and RV:PA coupling with exercise can reveal distinctive PH phenotypes and Central arterial stiffness is an independent predictor of cardiovascular have diagnostic value. and total mortality. It can be diagnose directly by aortic pulse wave velocity (aPWV ) or indirectly by central aortic pressures (CAP). SphygmoCor , a non-invasive device using applanation tonometry, is the gold standard to measure CAP. However, its complexity limits its use in clinical practice. The aim of this study is to evaluate the accuracy of a novel non- invasive device, pOpmètre (Axelife SAS, Saint-Nicolas de Redon, France), to measure CAP in suspected peripheral arterial disease (PAD) patients. Systolic, diastolic and central pulse pressures measured with pOpmè- ® ® tre are compared with those measured with SphygmoCor . In this pilot, monocentric, prospective study, 53 suspected PAD patients were included. Among them: i) 26 patients (age: 69 ± 10y; 65% men) were diagnosed with peripheral arterial obstructive disease (PAOD) defined by a toe-brachial index ≤ 0.7 and/or an ankle-brachial index (ABI) ≤ 0.9; ii) 10 patients (age: 74 ± 9y; 70% men) were diag- nosed with peripheral arterial stiffness (mediacalcosis) defined by an ABI > 1.4; iii) 20 patients (age: 55 ± 16; 40% men) without PAD diagno- sis. There was a significant correlation between systolic, diastolic and central pulse pressures measured by pOpmètre compared with those measured by SphygmoCor in PAD patients (respectively, R2 = [0.94, 1.00, 0.84]; p = [10e − 16, 10e − 16, 10e − 11]), peripheral arterial stiffness patients (respectively, R2 = [0.96, 1.00, 0.84]; p = [10e − 8, 10e − 13, 10e − 7]) and no PAD patients (R2 = [0.98, 1.00, 0.97]]; p = [10e − 12, 10e − 16, 10e − 8]). CAP assessed by pOpmètre could be used in clinical practice to References: detect central arterial stiffness in suspected PAD patients. [1] Rosenkranz, S et al., Circulation, 141(8):678–693, 2020. Reference [2] Al‑ Omary, MS et al., Hypertension, 75(6):1397–1408, 2020. McEniery CM, Cockcroft JR, Roman MJ, Franklin SS, Wilkinson IB. Central blood [3] Vanderpool, RR et al., Annals of Biomedical Engineering, 38(5):1854–1861, pressure: current evidence and clinical importance. Eur Heart J. 7 juill 2010. 2014;35(26):1719‑25. [4] Sabbahi, A et al., Expert Review of Respiratory Medicine, 14(3):317–327, Keywords: Central aortic pressure, Peripheral arterial disease Keywords: Impedance, Coupling, Hypertension, Exercise. P.027 Obesity, metabolic disorders and cardiovascular disease Analyses of pulsatile pulmonary hemodynamics and right ventricular function during exercise P.030 1 1 1 Christopher Lechuga , Farhan Raza , Mitchel J. Colebank , Naomi C. Relationship between aortic and carotid stiffness with measures Chesler. of adiposity in adolescents. The maciste study University of California, Irvine, Irvine, United States 1,2 3 3 Giacomo Pucci , Mariella Martina , Elisabetta Bianchini , Vincenzo 3 1,2 1,2 4 Gemignani , Marco D’Abbondanza , Rosa Curcio , Francesca Battista , Background: Pulmonary hypertension (PH) leads to a mismatched 5 1,2 Fabio Anastasio, Gaetano Vaudo right ventricular (RV)-pulmonary arterial (PA) relationship (uncou- pling), which increases mortality [1]. Current diagnostic strategies 1 Department of Medicine and Surgery—University of Perugia, Perugia, utilize pulmonary vascular resistance (PVR) [2] but disregard the oppo- 2 3 Italy, "Santa Maria" University Hospital, Terni, Italy, Institute of Clinical sition to pulsatile flow as well as response to exercise [3,4]. We hypoth- 4 Physiology—National Council of Research, Pisa, Italy, Sports Medicine— esize that pulsatile pulmonary hemodynamics during exercise and 5 University of Padua, Padua, Italy, Cardiology Division—Mondovì Hospital, their relationship to RV-PA coupling can differentiate PH phenotypes Cuneo, Italy and refine diagnoses. Methods: 13 adult subjects with precapillary PH (PAH; n = 5), isolated Background: We evaluated the differential association between arte - postcapillary PH (Ipc-PH; n = 5), or no PH (No PH; n = 1) performed rial stiffness, taken at different arterial segments (aortic and carotid), invasive cardiopulmonary exercise testing with echocardiography- with global and local measures of adiposity, accounting for BP as a based pulmonary vascular pressure-flow and catheter-based RV pres- mediator of the relationship between fat accumulation and increased sure–volume data collection. Characteristic impedance ZC, effective arterial stiffness. Artery Research Bessa LR, Cruz LAB, Lima RLS, Presta MCLF, Alves Filho AAO, Cunha, RCA, et al. Methods: 322 healthy Italian adolescents from the MACISTE Study Correlation between Neck Circumference and Pulse Wave Velocity: A (Metabolic and Cardiovascular Investigation at School, TErni), were Population‑based Study. Rev Artery Research 2020. evaluated. BMI, waist, hip and neck circumferences (NC) were taken Instituto Brasileiro de Geografia e Estatística (IBGE). CensoIBGE 2010. Brazil: as measures of adiposity. Laboratory measures of adiposity were also IBGE; 2010. collected. Arterial stiffness was measured through carotid-femoral pulse wave velocity (applanation tonometry, SphygmoCor), and at the Keywords: Obesity, Pulse wave speed, Arterial stiffness carotid level (Cardiovascular suite, Quipu, Italy). Results: Mean age 17 ± 1.4 years, 56% boys, 40 (12%) with overweight. All central and peripheral measures of BP were higher in overweight vs normoweight (all p < 0.01) excluding peripheral and central DBPs, P.032 which were lower in overweight. The aortic-to-brachial pulse pressure In vivo measurement of blood pressure and pulse wave velocity amplification was reduced in overweight vs normoweight (1.51 ± 0.13 in streptozotocin‑induced type 1 diabetes in mice vs 1.58 ± 0,13, p < 0.01). Carotid and aortic stiffness were positively cor - 1,2 1,3 3,4 related with anthropometric and laboratory measures of adiposity. Margarita G. Pencheva , Eline Berends , Peter Leenders , Myrthe M. 1,2 2 2,5 After adjustment for MAP, only NC remained associated with carotid van der Bruggen , Koen W.F. van der Laan , Alessandro Giudici , Koen 2 3 2,6 1 (β = 0.24, p < 0.01) and aortic stiffness (β = 0.16, p = 0.02). After adjust- D. Reesink , Sébastien Foulquier , Bart Spronck , Casper G. Schalkwijk ment for central PP, only carotid (β = 0.15, p = 0.04), but not aortic stiff- Depatrment of Internal Medicine, CARIM School for Cardiovascular ness (β = 0.12, p = 0.07) was associated with NC. Diseases, Maastricht University, Maastricht, The Netherlands, Dept. Conclusions: Arterial stiffness, when assessed at different levels of of Biomedical Engineering, CARIM School for Cardiovascular Diseases, central arteries, showed site-specific associations with measures of Maastricht University, Maastricht, The Netherlands, Dept. of Pharmacol‑ body fat adiposity. NC was the only measure of adiposity to show a ogy and Toxicology, CARIM School for Cardiovascular Diseases, Maastricht BP-independent association with carotid stiffness. Carotid stiffness is University, Maastricht, The Netherlands, Dept. of Biochemistry, CARIM a promising marker of pressure-independent vascular damage pro- School for Cardiovascular Diseases, Maastricht University, Maastricht, The moted by overweight status. Netherlands, GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands, Macquarie Medical School, Keywords: Adolescents, adiposity, carotid stiffness, blood pressure Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia P.031 Background: In humans, type 1 diabetes (T1D) is associated with Obesity and Cardiovascular Risk Factors in the Outcome arterial stiffening as assessed by carotid-femoral pulse wave velocity of Arterial Stiffness (cfPWV) [1]. To experimentally study the underlying mechanism of this 1 1 1 Gabriela Portugal , Mariana Mendes , Laysa Rebouças , Lucelia stiffening, we investigated blood pressure (BP) and cfPWV in strepto - Magalhães zotocin (STZ)-induced diabetes in mice. Methods: Twenty-four 9-week-old male C57BL/6  J mice were divided Uniftc, Salvador, Brazil equally among diabetic (induced through once-daily 50  mg/kg STZ Obesity is one of the biggest health problems in the world. It is injections for five days) and control (sham injections using citrate constituted as the second most important risk factor for the devel- buffer) groups, and were kept to an age of 24  weeks. Fasting glucose opment of chronic non-communicable diseases. In this sense, it is was measured every 4–5  weeks via tail blood collection with levels assumed that the increase in arterial stiffness is on the path between of 15  mmol/L and higher considered diabetic. Non-invasive tono- obesity and cardiovascular diseases. The objective of this study was metric cfPWV was measured in anaesthetised animals (1% isoflurane) to evaluate the correlation between obesity and cardiovascular risk 24  h prior to euthanasia; tail-cuff BP was measured directly prior to factors with arterial stiffness in patients treated at a teaching clinic euthanasia. in the university center, Salvador-Ba, in 2022. This is an observa- Results: Diabetic mice exhibited higher fasting glucose than controls tional, cross-sectional and analytical study. The studied population (p < 0.0001, two-way ANOVA with Tukey post-hoc test; Fig. A). There comprised individuals residing in the Valley of Ogunjá neighbor- was no difference in systolic BP (110 ± 4 vs. 104 ± 3  mmHg, p = 0.26, hood, Acupe in Brotas, both sexes, over 18  years of age and obese. mean ± SE, unpaired t-test) and cfPWV (2.60 ± 0.14 vs. 2.55 ± 0.11 m/s, The indicators of obesity were: waist circumference (women > 88 cm p = 0.80) between diabetic and control mice (Fig. B-C). and men > 90 cm), cervical (> 34 cm in women and > 37 cm in men), Discussion: In the popular animal model of STZ-induced T1D, existing waist-hip ratio (> 0.80 in women and > 0.95 in men), body mass literature on systolic BP is not consistent [2,3]. Literature about cfPWV index (BMI) (> 30 kg/m ) and evaluation of the carotid-femoral pulse is limited: in contrast to our data, one report showed an STZ-induced wave velocity (PWV ) (> 10 m/s). The results obtained denote a direct increase in ultrasound-derived cfPWV [4]. Discrepancies between stud- to statistically significant linear correlation: waist circumference indi- ies could be due to different methods of measuring BP and cfPWV [5]; cator associated with PWV (p value 0.055), waist-hip ratio (p-value the choice of measurement methods therefore needs critical appraisal. 0.003), cervical circumference (p-value 0.004). Only the BMI indicator Conclusion: In the murine model of STZ-induced T1D, we did not find associated with PWV (p value 0.584) was not statistically significant. elevated BP or increased arterial stiffness. It is concluded that the indicators of abdominal and cervical circum- ference and waist-hip ratio obtained statistical significance when attributed to PWV and can be used as indicators of arterial stiffness. References Associação Brasileira para o Estudo da Obesidade e Síndrome Metabólica. Mapa da Obesidade [internet]. Higienópolis: 2021 [citied: Out 24 2021]. Available from: https:// abeso. org. br/ obesi dade‑e‑ sindr ome‑ metab olica/ mapa da‑ obesidade/. Brasil. Saúde prepara ações para controle do excesso de peso e da obesidade Despite clearly increased fasting blood glucose (A), streptozotocin- [Internet]. Brasília: Ministério da Saúde,2020 [cited: Out 24 2021]. Available induced diabetic mice did not show increased blood pressure (B) from: https:// aps. saude. gov. br/ notic ia/ 10137#: ~: text=O% 20Min ist% C3% or arterial stiffness (C). Shown are mean ± SE; ****p < 0.0001; ns, not A9rio% 20da% 20Sa% C3% BAde% 20ir% C3% A1,de% 20pro mo% C3% A7% significant. C3% A3o% 20de% 20da% 20sa% C3% BAde. A rtery Research References: LVET (left) and iLVET (right) against EF Simpson, effect direction 1. Tougaard NH, Theilade S, Winther SA, Tofte N, Ahluwalia TS, Hansen TW, et al. between second and first visit. Gray arrows show individual meas- J Am Heart Assoc. 2020;9:e017165. urements, the blue arrow shows the mean effect over 37 subjects. 2. Gurley SB, Clare SE, Snow KP, Hu A, Meyer TW, Coffman TM. Am J Physiol Renal Physiol. 2010;298:F788‑795. References 3. Zhong F, Chen H, Wei C, Zhang W, Li Z, Jain MK, et al. Kidney Int. [1] A. Haiden, B. Eber, and T. Weber, ‘U‑Shaped Relationship of Left Ventricu‑ 2015;87:382–395. lar Ejection Time Index and All‑ Cause Mortality’, American Journal of 4. Heath JM, Sun Y, Yuan K, Bradley WE, Litovsky S, Dell’Italia LJ, et al. Circ Res. Hypertension, vol. 27, no. 5, pp. 702–709, Mai 2014, https:// doi. org/ 10. 2014;114:1094–1102. 1093/ ajh/ hpt185. 5. Leloup AJ, Fransen P, Van Hove CE, Demolder M, De Keulenaer GW, Schrijvers [2] A. Bauer, B. Hametner, T. Weber, and S. Wassertheurer, ‘Method Comparison DM. Hypertension. 2014;64:195–200. and Validation of the Determination of Ejection Duration from Oscillo‑ metric Measurements’, IFAC‑PapersOnLine, vol. 51, no. 2, pp. 343–348, Jan. Keywords: Diabetes, streptozotocin, blood pressure, pulse wave 2018, https:// doi. org/ 10. 1016/j. ifacol. 2018. 03. 059. velocity [3] Lewis R P, Rittogers S E, Froester W F, and Boudoulas H, ‘A critical review of the systolic time intervals.’, Circulation, vol. 56, no. 2, pp. 146–158, Aug. 1977, https:// doi. org/ 10. 1161/ 01. CIR. 56.2. 146. P.033 Pulse waveform analysis for monitoring of left ventricular function in patients with severely reduced ejection fraction P.034 Sex‑specific association between the metabolic score for insulin 1,4 1 1 Stefan Orter , Bernhard Hametner, Siegfried Wassertheurer , Kathrin resistance and arterial stiffness in middle‑aged adults 2 3 3 4 Danninger , Antonis Ar gyris , Athanase Protogerou , Eugenijus K aniusas , with metabolic syndrome 2 2 Ronald Binder, Thomas Weber 1 2,3 3 Jurgita Mikolaitytė , Agnė Laučytė‑Cibulskienė , Ligita Ryliškytė , Center for Health & Bioresources, AIT Austrian Institute of Technology, 1,3 Jolita Badarienė Vienna, Austria, Cardiology Department, Klinikum Wels‑Grieskirchen, 3 1 Wels, Austria, Cardiovascular Prevention and Research Unit, Laiko Hospi‑ State Research Institute Centre for Innovative Medicine, Vilnius, Lithu‑ 4 2 tal, Athens, Greece, Institute of Biomedical Electronics, Vienna University ania, Department of Nephrology, Lund University, Malmö, Sweden, of Technology, Vienna, Austria Faculty of Medicine, Vilnius University, Vilnius, Lithuania Background: Impaired systolic function of the left ventricle leads to Background: The Metabolic Score for Insulin Resistance (METS-IR) is shortening of the left ventricular ejection time (LVET ) and heart rate a non-insulin-based metabolic index used as a substitution marker of adjusted LVET (iLVET)[1]. The aim of this study is the investigation insulin resistance and cardiometabolic risk. Previous studies have sug- of the improvement in left ventricular function using radial pulse gested that insulin resistance is significantly related to the develop - waveforms compared to improvement assessed by ejection fraction ment and progression of coronary atherosclerosis and adverse plaque (EF). characteristics. The main objective of this study was to evaluate the Methods: 37 patients (7 females) with heart failure (HF) with reduced sex-specific relationship between METS-IR and arterial parameters in ejection fraction (HFrEF) were treated according to HF guidelines. EF the middle-aged Lithuanian population with metabolic syndrome. and its changes under treatment were monitored with echocardiogra- Methods: A total of 2064 subjects (1136 women and 928 men). phy (EPIQ, Philips, Simpson method with apical 4-chamber view), and Anthropometric, laboratory testing, and cardiovascular risk factors LVET was monitored with tonometry (SphygmoCor, AtCor Medical, along with arterial parameters (carotid-radial pulse wave velocity method based on numerical derivatives)[2]. Furthermore, LVET was (crPWV ), carotid-femoral pulse wave velocity (cfPWV ), carotid intima- adjusted for heart rate[3]. Visualization of differences between first media thickness (CIMT), ankle-brachial index (ABI), cardio-ankle vas- and second visit was done by 4-quadrant plots (Fig.  1) and concord- cular index (CAVI) and atherosclerotic plaques) were evaluated. ance rate was calculated. Results: After stratifying subjects into sex-specific METS-IR quartiles, Results: Patients mean age and body height were 54  years, and we observed statistically significant differences in all arterial param- 174 cm respectively. Their average weight decreased from 89 to 88 kg. eters among METS-IR quartiles, except for crPWV in men (p = 0.533). Measured basic parameters on first and second visit were HR (68BPM Differences between men and women in the METS-IR quartiles were vs. 60BPM), SBP (128  mmHg vs. 128  mmHg), DBP (81  mmHg vs. observed only in cfPWV (p < 0.05), CAVI (p < 0.05), and CIMT (p < 0.001). 76 mmHg), EF (25% vs. 42%), LVET (0.266 s vs. 0.289 s), iLVET (0.380 vs. In a fully adjusted linear regression analysis, METS-IR was associated 0.389), percentage of patients with betablocker intake (76% vs. 97%), with CAVI in both men (p = 0.005) and women (p < 0.001). However, and percentage of patients with ACE-I/ARB/ARNI intake (92% vs. 97%). ABI—only in men (p = 0.040), and CIMT – in women (p = 0.025). The mean timespan between first and second measurements was Conclusion: Insulin resistance measured by METS-IR is associated with 100  days. A concordance rate of 0.84 for LVET and 0.65 for iLVET was CAVI in both men and women in the middle-aged Lithuanian popula- observed. tion with metabolic syndrome. Additionally, in men, it is also associ- Conclusions: Automatically measured LVET and iLVET from radial ated with ABI, whereas in women – with CIMT. pressure waveforms is suitable for monitoring the improvement of EF with medical treatment in HFrEF. Keywords: Arterial stiffness, cardio-ankle vascular index, carotid intima-media thickness, ankle-brachial index, Metabolic Score for Insu- lin Resistance P.036 The effects of different types of calorie restriction on atherosclerosis‑related miRNAs in mice 1 2 2 Dilara Buse Durdabak , Nazim Arda Keles , Soner Dogan , Bilge Guvenc Tuna Department of Biophysics, School of Medicine, Yeditepe University, Istanbul, Turkey, Department of Medical Biology, School of Medicine, Yeditepe University, Istanbul, Turkey Artery Research Atherosclerosis is a chronic inflammatory blood vessel disease.Stud- Pulse-Wave-velocity (cfPWV), central pulse pressure (CPP) (Sphyg- ies highlight the importance of epigenetic modifications specifically mocor); 6. Autofluorescence- Advanced glycation end-products miRNAs in the development and progression of atherosclerosis.Calo- (AGE-Reader); 7. Carotid intima-media thickness (CIMT). We per- rie restriction(CR) is one of the best-known interventions to prolong formed one-way ANOVA to compare differences in the three groups. lifespan and impact lowering the risk of atherosclerosis.In the present Results: Demographics and anthropometry (BMI and waist circum- study, the effects of different types of CR on atherosclerosis-related ference) were comparable in all three groups. When compared to miRNA were studied. Groups 2 and 3, In Group 1: Troponin and the red cell distribution width (RDW) was higher (p < 0.05); Sphygmocor based cfPWV & Female mice were enrolled into three groups; ad-libitum (AL), Chronic- CPP, was higher (p < 0.001); RHI-EndoPAT based AI (@75) was higher CR (CCR, 15% CR), and Intermittent-CR (ICR) which 60% CR was applied and HRV(SDNN) was lower (p < 0.05); AGE was higher (p < 0.01) (see for one week (ICR-R, restricted) followed by three weeks of AL feed- Fig. 1). ing (ICR-RF, refeed).Blood and brain samples were collected at week Conclusion: Measures of arterial-stiffness (cf-PWV & AI@75) and HRV 49/50 to measure miRNA expression levels using Affymetrix GeneChip are more significantly impaired in DM when compared to hyper - miRNA 4.1 Array.The targets of differentially expressed(DE) miRNAs tension/hyperlipidemia, one year post COVID-19 recovery. These that are enriched in atherosclerosis-related molecular pathways were measures are higher when compared to similar matched diabe- analyzed. tes patients with no history of COVID-19 infection. COVID-19 DM In blood, a total of 12 miRNAs were DE among dietary groups.There patients need to be followed up to study long-term impact on vas- were common miRNAs that differ in dietary regimes when compared cular complications and autonomic neuropathy. to the AL group; miR-709(17,09-fold higher), miR-30b-5p(7,12-fold lower), and miR-19b-3p(5,72-fold lower) in CCR.The overexpression of miR-709 is shown to have a cardioprotective effect , while miR- 2 3 30b-5p and miR-19b-3p are considered pro-atherosclerotic.GO- KEGG analyses revealed that targets of atherosclerosis-related miRNAs that were affected with CR were also enriched in aging and cancer- related molecular pathways.In the brain, a total of 6 miRNAs were dif- ferentially expressed.Interestingly, there was no significant change in atherosclerosis-related miRNAs between blood and brain. In conclusion, even though CR has different effects on blood and brain tissues, some common miRNAs might have protective effects on ath- erosclerosis, suggesting the link between the brain and vascular axis. References 1. Li M, Chen H, Chen L, Chen Y, Liu X, Mo D. miR‑709 modulates LPS‑induced inflammatory response through targeting GSK ‑3β. Int Immunopharma‑ col. 2016 Jul;36:333–8. 2. Qi X, Wang H, Xia L, Lin R, Li T, Guan C, et al. miR‑30b ‑5p releases HMGB1 Table showing various vascular measures and figure showing box via UBE2D2/KAT2B/HMGB1 pathway to promote pro‑inflammatory plot on the pulse-wave-velocity in the three groups polarization and recruitment of macrophages. Atherosclerosis. 2021 May;324:38–45. 3. Wang J, Xu X, Li P, Zhang B, Zhang J. HDAC3 protects against atherosclerosis through inhibition of inflammation via the microRNA‑19b/PPARγ/NF‑κB axis. Atherosclerosis. 2021 Apr;323:1–12. Keywords: Atherosclerosis, calorie restrictions, miRNA P.037 Diabetes Mellitus is associated with relatively higher arterial stiffness when compared to hypertension or hyperlipidemia post‑recovery from COVID‑19 1,2 2,3 2,3 2 Rinkoo Dalan, Barnaby Young , David Lye , Bernhard Boehm. 1 2 Tan Tock Seng Hospital, Singapore, Singapore, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore, National Centre for infectious diseases, Singapore, Singapore Background: COVID-19, is associated with vascular dysfunction, arte- rial stiffness and worse outcomes in diabetes mellitus (DM) (1). We hypothesise that longer-term impact in COVID-19 DM patients will be worse when compared to other metabolic conditions, 1  year after recovery from COVID-19. Reference Methods: We recruited 63 patients belonging to the three groups: 1. Zota IM, Stătescu C, Sascău RA, et al. Acute and Long‑ Term Consequences group 1 – recovered COVID-19 DM-type 2, n = 14; Group 2- recov- of COVID‑19 on Arterial Stiffness‑A Narrative Review. Life (Basel). ered COVID-19, non-diabetes hypertension or hyperlipidemia, 2022;12(6):781. n = 29 and Group 3- non-COVID-19 DM, n = 14. Data collected: 1. Demographics, 2. Anthropometry, 3. Metabolic profile, 4. Reac - Keywords: COVID-19; arterial-stiffness, pulse-wave-velocity, tive Hyperaemia index (LnRHI), Augmentation index (AI@75), diabetes Heart Rate variability (HRV) (RHI-EndoPAT), 5. Carotid-femoral A rtery Research P.038 Clinical aspects Large artery stiffness using Sphgymocor technology shows higher augmentation index in pre‑diabetes and diabetes in multi‑ethnic P.042 Singapore Estimating pulse wave velocity in Community Pharmacies improves CV‑risk stratification compared to SCORE Ying Jie Chee , Rinkoo Dalan 1,2 3 3 3 Enrique Rodilla , Manuel Adell, Vicente Baixauli , Otón Bellver , Lidón Tan Tock Seng Hospital, Singapore, Singapore 3 3 3 3 Castillo , Santiago Centelles , Edelmira Córcoles , Rosario Hernández , 3 3 3 3 Background: The Sphygmocor technology uses applanation tonometry Sara Martínez , Zeneida Perseguer , Rosa Prats , Javier Reig , Desiré 3 3 2,3 2 2 to measure large artery stiffness. Although the carotid-femoral pulse Ruiz , Fanny Ruiz , Luis Salar , José‑Antonio Costa , José Chordá , Julio 1 1 3 wave velocity (cfPWV) is higher in diabetes, an association with pre-dia- Vicente , Ana Gómez , Maite Climent betes has not been observed.(1,2) There is limited data on augmentation 1 2 Hospital Universitario de Sagunto, Puerto De Sagunto, Spain, Universi‑ index (AIx). We aimed to study the correlation of arterial stiffness among dad Cardenal Herrera‑CEU, CEU Universities, Moncada ( Valencia), Spain, healthy, pre-diabetes, or diabetes in multi-ethnic Singapore. Sociedad Española de Farmacia Familiar y Comunitaria (SEFAC‑Valencia), Methods: Population: n = 130; Age = 44.8 (9.6) years; Male = 41 (31%), Valencia, Spain Chinese = 93, Indians = 12, Malays = 15, Others = 10. All participants underwent a standard 75 g oral glucose tolerance test and applanation Background: Arterial stiffness is considered to be an intermediate tonometry to assess cfPWV, central pulse pressure (CPP) and AIx. One- marker of CV risk with independent prognostic value. The objective of way ANOVA was done to study the differences in the arterial measure - this study is to assess whether the estimation of arterial stiffness can ments based on diabetes status. improve CV risk stratification compared to SCORE in patients at Commu- Results: Healthy (n = 81), Prediabetes (n = 27), Diabetes (n = 22). While nity Pharmacies. cfPWV was higher in diabetes (mean (SD): 7.2(1.6)) compared to absence Methods: Observational prospective epidemiological study in which of diabetes (6.5(1.0)); p < 0.01), there was no difference between healthy consecutive individuals entering a participating Community Pharmacy 6.5(1.1) and pre-diabetes (6.4(1.0)); p > 0.01. An increasing trend was are offered a voluntary measurement of blood pressure and estimation seen in AIx, healthy (mean (SD): 9.5(4.3)) < pre-diabetes (mean (SD): of pulse wave velocity by oscillometry (AGEDIO, IEM ) to stratify their 11.1(5.4)) < diabetes (mean (SD):13.1(7.0)); p < 0.01. No statistically signifi- CV risk according to SCORE compared to the use of arterial stiffness. cant difference was seen in CPP (p > 0.01). Results: After nine months of recruitment, data from 923 patients Discussion: AIx may reflect early markers of impaired glucose tolerance (173 women, 102 men) were collected. 16/122 (13.1%) patients under or pre-diabetes. Moreover, as AIx is determined by the properties of the 40 years and 72/364 (19.8%) over 65 years of age presented pathologi- distal vasculature, it may be used as an early marker of distal circulatory cal stiffness and could be classified as high-risk, even though being dysfunction involving the small arterioles, which precede abnormalities out of the age-range of SCORE. Of the 437 (47.3%) patients who were in pulse wave velocities. AIx can be a valuable marker of early vascular susceptible to calculating SCORE, 42/437 patients (9.6%) presented dysfunction, especially among individuals with pre-diabetes. Further pathological arterial stiffness. Cholesterol values were available in 281 studies are needed to understand the mechanistic basis of this trend. patients (64.3%). Among them, according to SCORE, only 6 (2.1%) fell into the high-risk category. Conclusions: More than half of the subjects who randomly enter a community pharmacy had ages that make it impossible to calculate the CV risk by SCORE. Among them, arterial damage was detected in 18.1%. Of the other half, 9.6% presented arterial damage and, there- fore, high CV risk, when SCORE only detected it in 2.1%. Therefore, esti- mating arterial stiffness in community pharmacies markedly improves detection of high CV risk compared to SCORE. Fig. 1 (A) augmentation index and (B) pulse wave velocity in healthy, pre‑ diabetes and diabetes References 1. Henry RM, Kostense PJ, Spijkerman AM, Dekker JM, Nijpels G, Heine RJ, et al. Arterial stiffness increases with deteriorating glucose tolerance status: the Hoorn Study. Circulation. 2003 Apr;107(16):2089–95. https:// doi. org/ 10. 1161/ 01. CIR. 00000 65222. 34933. FC. 2. Prenner SB, Chirinos JA. Arterial stiffness in diabetes mellitus. Atherosclerosis. 2015 Feb;238(2):370–9. https:// doi. org/ 10. 1016/j. ather oscle rosis. 2014. 12. Keywords: Arterial stiffness, augmentation index, pre-diabetes, diabetes Artery Research References Background: Remote ischemic preconditioning (RIPC) is a phenom- ‑ Rodilla Sala E, Adell Alegre M, Giner Galvañ V, Perseguer Torregrosa Z, Pascual enon in which short episodes of ischemia are applied to distant organs Izuel JM, Climent Catalá MT, et al. Arterial stiffness in normotensive and to prepare target organs for more prolonged ischemia and induce hypertensive subjects: frequency in community pharmacies. Med Clin protection against ischemia–reperfusion injury [1]. The aim of this (Barc) 2017;149:469–76 [Article in English, Spanish]. study was to evaluate whether preoperatively performed RIPC affects ‑ Nunan D, Fleming S, Hametner B, Wassertheurer S. Performance of pulse metabolome following vascular surgery and assess if metabolomic wave velocity measured using a brachial cuff in a community setting. changes correlate with heart and kidney injury markers. Blood Press Monit. 2014;19:315–9. Methods: A randomized-controlled, double-blinded trial was con- ducted in the Tartu University Hospital. Patients undergoing open Keywords: Pulse wave velocity, brachial oscillometry, risk stratifica- surgical repair of abdominal aortic aneurysm, surgical lower limb tion, pharmacies revascularization, and carotid endarterectomy were recruited. A RIPC consisting of four cycles of 5 min of ischemia followed by 5 min of rep- erfusion was applied before the operation. The blood was collected P.043 preoperatively and approximately 24  h postoperatively. The metabo- Evaluation of office and ambulatory central blood pressure lome was analyzed with the AbsoluteIDQ p180 Kit. by two methods and their changes after lifestyle or medical Results: The final analysis included 45 patients from the RIPC and 47 interventions in hypertension from the sham group. Baseline characteristics and values of metabo- 1 2 1 3 János Nemcsik , Helga Gyöngyösi , Dóra Batta , Andrea László , Dr. lites were statistically similar between groups. RIPC did not cause sta- 1 1 4 5 Péter Torzsa , Beáta Kőrösi , Zsófia Nemcsik‑Bencze , Orsolya Cseprekál , tistically significant changes in metabolites 24 h postoperatively. There András Tislér was a significant positive correlation between the change Kynure - nine/Tryptophan ratio and the changes of hs-Troponin T (r = 0.570, p Semmelweis University, Department Of Family Medicine, Budapest, Hun‑ ˂0.001), NT-proBNP (r = 0.552, p ˂0.001), Cystatin C (r = 0.534, p ˂0.001) gary, Semmelweis University, Faculty of Medicine, Budapest, Hungary, 3 4 and Beta-2-Microglobulin (r = 0.504, p ˂0.001). Norisana‑ MVZ Rosenau, Nuremberg, Germany, Semmelweis University, Conclusions: Preoperatively performed RIPC did not significantly Department of Neuroradiology, Budapest, Hungary, Semmelweis Univer‑ affect metabolome 24  h after vascular surgery. The positive linear sity, Department of Transplantation and Surgery, Budapest, Hungary, correlation between Kynurenine/Tryptophan ratio and heart and Semmelweis University, Department of Internal Medicine and Oncology, kidney injury markers suggests that the Kynurenine-Tryptophan Budapest, Hungary pathway can play a role in RIPC-associated cardio- and nephropro- Background: Central systolic blood pressure (cSBP) can be evaluated tective effects. in office and also in ambulatory condition, during 24-h monitoring. The aim of our study was to measure office brachial systolic BP (bSBP) Reference and cSBP in the office and brachial SBP and cSBP in 24-h setting. 1. Anttila V, Haapanen H, Yannopoulos F, Herajärvi J, Anttila T, Juvonen T. Methods: Office cSBP was measured with PulsePen (PP cSBP), while Review of remote ischemic preconditioning: from laboratory studies to 24-h ambulatory brachial SBP (24  h bSBP), and cSBP were evaluated clinical trials. Scand Cardiovasc J. 2016 Oct‑Dec;50(5–6):355–361. with Mobil-O-Graph. For the calculation of 24-h cSBP both systolic/ diastolic and systolic/mean BP calibration methods were considered Keywords: Metabolomics, remote ischemic preconditioning, vascu- (24  h cSBPC1 and 24  h cSBPC2, respectively). In new hypertensive lar surgery patients (HT) the measurements were repeated 3  months after the initiation of antihypertensive medication. In white-coat hypertensive patients (WhHT) after lifestyle modifications the measurements were P.045 repeated at 12 months. Repeated SBP Measurements during a Single Visit Results: 105 patients were involved with 22 HT and 22 WhHT and Cardiovascular Prediction: Analysis of CARTaGENE subjects. bSBP (140.8 ± 17  mmHg) was higher than PP cSBP (128.2 ± 13.1  mmHg, p < 0.05). 24  h bSBP (128.3 ± 10.3  mmHg) was 1,2 1,2 Louis‑Charles Desbiens , Annie‑Claire Nadeau‑Fredette , François higher than 24 h cSBPC1 (117.8 ± 9.3 mmHg, p < 0.05), but equal with 2,3 4,5 2,3 Madore , Mohsen Agharazii , Rémi Goupil 24  h cSBPC2 (131.1 ± 11.1  mmHg). For medical intervention bSBP 1 2 Hopital Maisonneuve‑Rosemont, Montreal, Canada, Université de Mon‑ (Δ20.4  mmHg) and PP cSBP (Δ16 mmHg) decreased markedly, and tréal, Montréal, Canada, Hôpital du Sacré‑Coeur de Montréal, Montréal, 24 h bSBP (Δ10.9 mmHg), 24 h cSBPC1 (Δ10.1 mmHg) and 24 h cSBPC2 4 5 Canada, CHU de Québec, Québec, Canada, Université Laval, Québec, (Δ9 mmHg) decreased equally (all p < 0.05). For lifestyle changes only Canada bSBP changed significantly (Δ6.2 mmHg). Conclusions: These results suggest differences in absolute values of Background: Blood pressure (BP) has high intra-individual variabil- cSBP in office and 24  h with different calibrations, but similarities in ity. Several guidelines recommend averaging BP measurements to the changes of the magnitude of cSBP in office and 24-h with bSBP in monitor hypertension as it correlates more closely with ambulatory the similar settings. BP. However, whether these averages improve cardiovascular pre- diction has never been evaluated yet. Keywords: Central systolic blood pressure Methods: We studied individuals aged between 40 and 69 from the CARTaGENE cohort (Canada). Three SBP measurements (SBP , SBP, SBP ) at two-minute intervals were taken with an Omron 907L 2 3 P.044 device. These values were averaged to generate SBP (mean of SBP 12 1 The effects of RIPC on metabolome in patients undergoing and SBP), SBP (SBP and SBP ), and SBP (SBP, SBP and SBP ). 2 23 2 3 123 1 2 3 vascular surgery: a randomized controlled trial Major adverse atherosclerotic events (MACE: cardiovascular death, 1,2,3 1,2,3 1,2,3 4 1,5,6 Kadri Eerik, Teele Kasepalu , Jaan Eha , Aigar Ottas , Jaak Kals stroke, myocardial infarction) during a 10-year follow-up were obtained using medico-administrative databases. Associations of 1 2 Endothelial Research Centre, University of Tartu, Tartu, Estonia, Depart‑ SBP parameters with MACE were obtained using fully adjusted Cox ment of Cardiology, Institute of Clinical Medicine, University of Tartu, models. Predictive performance was assessed with 10-year athero- Tartu, Estonia, Heart Clinic, Tartu University Hospital, Tartu, Estonia, sclerotic cardiovascular disease scores (ASCVD; using pooled cohort Department of Biochemistry, Institute of Biomedicine and Translational equations) for each SBP parameter and associated C-statistics. Medicine, Centre of Excellence for Genomics and Translational Medi‑ cine, University of Tartu, Tartu, Estonia, Department of Surgery, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia, Surgery Clinic, Tartu University Hospital, Tartu, Estonia A rtery Research Results: From 17,966 individuals, 2,378 had a MACE during the fol- individuals in the study, the above can be explained by the inherent low-up. SBP values at baseline were 126.5 mmHg (SBP ), 123.2 (SBP ) hormonal effects of each sex. 1 2 and 122.5 (SBP ). After adjustment, SBP had the strongest associa- 2 3 tion with MACE. This association was significantly greater than that References observed for SBP , SBP , or SBP . In comparison to SBP , SBP and 1. Romero‑Martínez M, Shamah‑Levy T, Vielma‑ Orozco E, Heredia‑Hernández 1 12 123 1 2 SBP increased the risk attributable to SBP by up to two times. When O, Mojica‑ Cuevas J, et al. Encuesta Nacional de Salud y Nutrición included in ASCVD scores, SBP yielded the highest C-statistic, which 2018–19:Resultados nacionales. salud publica mex.2020 Jan 13;61(6). was significantly higher than all other SBP parameters except SBP . 2. Zoungas S, Arima H, Gerstein HC, Holman RR, Woodward M et al. Eec ff ts Conclusion: Averaging SBP measurements during a single visit of intensive glucose control on microvascular outcomes in patients improves cardiovascular prediction compared to a single meas- with type 2 diabetes: a meta‑analysis of individual participant urement. Discarding the first SBP value maximises predictive data from randomised controlled trials. The Lancet Diabetes and performance. Endocrinology.2017;5(6):431–7. 3. Korkmaz H, Onalan O. Evaluation of endothelial dysfunction: Flow‑ Table mediated dilation. Endothelium: Journal of Endothelial Cell Research. 2008;15(4):157–63. 4. Poredos P, Jezovnik MK. Testing Endothelial Function and its Clinical Rel‑ evance. Journal of Atherosclerosis and Thrombosis. 2012;20(1):1–8. Keywords: FMD, Type 2 Diabetes, Endothelial function Epidemiology P.051 The association of measures of hyperglycemia and the different frequency domains of microvascular flowmotion: the Maastricht Study 1 1 1 1 Xiaofei Zhao , Casper Schalkwijk , Bram Kroon , Coen Stehouwer , Dr. Keywords: Hypertension Prediction Monitoring Boy Houben. CARIM School for Cardiovascular Disease, Department of Internal Medi‑ P.046 cine, Maastricht University Medical Center + , Maastricht, Netherlands Flow‑mediated vasodilation and endothelial function in Mexican Introduction: MVD may develop early and contribute to impaired patients with type 2 diabetes mellitus, a cross‑sectional study insulin-mediated glucose uptake and subsequent metabolic insulin in western Mexico resistance, characterized by hyperglycemia. However, apart from hyper- 1,2,3 1,2,3 Luis Ricardo Balleza Alejandri , Fernando Grover Páez , Erick glycemia being a consequence of MVD, hyperglycemia can also (fur- 1,2,3 1,2,3 González Campos , Carlos Gerardo Becerra Ramos , German ther) impair microvascular function, constituting a vicious cycle. Our 1,2,3 1,2,3 Cardona Gutierrez , Sara Pascoe Gonzalez , Claudia Yanette Galan aim was to study whether measures of hyperglycemia are associated 1,2,3 1 1,2,3 Ruiz , Javier Esparza Pimentel , David Cardona Müller with different components of skin microvascular flowmotion (SMF). 1 2 Universidad de Guadalajara, Guadalajara, Mexico, Departamento de Methods: SMF was measured using laser-Doppler flowmetry (LDF). Fisiología, Guadalajara, México, Instituto de investigación clínica y ter‑ The relative contribution (percentage of the total) of the SMF com- peútica (INTEC), Guadalajara, México ponents was used as outcome measures. We investigate the asso- ciations of measures of hyperglycemia (Fasting plasma glucose[FPG], Flow‑mediated vasodilation and endothelial function in Mexican 2-h plasma glucose[2-h PG], HbA1c, advanced glycation end- patients with type 2 diabetes mellitus, a cross-sectional study in west- products[AGEs] assessed as skin autofluorescence [SAF]), and indices ern Mexico. of glucose variability (incremental glucose peak [IGP] and continuous glucose monitoring [CGM] -assessed as standard deviation [SD]) with Introduction: Mexico is a country with high mortality due to diabe- total SMF and the relative contribution of five different components. tes complications (1); constant hyperglycemia in patients with diabe- Results: Greater FPG, 2-h PG, and HbA1c were statistically significant tes leads to endothelial damage, which is the main risk factor for the associated with lower Endothelial Power component(%) (per SD, development of macro and microvascular complications, leading to respectively − 0.035 [− 0.066; − 0.004]; − 0.047 [− 0.079; − 0.015]; and an increased risk of mortality (2). Flow-mediated vasodilation (FMD) is − 0.030 [− 0.061; − 0.001]). Greater FPG, and 2-h PG were statistically one of the most widely used techniques for the evaluation of endothe- significant associated with higher Neurogenic Power component(%) lial function and can be used as predictor of cardiovascular risk (3,4). (per SD, respectively 0.031 [0.000; 0.062]; and 0.048 [0.016; 0.079]). Objective: The objective of this study is to determine the FMD values Greater FPG, 2-h PG, and HbA1c were statistically significant associ- and hemodynamic characteristics in Mexican patients with type 2 dia- ated with higher Myogenic Power component(%) (per SD, respectively betes mellitus in western Mexico. 0.039 [0.008; 0.071]; 0.040 [0.008; 0.072]; and 0.039 [0.008; 0.070]). Methods: FMD were measured with a high-resolution semi-automatic Conclusion: Higher levels of hyperglycemia and daily glucose vari- ultrasound UNEX-EF 38G (UNEX Co. Ltd Nagoya Japan). Measurement ability were associated with a lower relative contribution of endothe- of arterial tension were made with an OMRON electronic digital sphyg- lial skin flowmotion component and, a higher relative contribution of momanometer (HEM 907 XL). neurogenic and myogenic components. Results: 65 patients, (28 men and 37 women) with a mean age of 52.46 ± 11.71, we found a difference between the basal and final References diameters and blood flow between men and women (4.67 ± 0.76 vs Houben, A.J.H.M. and C.D.A. Stehouwer, Microvascular dysfunction: Deter‑ 3.42 ± 0.69 p 0.001; 4.96 ± 0.76 vs 3.66 ± 0.70 p 0.001; (10.5 ± 8.05 vs minants and treatment, with a focus on hyperglycemia. Endocrine and 4.59 ± 3.56 p 0.020); an inverse correlation was found between FMD Metabolic Science, 2021. 2. and SBP (r = − 0.265 p 0.33). Stefanovska, A., M. Bracic, and H.D. Kvernmo, Wavelet analysis of oscillations in Conclusion: We found a lower FMD in women than in men, it is also the peripheral blood circulation measured by laser Doppler technique. noteworthy the differences found in the flow and bIMT between the IEEE Transactions on Biomedical Engineering, 1999. 46(10): p. 1230–1239. Artery Research Keywords: Microvascular dysfunction (MVD), Skin microvascular flow - Methods: Participants were recruited from the Avon Longitudinal motion (SMF), Type 2 diabetes (T2D) Study of Parents and Children (ALSPAC) (http:// www. alspac. bris. ac. uk). Ethical approval was obtained from the ALSPAC Law and Ethics P.053 Committee and the Local Research Ethics Committee. Participants pro- Agreement between cuff device versus radial tonometry vided written informed consent. 14 participants (age 17.8y (SD = 0.2); to measure central blood pressure and pulse wave analysis 7 male) underwent 2 repeated measurements of sitting BP using an in adolescents Omron 705-IT and radial artery tonometry (Sphygmocor). Radial wave- 1 forms were calibrated to systolic and diastolic pressure according to Alun Hughes manufacturer recommendations. Bland–Altman analysis was per- UCL, London, United Kingdom formed, repeatability was assessed as the mean difference with limits of agreement, and Lin’s concordance coefficient (CCC) was calculated Background: Cuff-based devices are increasingly used to measure as a measure of reliability. central blood pressure (BP) and perform pulse wave analysis. Cuff Results: Reproducibility results are shown in Table 1. devices have been compared to arterial tonometry in adults, [1] but Conclusions: Most parameters showed acceptable reliability, although information in adolescents is limited. Brachial amplification is large in AIx and T1 were poorly reproducible, possibly due to the large central young people and may influence agreement between methods. to brachial amplification. Methods: Participants were recruited from the Avon Longitudinal Study of Parents and Children (ALSPAC) (http:// www. alspac. bris. ac. Table 1 Reproducibility of pulse wave analysis measures. uk). Ethical approval was obtained from the ALSPAC Law and Ethics Committee and the Local Research Ethics Committee. Participants pro- vided written informed consent. 136 participants (age 17.6y (SD = 0.4); 68 (50%) male) had measurements of brachial suprasystolic wave- forms (Pulsecor; BP +) and radial artery tonometry (Sphygmocor; SP) at the same clinic visit. Waveforms were calibrated to sitting BP accord- ing to manufacturer recommendations. Agreement was tested using Bland–Altman analysis and summarised as the mean differences with limits of agreement. Coefficient of variation (CV) and Pearson’s correla- tion coefficient (r) were also calculated. Results: Central systolic BP (cSBP) and maximum dp/dt were on aver- age higher for BP + , but BP + and SP were closely correlated. Periph- eral augmentation index (pAI) was on average lower for BP + than SP , and there was no bias for ejection duration (ED), while correlations were moderate for both. CV was ≤ 10% for all parameters except pAI (Table 1). Conclusions: The two devices showed acceptable agreement. Dif- ferences in some parameters may reflect the influence of calibration, waveform morphology, or the use of different algorithms by devices. Reference 1. Ferreira DL, Fraser A, Howe LD, Jones S, Smith GD, Lawlor DA, et al. Associa‑ tions of Central and Peripheral Blood Pressure With Cardiac Structure and Function in an Adolescent Birth Cohort: The Avon Longitudinal Study of Parents and Children. J Am Coll Cardiol. 2015;65(18):2048–50. Keywords: Blood pressure, Pulse wave analysis, Adolescence, Reproducibility Reference Park CM, Korolkova O, Davies JE, Parker KH, Siggers JH, March K, et al. Arterial pressure: agreement between a brachial cuff‑based device and radial Interventions tonometry. J Hypertens. 2014;32(4):865–72. Keywords: Central blood pressure, pulse wave analysis, method P.055 comparison. The role of RIPC in preventing organ damage, inflammation and oxidative stress during lower limb DSA: a randomised controlled trial. P.054 1,2,3 1,2,3 3 1,2 Reproducibility of pulse wave analysis in adolescents. Karl Kuusik, Teele Kasepalu , Mihkel Zilmer , Jaan Eha , Mare 4 5 6 3,6,7 1 1 1 Vähi , Liisi Anette Torop , Jüri Lieberg , Jaak Kals Alun Hughes , Alicja Rapala , Nish Chaturvedi. Department of Cardiology, Institute of Clinical Medicine, University UCL, London, United Kingdom of Tartu, Tartu, Estonia, Heart Clinic, Tartu University Hospital, Tartu, Background: Previous studies have examined the reproducibility of Estonia, Department of Biochemistry, Institute of Biomedicine and Trans‑ central blood pressure (BP) and pulse wave analysis (PWA) in adults, lational Medicine, Centre of Excellence for Genomics and Translational but information in adolescents is limited. This is particularly relevant Medicine,University of Tartu, Tartu, Estonia, Institute of Mathematics since central to brachial amplification is large in young people [1]. A rtery Research and Statistics, University of Tartu, Tartu, Estonia, Pathology Service, Tartu Methods: We performed a 24-week single center randomized con- University Hospital, Tartu, Estonia, Department of Vascular Surgery, trolled trial comparing dapagliflozin and ramipril (D + R) versus rami- Surgery Clinic, Tartu University Hospital, Tartu, Estonia, Department pril (R) on markers of arterial ageing in people with T2DM with residual of Surgery, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia albuminuria despite maximum tolerated renin angiotensin system (RAS) inhibition. Primary endpoint was change in urine albumin excre- Background: Digital subtraction angiography (DSA) and percu- tion rate (AER).Secondary endpoints included Ao-PWV (by applana- taneous transluminal angioplasty (PTA) are common procedures tion tonometry),central aortic blood pressure, mediators of the RAS for diagnosing and treating symptomatic lower extremity arterial (plasma renin activity,aldosterone,ACE-2 and angiotensin 1–7/1–9 disease (LEAD) . However, organ damage following DSA and PTA is levels) and biomarkers of arterial ageing [soluble Klotho (sKlotho) and 2,3 often under-recognised and hence undiag nosed . To reduce the fibroblast growth factor 23 (FGF-23)]. risk induced by invasive procedures in symptomatic LEAD patients, Results: 33 participants (male 72.7%) were randomized to Dapa- the method of remote ischemic preconditioning (RIPC) has been gliflozin and Ramipril (n = 17) or Ramipril (n = 16). After 24  weeks 4,5 suggested . The aim of the current study was to assess the effect of treatment AER fell significantly [mean (95% CI)] only in D + R by of RIPC intervention on the organ damage markers profile, oxidative 43.5% (− 57.4 to − 29.6%) (p < 0.01) as compared to 5% (− 48.3 to stress and inflammation biomarkers in LEAD patients undergoing 38.3%) (p = 0.36) in R. Ao-PWV did not change significantly from base - DSA and PTA procedure. line (D + R 9.06 ± 1.91  m/s to 9.13 ± 2.03  m/s vs R 9.88 ± 2.12  m/s to Methods: The RIPC intervention was performed by inflating a stand- 10.0 ± 1.84  m/s).No significant changes were noted in central aortic ard blood pressure cuff on the patient’s upper arm to 200  mmHg blood pressure, augmentation index, sKlotho or FGF-23. for 5  min four times with 5-min perfusion between each cycle. The Conclusion: The combination of Dapagliflozin and Ramipril for sham intervention was performed similarly, but the cuff was inflated 24  weeks significantly reduces albuminuria but does not impact on to 20  mmHg. Changes in the cardiac and renal damage biomarkers’ Ao-PWV or other mediators of arterial ageing in people with T2DM. profile, oxidative stress and inflammation biomarkers were recorded before and 24 h after DSA or DSA-PTA. References Results: RIPC significantly limited the increase of adiponectine 1. C. Wanner et al., Empagliflozin and Progression of Kidney disease in Type 2 levels after DSA/PTA procedure, compared to sham intervention Diabetes, N. Eng. J. Med. 2016. (p = 0.020), but CK-MB levels were markedly lower in the sham 2. C. Vlachopoulos et al., Prediction of cardiovascular events and all‑ cause group (p = 0.047) after DSA procedure. There was no significant dif- mortality with arterial stiffness: a systematic review and meta‑analysis, J ference between the RIPC and the sham group in mean changes in Am Coll Cardiol. 2010. hs-Troponin-T (p = 0.25), NT-proBNP (p = 0.24), creatinine (p = 0.76), eGFR (p = 0.61), urea (p = 0.95), beta-2-microglobuline (p = 0.34) or Keywords: Arterial ageing;SGLT-2is;Diabetic kidney disease cystatine C (p = 0.24) levels. Conclusions: In this controlled clinical study RIPC failed to improve P.058 the profile of renal and cardiac biomarkers in patients with LEAD Preliminary findings of the VALIDATion of central blood periprocedurally. pressure Estimation in advanced Chronic Kidney Disease study (VALIDATE‑CKD). References 1—Gerhard‑Herman MD et al. 2016 AHA/ACC Guideline on the Management 1,2 1 1 2 Nadège Côté, Yasmine Abbaoui, Théo Spanneut , Mohsen Agharazii , of Patients With Lower Extremity Peripheral Artery Disease. Circulation 1 Rémi Goupil 2017;135(12):e726–79. Hôpital du Sacré‑Cœur de Montréal, Université de Montréal, Montréal, 2—Schillinger M et al. Balloon angioplasty and stent implantation induce a Canada, CHU de Québec Research Center, L’Hôtel‑Dieu de Québec vascular inflammatory reaction. J Endovasc Ther. 2002;9(1):59–66. Hospital, Université Laval, Québec, Canada 3—Geenen RWF et al. Contrast‑induced nephropathy: pharmacology, patho ‑ physiology and prevention. Insights Imaging. 2013;4(6):811–20. Background: Brachial cuff blood pressure (BP) is used as a convenient 4—Totzeck M et al. Concepts of hypoxic NO signaling in remote ischemic surrogate to aortic BP, the true determinant of blood perfusion to cen- preconditioning. World J Cardiol. 2015;7(10):645–51. tral organs. In the general population, brachial cuff systolic BP (SBP) 5—Yang J et al. Peripheral Mechanisms of Remote Ischemic Conditioning. has an acceptable accuracy towards aortic BP but less is known in pop- Cond Med. 2019;2(2):61–8.l ulations with high aortic stiffness, such as in advanced CKD. Central BP devices were designed to directly estimate the aortic BP through Keywords: Remote Ischaemic Preconditioning. Lower extremity arte- pulse wave analysis to a greater accuracy than brachial cuff BP, but rial disease. Digital Subtraction Angiography these were never validated in the advanced CKD population. The aim of the ongoing VALIDATE-CKD study is to compare the accuracy of Kidney brachial and central BP readings towards the intraarterial aortic SBP, in patients with and without advanced CKD (eGFR < 30  ml/min/1.73 m and dialysis). P.057 Methods: In patients with and without CKD stage G4-G5 undergoing Dapagliflozin does not influence arterial stiffness or other non-urgent coronary angiograms, invasive aortic and non-invasive bio‑markers of arterial ageing in people with type 2 diabetes (WatchBP and Mobil-o-graph devices) BPs were measured simulta- and kidney disease neously in accordance to the ARTERY Society protocol. Accuracy was 1 1 1 Nikolaos Fountoulakis , Dimitra Stathi , Maria Flaquer , Antonella defined by the mean difference (± SD) between the aortic SBP and the 1 1 1 1 Corcillo , Angeliki Panagiotou , Anastasios Mangelis , Salma Ayis , Luigi simultaneously measured non-invasive SBP. 1 1 Gnudi , Janaka Karalliedde. Results: To date, we enrolled 18 individuals with advanced CKD and 69 1 control subjects, with an aim to enroll 85 subjects in each group. King’s College London, London, United Kingdom Conclusions: These early preliminary results suggest that brachial cuff Background: Sodium glucose co-transporter 2 (SGLT-2) inhibitors SBP significantly underestimates aortic SBP in patients with advanced have demonstrated renal benefits in people with type 2 diabetes CKD. Furthermore, central BP devices may provide a better accuracy in (T2DM) . Arterial stiffness as measured by aortic pulse wave veloc - this population. The ongoing VALIDATE-CKD study could support the ity (Ao-PWV) is an index of arterial ageing and predicts cardio-renal use of central BP devices to enhance BP management in advanced outcomes . The effect of SGLT-2 inhibitors on Ao-PWV and other mark - CKD. ers of arterial ageing is unknown. Artery Research speculate that in such case, actin-myosin unit rearrangement may be impaired [4], as typically VSMCs operate below their optimal length. Table  1 Clinical characteristics and SBPs accuracies in patients with and without advanced CKD Keywords: Central blood pressure, brachial blood pressure, chronic kidney disease Models and methodologies P.061 A clinically applicable model of active arterial mechanics accounting for the length dependency of smooth muscle cell contraction 1 2,3 1,4 Cindy Van Loo , Ryan Pewowaruk , Alessandro Giudici , Koen 1 5 1 2,3 Reesink , Leon Schurgers, Tammo Delhaas , Adam Gepner , Bart 1,6 Spronck Dept. of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands, William S. Middleton Memorial Veterans Hospital, Madison, USA, Dept. of Medi‑ cine—Division of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison, USA, GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands, Dept. of Biochemistry, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Mac‑ quarie University, Sydney, Australia Background: The mechanical role of contraction of vascular smooth muscle cells (VSMCs) in large arteries is often overlooked. Recently, Pewowaruk and Gepner proposed a clinically applicable mathemati- cal model separating the passive and active contributions to arte- rial mechanics [1]. Subsequently, they applied the model to < i > in vivo < /i > data from human carotid arteries (< i > n < /i > = 40) at base- line and after nitroglycerin-mediated vasodilation (Fig. A) [2]. In two participants, the VSMCs’ active contribution decreased with increasing pressure from diastolic to systolic, which could not be captured with the original model (Fig. B). VSMC tension, generated by actin-myosin interaction, is maximal at the length with optimal filament overlap and is lower at other lengths. We hypothesised that, in these two partici- Example of original model fit without (< b > A < /b >) and with pants, VSMCs operated beyond their optimal length. Accordingly, we (< b > B < /b >) residual errors; < b > C < /b > , < b > E < /b > : Passive and modelled active VSMC tension as a function of length using a Gauss- active contributions to baseline data; < b > D < /b > , < b > F < /b > : ian-shaped function [3]. Total and contraction model curves; < b > G < /b > : Proposed model Methods: The baseline tension–diameter data for the two participants equation. were fitted using the combined exponential (passive) and Gaussian (active) expression in Fig. G [3]. References Results: In participant 1, VSMC contribution to tension was nearly [1] Pewowaruk RJ, Gepner AD. Smooth muscle tone alters arterial stiffness. J diameter-independent, indicating VSMC was near its maximum con- Hypertens 2022; 40: 512–519. traction length (Fig. C–D). In participant 2, the VSMC contribution [2] Pewowaruk RJ, Hein AJ, Carlsson CM, Korcarz CE, Gepner AD. Eec ff ts of showed a strong negative relation with diameter (Fig. E–F), indicating nitroglycerin Induced vasodilation on elastic versus muscular artery stiff‑ VSMCs were beyond their maximum contraction length. ness in older veterans. Hypertens Res 2022; [accepted]. Conclusions: Our proposed Gaussian function enables capturing [3] Carlson BE, Secomb TW. A theoretical model for the myogenic response VSMC active tension behaviour in patients with VSMCs operating based on the length–tension characteristics of vascular smooth muscle. beyond their optimal length, based on pressure-diameter data. We Microcirculation 2005; 12: 327–338. A rtery Research [4] Herrera AM, McParland BE, Bienkowska A, Tait R, Paré PD, Seow CY. `Sar‑ P.064 comeres’ of smooth muscle: functional characteristics and ultrastructural Identification of constitutive arterial tissue parameters using evidence. J Cell Sci 2005; 118: 2381–2392. inverse deformation analysis from passive inflation experiments 1 1 1 Fethi Okyar , Omer Faruk Buyukkaya , Cevat Volkan Karadag , Bilge Keywords: Biomechanics, Vasodilation, Mathematical model, Tuna Human carotid artery Yeditepe University, Istanbul, Turkey Background: Changes in the mechanical properties of arteries due P.063 to growth, remodeling, or aging are related with cardiovascular dis- Estimation of central aortic pressure waveform and hemodynamic eases. These changes can quantitatively be assessed if a set of suitable parameters from finger photoplethysmography biomaterial constitutive parameters could be fitted onto the in  vitro 1 2 2 2 2 Ahmad Qasem , James Cox , Mark Butlin , Alberto Avolio, Isabella Tan response pressure-diameter curve(s). The aim of this study is to deter- 1 2 mine the multi-variable optimization and parameter identification by Atcor Medical, Sydney, Australia, Faculty of Medicine, Health & Human using inverse deformation mapping. Sciences, Macquarie University, Sydney, Australia Methods: For this purpose, in  vitro pressure-diameter relations were Background: Non-invasive estimation of the central aortic pressure measured from published experimental results where the excised waveform is a valuable clinical tool to assess cardiovascular func- arterial sample was tethered between axially aligned canulae. An ana- tion. Current reliable methods require peripheral pulses from either lytical continuum-based computational procedure is defined to pull the radial artery using tonometry or the brachial artery using the the current state back to the excised (reference) state. Before applying oscillometric signal from a pneumatic cuff. This study aimed to esti- the multi-variable optimization for parameter identification, the data mate and validate the central pressure waveform derived from the is first pulled-back using this procedure, if required. finger photoplethysmography (PPG) signal during controlled and Results: In Simon et al. (1970) [1], a pressure-diameter dataset reflect - altered haemodynamic conditions. ing the internal pressurization (P) stage was provided. However, this Methods: Continuous recordings of radial tonometry (Sphyg- data did not include the excised (E) state. When the above proce- moCor) and finger PPG signals were obtained during base- dure was applied to the simple exponential model, a nearly tenfolds line conditions (2  min) and following an isometric hand-grip decrease in the shear modulus and about 60% increase in the exponen- manoeuvre (3  min) from 34 participants (age: 19–82  years, 18 tial constant were observed as a result of the pull-back to the excised male, BMI: 18–35  kg/m2, seated systolic and diastolic pressures state (coefficient of determination was found as 0.991, for both cases of 95–169  mmHg and 52–106  mmHg, respectively). Central pres- with and without pull-back). Similar observations were accounted for in sure parameters were estimated from PPG and radial signals using the hyperelastic fibre-reinforced continuum model [2]. more than 300 averaged signals. Participants were divided into a Conclusions: The parameter identification process may be hindered system model estimation group (n = 5) and a test group (n = 29). as a result of an incomplete or partial dataset. Inverse deformation Comparisons were made between PPG-derived and radial-derived mapping may be used to produce the missing data. central systolic blood pressure (cSBP), augmentation index (AIx), sub-endocardial viability ratio (SEVR) and pulse pressure amplifica- tion (PPamp). Results: The PPG-derived cSBP, AIx, SEVR and PPamp average error was − 3.5 ± 1  mmHg, 3 ± 6%, 4 ± 7%, 1 ± 1.6%, respectively, for the total recordings. All correlations between the PP-derived and radial- derived parameters were > 0.85 for all parameters (p < 0.001). PPG- derived central parameters test results were similar under controlled and altered haemodynamic conditions. Conclusion: Central hemodynamic parameters can be accurately derived from a finger PPG signal under controlled and altered haemodynamic conditions. References 1. Chen CH, Nevo E, Fetics B, Pak PH, Yin FC, Maughan WL, et al. Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function. Circulation. 1997;95:1827–1836. The procedure is depicted in the above diagram (a). Fitting of the 2. Pauca AL, Wallenhaupt SL, Kon ND, Tucker WY. Does radial artery pressure exponential model is shown in (b) while the fiber-reinforced (HOG) accurately reflect aortic pressure? Chest. 1992 Oct;102(4):1193–8 model is fitted in (c). 3. Pauca A, O’Rourke M, Kon N. Prospective Evaluation of a method for estimat‑ ing ascending aortic pressure from the radial artery pressure waveform. References Hypertension. 2001;38:932–937 [1] Simon, B. R., Kobayashi, A. S., Strandness, D. E., and Wiederhielm, C. A. (June 1, 1971). "Large Deformation Analysis of the Arterial Cross Section." ASME. Keywords: Central aortic pressure waveform, finger photoplethys- J. Basic Eng. June 1971; 93(2): 138–145. mography, central hemodynamic parameters, Augmentation Index, [2] Holzapfel, G.A., Gasser, T.C. & Ogden, R.W. A New Constitutive Framework isometric hand-grip manoeuvre, central systolic blood pressure, for Arterial Wall Mechanics and a Comparative Study of Material Models. sub-endocardial viability ratio, pulse pressure amplification, Transfer Journal of Elasticity 61, 1–48 (2000). Function Keywords: Constitutive models, arterial stiffness, inverse deformation, parameter identification Artery Research P.065 traditional smooth wall phantom (A). Diametrical compliance behav- Assessment of large and smal l arteries stiffness in upper ior was observed under quasistatic hydraulic inflation and pulse wave and lower limbs amputees: a numerical study velocities were measured over a range of mean pulse wave pressures. 1 3 4 5 Results: As luminal pressure increased (5–35  mmHg), corrugated Hasan Obeid, Vasiliki Bikia , Patrick S egers , Pierre Bout ouyrie , Nikos 3 1,2 phantom diametrical compliance decreased (p < 0.01) whereas Stergiopulos , Mohsen A gharazii smooth wall phantom compliance did not. Compliance was axially 1 2 Chu De Quebec, Quebec, Canada, Division of Nephrology, Depart‑ anisotropic (p < 0.05), increased in the axial mid-span and towards ment of Medicine, Faculty of Medicine, Université Laval, Quebec, Canada, the upper build height. Corrugated phantom pulse wave velocities Laboratory of Hemodynamics and Cardiovascular Technology, Swiss increased (1.7–4 m/s) as did pulse wave velocity slopes (p < 0.01) with Federal Institute of Technology, Lausanne, Switzerland, bioMMeda – increased mean wave pressure (5–40 mmHg). Pulse wave velocity was Institute for Biomedical Engineering and Technology, Ghent University, lower in the 50 vs 100 mm axial mid-span region (p < 0.01). Ghent, Belgium, AP‑HP, Pharmacology Unit, Hôpital Européen Georges Conclusions: As determined by quasistatic diametrical compliance Pompidou, University Paris Descartes, Sorbonne Paris Cité, Paris, France and pulse wave velocity, corrugated phantom circumferential elastic response was consistent with the physiologic behaviour of arteries, Arterial stiffness, as assessed via pulse wave velocity (PWV), has been stiffening with increasing pressure. Elasticity varied significantly with related to increased cardiovascular morbidity and mortality but has wall design (p < 0.05); however, height associated printing artefacts not been previously sufficiently evaluated in amputees. In the present decreased while end fixation increased compliance. The functional study, we investigated the intrinsic effect of biomechanical alterations structure wall approach is novel in arterial phantom construction and caused by limb-amputation on arterial stiffness. further development will improve the utility of phantoms in pulse wave behavior research. We used a detailed 1D arterial network model coupled with heart model. The PWV was determined by measuring the foot-to-foot pulse P.067 transit time. We calculated arterial stiffness of large, medium, and Beat‑to‑beat variability of invasive pulse wave velocity: small-sized vessels via carotid-femoral PWV (cfPWV), carotid-radial implication for the validation of non‑invasive devices PWV (crPWV), and radial-digital PWV (rdPWV) in five different set - 1,2 3 4 1 tings:1) healthy subject (complete model with upper and lower limbs Alessandro Giudici , Andra Grillo , Filippo Scalise , Koen D Reesink , 1 5 5,6 1,7 present), 2) right leg amputee (right lower-limb arteries were removed Tammo Delhaas , Paolo Salvi , Gianfranco Parati , Bart Spronck from the model), 3) two legs amputee (right and left lower-limb arter- Department of Biomedical Engineering, CARIM School for Cardiovascu‑ ies were removed from the model), 4) two legs and one-hand amputee lar Diseases, Maastricht University, Maastricht, The Netherlands, GROW (right and left lower-limb and right upper-limb arteries were removed School for Oncology and Reproduction, Maastricht University, Maastricht, from the model), 5) two legs and two hands amputee (right and left The Netherlands, Department of Medicine, Surgery and Health Sci‑ lower and upper limbs were removed from the model). ences, University of Trieste, Trieste, Italy, Department of Interventional In this numerical model, output cfPWV’s were 6, 6.9, 7.5, 8.2 and 9 m/s Cardiology, Policlinico di Monza, Monza, Italy, Department of Cardiology, respectively for setting 1,2,3 and 4. The crPWV’s were 6.3, 7.1 and Istituto Auxologico Italiano, IRCCS, Milan, Italy, Department of Medicine 7.8  m/s respectively for setting 1,2 and 3. The rdPWV’s were 10, 10.7 and Surgery, University of Milano‑Bicocca,, Italy, Macquarie Medical and 10.9 m/s respectively for setting 1,2 and 3. School, Faculty of Medicine, Health and Human Sciences, Macquarie These simulations suggest, that with incremental limb amputations, there is University, Sidney, Australia a stepwise increase in arterial stiffness, which is relatively more pronounced for aorta. Further analyses are needed to mimic more realistic setting. Background: Invasive foot-to-foot pulse wave velocity (PWV) shows beat-to-beat variability due to acute changes in haemodynamic con- Reference ditions and data processing issues. Though current device validation Obeid H, Bikia V, Fortier C, Paré M, Segers P, Stergiopulos N, et al. Assessment of guidelines suggest averaging over n_beats ≥ 3 heartbeats to cope Stiffness of Large to Small Arteries in Multistage Renal Disease Model: A with variability [1], quantitative data on PWV’s beat-to-beat variability Numerical Study. Front Physiol. 2022;13:832,858. is lacking. We aimed to quantify this variability and its impact on the confidence of the PWV estimate for intersecting tangent (PWVIT) and Keywords: Arterial stiffness, 1-D modelling, limb amputees second derivative (PWV2nd) foot detection methods. Methods: Pressure waveforms were simultaneously acquired in n = 40 individuals in the ascending aorta and iliac bifurcation via intra-aortic catheters. We calculated PWV_IT and PWV_2nd over m = 40 consecu- P.066 tive heartbeats and used Kernel density plots to visualise the variabil- Experimental arterial models (phantoms) that stiffen ity and distribution of PWV values. Furthermore, we estimated how when distended: a structural design and direct 3D‑print approach averaging over n_beats (with n_beats = 2 to 40) affects the standard 1 1 1 Bruce Guest , Luis Arroyo , John Runciman deviation (SD) of such n_beats-averaged assessment of PWV. Results: PWV_IT was significantly higher (10.40 ± 2.65 vs University Of Guelph, Guelph, Canada 10.00 ± 2.65  m/s, mean ± SD, p = 0.015) and showed lower beat-to- beat SD than PWV_2nd (0.52 ± 0.33 vs 0.62 ± 0.32  m/s, p = 0.046). Background: Despite the arterial pulse wave’s pathophysiologic impor- This is also visible in subject-specific density plots of PWV_IT (Figure, tance its basis is not fully elucidated . Experimental cardiovascular mod- Panel A) and PWV_2nd (Panel B), and in the average plots in Panel C. elling is useful in arterial mechanical and haemodynamic research ; Increasing n_beats from 2 to 40 decreased the effective SD from 0.36 however, current phantom construction techniques limit replication to 0.08 m/s for PWV_IT and from 0.44 to 0.10 m/s for PWV_2nd (Panel of arterial elastic and anatomic c omplexities . The elastic-pressure D). For n_beats = 3 (i.e., the guidelines’ lower limit), SD = 0.29 (PWV_IT ) response of phantoms incorporating longitudinal structural corruga- and 0.36 m/s (PWV_2nd). tions was investigated. Conclusions: Although invasive PWV shows considerable beat-to-beat Methods: Polyester-polyurethane phantoms (160  mm length) were variability (~ 0.5–0.6  m/s), said variability is reduced by ~ 70% when printed with a fused filament fabrication 3D printer. Five designs dif- n_beats = 10, providing a reliable measurement for validation studies. fering by corrugation number or magnitude (B-F) were compared to a A rtery Research Methods: 80 sedentary male and female participants (40 statin naïve and 40 statin users) aged between 50 and 65  years, with a 10-year CVD-risk score ≥ 10% (estimated via QRISK3) and no established CVD will be recruited onto the study. The statin naïve and statin user groups will be further randomised into the exercise intervention or standard (no exercise) primary care comparator group. The intervention will consist in a 12-week supervised aerobic exercise programme of mod- erate-intensity. Both groups will complete baseline and 12-week (post intervention) vascular function and structure assessments. Changes in flow-mediated dilation (FMD) and aortic pulse wave velocity (aPWV) will serve as the primary outcome measures. Secondary outcome measures include changes in cardiorespiratory fitness (CPET), carotid intima-media thickness (CIMT), 24-h brachial and aortic blood pres- sure and lipid profiles. Conclusion: Using a randomised controlled protocol, the study aims to evaluate the interaction between exercise training and statin ther- apy on vascular structure and function in the primary care setting. a) Corrugated design diametrical compliance (B-F) varies and decreases with pressure. b) Axial compliance anisotropy. c) Pulse wave velocity increases with pressure and d) is lower in more compliant region. References 1. Segers, P, O’Rourke, MF, Parker K, et al. Towards a consensus on the under‑ standing and analysis of the pulse waveform: results from the 2016 workshop on arterial hemodynamics: past, present and future. Artery Res 2017; 18: 75–80. https:// doi. org/ 10. 1016% 2Fj. artres. 2017. 03. 004 2. Lillie, JS, Liberson, AS, Mix, D, et al. Pulse wave velocity prediction and com‑ pliance assessment in elastic arterial segments. Cardiovasc Eng Technol 2015; 6(1): 49–58. https:// doi. org/ 10. 1007/ s13239‑ 014‑ 0202‑x 3. Ionita, CN, Mokin, M, Varble, N, et al. Challenges and limitations of patient‑ Study flow diagram specific vascular phantom fabrication using 3D Polyjet printing. Proc SPIE Int Soc Opt Eng 2014; 13: 9038:90380 M. https:// doi. org/ 10. 1117/ 12. Keywords: Cardiovascular disease, Primary prevention, Exercise, Vas- 20422 66 cular function Keywords: Arterial phantom, Arterial compliance, Pulse wave velocity, Pulse wave P.069 Unique humanized mouse models of von Willebrand disease type 2A P.068 1 1 1 Marco Heestermans , Geneviève Mc Cluskey , Ivan Peyron , Christelle Study protocol of a randomized control trial investigating 1 1 1 1 Reperant , Olivier D Christophe , Cécile V Denis , Peter J Lenting , the effects of exercise on endothelial function and pulse wave Caterina Casari velocity in the prevention of cardiovascular disease in statin Inserm U1176, Le Kremlin Bicêtre, France and non‑statin users. 1 1 3 2 Xela Dafauce Bouzo , Jemima Benson , Eric Stöhr , James C oulson , Background: Angiodysplasia is a vascular malformation associated 1 1 Barry McDonnell , Christopher JA Pugh. with gastrointestinal bleeding, generally observed in the elderly. This 1 2 condition is unexpectedly more frequent in patients with von Wille- Cardiff Metropolitan University, Cardiff, United Kingdom, Cardiff Univer ‑ 3 brand disease (VWD)-type 2A having low levels of VWF high-molec- sity, Cardiff, United Kingdom, Leibneiz University, Hannover, Germany ular-weight-multimers (HMWMs) and increased VWF-degradation Background: Regular exercise is widely recommended to reduce car- fragments (1). diovascular disease (CVD) risk. Recent healthcare guidelines for CVD Aim: To develop an innovative murine model of VWD-type 2A and primary prevention stipulates that individuals with a relatively low risk study the role of degraded-VWF in vascular processes. of CVD (10-year risk score ≥ 10%;) should take a statin. Exercise pro- Methods: Mice expressing human (h) VWF, carrying the type 2A vides a variety of cardiovascular benefits, including improvements in (p.R1597W) variant or wild-type (as control) and human GPIbα, vascular function. Moreover, statin therapy primarily reduces CVD risk have been generated (hVWF(p.R1597W) + / + /hGP1BA + / + and by lowering cholesterol, however, may also improve vascular function. hVWF + / + /hGP1BA + / +). Haemoglobin (Hb), VWF:Ag, propeptide, Whilst both therapies can independently reduce CVD risk, the interac- multimer pattern and factor VIII activity were analyzed. Tail-clip and tion between exercise training and statin therapy on vascular function tail-vein-transection (TVT ) bleeding assays were assessed. has never been directly compared in the primary prevention setting. Artery Research Results: Control hVWF + / + /hGP1BA + / + -mice expressed 15 ± 4% VWF:Ag, 44 ± 8% FVIII activity and normal VWF multimers. hVWF(p. R1597W) + / + /hGP1BA + / + -mice are viable and do not display spon- taneous bleeding manifestations. These mice expressed 3 ± 1% VWF:Ag and 7 ± 1% FVIII activity combined with an abnormal multimer pattern, with only low multimers and few degradation bands visible. Despite the relatively low VWF:Ag levels, hVWF + / + /hGP1BA + / + -mice dis- played normal haemostatic responses in both the severe- (tail-clip) and milder- (TVT) bleeding assays. In contrast, hVWF(p.R1597W) + / + / hGP1BA + / + -mice had a severe bleeding phenotype. Interestingly, in the TVT model, although the amount of blood shed was consistent with severe bleeding, 57% of type 2A mice were capable of forming an occlusive, although unstable clot within 15  min of the injury, differing from the bleeding profile of VWF-deficient mice. Conclusion: We developed a unique humanized mouse models for VWD-type 2A. Experiments are ongoing to study the vasculature of these mice. Reference Castaman G, Federici AB, Tosetto A, La Marca S, Stufano F, Mannucci PM, et al. Different bleeding risk in type 2A and 2 M von Willebrand disease: a 2‑ year prospective study in 107 patients. J Thromb Haemost. 2012 Apr;10(4):632–8. Keywords: VWF, VWD, angiodysplasia, vascular malformation Fig. 1 Receiver operating characteristic curve of the proposed ensemble P.070 Reference Pulse waveform‑based prediction of vascular calcifications Zhang L, Li L, Feng G, Fan T, Jiang H, Wang Z. Advances in CT Techniques in in patients with end stage renal disease Vascular Calcification. Front Cardiovasc Med. 2021 Sep 29;8:716–822. 1 1 2,3 3 Urszula , Małgorzata Dębowska , Lu Dai , Abdul Qureshi , Magnus https:// doi. org/ 10. 3389/ fcvm. 2021. 716822. PMID: 34660718; PMCID: 4 3 3 1 Soderberg , Bengt Lindholm , Peter St envinkel , Jan Poleszczuk PMC8511450. Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Keywords: Vascular calcifications, machine learning Academy of Sciences, Warszawa, Poland, Aging Research Center, Depart‑ ment of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden, Renal Medicine and Bax‑ ter Novum, Department of Clinical Science, Intervention and Technology, P.071 Karolinska Institutet, Stockholm, Sweden, Pathology, Clinical Pharmacol‑ Brachial pressure gradient as an alternative tool for assessment ogy and Safety Sciences, AstraZeneca R&D, Gothenburg, Sweden of endothelial function and cardiovascular disease severity 1,2 1 1 1 Smriti Badhwar , Dinu Chandran , Ashok Jaryal , Chetan Patel , Rajiv Background: Medial vascular calcification (VC) is associated with an 1 1 Narang , Kishore Kumar Deepak increased risk of cardiovascular disease and it is particularly prevalent in patients with chronic kidney disease (CKD). Currently, computed 1 2 All India Institute of Medical Sciences, New Delhi, India, York University, tomography is a conventional method of VC assessment. However, Toronto, Canada exposure to radiation and high costs of the examination are potential concerns. Moreover, it cannot distinguish between medial and intimal Introduction: Flow alteration can affect endothelial function, which VC. Therefore, we propose a novel, non-invasive technique of detect- is associated with cardiovascular disease (1). Peripheral arterial flow is ing medial VC in patients with CKD which utilizes brachial pulse wave determined by the pressure gradient between the proximal and distal measurements. points in the vessel. The pressure gradient could be a potential alterna- Methods: In 97 patients who underwent kidney transplant, medial tive for assessing vascular health. VC presence was examined in epigastric artery. Additionally, the Methods: Anterograde and retrograde brachial artery pressure gra- patients’ brachial pulse waves were non-invasively measured dients were estimated from the positive and negative components of (SphygmoCor, AtCor Medical, Australia). We analyzed the waveforms the first derivative of the non-invasive beat-to-beat brachial pressure in the frequency domain and extracted features based on the first waveform and carotid-radial pulse wave velocity in 90 patients with 20 frequencies. Additionally, patients’ characteristics such as age, ischemic heart disease. Retrograde flow was assessed using a pulsed- sex and diabetes were utilized as input variables. An ensemble of wave doppler. Cardiovascular disease severity was evaluated using three logistic regression models in combination with different sub - Single Positron Emission Computerized Tomography imaging and sets of features was built to identify medial VC presence. quantified as %perfusion defect from the summed stress score, using Results: Results show that the features derived from brachial pulse a 20-segment cardiac model. Endothelial function was assessed by wave signal contribute to prediction of medial VC presence in CKD ultrasound-based measurement of flow-mediated dilation (FMD). patients. The model, assessed using leave-one-out cross-validation, Results: A significant association was seen between retrograde flow achieved accuracy = 0.91 and F-score = 0.94. Figure 1 shows receiver velocity (RBFVAUC and RBFVpeak) and retrograde pressure gradi- operating characteristic (ROC) curve of the proposed classifier. ent (Rt-dP/dxAUC and Rt-dP/dxpeak) (r = 0.34, p = 0.003 and r = 0.38, Conclusions: In this proof-of-concept research, we showed that p = 0.0006 respectively). RBFVAUC and Rt-dP/dxpeak showed a sig- medial VC in CKD patients can be detected using the features nificant negative correlation with %FMD (r = − 0.24, p = 0.026 and derived from brachial pulse waveforms. The proposed method is r = − 0.22, p = 0.047 respectively). Ratio of retrograde to total pres- easy to implement and may contribute to a higher accessibility of sure gradient (Rt-dP/dxpeak/(At-dP/dxpeak + Rt-dP/dxpeak) showed medial VC detection in CKD patients. a significant positive correlation with %perfusion defect (r = 0.24, A rtery Research p = 0.025). This association was independent of aortic systolic pres- overall P = 0.02). PWV (P = 0.005) and hsIL-6 (P = 0.042) were inde- sure, age, heart rate and total cholesterol. pendent predictors of improvement after adjusting for age, hyperten- Conclusion: Brachial pressure gradient is related to pathophysiologi- sion and diabetes. The decrease in PWV throughout the study period cal alterations in arterial flow and can be incorporated into developing correlated with the reduction in hsIL-6 (r = 0.36, P < 0.01). an alternative method for assessing endothelial dysfunction and car- Conclusions: Intravitreal ranibizumab injections lead to a decrease in diovascular disease severity. PWV and hsIL-6. Both parameters predict clinical improvement and may aid in improving treatment targeting and therapeutic outcome in AMD patients. Keywords: Arterial stiffness, inflammation, anti-VEGF, hypertension Vascular aging P.091 Two age‑related pathologies: the relation of arterial stiffness to aortic valve stenosis in men and women. 1 1 1 Renske , Jeannette Goudzwaard , Nicolas van Mieghem , Peter de 1 1 Jaegere , Francesco Mattace‑Raso. Anterograde and Retrograde brachial pressure gradients were calcu- Erasmus MC University Medical Center, Rotterdam, Netherlands lated separately from the peak and mean of the first derivative of the Introduction: There are similarities in etiology and pathophysiol- brachial pressure waveform and the carotid-radial pulse wave velocity. ogy between aortic valve stenosis and arterial stiffness. We stud- ied whether arterial stiffness, measured as arterial pulse wave References velocity (aPWV), was associated to aortic valve stenosis in both men 1. Bretón‑Romero R, Wang N, Palmisano J, Larson MG, Vasan RS, Mitchell GF, and women. et al. Cross‑Sectional Associations of Flow Reversal, Vascular Function, Method: We included 333 patients (172 men and 161 women) with and Arterial Stiffness in the Framingham Heart Study. Arterioscler Thromb aortic valve stenosis and information on the aPWV who were included Vasc Biol. 2016 Dec;36(12):2452–9. in an ongoing observational cohort study. The aPWV was measured with a brachial cuff-based oscillometric measurement (Mobil-O-Graph Keywords: Endothelial Function, Retrograde flow, Cardiovascular dis- 24 h PWA Monitor, I.E.M. Gmbh, Stolberg, Germany). The median aPWV ease, brachial pressure wave was used to differ between low and high arterial stiffness group. Aortic valve stenosis was assessed with use of an echocardiogram and multi- slice computed tomography. Results were stratified for sex. Special Populations Results: In men the peak aortic valve velocity and mean aortic valve pressure gradient were both higher in patients with a high aPWV (3,8 m/s vs 4,05 m/s (P = 0.018) and 32 mmHg vs 41 mmHg (P = 0.010), P.081 respectively). In women there were no differences found in diagnostic Aortic stiffness and systemic inflammation as therapeutic targets measurements of aortic valve stenosis between the low or high aPWV to intravitreal anti‑vascular endothelial growth factor therapy groups. in patients with age‑related macular degeneration Conclusion: We found aortic valve peak velocity and the mean aor- 1 2 Nikolaos Ioakeimidis , Ioanna Gourgouli , Dimitrios tic valve pressure gradient was higher in men with a high aPWV. We 1 2 Terentes‑Printzios , Danai‑Magdalini Gourgouli , Christos found no relation between aortic valve stenosis and arterial stiffness 1 1 2 Georgakopoulos , Konstantinos Aznaouridis , Sofia Spai , Dimitrios in women. 1 1 1 Tousoulis, Konstantinos Tsioufis , Charalambos Vlachopoulos. First Department of Cardiology, Hippokration Hospital, Athens Medical, Athens, Ελλάδα, Ophthalmology Department, General Hospital of Ath‑ ens "Sismanoglio‑Amalia Fleming", Athens, Greece, Athens, Greece Background: Aortic stiffness and inflammation are predictors of cardiovascular risk. Anti-vascular endothelial growth factor agents (anti-VEGF), injected intravitreally, can reverse the course of exudate age-related macular degeneration (AMD). We investigated the associa- tion of changes in aortic stiffness and inflammation with response to anti-VEGF therapy. Methods: 54 patients (mean age: 76 ± 10  years) with AMD received two consecutive monthly intravitreal injections of ranibizumab (0.5 mg). The primary outcome measure was change in carotid-femo- ral pulse wave velocity (PWV) from baseline to 1 month after the sec- ond injection. Results: Ranibizumab caused a decrease in PWV after the first (by 0.36 ± 1.4  m/s) and the second injection (by 0.31 ± 1.4  m/s) and remained decreased 1  month after the second injection (overall P < 0.05). PWV decreased significantly in good responders (according to clinical criteria and fundus findings, P = 0.004), whereas it increased numerically in poor responders (P = 0.21) over the study period. In Keywords: Aortic valve stenosis, Arterial stiffness, Vasculair aging responders, hsIL-6 decreased after the first injection and remained decreased 1  month after the second injection (by 0.63 ± 0.35  pg/ml, Artery Research P.092 Methods: In a cross-sectional study of heterogeneous group of sub- Carotid‑femoral pulse wave velocity variability: Beyond errors jects, aortic stiffness was assessed by the Complior Analyse device in measurements using 2nd derivative. The pulse waveforms were extracted and used 1 1 1 2,3 for analysis by custom MATLAB algorithm for intersecting tangents, Amira Tairi , Hasan Obeid , Catherine Fortier , Alessandro Giudici , Bart 3,4 1 and the results were then compared to Millasseau’s formula. Spronck , Mohsen A gharazii Results: The preliminary results of the first 44 patients (men: 50%; CHU de Québec Research Center, L’Hôtel‑Dieu de Québec Hospital, mean age: 47 ± 18  years) show that Millasseau’s formula underesti- Quebec, Canada, Department of Biomedical Engineering, CARIM mates the transit times values by about 6% in comparison with the School for Cardiovascular Diseases, Maastricht University, Maastricht, The transit times obtained by the intersecting tangents method using Netherlands, GROW School for Oncology and Reproduction, Maastricht MATLAB software (63 ± 23  ms vs 67 ± 21  ms; P < 0.001). This results in University, Maastricht, The Netherlands, Macquarie Medical School, an overestimation of the pulse wave velocities values by about 10% Faculty of Medicine, Health and Human Sciences, Macquarie University, (11.1 ± 5.2 m/s vs 10.2 ± 3.6 m/s; P < 0.001). Sydney, Australia Conclusions: Based on these preliminary results, the values of pulse wave velocities obtained with Millasseau’s formula overes- Background: Variability of carotid-femoral pulse wave velocity timate values as compared to the values obtained by intersecting (CFPWV) measurements may be related to measurement errors, but tangents method. Therefore, there is a need for a better conversion also to physiological beat-to-beat variations in pulse transit time (TT). formula. We aimed to (1) evaluate beat-to-beat variability of CFPWV on simul- taneous non-invasive carotid and femoral waveforms without signal �t − 14.96 maxmal upstroke artefacts, and (2) explore its clinical and hemodynamic determinants. �t = (ms) intersecting tangent Methods: In 44 adult patients (47 ± 18 years; 50% men; 32% hypertensive, 0.8486 27% with chronic kidney disease, 9% diabetic and 5% with cardiovascu- References lar disease), three 10  s-long acquisitions of carotid and femoral pressure waveforms were performed using Complior Analyse. Raw data of the three 1. Millasseau SC, Stewart AD, Patel SJ, Redwood SR, Chowienczyk PJ. Evaluation recordings were extracted, checked to be artefact-free, concatenated, and of carotid‑femoral pulse wave velocity: influence of timing algorithm and subjected to a custom 2nd derivative-based foot detection algorithm. heart rate: Influence of timing algorithm and heart rate. Hypertension Mean, beat-to-beat standard deviation (SD), and coefficient of variation [Internet]. 2005;45(2):222–6. Available from: http:// dx. doi. org/ 10. 1161/ 01. (CV) of CFPWV (80% of direct distance) and heart rate were determined. HYP. 00001 54229. 97341. d2 Regression analysis was used to identify determinants of CV of CFPWV. Results: 44 ± 3 (mean ± SD) beats per individual were analysed, and Keywords: Kidney, Hypertension, Pulse wave velocity measurements, the mean CFPWV was 7.7 ± 2.6  m/s. The SD and CV of CFPWV were Mathematical algorithms 1.2 ± 0.8 m/s and 13.9 ± 6.5%, respectively. In multivariable regression analysis, age (standardized ß = 0.470, p < 0.001) and intra-individual SD of heart rate (ß = 0.430, p < 0.001) explained 63% of changes in CV of P.095 CFPWV. Systolic/diastolic blood pressures were not significant deter - Carotid artery stiffness in COVID‑19 survivors and its relationship minants of CV of CFPWV. with baroreflex sensitivity Conclusions: There is a variability in beat-to-beat pulse transit time 1 1 2 3 that is not explained by poor signal quality, but by higher physi- Dinu Santha Chandran , Prachi Srivastava , P. M. Nabeel , Kiran Raj , 2,3 1 ological variations of beat-to-beat transit time, which is explained by Jayaraj Joseph , Kishore Kumar Deepak advancing age and beat-to-beat heart rate variability. Department of Physiology, All India Institute of Medical Sciences, New Keywords: Signal analysis, pulse wave velocity algorithms Delhi, India, Healthcare Technology Innovation Centre, Indian Institute of Technology, Madras, India, Department of Electrical Engineering, Indian Institute of Technology, Madras, India P.093 Background: Stiffening of the barosensitive regions of large arter - Pulse wave velocity: intersecting tangents versus second ies have been previously linked to baroreflex dysfunction in various derivative on same pressure wave recordings. patient populations (1). We evaluated the local stiffness of carotid 1,2 1,2 1,2 1,2 Amira Tairi , Hasan Obeid , Catherine Fortier , Mathilde Paré , artery in COVID-19 survivors and investigated its relationship with 1,2 1,2 1,2 Nadège Côté , Emy Philibert , Charles‑Antoine Garneau , Rémi non-invasively assessed baroreflex sensitivity. 3,4 1,2 Goupil , Mohsen A gharazii Methods: Sixty COVID-19 survivors (age range – 22 to 66  years; 27 females) participated in the study at 3–6  months of clinical recovery CHU de Québec Research Center, L’Hôtel‑Dieu de Québec Hospital, Quebec, from RT-PCR positive mild COVID-19. Control group consisted of 53 Canada, Division of Nephrology, Faculty of Medicine, Laval University, Quebec, healthy volunteers matched for age, gender, BMI, and blood pressure Canada, Department of Medicine, Université de Montréal, Montreal, Canada, whose arterial stiffness data was acquired prior to the onset of COVID- Hopital du SacréC ‑ œur de Montréal Research Center, Montreal, Canada 19 pandemic. Stiffness of the common carotid artery was assessed Background: Aortic stiffness is assessed by determination of pulse using ARTSENS —a clinically validated, image-free, ultrasound-based wave velocity using pulse transit time and the distance between arterial wall tracking technology (2). Heart rate and beat-to-beat blood carotid and femoral arteries. Transit time is obtained by using inter- pressure was non-invasively acquired for 5 min to compute baroreflex secting tangents algorithm or the point of maximal upstroke during sensitivity (BRS) using spontaneous sequence and spectral methods. systole (2nd derivative). Millasseau et  al. [1] have proposed a formula Results: Pressure-strain elastic modulus – Ep (87.18 ± 25.57  kPa vs for converting transit time between methods using SphygmoCor 71.42 ± 26.79  kPa; p = 0.0002), and One point pulse wave velocity— (intersecting tangents) and the Complior SP (2nd derivative). The PWVβ (5.706 ± 0.7876  m/s vs 5.139 ± 1.011  m/s; p = 0.0001) were sig- objective of the present study is to compare the two methods using nificantly elevated in the COVID-19 survivor group in comparison to the same pressure waveforms obtained by the newer generation of Complior and using Millasseau’s formula. A rtery Research the historical control group. Spectral estimate of BRS in the high fre- underwent vascular assessment with pOpmètre (Axelife—France). The quency band correlated negatively (r = -0.31; p = 0.016) with PWVβ in following parameters were measured in each patient, PWV, ABI and the COVID-19 survivor group. central Blood Pressure, non-invasively and without cuff compression. Conclusions: Local stiffness of the carotid artery is significantly Results: PWV correlated with the degree of retinopathy (F = 13.80; elevated in COVID-19 survivors at 3–6  months of clinical recovery. p < 10^(− 4)) and with aging (r = 0.25; p < 10^( − 4)), and with dia- Deranged baroreflex function in COVID-19 survivors might be linked betes duration (r = 0.12; p < 0.002) independently of gender, HbA1c, to the stiffening of barosensitive regions of central arteries. smoking, BMI, diabetes duration or lipid profile. Aging and diabetes duration were not associated (ANOVA, p = 0.5) to the degree of retin- opathy unlike PWV. Conclusions: There is a high interdependence between microvascular and macrovascular lesions in this population of well treated type I dia- betic patients with or without retinopathy. Reference Obeid H, Khettab H, Marais L, Hallab M, Laurent S, Boutouyrie P. Evaluation of arterial stiffness by finger ‑toe pulse wave velocity: optimization of signal processing and clinical validation. J Hypertens. août 2017;35(8):1618‑25. Keywords: Arterial stiffness, diabetes, retinopathy P.099 FRailty and Arterial stiffness – the role of oXidative stress and Inflammation (FRAXI study) 1 1,2 3 1 Ekow Mensah , Khalid Ali, Winston Banya , Frances Ann K irkham , 2 4 1,2 Manuella Mengozzi , Pietro Ghezzi , Chakravarthy Rajkumar Brighton and Sussex Clinical Trials Unit, University Hospitals Sussex NHS Trust, Brighton, UK, Brighton—East Sussex, United Kingdom, Depart‑ Comparison of Pressure-strain elastic modulus of common carotid ment of Medicine, Brighton and Sussex Medical School, University artery in Covid survivors versus control group. of Sussex, Brighton, UK, Brighton, United Kingdom, Research Office, Royal Brompton and Harefield Clinical Group, Guy’s and St. Thomas’ NHS References Foundation Trust, London, UK, London, United Kingdom, Università degli 1. Okada Y, Galbreath MM, Shibata S, Jarvis SS, VanGundy TB, Meier RL, et al. Studi di Urbino, Italy, Urbino, Italy Relationship between sympathetic baroreflex sensitivity and arterial stiff‑ Background: There is an association between frailty and arterial stiff- ness in elderly men and women. Hypertension. 2012 Jan;59(1):98–104. ness1. However, arterial stiffness does not uniformly correlate with the 2. Nabeel PM, Chandran DS, Kaur P, Thanikachalam S, Sivaprakasam M, Joseph spectrum of frailty states. Both oxidative stress and inflammation con- J. Association of incremental pulse wave velocity with cardiometabolic tribute to vascular aging2. There are no human studies exploring links risk factors. Sci Rep. 2021 Jul 29;11(1):15,413. between arterial stiffness, oxidative stress, inflammaging and frailty. Methods: An observational longitudinal cohort study will be used Keywords: COVID-19, Arterial stiffness, Baroreflex sensitivity, Carotid to examine the association between arterial stiffness, oxidative artery stress, and inflammation in 50 older adults (≥ 70 years) with clinical frailty scores (CFS) ≤ 6 over six months. Frailty assessments include hand-grip strength, timed-up and go test, mini-mental state exami- P.097 nation, geriatric depression scale and sarcopenia using body com- Relationship between microangiopathy and macroangiopathy position measurements. Arterial stiffness measurements includes in diabetic patients carotid-femoral pulse wave velocity and carotid-radial pulse wave 1 2 1 velocity using Complior. CAVI device will measure Cardio-ankle vas- Kornelia Eveilleau, Hester Wessels , Hasan Obeid , Georges 4 1 3 1 2 cular index and ankle brachial index. Oxidative stress blood mark- Leftheriotis , Magid Hallab , Michel Marre , Imad Abi‑Nasr , David Segal ers nitrotyrosine and 8-hydroxy-2’-deoxyguanosin and inflammation 1 2 Clinique Bizet, Department of Cardiology, Paris, France, Center markers high-sensitive C-reactive protein and interlukin-6 will be for Diabetes and Endicrinology, Houghton Estate, South Africa, Clinique measured at baseline and 6-months. Ambroise Paré, Diabétologie‑Endocrinologie, Paris, France, Service de Data Analysis: Descriptive statistics for continuous data using Médecine et d’Exploration Vasculaires, CHU de Nice, Nice, France means and standard deviations for normality distributed variables or medians and inter-quartile ranges for skewed variables will be Background: Diabetes patients are known to produce diabetic retin- used. Participants will be categorized into CFS 1–3, and CFS 4–6. opathy. Pulse wave velocity (PWV) provides arterial stiffness and Categorical data will use frequencies and comparison between hemodynamic parameters. We studied the effect of diabetic retinopa- groups. Change in frailty between the groups over 6 months will be thy in different stages on arterial stiffness in diabetics. We measured compared using paired t-test. Simple linear regression will be done vascular aging with a new system (pOpmètre) that measures PWV, between frailty measures, and exposure variable with significance at Ankle-Brachial Index (ABI) and Central Blood pressure. p < 0.5. Methods: 83 type 1 diabetes patients attending the clinic (59% male) Conclusion: This study data will inform a larger, multi-centre study aged (42 ± 1.54 years). Insulin dependent diabetic patients with retin- exploring further the interplay between frailty, biomarkers, and opathy (N = 61) or without retinopathy (N = 22) with abnormal albu- arterial stiffness parameters. minuria ratio (17%), mean diabetes duration 26  years. All patients Artery Research References self-administered questionnaire related to SPA compared to same- 1. Orkaby, A. R. et al. Cross‑sectional association of frailty and arterial stiffness in aged/sex peers graded: younger, no difference, older. Aortic stiff- community‑ dwelling older adults: The framingham heart study. Journals ness was assessed by carotid-femoral pulse wave velocity (c-f PWV; Gerontol.—Ser. A Biol. Sci. Med. Sci. 74, 373–379 (2019). SphygmoCor), defined as > 10  m/s. Logistic regression models were 2. Inglés, M. et al. Oxidative stress is related to frailty, not to age or sex, in a adjusted for chronological age and sex. geriatric population: Lipid and protein oxidation as biomarkers of frailty. J. Results: Aortic stiffness occurred in 234 (6.6%) subjects. Mean Am. Geriatr. Soc. 62, 1324–1328 (2014). age decreased gradually between all three SPA categories, with the highest mean age observed in subjects who perceived them- Keywords: Frailty, arterial stiffness, oxidative stress, inflammaging. selves as younger than same-aged/sex peers (49 ± 1 vs. 40 ± 1 vs. 32 ± 1 years, p < 0.001). In crude model, subjects with aortic stiffness perceived themselves as younger than same-aged/sex peers (OR: 0.40, p = 0.002). Adjustment for sex did not change this association P.103 (OR: 0.67, p = 0.003). Upon adjustment for sex and chronological Ideal Life’s Simple 7 score relates to carotid intima‑media older SPA was associated with almost twofold increased likelihood thickness in the healthy population of aortic stiffness (OR: 1.97, p = 0.038). Sex-stratification demon- 1 1 1 1 strated a stronger 2.5-fold likelihood of aortic stiffness in men (OR: Gilles Nève, Jonathan Wagner , Raphael K naier , Denis Infanger , 1,2 1 1 1 2.50, p = 0.042), but no significant association in women (OR: 1.46, Christopher Klenk , Justin Carrard, Timo Hinrichs , Henner Hanssen , 1 1 p = 0.43). Arno SchmidtT ‑ rucksaess , Karsten Königstein Conclusions: A negative self-perceived age (feeling older than same- 1 2 University of Basel, Basel, Switzerland, Technical University Munich, aged/sex peers) is associated with a 2.5-fold increased likelihood of Munich, Germany aortic stiffness (vascular ageing) in men when adjusted for chronologi- cal age, but not in women. Background: Health scores such as the Life’s Simple 7 (LS7) from the American Heart Association and the assessment of carotid intima- media thickness (cIMT) are independently used to predict future cardiovascular health burden. However, evidence of their associa- tion remains scarce, especially in healthy populations. Methods: A community sample of the healthy Swiss population aged 50–91  years was included as part of the COmPLETE cohort study. CIMT was measured with a semiautomatic state-of-the-art ultrasound system. The LS7 cardiovascular health score was calcu- lated from body-mass index, cholesterol, systolic blood pressure, hemoglobin A1c, smoking status, physical activity, and diet. For every biomarker two points were given for an ideal health metric level, intermediate scores 1 point, and poor scores 0 points. Interme- diate health corresponded to a total of 5–9 points and ideal health to 10–14 points. Results: 280 participants (50.7% male) were included in statistical analyses. Age- and sex-adjusted analyses showed an association of “ideal health” with lower cIMT (− 0.038  mm, 95% CI − 0.069  mm to − 0.007 mm, p = 0.017) compared to “intermediate health”. Conclusions: Even in a healthy community-dwelling sample of middle-aged to older adults, individuals with an ideal cardiovascular health score showed more favorable carotid properties than those with an intermediate score. This stresses the relevance of promoting an optimal lifestyle, even among the healthy population, for optimal vascular aging. Keywords: Life’s simple 7, arterial stiffness, cardiovascular risk, carotid intima-media thickness P.104 Vascular ageing in relation to chronological and self‑perceived age: A Swedish population‑based study Comparison of self-perceived age with same-aged/sex peers between 1,2 1 men and women with and without aortic stiffness (vascular ageing) in Madeleine Johansson , Peter M N ilsson the general population. 1 2 Lund University, Malmö, Sweden, Dept. of Cardiology, Skåne University Hospital, Malmö, Sweden References 1.Hughes ML., Touron DR. Aging in Context: Incorporating Everyday Experi‑ Background: Chronological age is a key clinical determinant of ences Into the Study of Subjective Age Front. Psychiatry. 2021. aortic stiffness. Self-perceived age (SPA) is a strong predictor of 2.Stephan Y, Demulier V, Terracciano A. Personality, self‑rated health, and well-being and long-term health . We aimed to investigate the subjective age in a life‑span sample: The moderating role of chronologi‑ association between SPA, chronological age, and aortic stiffness cal age. Psychol Aging. 2012. (vascular ageing) in the general population. Methods: Cross-sectional analysis of a population-based study, Keywords: Vascular ageing, Aortic stiffness, Epidemiology, Malmö Offspring Study (n = 3563). Mean age 42 ± 14  years, Self-perception age range 18–74, 53.4% women. Participants completed a A rtery Research P.105 for calculating baPWV, whereas the mean of two measurements on Factors affecting short‑term repeated measurements of central the right side (median for 3) was used for cfPWV. The Bland–Altman augmentation index: a randomized cross‑over study with two Analysis was used for finding the agreement between the two types of devices pulse wave velocities. 2 2 1 1 Results: 30 patients (63% men, age 67 ± 12.75  years, BMI Mario Podrug , Borna Sunjic , Anamarija Bekavac , Pjero Koren , Varja 1 1 1 1 25.73 ± 3.84  kg/m2, MBP 92.866 ± 10.13  mmHg). CfPWV was Đogaš , Ivana Mudnic , Mladen Boban , Ana Jeroncic 12.25 ± 2.56 m/s and baPWV was 11.67 ± 1.90 m/s. cfPWV and baPWV 1 2 University of Split School of Medicine, Split, Croatia, University Depart‑ were linearly correlated with each other (r = 0.6079, p = 0.0004, Inter- ment of Health Studies, University of Split, Split, Croatia cept 2.6331, Slope 0.8255). Both were positively correlated with age (cfPWV: r = 0.6135, p = 0.0004, baPWV r = 0.4688, p = 0.0103). The two Background: Central augmentation index (cAIx) is predictive of future metrics showed a substantial agreement, with no significant bias (bias cardiovascular events in subjects free of overt cardiovascular disease. CI 95% − 0.597, 95.0% lower confidence limit − 1.367, 95.0% upper Although cAIx can provide clinically useful information beyond bra- confidence limit 0.173). chial blood pressures, its use in longitudinal studies is limited. Data Conclusions: In a population of individuals undergoing cardiovascular on short-term repeated measurement error and factors affecting it are screening, a good agreement between cfPWV an baPWV was found. needed to determine the minimal detectable clinical change of cAIx These preliminary results need to be confirmed in a larger cohort. and reduce this error. Methods: We conducted a longitudinal, block-randomised cross-over study with two observers and two validated devices that use different measurement techniques: SphygmoCor CvMS and Arteriograph; to monitor cAIx changes over 2 weeks. Each participant was recorded 12 times over the course of three visits, separated by one week. During each visit, recordings were taken twice in the morning and twice in the afternoon. Experimental, metreorological and physiological factors affecting cAIx were identified using multilevel mixed-effect models. Results: Participants (N = 35) were uniformly and widely distributed by age (range 20–60  years), BMI (19–39), sex, and hypertensive sta- tus. On average, within-subjects cAIx measurements differed by 5.9% (95% CI 5.1–6.8) and 4.7% (4.2–5.3) for SphygmoCor and Arteriograph, respectively. Older age, female sex, and morning recordings signifi- cantly increased SphygmoCor’s cAIx values. Mean arterial pressure (MAP), outdoor temperature, and their interaction also significantly affected these values but due to interaction, main effects were not unambiguously interpretable (P ≤ 0.029 for all). For Arteriograph, we found that older age, MAP, shorter height, morning recordings, and 1st visit significantly increased cAIx (P < 0.001 for all). Conclusion: We evaluated measurement error of cAIx and made sug- gestions for reducing it in longitudinal studies. Reference References Vlachopoulos C, Aznaouridis K, O’Rourke M Fet al. Prediction of cardiovascular Kollias A, Kyriakoulis KG, Gravvani A, Anagnostopoulos I, Stergiou GS. Auto‑ events and all‑ cause mortality with central haemodynamics: a systematic mated pulse wave velocity assessment using a professional oscillometric review and meta‑analysis. Eur Heart J 2010; 31(15): 1865–1871. office blood pressure monitor. The Journal of Clinical Hypertension. 2020 Oct;22(10):1817–23. Keywords: cAIx, measurement error, factors Segers P, Rietzschel ER, Chirinos JA. How to measure arterial stiffness in humans. Arteriosclerosis, thrombosis, and vascular biology. 2020 May;40(5):1034–43. P.106 Validation of an oscillometric device for brachial‑ankle PWV: Keywords: Vascular ageing device validation, vascular assessment, preliminary results branchio-ankle pulse wave velocity, pulse wave velocity validation study Maryam Jadoon, Hakim Khettab, Justin Junior, Pierre Boutouyrie, Rosa‑Maria Bruno P.110 Paris cardiovascular research center, Inserm U970,Université Paris Cité, Beamforming LDV‑data for carotid‑femoral pulse‑wave velocity Paris, France estimation 1 3,4 5 2 Introduction: Arterial stiffness is independent and clinically rel- Simeon Beeckman, Yanlu Li , Pierre Boutouyrie , Nilesh Madhu , evant prognostic biomarker, which can be measured by different Patrick Segers techniques, including carotid-femoral Pulse wave velocity (cfPWV), 1 2 IBiTech‑bioMMeda, Ghent University, Ghent, Belgium, IDlab, Ghent Branchial-ankle PWV baPWV. The aim of this study is to investigate if University—imec, Ghent, Belgium, Photonics Research Group, Ghent there is an agreement between ankle-branchial and Carotid-femoral University‑imec, Ghent, Belgium, Center for Nano‑ and Biophotonics, pulse wave velocity. Ghent, Belgium, INSERM U970, Université de Paris, Paris, France Methods: The carotid- femoral and Branchio-ankle Pulse wave veloc- ity of 30 patients coming for routine clinical checkup of cardiovas- Background: Carotid-femoral pulse-wave velocity (cfPWV) has been cular risk evaluation were measured with SphygmoCor CVSM (Atcor recognized as a biomarker for arterial stiffness. It is therefore valuable Medical, Australia) and WatchBP Office Vascular (Microlife, Widnau, to be able to estimate this value easily and quickly for a wide range Switzerland). The mean of left and right leg measurements was used of potential patients [1]. We are developing a novel device based on Artery Research multi-beam laser-doppler vibrometry. It can measure pulse-induced Vascular biology and pathophysiology vibrations of high spatial and temporal resolution on bare skin the neck and groin. Two methods of estimating carotid-femoral pulse tran- P.121 sit time (cfPTT ) were tested. Direct link between aortic displacement and carotid artery Methods: We applied a dedicated beamforming algorithm to combine longitudinal wall behaviour: a cadaver case study and improve the data from 6 parallel signals of simultaneous measure- 1 1 2 1 Kailey Stevens , Chloe Athaide , Cindy van Loo, Tamara Maciel , Bart ments at both carotid and femoral measurement sites. This was done 2,3 1 Spronck , Jason Au on a subset of N = 54 high-quality carotid-femoral LDV measure- 1 2 ments [2]. We then calculated cfPTT (1) using all pair-wise combina- University Of Waterloo, Waterloo, Canada, Maastricht University, Maas‑ tions of the raw signals from all channels (brute-force method) and (2) tricht, Netherlands, Macquarie University, Sydney, Australia using the beamformed signals. The final cfPTT estimate, in each case, Background: Carotid artery longitudinal motion (CALM) describes was computed as the average of all estimated cfPTT’s per dataset. movement of the arterial wall with (anterograde, forward) and against These cfPTT’s were then compared to reference cfPTT’s (Sphygmocor (retrograde, backward) blood flow . Determinants of beat-to-beat system). regulation of CALM are not fully understood. Influences of blood flow Results: As the number of generated cfPTT’s in a given measurement and cardiac contraction on CALM have previously been investigated , increased (> 75), so did the correspondence of the final cfPTT estimate although separation of these factors in  vivo is challenging. Human with the reference (see Fig.  1). The same effect was observed with cadaveric specimens allow the opportunity to view the isolated increasing number of timepoints (> 5) at which a cfPTT was able to be impact of central force application versus the influence of shear forces calculated. This held true for cfPTT’s estimated using both beamform- on longitudinal motion. Accordingly, we aimed to study the poten- ing and brute-force techniques. tial influences of central cardiovascular factors on longitudinal wall Conclusions: Accurate cfPTT estimates are obtained for good-quality motion. LDV-measurements, where sufficient discernable heartbeats were rec - Methods: A thoracic dissection of a 19-year-old male donor was per- ognized using the beamforming and brute-force methods. formed to reveal the ascending aorta. A clamp fastened in series to a load cell was attached to the aortic root, and caudal force was applied up to 11.5 and 13.2  N over 3.5  s. Longitudinal wall displacement was measured via vascular ultrasound at the left common carotid artery. Results: Longitudinal wall displacement was measured as 1.44  mm and 1.27  mm, for each respective force application. The longitudinal pre-stretch value was 1.24 for the left common carotid artery (3.00 cm in  situ, 2.41  cm excised) . For comparison, the representative maxi- mum displacement for a 19-year-old active male is 0.70 mm over a sin- gle cardiac cycle. Conclusion: Caudal force application on the aorta generates a trace similar to the retrograde phase seen in CALM. This is the first evidence to suggest direct influence of cardiac contraction on retrograde motion, providing a plausible mechanistic theory on 2D arterial wall motion . Fig. 1 A comparison of PTT estimates in qualitative carotid‑femoral LDV A: longitudinal displacement from 11.5  N (black) and 13.2  N (blue) measurements with their reference PTT’s. Estimates made via brute‑force force applications; B: representative CALM trace over a single cardiac method are shown in black, via beamforming in blue cycle for a 19-year-old male. References References [1] Segers P, Rietzschel ER, Chirinos JA. How to Measure Arterial Stiffness in 1. Athaide CE, Spronck B, Au JS. Physiological basis for longitudinal motion of Humans. Arterioscler Thromb Vasc Biol. 2020;40(5):1034–1043. http:// doi. the arterial wall. American Journal of Physiology‑Heart and Circulatory org/ 10. 1161/ ATVBA HA. 119. 313132 Physiology. 2022 May 1;322(5):H689‑701. [2] Seoni S, Beeckman S, Li Y, et al. Template Matching and Matrix Profile for 2. Cinthio M, Ahlgren AR, Bergkvist J, Jansson T, Persson HW, Lindstrom K. Signal Quality Assessment of Carotid and Femoral Laser Doppler Vibrom‑ Longitudinal movements and resulting shear strain of the arterial wall. eter Signals. Front Physiol. 2022;12:775,052. Published 2022 Jan 11. http:// American Journal of Physiology‑Heart and Circulatory Physiology. 2006 doi. org/ 10. 3389/ fphys. 2021. 775052 Jul;291(1):H394‑402. 3. Horný L, Netušil M, Voňavková T. Axial prestretch and circumferential disten‑ Keywords: Laser Doppler Vibrometry (LDV), Carotid-femoral sibility in biomechanics of abdominal aorta. Biomechanics and modeling pulse-wave velocity (cfPWV), Pulse transit-time (PTT) estimation, in mechanobiology. 2014 Aug;13(4):783–99. Beamforming. Keywords: Wall behaviour; pre-stretch; stiffness A rtery Research 3. Hossam A. Shaltout, James C. Rose, Mark C. Chappell and Debra I. ANG‑(1–7) P.122 Deficiency and baroreflex impairment precede the antenatal betametha‑ An increase in circulating Angiotensin 1–7 levels sone exposure induced elevation in blood pressure. Hypertension. 2012; post‑angiotensin‑converting enzyme inhibition is associated 59(2): 453–458. with delayed vascular ageing and improvement in baroreflex function in type 2 diabetic patients with hypertension Keywords: Angiotensin 1–7, Baroreflex Sensitivity, Arterial Stiffness, 1 1 1 1 Prachi , Dinu S Chandran , Viveka P Jyotsna , Ashok Kumar Jar yal , Vascular ageing Kishore Kumar Deepak. Department of Physiology, All India Institute of Medical Sciences, New Delhi, India P.123 Background: Angiotensin 1–7 (Ang1-7) is a novel peptide which has Carotid arterial wall viscosity and stiffness are increased in type 2 a vaso-protective role, as reported in animal studies(1–3). However, it’s diabetes patients role in human vascular ageing is not fully known. We evaluated associ- 1,2 1,2 1,2 Frédéric Roca , Louise Zmuda , Michaela Iacob , Lucile ation between the increment in Ang1-7 levels and vascular functions, 3 3 1,2 Moreau‑Grangé , Gaetan Prevost , Robinson Joannides , Jeremy post ACE inhibition. 1,2 Bellien Methods: Sixty diabetic hypertensive patients (mean age 1 2 46.2 ± 8.1 years) participated in the study. Beat-to-beat blood-pressure Pharmacology, Rouen University Hospital, Rouen, France, INSERM and electrocardiogram were recorded for 5-min to compute baroreflex U1096, Rouen, France, Diabetology‑Endocrinology, Rouen University sensitivity. Circulating levels of angiotensinII, angiotensin1-7, Angio- Hospital, Rouen, France tensin-Converting-Enzyme 2 (ACE2), hsCRP and Interleukin-10 (IL-10) Background: Type 2 diabetes (T2D) is associated with an increase in were measured using ELISA. Flow-mediated-dilation (FMD) of Brachial arterial stiffness. However, changes in arterial wall viscosity (AWW) artery and carotid-intima-media-thickness (CIMT) were measured during T2D have been little investigated (1,2). Moreover, despite many by ultrasonography. Carotid-femoral Pulse-wave-velocity (cf-PWV) studies describing an increase in cfPWV, few studies investigated the and Augmentation-Index (AIx) were measured using applanation change in local carotid stiffness during T2D (3). Our aim was to inves- tonometry. tigate changes in AWV and in local carotid stiffness, considering work - Results: Patients were categorized into two groups based on the ing conditions, in patients with T2D. incremental changes in Ang1-7 from baseline to 3  months (3  M-BL) post ACE inhibition. The comparisons were made between the high- Methods: In this cross-sectional, monocentric study we compared 19 est (Group-1) and the lowest (Group-2) quartiles. Greater improvement middle-aged patients (median age: 65[60–66] years) with T2D to 30 was observed in systolic, diastolic ALL-BRS and FMD in group-1 when non-diabetic (ND) controls (median age: 56[52–61] years). The pres- compared to group-2 [SBP-ALL-BRS3M-BL(ms/mmHg):6.1 ± 4.1 Vs sure-LCSA loop was obtained by carotid tonometry and contralateral 1.6 ± 7.3, p = 0.02; DBP-ALL-BRS3M-BL(ms/mmHg):9 ± 9.6 Vs 1.2 ± 7.4, carotid echo-tracking. The absolute viscosity (WV), corresponding to p = 0.007; FMD3M-BL(cm.):0.02 ± 0.01 Vs 0.01 ± 0.01, p = 0.006]. cf- the area of the loop, and the relative viscosity (WV/WE), correspond- PWV, CIMT and AIx showed greater decrement in group-1 in com- ing to the ratio between WV and the elastic energy stored within the parison to group-2 [cf-PWV3M-BL(m/s):(-3.3) ± 2.2 Vs (− 0.39) ± 2.9, arterial wall (WV/WE), were calculated. Carotid geometry, midwall p = 0.001; CIMT3M-BL(mm): (− 0.17 ± 0.18 Vs − 0.004 ± 0.13, p = 0.001; stress, distensibility and elastic modulus were also compared between AIx3M-BL(%): (− 8.3) ± 8.5 Vs (− 2.4) ± 9.8, p = 0.04]. IL-10 showed a groups. significant increase [IL-103  M-BL(pg/ml):{4.4(1.2–9.04) Vs 0.61 (− 12.2) Results: T2D patients were older and had more frequently hyperten- − 4.09}, p = 0.03] while hsCRP decreased [hsCRP3M-BL(mg/L): (− 6.3) sion. Internal diameter, pulse and mean central blood pressure were {(− 14.4)–( − 1.7)} Vs (− 0.19) {(− 2.5)–0.78}, p = 0.002] in group-1 com- higher in T2D patients but midwall stress was similar to ND. Carotid pared to group-2. distensibility was lower and elastic modulus higher in T2D patients. Conclusions: Greater increment in Ang1-7 post-ACE inhibition is asso- WV (ND: 11[7–18] vs. T2D: 23[16–41] mmHg.mm2, p = 0.007) and WV/ ciated with improvement in BRS, endothelial function, arterial stiffness WE (ND: 12% [8–17] vs. T2D: 21% [17–25], p < 0.001) were higher in and inflammation. Ang1-7 may play a role in delaying vascular ageing. T2D patients even after adjusting for confounding factors such as age, hypertension or midwall stress. Conclusions: Type 2 diabetes is associated with an increase in arterial wall viscosity and in local carotid arterial stiffness. References 1. Giudici A, Palombo C, Kozakova M, Morizzo C, Penno G, Jamagidze G, Della Latta D, Chiappino D, Cruickshank JK, Khir AW. Noninvasive carotid pressure‑ diameter loops to identify viscoelastic properties in ageing, hypertension and type 2 diabetes. Journal of Hypertension. 2021;39(11):2307–2317. Showing greater improvement in A. SBP ALL-BRS (ms/mmHg), B. Flow- 2. Toutouzas K, Stefanadis C, Tsiamis E, Vlachopoulos C, Tousoulis D, Tsioufis Mediated-Dilatation (cm.), and a decrease in C. cf-PWV (m/s) from C, Toutouzas P. Aortic pressure‑ diameter relation in patients with baseline to 3 months (3 M-BL) post ACE inhibition. non‑insulin dependent diabetes mellitus: new insights. Diabetologia. 2000;43(8):1070–1075. References 3. Prenner SB, Chirinos JA. Arterial stiffness in diabetes mellitus. Atherosclerosis. 1. Valencia I, L. Shamoon, A. Romero, F. De la Cuesta, C.F. Sanchez‑Ferrer, C. 2015;238(2):370–379. Peiro. Angiotensin‑(1 − 7), a protective peptide against vascular aging. Peptides 152 (2022) 170–775. Keywords: Diabetes, arterial wall viscosity, local carotid stiffness 2. Fan Jiang, Jianmin Yang, Yongtao Zhang, Mei Dong, Shuangxi Wang, Qunye Zhang, et al. Angiotensin‑ converting enzyme 2 and angiotensin 1–7: novel therapeutic targets. Nat Rev Cardiol. 2014 Jul;11(7):413–26. Artery Research P.124 Methods: 32 male patients with symptomatic PAD (aged 62 ± 9 years) Optogenetic control of PI3K gamma reveals its role in smooth undergoing DSA for the assessment and/or endovascular therapy of muscle cell contractility. lower-extremity arteries were studied. Aortic pulse wave velocity, a 1 1 1 gold standard indicator of arterial stiffness, was measured at baseline Damien Ramel , Marie‑Kergulen Sarthou, Amandine Wahart , Nicole 1 1 1 and 24 h after DSA. Venous blood samples were drawn from subjects Malet , Stéphanie Gayral , Matthias Wymann, Muriel Laffargue at baseline, 2  h after DSA and 24  h after DSA, and analysed primarily Inserm 1297, Toulouse, France for metabolic alterations. Results: No statistically significant subacute influence on arterial stiff- Background: PI3Kγ is a major signaling enzyme of the immune and ness was observed in our study. Various shifts in metabolome were cardiovascular compartments downstream of Gi-coupled GPCR. This observed 2  h and 24  h after DSA. The iodine contrast dose adminis- kinase is composed of three subunits, one catalytic (p110γ) and one tered during DSA independently influenced the levels of two low- of the two adapters (p84 and p101) and forms two distinct complexes. molecular metabolites at 2  h after DSA: lysophosphatidylcholine a To date, the molecular mechanism underlying PI3Kγ functions and the C20:3 and putrescine. implication of the two PI3Kγ complexes is still unclear. Conclusions: The results appear to be reassuring for the general safety Methods: Here, using optogenetic manipulation of each PI3Kγ com- of DSA in patients with PAD and provide some novel insight into DSA-s plexes, primary cells and original mice models, we investigate the effect on the metabolome of these patients. selective functions of the p101 and p84 PI3Kγ complexes in order to modulate the cellular PI3Kγ-dependent processes. References Results: We demonstrate that the p84/p110γ but not p101/ p110γ 1.Vlachopoulos C, Aznaouridis K, O’Rourke M, Safar ME, Baou K, & Stefanadis C. complex control cell contractility through its kinase activity and cal- Prediction of cardiovascular events and all‑ cause mortality with central cium signaling in human vascular smooth muscle cells. Moreover, we haemodynamics: A systematic review and meta‑analysis. European Heart demonstrated that p84 but not p101 is specifically engaged under Journal 2010;31(15):1865–1871. angiotensin II stimulation, a typical regulator of VSMC function. Finally, 2.Ben‑Shlomo Y, Spears M, Boustred C et al. Aortic pulse wave velocity new mouse models of p84 and p101 invalidation allowed us to dem- improves cardiovascular event prediction: an individual participant meta‑ onstrate the p84/p110γ critical role in VSMC contractile phenotype analysis of prospective observational data from 17,635 subjects. J Am Coll maintenance in primary cells and characterize the in  vivo conse- Cardiol 2014;63:636–646. quences of p84 deletion in entire aortas. Conclusions: Altogether, our study shed in light how a particular Keywords: Peripheral artery disease, Digital subtraction angiography, PI3K-adaptor module could differentially control key physiological Metabolome, Arterial stiffness responses according to its regulatory partner. References P.127 Lupieri, A., R. Blaise, A. Ghigo, N. Smirnova, M.K. Sarthou, N. Malet, I. Limon, P. Focal adhesions modulate aortic viscoelasticity under altered Vincent, E. Hirsch, S. Gayral, D. Ramel, and M. Laffargue. 2020a. A non‑ pulsatile conditions catalytic function of PI3Kgamma drives smooth muscle cell proliferation 1 1 1 1 Cédric Neutel, Callan Wesley , Guido De Meyer, Wim Martinet , after arterial damage. J Cell Sci. 133. PieterJan ‑ Guns Lupieri, A., N.F. Smirnova, R. Solinhac, N. Malet, M. Benamar, A. Saoudi, I. Santos‑ University of Antwerp, Edegem, Belgium Zas, L. Zeboudj, H. Ait‑ Oufella, E. Hirsch, P. Ohayon, T. Lhermusier, D. Carrie, J.F. Arnal, D. Ramel, S. Gayral, and M. Laffargue. 2020b. Smooth muscle Introduction: The aortic wall is composed of different functional ele - cells‑ derived CXCL10 prevents endothelial healing through PI3Kgamma‑ ments, such as vascular smooth muscle cells (VSMCs), that together dependent T cells response. Cardiovascular research. 116:438–449. define its viscoelastic properties. This study aimed to investigate how VSMCs influence the viscous and elastic properties of aortic tissue and Keywords: PI3K, Smooth muscle cells whether the focal adhesion – F-actin axis is involved. Methods: Aortic segments from C57Bl6/J mice were mounted in a P.126 Rodent Oscillatory Set-up for Arterial Compliance (ROTSAC) and sub- Eec ff ts of lower‑extremity digital subtraction angiography jected to high frequency cyclic stretch. Diastolic and systolic diameter as on arterial stiffness and metabolome in patients with peripheral well as the Peterson modulus (Ep), as a measure of aortic stiffness, were artery disease determined. Viscous modulus (Eη) was extracted from pressure-diameter 1,2 1,3,4 5,6 5,6 5,6 tracings by eliminating loop hysteresis. Afterwards, the elastic modulus Holger Post , Kaido Paapstel , Kalle K ilk , Aigar Ottas , Anneli Piir , 1,2,5,6,7 (EE) was calculated as the slope of the resulting pressure-diameter trac- Jaak Kals ing. Phenylephrine (2  µM, PE) was used to elicit VSMC contraction. PP2 1 2 Endothelial Research Centre, University of Tartu, Tartu, Estonia, Depart‑ (10  µM) and cytochalasin D (10  µM, CytoD) were used to inhibit focal ment of Surgery, Institute of Clinical Medicine, University of Tartu, Tartu, adhesion and F-actin function, respectively. The thoracic ascending Estonia, Department of Cardiology, Institute of Clinical Medicine, Univer‑ aorta (ASC) and the abdominal infrarenal aorta (AIA) were investigated sity of Tartu, Tartu, Estonia, Heart Clinic, Tartu University Hospital, Tartu, in parallel. Estonia, Department of Biochemistry, Institute of Biomedicine and Trans‑ Results: PE increased both Eη and EE this effect was more pronounced lational Medicine, University of Tartu, Tartu, Estonia, Centre of Excellence in the AIA as compared to the ASC, indicating a larger impact of VSMC for Genomics and Translational Medicine, Tartu, Estonia, Surgery Clinic, tonus in distal aortic regions. Moreover, increasing pulsatile load by Tartu University Hospital, Tartu, Estonia increasing pulse frequency from 1 to 25  Hz decreased Eη. The effect of pulse frequency was attenuated by both PP2 and CytoD. High pulsatile Background: Arterial stiffness has been shown to predict future car - load decreased the contractility of aortic segments. diovascular events and mortality [1,2]. Assessment of metabolites in Conclusion: The focal adhesion—F-actin axis responds to altered pulsa- biological systems has been increasingly applied to several diseases, tile conditions, modulating the viscous properties of aortic tissue. leading to recent discoveries in disease-specific biomarkers and their Keywords: Viscoelasticity, Vascular Smooth Muscle Cells, Focal Adhesion, mechanistic implications. The potential effect of angiographic studies F-actin with iodine contrast on arterial stiffness and metabolome has not yet been addressed in the literature. The aim of this study was to provide insight into the subacute effects of digital subtraction angiography (DSA) on arterial stiffness and metabolomic profiles of patients with peripheral artery disease (PAD). A rtery Research References P.128 1. Schram MT, Sep SJ, van der Kallen CJ, Dagnelie PC, Koster A, Schaper N, Existing bias between vascular ultrasound echo‑tracking systems: Henry RMA, Stehouwer CDA, The Maastricht Study: an extensive pheno‑ Switching devices warrants a comparison typing study on determinants of type 2 diabetes, its complications and 1 1,5 1 2 Afrah Malik , Alessandro Giudici , Koen van der Laan , Jos op’t Roodt , its comorbidities. Eur J Epidemiol. 2014; 29:439–451. 3 1 1,4 1 Werner Mess, Tammo Delhaas , Bart Spronck , Koen Reesink Department of Biomedical Engineering, CARIM School for Cardiovas‑ Keywords: Echo-tracking; vascular ultrasound; arterial properties; cular Diseases, Maastricht University, Maastricht, Netherlands, Depart‑ arterial stiffness ment of Internal Medicine, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, Netherlands, Department of Clinical Neurophysiology, CARIM School for Cardiovascular Diseases, Maastricht P.130 University, Maastricht, Netherlands, Macquarie Medical School, Faculty Endothelial glycocalyx degradation depends rather of Medicine, Health and Human Sciences, Macquarie University, Sydney, on inflammatory status than hemodynamic conditions Australia, GROW School for Oncology and Reproduction, Maastricht 1 1 1 Mohammad Jahangiri , Nathalie Mercier, Simon Toupance , Arthur University, Maastricht, Netherlands 1 1 1 1 Thomas , Carlos Labas, Véronique Regnault , Athanase Benetos , Patrick 1 1 Purpose: The Esaote MyLab70 + ART.LAB ultrasound system has been Lacolley , Jeremy Lagrange extensively used to evaluate arterial properties. Since the system reached Inserm1116, Vandoeuvre‑lès‑nancy, France its end-of-service-life, ongoing studies are forced to switch devices, with some opting for the MyLabOne [1]. Bias might exist between the two Background and Objectives: Glycocalyx, a thin layer of carbohydrates systems, which, if uncorrected, potentially leads to misinterpretation of covering endothelial cells, is important for interactions between blood results. The present study aims to evaluate potential bias between these components and the vascular wall. It is implicated in circulating cells two devices. Moreover, we also aim to compare two identical MyLabOne adhesion, inflammation, and coagulation regulation and can be dam- systems. aged in some diseases. The prevailing hypothesis is that hypertension Methods: Using a phantom set-up consisting of a silicone tube (for is the primary factor involved in glycocalyx degradation. However, our diameter and wall thickness measurements) and an eccentric wheel (for preliminary data challenge this view and point to a more important role distension measurement), we performed n = 60 and n = 40 measure- of inflammation. The objective of this study was to assess the respective ments for the inter- and intra-system model comparisons, respectively. roles of inflammation and hemodynamic on the endothelial glycocalyx Statistical significance was evaluated using independent t-tests. degradation. Results: Both comparisons led to significant biases for diameter (relative Methods and Results: Plasma concentrations of syndecan-1, a gly- bias: − 0.27%, p = 0.001 and − 0.30%, p < 0.001 for inter- and intra-sys- cocalyx degradation marker, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 tem comparisons, respectively) and wall thickness (relative bias: 0.38%, were quantified by ELISA in 327 participants (62 ± 14  years). Subjects p = 0.004 and − 1.23%, p < 0.001 for inter- and intra-system comparisons, were categorized as atherosclerotic cardio-vascular diseases (ASCVD) respectively), but not for distension (relative bias: 0.48%, p = 0.333 and patients or controls and performed all a blood pressure and pulse − 0.12%, p = 0.892 for inter- and intra-system comparisons, respectively). wave velocity assessment. Syndecan-1 was positively associated Conclusion: Biases in diameter and wall thickness measurements were with circulating IL-6 (p < 0.001), IL-8 (p = 0.002), and IL-10 concentra- observed between ultrasound systems, regardless of whether these sys- tions (p = 0.006) and with adhesion molecules ICAM-1 and VCAM-1 tems were (apparently) identical. Biases estimated here can therefore not (p < 001). No relation was observed between syndecan-1 and hemo- be generalized to any other pair of similar systems. Therefore, longitudi- dynamic parameters, thus confirming the major role of inflammatory nal studies with large sample sizes that switch between systems should status in the degradation of endothelial glycocalyx. Interestingly, sub- compare their devices to evaluate potential biases and to facilitate jects with higher plasma concentration of syndecan-1 (third tertile) robust interpretation of outcomes. displayed more clinical manifestation of atherosclerosis (65 vs 42%; p < 0.001) than those with lower concentration (first tertile). Conclusions: Endothelial glycocalyx degradation is rather associated with inflammatory status than hemodynamic parameters. Higher degradation of glycocalyx is associated with increased percentage of ASCVD suggesting a direct relation between glycocalyx degradation and increased risk of atherosclerotic diseases. Keywords: Endothlium, glycocalyx, atherosclerotic cardio-vascular diseases P.131 Role of platelets and von Willebrand factor in pro‑coagulant state in inflammatory bowel disease 1 1 2 2 Célia Schellenberg, Véronique Regnault , Cécile Denis , Peter Lenting , 1 3,4 1 Lacolley Patrick , Laurent Peyrin‑Biroulet , Jeremy Lagrange 1 2 Inserm1116, Vandoeuvre‑lès‑nancy, France, inserm1176, Le Krem‑ 3 4 lin‑Bicêtre, France, inserm1256, Vandoeuvre‑lès‑nancy, France, Depart‑ ment of Gastroenterology, Vandoeuvre‑lès‑nancy, France Introduction: Inflammatory bowel disease (IBD) represents an independent risk factor for thrombosis. However, the causes of this increased risk of thrombosis are still elusive. Relative bias and 95% confidence intervals (CI) obtained for inter- and intra-scanner model comparisons for diameter, wall thickness, and dis- Objectives: We aim to decipher the main players in the procoagulant tension, normalized with respect to mean values of both devices. phenotype associated with IBD. Artery Research Methods and results: Coagulation phenotype assessment was performed P.133 in IBD patients included in the “I-BANK project” (CHRU Nancy), a prospective Impact of β3‑adrenergic receptor modulation on vascular monocentric study recruiting 1000 IBD patients and in a mouse model of function during experimental septic shock IBD (dextran sulphate sodium: DSS). We found an increase in platelet count 1 Eugénie Hagimont , Manon Durand, Antoine Kimmoun in active IBD patients and an increased thrombin generation (TG) in plate- UMR_S1116 Acute and chronic cardiovascular failure, Vandoeu‑ let-rich plasma. Similar results were obtained in mice treated with DSS. In vre‑Lès‑Nancy, France platelet-poor plasma, TG was not increased, highlighting the role of plate- lets in this phenotype. In addition, both mice and active patients showed Rationale: Dysautonomia, an adverse event in septic shock (SC) asso- platelet agglutination on blood smears. As circulating von Willebrand factor ciated with loss of cardiovascular variability, is due to an excess of cat- (VWF), which has a procoagulant function and may be involved in platelet echolamines. Blockade of β1-adrenergic receptors (AR) is associated agglutination, is elevated in IBD patients, we used VWF-deficient mice. In with vasoreactivity benefits however this receptor is not expressed at these mice, TG in platelet-rich plasma was not increased in response to DSS the vascular level (1). Unlike β1-AR, β3-ARs are widely expressed on treatment. In contrast, VWF-deficient mice receiving DSS showed worsened endothelial cells and, when stimulated, cause vasorelaxation (2,3). We colonic tissue damage, highlighting the importance of maintaining a nor- hypothesize that during SC, vascular function could also be mediated mal coagulation balance in IBD. by β3-ARs. Conclusion: The procoagulant phenotype in IBD depends on platelet agglutination via VWF. Further studies are needed to assess the pos- Objective: To evaluate the impact of the modulation of β3-ARs at the sible beneficial effect of VWF inhibition in IBD patients at high risk of level of endothelial cells on vascular function during SC. thrombosis without aggravating tissue damage. Methods and results: The modulation of β3-ARs is studied in  vitro with an endotoxin-induced inflammatory model on human microvas- Keywords: Thrombosis, Platelets, Inflammatory bowel disease cular endothelial cells (HMVECs). First, we demonstrate that endotoxine induce an increase in the expression of endothelial surface inflammatory markers (VCAM1, P.132 ICAM1) and an activation of NFκB. Moreover, a decrease of eNOS was Differential involvement of smooth muscle cells in pro‑ found, while iNOS was increased. Second, the transcriptional expres- and antithrombotic activities of abdominal versus ascending sion of β1 and 2-ARs decrease. At the same time, protein expression aorta aneurysms in human of β3-AR was unchanged. These in  vitro results correlate with those 1 1 2 1 Jeremy Lagrange , Mélusine Didelot , Véronique Olivier , Aurélie Ruch , found in clinical and experimental studies. Thus, we now focus on eval- 1,3 1 1 Serguei Malikov , Patrick Lacolle y , Jean‑Baptiste Michel , Véronique uating the modulation of β3-ARs. Regnault Conclusion: The concept of decatecholamines emerged in order to 1 2 minimize the use of catecholamines in SC. Blockade of β-AR receptors Inserm1116, Vandoeuvre‑lès‑nancy, France, inserm1148, Paris, France, is a therapeutic approach aimed at downregulating adrenergic stimu- Vascular surgery department CHRU Nancy, Vandœuvre‑lès‑Nancy, lation during SC. While β1-ARs have been widely studied, there are no France data on β3-ARs. The characteristics of this AR could make it a major Introduction: Aneurysms of the ascending (TAA) and the abdominal player in vasoreactivity. aorta (AAA) share the common feature of dilation of the aorta but differ by their respective physiopathology and tissue environment in References human. AAA is characterized by associated thrombosis forming an 1. Annane D, Trabold F, Sharshar T, Jarrin I, Blanc AS, Raphael JC, et al. Inappro‑ intraluminal clot, whereas thrombotic events are extremely rare in priate sympathetic activation at onset of septic shock: a spectral analysis TAA, suggesting different coagulant properties between AAA and TAA. approach. Am J Respir Crit Care Med. août 1999;160(2):458‑65. 2. Van Loon LM, van der Hoeven JG, Lemson J. Hemodynamic response to Objectives: To compare coagulation capacities at tissue and cellular β‑blockers in severe sepsis and septic shock: A review of current litera‑ levels, derived from both AAA and TAA. ture. J Crit Care. avr 2019;50:138‑43. Methods and results: Human healthy aorta, AAA or TAA tissues and 3. Dessy C, Saliez J, Ghisdal P, Daneau G, Lobysheva II, Frérart F, et al. Endothelial primary cultures of aortic smooth muscle cells (SMCs) were used. beta3‑adrenoreceptors mediate nitric oxide ‑ dependent vasorelaxation of Thrombin generation was monitored by thrombography in the pres- coronary microvessels in response to the third‑ generation beta‑blocker ence of healthy plasma. AAA tissues and SMCs have a higher ability nebivolol. Circulation. 23 août 2005;112(8):1198‑205. to promote fibrin formation, to activate prothrombin, and to mobilize the tissue factor (TF) pathway, whereas TAA tissues and derived SMCs Keywords: Septic shock, β-blockers, β3-adrenergic receptor, Vascular express an anti-thrombotic phenotype. Activation of the TF pathway in AAA tissue and SMCs is provoked by oxidative stress, protease-acti- P.134 vated receptor 2 (PAR-2) overexpression and nuclear factor-kappa B Arterial stiffness and obstruction in western Mexican healthy (NF-κB) mobilization which could be reproduced by SMC efferocytosis population and patients with type 2 diabetes, a cross‑sectional of senescent red blood cells. Moreover, the high coherence between study what was observed ex  vivo in tissue and in passaged SMCs in  vitro, 1 1 Erick Gonzalez Campos , Luis Ricardo Balleza Alejandri , Fernando demonstrated a procogulant phenotype shift in AAA SMCs, potentially 1 1 1 Grover Paez , Carlos Gerardo Ramos Becerra , David Cardona Müller , as an imprinting of environmental pro-oxidative conditions of AAA. Ernesto German Cardona Munoz Conclusion: Our data indicate that oxidative stress-induced activation of the PAR-2 – NF-κB axis and leads to an increase in TF activity and 1 Universidad De Guadalajara, Guadalajara, Mexico prothrombotic properties of SMCs from AAA. Background: Nowadays does not exist enough studies related with Keywords: Vascular smooth muscl cells, Aneurysm, thrombotic cutoff points of arterial stiffness and obstruction in Mexican popula- properties tion compared with patients with T2DM [1]; also, is important to have a landmark on these clinical assessments to identify arterial stiffness and obstruction timely to provide also an early treatment [2–3]. Aim: To identify cutoff points, differences and correlations of arterial stiffness and obstruction between healthy/T2DM population. Methods: In a cross-sectional study, a total of 296 western Mexican individuals (163 healthy, 133 with T2DM according with ADA 2022 [4]) A rtery Research were enrolled, aged 40–65  years (mean 52.7 ± 6.6). Variables like sex, functions. How these alterations favor IA formation now need to be BMI, baPWV and ankle-brachial index (ABI) were measured. T-student understood. was used for equality of means and Pearson’s test for correlation. Results: When comparing groups (healthy/T2DM), there was not a sig- References nificative difference on age (52.07 ± 6.30, 53.59 ± 0.09, p:0.052) and 1.Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intrac‑ ABI (1.12 ± 0.07, 1.13 ± 0.13, p:0.55); we found a significative difference ranial aneurysms, with emphasis on sex, age, comorbidity, country, and on BMI (25.96 ± 3.29, 29.41 ± 5.08, p: < 0.01), beats/min (62.17 ± 10.63, time period: a systematic review and meta‑analysis. Lancet Neurol. juill 70.5 ± 13.3, p: < 0.01) and baPWV (1310.31 ± 186.75, 1595.33 ± 321.99, 2011;10(7):626–36. p: < 0.01); additionally there were a significative correlation between age 2.Bourcier R, Le Scouarnec S, Bonnaud S, Karakachoff M, Bourcereau E, & baPWV (r = 0.358, p: < 0.01) and baPWV & ABI (r = 0.188, p: < 0.01). Heurtebise‑ Chrétien S, et al. Rare Coding Variants in ANGPTL6 Are Associ‑ Conclusion: We found a greater arterial stiffness in T2DM patients, BMI ated with Familial Forms of Intracranial Aneurysm. Am J Hum Genet. 4 and beats/min; also, a correlation between age, ABI with arterial stiff- janv 2018;102(1):133‑41. ness; and there were not differences between healthy/T2DM on ABI, and provide cutoff points for further studies. Keywords: Angiopoietin-like 6, intracranial aneurysm, mouse References P.138 1. Díaz‑ Cruz C, Patiño‑Laguna ADJ, et al. Ambulatory arterial stiffness index in Chronic dopamine receptor stimulation improves endothelial diabetic patients. Rev Médica Chile. 2020 Apr;148(4):496–9. function and hemodynamics in autosomal dominant polycystic 2. Gómez‑Sánchez M, Patino ‑Alonso MC, et al. Reference values of arte ‑ kidney disease rial stiffness parameters and their association with cardiovascular risk factors in the Spanish population. The EVA Study. Rev Esp Cardiol. 2020 1 1 1 Audrey Dumont , Mouad Hamzaoui , Dominique Guer rot , Jeremy Jan;73(1):43–52. 1 Bellien. 3. Ohkuma T, Ninomiya T, et al. Brachial‑Ankle Pulse Wave Velocity and Rouen University Hospital and INSERM U1096, Rouen, France the Risk Prediction of Cardiovascular Disease. Hypertension. 2017 Jun;69(6):1045–52. Background: Altered polycystin-mediated endothelial flow mecha- 4. ADA Professional Practice Committee. Classification and Diagnosis of Dia‑ nosensitivity contribute to the development of hypertension and betes: Standards of Medical Care in Diabetes—2022. Diabetes Care. 2021 cardiovascular complications in patients with autosomal dominant Dec 16;45:S17–38. polycystic kidney disease (ADPKD). Stimulation of dopamine receptors may compensate polycystin deficiency but the chronic impact of this Keywords: Arterial stiffness, Arterial obstruction, Type 2 Diabetes Mel- approach has to be evaluated in patients with ADPKD. litus, brachial-ankle PWV Methods and Results: ADPKD patients on standard care therapy were randomized to receive during 2  months the dopamine receptor ago- nist rotigotine using transdermal patches at 2  mg/24  h (n = 10) and 4  mg/24 (n = 9) h or were not treated (n = 10). Rotigotine at the dose P.136 of 4  mg/24  h increased radial artery endothelium-dependent flow- Characterization of an ANGPTL6 variant predisposing mediated dilatation, measured by high-resolution echotracking, and to intracranial aneurysm formation NO release in response to hand skin heating. Systemic hemodynamics 1 1 1 1 Milene Freneau , Celine Baron‑Menguy , Vincent L’Allinec , Marc Rio , were not significantly modified but aplanation tonometry showed that 1 1 Anne‑Clemence Vion , Gervaise Loirand rotigotine at 4  mg/24  h reduced aortic augmentation index and pulse Nantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, pressure without affecting carotid-to-femoral pulse wave velocity. F‑44000 Nantes, France, Nantes, France Plasma creatinemia and urea levels, the urinary levels of copeptin, a sur- rogate marker of vasopressin, and cAMP that contribute to the growth Background: Intracranial aneurysms (IA) are abnormal dilations of of kidney cysts in ADPKD, were not affected by rotigotine. Furthermore, cerebral artery arising at bifurcations of the circle of Willis that can chronic infusion of fenoldopam, a dopamine receptor agonist that does rupture and cause subarachnoid hemorrhage (1). By whole exome not cross the blood–brain barrier in contrast to rotigotine, also improved sequencing in familial IA, we identified a rare variant of the ANGPTL6 mesenteric artery flow-mediated dilatation and reduced blood pressure gene that predisposes to IA. This variant leads to the expression of a in mice with a specific deletion of polycystin-1 in endothelial cells. non-secreted truncated angiopoietin-like 6 (p.Lys460Ter-ANGPTL6) Conclusion: Chronic stimulation of dopamine receptors improves protein (2). Our aim is to understand why this variant predisposes to conduit artery endothelial function through the increase in flow- IA. induced NO release as well as hemodynamics in ADPKD, representing Methods: We generated Angptl6-knock in (Angptl6-KI) mice express- thus a promising pharmacological approach to prevent the cardiovas- ing the identified variant. Morphology of cerebral arteries was cular complications of this disease. assessed by micro-computed tomography and confocal imaging on thick slices of adult cerebral arteries and on mouse pup retinas Func- Keywords: Endothelium, ADPKD, dopamin tional analyses were done ex  vivo on cerebral arteries and in  vitro on smooth muscle cells (SMC). Results: Mean diameter of linear parts of cerebral arteries was signifi- P.139 cantly larger in Angplt6-KI mice than in controls. Mutant mice also dis- Vascular smooth muscle cells as platelet cleaner and role played hyperdensities corresponding to focal dilations and local wall of extracellular macromolecular crowding deformations adjoining the center of arterial bifurcations. During reti- 1 1 2 Rümeyza Bascetin , Gabrielle Van De Velde , Patrick Lacolley , nal angiogenesis, arterial coverage by SMC was delayed in Angplt6-KI Véronique Regnault mice compared to controls. Consistently, in  vitro, SMC adhered faster 1 2 on ANGPTL6-coated plates than on uncoated surface. Ex vivo, cerebral Université De Lorraine, Vandœuvre‑lès‑nancy, France, DCAC UMR arteries of mutant mice exhibited a reduced flow-mediated dilation s‑1116, Vandœuvre‑lès‑nancy, France resulting from a decreased endothelial NO production. Background: With aging and atherosclerosis plaque development, Conclusions: These data suggest that the expression of the IA-pre- endothelial permeability increases leading to blood and platelets disposing ANGPTL6 variant is sufficient to induce alterations of the (PLT) infiltration into the vascular wall. In the media, vascular smooth cerebral arteries and impact both vascular SMC and endothelial cell Artery Research muscle cells (VSMCs) are crucial for clearance of infiltrated molecules Results: Quantifying Ter-119 staining density in liver and spleen and cells including senescent red blood cells (1). Moreover, blood has showed that PS003biv decreased RBC accumulation and VOC (liver 6 6 a high concentration of macromolecules making it a macromolecu- control 13.57 ± 1.46 × 10 versus PS003biv 7.28 ± 0.38 × 10 AU; and 7 7 larly crowded environment (MMC). spleen control 5.64 ± 0.21 × 10 vs PS003biv 5.03 ± 0.03 × 10 AU, The objective is to decipher the clearance mechanisms of PLT by p < 0.05). Biomarkers for hemolysis were lower in PS003biv-treated VSMCs and the influence of MMC on it. mice: bilirubin control 6.87 ± 0.21 vs PS003biv 4.88 ± 0.60  mg/dl; and Methods: Human VSMCs were cultured with either human: (i) fresh free heme control 133.0 ± 10.4 vs PS003biv 77.5 ± 5.3  µM. PS003biv PLT, (ii) ADP-activated PLT, (iii) senescent PLT. PLT and VSMCs were decreased thrombin-antithrombin complexes (control: 10.14 ± 0.72 vs stained with fluorescent tracers prior their co-culture. We also cultured PS003biv 7.47 ± 0.33 ng/mL, p < 0.05). VSMC in media supplemented with crowders to mimic MMC. Conclusions: PS003biv showed beneficial properties in the context Results: After three or seven days of co-culture, we observed that of a hypoxia/reoxygenation murine model of SCD, with reduced vaso- activated and/or senescent PLT, which are characterized by phosphati- occlusion, hemolysis, and coagulation activation. The mechanism of dylserine exposure, were localized within VSMCs. In contrast to fresh action of PS003biv needs to be determined. red blood cells that are not phagocytosed by VSMCs, fresh PLT were also entrapped within VSMCs. We then stained VSMCs with phalloidin, References an actin filament dye, revealing that PLT are surrounded by an actin 1. Gierula M, Ahnström J. Anticoagulant protein S‑New insights on interactions shell within the VSMC. In addition, we observed that MMC modified and functions. J Thromb Haemost. November 2020;18(11):2801–11. the deposition of extracellular matrix (fibronectin, laminin and sugar 2. Sedzro JC, Adam F, Auditeau C, Bianchini E, De Carvalho A, Peyron I, et al. moieties) by VSMCs. Antithrombotic potential of a single‑ domain antibody enhancing the Conclusions: VSMCs engulf PLT with an actin-dependent endocyto- activated protein C‑ cofactor activity of protein S. J Thromb Haemost. 21 sis process and MMC modifies the secretory phenotype of VSMC. PLT April 2022; engulfment could be an inducible pathogenic event that is responsi- 3. Whelihan MF, Lim MY, Mooberry MJ, Piegore MG, Ilich A, Wogu A, et al. ble for VSMC phenotypic switching in atherosclerosis and their pro- Thrombin generation and cell‑ dependent hypercoagulability in sickle coagulant status. cell disease. J Thromb Haemost. Oktober 2016;14(10):1941–52. Reference Keywords: Sickle Cell Disease, Vaso-occlusive crisis, Protein S, Single- 1. Delbosc S, Bayles RG, Laschet J, Ollivier V, Ho‑ Tin‑Noé B, Touat Z, et al. Eryth‑ domain antibody rocyte Eer ff ocytosis by the Arterial Wall Promotes Oxidation in Early‑Stage Atheroma in Humans. Front Cardiovasc Med. 2017 Aug 2;4:43. P.141 The impact of isolated proximal limb heating on arterial wave Keywords: Vascular smooth muscle cell, platelet, phagocytosis, mac- reflection romolecular crowding 1 1 1 1,2 Chloe Athaide , Jeremy Cohen , Kailey Stevens , Andrew Robertson , Jason Au P.140 Department of Kinesiology and Health Sciences, University Of Waterloo, A single‑domain antibody enhancing protein S activity reduces Waterloo, Canada, Schlegel‑University of Waterloo Research Institute vaso‑occlusion in a murine model of sickle cell disease for aging, University of Waterloo, Waterloo, Canada 1,4 2 1 Claire Auditeau , Thiago Trovati Maciel , Josépha‑Clara Sedzro , Background: Arterial wave reflection occurs in the peripheral circulation 3,4 3 1 Camille Roussel , Aurélie Fricot‑Monsinjon , Mariem Khamari , Olivier subsequent to each contraction of the left ventricle (1). Mathematical mod- 1 1 1 1 Christophe , Peter Lenting , Cécile Denis , François Saller , Delphine els and comparative physiology (2,3) suggest that the lower limbs are the 1,4 Borgel primary source of reflected waves; however, in vivo human evidence cor - 1 2 Inserm U1176, Université Paris‑Saclay, Le Kremlin‑Bicêtre, France, Institut roborating these observations is lacking. This study was designed to deter- IMAGINE INSERM U1163, Hôpital Necker Enfants Malades, Assistance mine whether the lower or upper limbs contribute more to the summated Publique‑Hôpitaux de Paris (AP‑HP), Paris, France, Biologie Intégrée du reflected wave. We hypothesized that heating of the lower limb will result Globule Rouge, Université de Paris Cité, Université des Antilles, Paris, in larger changes in central wave reflection compared to heating of the France, Service d’Hématologie Biologique, Hôpital Necker Enfants Mal‑ upper limb. ades, Assistance Publique‑Hôpitaux de Paris (AP‑HP), Paris, France Methods: Fifteen healthy adults (8 females, 24 ± 3.6  years) completed a within-subjects experimental crossover protocol with a washout Background: Protein S (PS) is a natural anticoagulant acting as a period. The right arm and leg were warmed in a randomized order cofactor for activated protein C (APC) for the inactivation of activated using 38 °C water-perfused tubing with a 30-min break between pro- factors V and VIII(1). We identified an anti-PS single-domain antibody tocols. Wave reflection was estimated at baseline and after 30  min of (PS003biv) that surprisingly enhanced the APC-cofactor activity of PS heating from pressure-flow relationships derived from aortic blood and exerted an in vivo antithrombotic effect(2). A moderate decrease flow and carotid blood pressure. in PS plasma levels is frequently observed in sickle cell disease (SCD) Results: There was a main effect of time for reflected wave mag- patients, with a further reduction during vaso-occlusive crises (VOC) nitude (12.8 ± 2.7 to 12.2 ± 2.6  mmHg) and augmentation index (3). We hypothesized that PS003biv might limit VOC in SCD. (− 7.49 ± 8.92 to − 4.45 ± 9.07%) (p = 0.029 and 0.034, respectively), Methods: HbSS-Townes mice were intravenously injected with 10 mg/kg but no significant differences for condition or interactions. PS003biv or vehicle (control). Mice were placed in a hypoxic atmosphere Conclusion: Proximal limb heating reduced central wave reflection chamber (8% O2) for 3  h, after which they were returned to room air. magnitude; however, the lack of a difference between conditions does Spleen, liver and plasma were collected. The intensity of vaso-occlusion not support the hypothesis that the lower limbs are the primary source was quantified by Ter-119 immunofluorecence staining of red blood cells of wave reflection. Further research is required to confirm the role of the (RBC) clogging the vessels in the liver and spleen. Bilirubin, free heme, limbs in generating central wave reflections, with recommendations for and thrombin-antithrombin complexes were measured in plasma. future studies to consider the role of the gastrointestinal vasculature. A rtery Research of Complutense; School of Pharmacy; Department of Pharmacology, Pharmacognosy and Botany, Madrid, Spain, Thema srl, Imola (BO), Italy, 10 11 Pisa University, Pisa, Italy, Yeditepe University, School of Medicine, Department of Biophysics, Istanbul, Turkey, Menzies Institute for Medi‑ cal Research, University of Tasmania, Hobart, Australia, AIT Austrian Institute of Technology GmbH, Center for Health & Bioresources, Medical Signal Analysis, Vienna, Austria Background: Regulation is part of the technology innovation pro- cess and has a key role within the lifecycle of a medical device aim- ing at ensuring effectiveness and safety for users (1). Ever-increasing regulatory requirements (e.g., the Regulation MDR (EU) 2017/745) impact on the development of novel and already approved sys- tems (2, 3). Debating and raising awareness is important since it can improve the transfer of knowledge and expertise among the relevant stakeholders. Thus, the implementation of a survey to explore knowl- edge and perception of the regulatory framework of medical devices for the assessment of vascular age can be helpful for the involved community. Methods: A multidisciplinary team including clinicians, research- ers and developers from VascAgeNet was established to design and implement a digital questionnaire. A secure, open-source, two-factor authentication system for generation, distribution, and data collec- tion of the survey supported by the European Commission (EUSurvey, https:// ec. europa. eu/ eusur vey) was adopted. Results: The questionnaire has received ethical clearance by National Council of Research, Italy (Notification 0063984/2021) and University College London (17999/002) Research Ethics Committees and is being distributed digitally (e.g., within VascAgeNet, Artery Society etc.). The anonymous questionnaire is available at https:// ec. europa. eu/ eusur vey/ runner/ REGUL ATORY Surve y2022 or by scanning the QR code below, it takes approximately 10 min to complete. Conclusions: A survey related to regulation and medical devices for vascular ageing assessment has been developed and is available for Fig. 1 Reflected wave amplitude (mmHg) before and after 30 min of the community. The results could inspire concrete actions reducing peripheral heating to the upper arm (left) and leg (right) gap between research and clinical practice. The survey was developed by the COST Action CA18216, VascAgeNet References supported by COST (www. cost. eu). 1. Nichols WW, O’Rourke M, Vlachopoulos C. McDonald’s Blood Flow in Arter‑ ies. 6th ed. McDonald’s Blood Flow in Arteries. London: Hodder Arnold; 2. Avolio AP, Nichols WW, O’Rourke MF. Exaggerated wave reflection in the kangaroo simulates arterial counterpulsation. Am J Physiol—Regul Integr Comp Physiol. 1984;15(2). 3. Avolio AP, Nichols WW, O’Rourke MF. Propagation of pressure pulse in kangaroo arterial system. Am J Physiol—Regul Integr Comp Physiol. 1985;18(3):335–40. Keywords: hemodynamics, heating, wave reflection Other P.151 Development of a tool to assess knowledge and perceptions of the regulatory framework applied to medical devices for vascular ageing evaluation 1 2 3 Maria Raffaella Martina , Chloe Park , Rosa Maria Bruno , Areti 4 5 6 Triantafyllou , Andrie G. Panayiotou , Dimitrios Terentes‑Printzios , 7 8 9 10 Soner Dogan , Marjan Manouchehri, Marisa Testa, Valentina Calderai , 11 12 13 Bilge Guvenc Tuna , Rachel Climie , Christopher C. Mayer , Elisabetta Bianchini Institute of Clinical Physiology (IFC), Italian National Research Council (CNR), Pisa, Italy, University College London (UCL), London, United Kingdom, Université Paris Cité, Inserm, PARCC, F‑75015, Paris, France, 4 5 Aristotle University of Thessaloniki, Thessaloniki, Greece, Cyprus References University of Technology, Limassol, Cyprus, First Department of Cardiol‑ 1. Bianchini E, Mayer CC. Medical Device Regulation: Should We Care About It?. ogy, National and Kapodistrian University of Athens, Medical School, Artery Res. 2022;28:55–60. https:// doi. org/ 10. 1007/ s44200‑ 022‑ 00014‑0 Hippokration Hospital, Athens, Greece, Yeditepe University, School 2. Fraser AG, Byrne RA, Kautzner J, Butchart EG, Szymanski P, Leggeri I, et al. of Medicine, Department of Medical Biology, Istanbul, Turkey, University Implementing the new European regulations on medical devices‑ clinical Artery Research responsibilities for evidence‑based practice: A report from the regulatory P.153 affairs committee of the European society of cardiology. Eur Heart J. No differences in FBN1 genotype between men with and without 2020;41(27):2589–2596. https:// doi. org/ 10. 1093/ eurhe artj/ ehaa3 82 abdominal aortic aneurysm. 3. Mayer CC, Francesconi M, Grandi C, Mozos I, Tagliaferri S, Terentes‑Printzios 1 1,2 1 IDA Åström Malm , Peter Blomstrand , Rachel De Basso. D, et al. Regulatory Requirements For Medical Devices And Vascular Age‑ Department of Natural Science and biomedicine School of Health ing: An Overview. Hear Lung Circ. 2021;30(11):1658–66. https:// doi. org/ and welfare Jönköping University, Jönköping, Sweden, Department 10. 1016/j. hlc. 2021. 06. 517 of Clinical Physiology, County Hospital Ryhov, Jönköping, Sweden, Jönköping, Sweden Keywords: Regulation, medical-devices, vascular-ageing, safety Background: Abdominal aortic aneurysm (AAA) is an aortic enlarge- P.152 ment with a diameter ≥ 30  mm. The modifiable risk factors, such as Comparative study of diagnostic accuracy for detect peripheral age, male gender, and smoking, are well-known, however, there is artery disease among individuals with diabetes mellitus less knowledge about the genetic factors (1–3). Fibrillin-1 (FBN1) is a 1 1 1 protein that coordinates the deposition of elastin fibers in the extra- Monique Cerqueira , Magno Mercês , Lucélia Magalhães , Amália 1 1 1 cellular matrix. Studies have found associations between the FBN1-2/3 Santana , Cecília Araújo , Daniele Brustolim genotype and arterial stiffness (4). Nevertheless, how FBN1 genotype, State University of Bahia, Salvador, Brazil AAA, and arterial stiffness are related is less investigated. This study aims to investigate if there is a difference in FBN1 genotype between Background: Ankle-brachial index (ABI) is the gold standard for the men with AAA and controls. A further aim is to study if the FBN1 gen- noninvasive diagnosis of peripheral arterial disease (PAD), however otype affects arterial wall stiffness differently in men with AAA com- its accuracy among people with diabetes mellitus (DM) is limited. This pared to a control group. study aims to compare the accuracy of pulse wave velocity (PWV) Methods: Pulse wave velocity and FBN1-genotyping were performed measurement against ABI to diagnose PAD among individuals with on 229 men (159 AAA, 70 controls). The participants were recruited DM. from ultrasound surveillance programs of known AAA or ongoing Methods: A cross-sectional study of diagnostic accuracy will be car- ultrasound screening programs. ried out on a population of diabetics residing in Salvador, Bahia, Bra- Results: The distribution of FBN1-genotype in the AAA and control- zil. To evaluate the measurement of ABI, the standard technique will group, were as followed, FBN1-2/2; 99 vs 45, FBN1-2/3; 13 vs 10, FBN1- be used. PWV and the Augmentation Index (Aix) will be calculated ® 2/4; 47 vs 15. However, men with AAA and FBN1-2/2 had increased using pulse tonometry with the SphygmoCor device. Measurements central pulse wave velocity (p < 0.005) compared to men without AAA in the carotid-femoral (PWVc-f ) and brachial-ankle (PWVb-a) territo- and FBN1-2/2 genotype. ries will be accessed. ABI values ≤ 0.9  mmHg or ≥ 1.3  mmHg, will be Conclusion: No differences were found regarding FBN1-genotypes definers of PAD and arterial stiffness, respectively; the value of PWVc- between men with and without AAA. Thus, the development of AAA f < 1000  cm/s and PWVb-t < 1700  cm/s will define arterial stiffness. in men seems not to be related to a specific FBN1-genotype. However, For Aix, an increase of ≥ 10% will be considered significant. For the men with FBN1-2/2 and AAA have increased central arterial stiffness analysis of accuracy measures, sensitivity, specificity, positive predic - compared to men with the same FBN1 genotype but without AAA. tive value and negative predictive value will be calculated, as well as the positive probability ratio and negative probability ratio of ABI and References PWV, considering Doppler as the gold standard. 1. Wanhainen A, Bergqvist D, Boman K, Nilsson TK, Rutegard J, Bjorck M. Risk Results: It will be possible to develop some protocols and some factors associated with abdominal aortic aneurysm: a population‑based important scientific papers, being: the prevalence of PAD among indi- study with historical and current data. Journal of vascular surgery. viduals with diabetes; factors associated with arterial stiffness; accu- 2005;41(3):390‑6. racy of PWV in diagnosing PAD. 2. Nordon IM, Hinchliffe RJ, Loftus IM, Thompson MM. Pathophysiology and Conclusions: The findings of the study will enable better attention epidemiology of abdominal aortic aneurysms. Nature Reviews Cardiol‑ and assistance to individuals with diabetes and PAD. ogy. 2010;8:92. 3. Golledge J, Muller J, Daugherty A, Norman P. Abdominal Aortic Aneurysm. References Arteriosclerosis, thrombosis, and vascular biology. 2006;26(12):2605‑13. 1. Boutouyrie P et al. Assessment of pulse wave velocity. Artery Res. 4. Powell JT, Turner RJ, Sian M, Debasso R, Lanne T. Influence of fibrillin‑1 geno ‑ 2009;3(1):3–8. type on the aortic stiffness in men. J Appl Physiol. 2005;99(3):1036‑40. 2. Butlin M, Qasem A. Large artery stiffness assessment using sphygmocor technology. Pulse. 2017;4(4):180–92. Keywords: AAA, FBN1, arterial stiffness 3. Davies, J. H.; Lewis, J. E. A.; Williams, E. M. The Utility of Pulse Volume Wave‑ forms in the Identification of Lower Limb Arterial Insufficiency. v. 14, n. 2, p. 5, 2014. 4. Normahani, P. et al. Study Protocol for a Comparative Diagnostic Accuracy Study of Bedside Tests Used to Detect Arterial Disease in Diabetes: TEst‑ ing for Arterial Disease in Diabetes ( TrEAD) Study. BMJ Open, v. 10, n. 2, p. e033753, fev. 2020. Keywords: Peripheral arterial disease, diabetes, tonometry, pulse wave analysis A rtery Research Author Index Butlin, Mark P.063 Abbaoui, Yasmine P.058 Buyukkaya, Omer Faruk P.064 Abi-Nasr, Imad P.025, P.097 Calderai, Valentina P.151 Accord, Ryan P.135 Canales, Sergio O.22 Acherar, Samir P.006 Cardona Gutierrez, German P.046 Adell, Manuel P.042 Cardona Muller, David P.046, P.134 Agbulut, Onnik P.003 Cardona Munoz, Ernesto German P.134 Agharazii, Mohsen O.10, O.17, O.5, P.045, P.058, P.065, P.092, P.093 Carracedo, Miguel O.8 Aizawa, Kunihiko O.19 Carrard, Justin P.103 Akbulut, Asim Cengiz P.135 Casal, Diogo P.011 Akhtar, Riaz O.9 Casanova, Francesco O.19 Alastruey, Jordi O.15 Casari, Caterina P.069 Ali, Khalid P.099 Castillo, Lidon P.042 Allanore, Yannick P.013 Catalan, Marta O.22 Anastasio, Fabio P.030 Caulk, Alexander W.O.27 Argyris, Antonis P.033 Cavinato, Cristina O.1 Arnardottir, Hildur O.8 Centelles, Santiago P.042 Arrieta, Vanessa O.21 Challande, Pascal P.004 Arroyo, Luis P.066 Chandran, Dinu P.071, P.122 Artiach, Gonzalo O.8 Charrier, Lise O.26 Athaide, Chloe P.121, P.141 Chaturvedi, Nish P.054 Au, Jason P.121, P.137, P.141 Chee, Ying Jie P.038 Auditeau, Claire P.140 Chen, Minghao O.1 Avolio, Alberto P.063 Chesler, Naomi C.P.027 Avril, Stephane O.3 Chorda, Jose O.22, P.042 Ayis, Salma P.057 Chowienczyk, Philip J O.2 Aznaouridis, Konstantinos P.081 Christophe, Olivier D P.069, P.140 Alvarez, Virginia O.21 Cleary, Sarah O.4 Astrom Malm, IDA P.153 Climent, Maite P.042 Back, Magnus O.8 Climie, Rachel O.23, P.151 Badarienė, Jolita P.034 Cohen, Jeremy N 0.6, P.141 Badhwar, Smriti P.071 Colebank, Mitchel J.P.027 Baixauli, Vicente P.042 Coletti, Dario P.004 Balleza Alejandri, Luis Ricardo P.046, P.134 Colhoun, Helen M O.19 Banya, Winston P.099 Colin, Melissa P.006 Barinas-Mitchell, Emma O.18 Corcillo, Antonella P.057 Baron-Menguy, Celine P.136 Corcoles, Edelmira P.042 Bascetin, Rumeyza P.139 Costa, Jose-Antonio O.22, P.042 Batta, Dora P.043 Cote, Nadege O.5, P.058, P.093 Battista, Francesca P.030 Coulson, James P.068 Baulmann, Johannes P.001, P.002 Cox, James P.063 Becerra Ramos, Carlos Gerardo P.046 Cseprekal, Orsolya P.043 Beeckman, Simeon P.110 Cunha, Michelle Rabello O.25 Bekavac, Anamarija P.105 Curcio, Rosa P.030 Bellien, Jeremy O.26, P.123, P.138 D’Abbondanza, Marco P.030 Bellver, Oton P.042 Dafauce Bouzo, Xela P.068 Belozertseva, Ekaterina P.004 Dai, Lu P.070 Ben Hassine, Amira O.3 Dalan, Rinkoo P.037, P.038 Benetos, Athanase P.130 Danninger, Kathrin O.16, P.033 Benson, Jemima P.068 De Meyer, Guido P.127 Berends, Eline P.032 Dębowska, Małgorzata P.070 Białończyk, Urszula P.070 Deepak, Kishore Kumar P.071, P.095, P.122 Bianchini, Elisabetta P.014, P.030, P.151 Delaitre, Celine P.006 Bidar , Elham P.135 Delhaas, Tammo P.022, P.061, P.067, P.128 Bikia, Vasiliki P.065 Denis, Cecile P.069, P.131, P.140 Binder, Ronald P.033 Desbiens, Louis-Charles O.10, P.045 Bitsch, Nicole P.022 Di Lascio, Nicole P.014 Blanc, Jocelyne P.003, P.004 Didelot, Melusine P.132 Blomstrand, Peter P.153 Dogan, Soner P.151 Boban, Mladen P.105 Dogan, Soner P.036 Boehm, Bernhard P.037 Dolgyras, Panagiotis P.015 Boleto, Goncalo P.013 Doumas, Michael O.14 Bollache, Emilie P.021 Dumont, Audrey P.138 Borgel, Delphine P.140 Dupuis, Francois P.006 Boutouyrie, Pierre P.013, P.025, P.065, P.106, P.110 Durand, Manon P.133 Brett, Sally O.2 Durdabak, Dilara Buse P.036 Breyer, Marie-Kathrin O.16 Duval, Karine O.5 Breyer-Kohansal, Robab O.16 de Jaegere, Peter P.091 Bruno, Rosa Maria P.013, P.014, P.106, P.151 de Souza, Dailson N.O.17 Burghuber, Otto O.16 Đogaš, Varja P.105 Buschges, Julia O.13 Eckert, Siegfried P.001, P.002 Artery Research Eerik, Kadri P.044 Hong, Jingyuan O.15 Eha, Jaan P.044, P.055 Hope, Suzy V O.19 El Omar, Reine O.7 Hossack, Martin O.9 Esparza Pimentel, Javier P.046 Houben, Boy P.051 Eveilleau, Kornelia P.097 Hughes, Alun P.053, P.054 Faconti, Luca O.2 Humphrey, Jay D.O.1, O.27 Farikh, Bushra O.2 Iacob, Michaela P.123 Fayon, Adrien O.7 Infanger, Denis P.103 Feigerlova, Eva P.005 Ioakeimidis, Nikolaos P.081 Fernandez-Celis, Amaya O.21 Jadoon, Maryam P.106 Figg, Nichola O.4 Jahangiri, Mohammad P.130 Fisher, Robert O.9 Jaminon, Armand 0.11 Flaquer, Maria P.057 Janiak, Philip O.26 Fortier, Catherine O.10, O.5, P.092, P.093 Jannot, Leo P.005 Foulquier, Sebastien P.006, P.022, P.032 Jaryal, Ashok P.071 Fountoulakis, Nikolaos P.057 Jaryal, Ashok Kumar P.122 Freneau, Milene P.136 Jeroncic, Ana P.105 Fricot-Monsinjon, Aurelie P.140 Jimenez, Iratxe O.22 G. Schalkwijk, Casper P.032 Joannides, Robinson P.123 Gainza, Alicia O.21 Johansson, Madeleine P.104 Galan Ruiz, Claudia Yanette P.046 Joseph, Jayaraj P.095 Ganizada, Berta 0.11 Jover Garcia, Eva O.21 Gao-Li, Jacqueline P.003 Junior, Edivaldo P.011 Garaikoetxea Zubillaga, Mattie O.21 Junior, Justin P.106 Garcia-Pena, Amaia O.21 Jyotsna, Viveka P P.122 Garneau, Charles-Antoine O.5, P.093 Kahn, Faisel O.19 Gates, Phillip E O.19 Kals, Jaak P.044, P.055, P.126 Gaucher, Caroline O.7 Kaniusas, Eugenijus P.033 Gayral, Stephanie P.124 Karadag, Cevat Volkan P.064 Gellert, Kapuaola O.18 Karalliedde, Janaka P.057 Gemignani, Vincenzo P.030 Kasepalu, Teele P.044, P.055 Gencer, Umit P.021 Kaufmann, Christoph O.16 Georgakopoulos, Christos P.081 Keles, Nazim Arda P.036 Gepner, Adam P.024, P.061 Khettab, Hakim P.013, P.025, P.106 Ghezzi, Pietro P.099 Kilk, Kalle P.126 Giudici, Alessandro P.001, P.002, P.032, P.061, P.067, P.092, P.128 Kimmoun, Antoine P.133 Gkaliagkousi, Eugenia O.14, P.015 Kirkham, Frances Ann P.099 Gnudi, Luigi P.057 Klein, Marcia Regina Simas O.25 Gomez, Ana P.042 Klenk, Christopher P.103 Goncalves, Isabel O.19 Klosinska, Aleksandra O.4 Gonzalez Campos, Erick P.046, P.134 Knaier, Raphael P.103 Gooding, Kim M O.19 Koletsos, Nikolaos O.14, P.015 Goudzwaard, Jeannette P.091 Konigstein, Karsten O.13, P.103 Goupil, Remi O.10, O.5, P.045, P.058, P.093 Korcarz, Claudiq P.024 Gourgouli, Ioanna P.081 Koren, Pjero P.105 Gourgouli, Danai-Magdalini P.081 Kőrosi, Beata P.043 Greaves, Danielle K 0.6 Kroon, Bram P.051 Grillo, Andrea P.067 Kuusik, Karl P.055 Grover Paez, Fernando P.046, P.134 Labas, Carlos P.130 Guerrot, Dominique P.138 Lacaze, Emmanuelle P.004 Guest, Bruce P.066 Lacolley, Patrick P.003, P.004, P.130, P.132, P.139 Guignandon, Alain O.3 Laffargue, Muriel P.124 Guns, Pieter-Jan P.127 Lagrange, Jeremy P.130, P.131, P.132 Guvenc Tuna, Bilge P.036 Laguna-Fernandez, Andres O.8 Gyongyosi, Helga P.043 Laime, Mathilde P.025 Hagimont, Eugenie P.133 L’Allinec, Vincent P.136 Hallab, Magid P.025, P.097 Lambrichts, Sara P.022 Hametner, Bernhard O.10, P.033 Lamprou, Stamatina O.14, P.015 Hamm, Rachael O.18 Lamy, Jerome P.021 Hamrouche, Marina O.26 Lariviere, Richard O.17 Hamzaoui, Mouad P.138 Lartaud, Isabelle P.006 Hanssen, Henner P.103 Laszlo, Andrea P.043 Hartl, Sylvia O.16 Latorre, Marcos O.1 Hedge, Eric T 0.6 Laučytė-Cibulskienė, Agnė P.034 Heestermans, Marco P.069 Lazaridis, Antonios P.015 Hein, Amy P.024 Le Pelletier, Laura O.12 Helle, Deborah O.7 Lecat, Sandra P.006 Henrion, Daniel P.004 Lechuga, Christopher P.027 Hernandez, Rosario P.042 Lecoq, Enzo P.005 Hinrichs, Timo P.103 Lee, David O.1 A rtery Research Leenders, Peter P.032 Neves, Mario O.25 Leftheriotis, Georges P.097 Newton, Michael A O.18 Lenting, Peter P.069, P.131, P.140 Nguyen, Vincent P.021 Li, Yanlu P.110 Nicol, Lionel O.26 Li, Zhenlin P.003, P.004 Nikolaidou, Barbara P.015 Lieberg, Juri P.055 Nilsson, Jan O.19 Lindholm, Bengt P.070 Nilsson, Peter M P.104 Liu, Xiao P.004 Obeid, Hasan O.5, P.025, P.065, P.092, P.093, P.097 Loirand, Gervaise P.136 Ofenheimer, Alina O.16 Lopez-Andres, Natalia O.21 Ohlow, Marc-Alexander P.001, P.002 Luo, Tao O.4 Okyar, Fethi P.064 Lutsey, Pamela L O.18 Olivier, Veronique P.132 Lye, David P.037 Omarjee, Loukman P.025 Maciel, Tamara P.121 Orter, Stefan P.033 Maciel, Thiago Trovati P.140 O’Shaughnessy, Kevin O.4 Mac-Way, Fabrice O.17 Ottas, Aigar P.044, P.126 Madhu, Nilesh P.110 Ozoux, Marie-Laure O.26 Madine, Jillian O.9 op ’t Roodt, Jos P.128 Madore, Francois O.10, P.045 Paapstel, Kaido P.126 Maessen, Jos 0.11 Palombo, Carlo O.19 Magalhaes, Lucelia P.031 Pan, Dan O.7 Malet, Nicole P.124 Panagiotou, Angeliki P.057 Malik, Afrah P.128 Panayiotou, Andrie G.P.151 Malikov, Serguei P.132 Parati, Gianfranco P.067 Mangelis, Anastasios P.015, P.057 Pare, Mathilde O.5, P.093 Manouchehri, Marjan P.151 Parikh, Shaiv 0.11 Marre, Michel P.097 Park, Chloe O.23, P.151 Martina, Maria Raffaella P.014, P.151 Parlakian, Ara P.003 Martina, Mariella P.030 Pascoe Gonzalez, Sara P.046 Martinet, Wim P.127 Patel, Chetan P.071 Martinez, Sara P.042 Patrick, Lacolley P.131 Martin-Nunez, Ernesto O.21 Pencheva, Margarita G.P.032 Mastrogiannis, Konstantinos O.14, P.015 Perez, Leticia O.22 Matilla Cuenca, Lara O.21 Perseguer, Zeneida P.042 Mattace-Raso, Francesco P.091 Petersen, Lonnie G 0.6 Mattos, Samanta O.25 Petit, Claudie O.3 Maureira, Jean-Pablo O.7 Pewowaruk, Ryan P.024, P.061 Mawson, David M O.19 Peyrin-Biroulet, Laurent P.131 Mayer, Christopher O.23, P.151 Qasem, Ahmad P.063 Mc Cluskey, Genevieve P.069 Qureshi, Abdul P.070 McDonnell, Barry P.068 Raj, Kiran V P.095 P.098, P.100, P.101, P.102, P.107, P.108 McNally, Ryan J O.2 Rajkumar, Chakravarthy P.099 Mendes, Mariana P.031 Ramachandra, Abhay B.O.27 Mendizabal, Andrea O.22 Ramaekers, Mitch 0.11 Mengozzi, Manuella P.099 Ramel, Damien P.124 Mensah, Ekow P.099 Ramos Becerra, Carlos Gerardo P.134 Menu, Patrick O.7 Raoul, Alexandre P.004 Mercier, Nathalie P.130 Rapala, Alicja P.054 Mess, Werner P.128 Raza, Farhan P.027 Meyer, Michelle O.18 Reboucas, Laysa P.031 Michel, Jean-Baptiste P.132 Reesink, Koen 0.11, P.022, P.032, P.061, P.067, P.128, Mikolaitytė, Jurgita P.034 Regnault, Veronique O.7, P.003, P.004, P.130, P.131, P.132, P.139 Mintziori, Gesthimani O.14 Reig, Javier P.042 Moreau-Grange, Lucile P.123 Reperant, Christelle P.069 Mousseaux, Elie P.021 Richard, Darren E.O.17 Mudnic, Ivana P.105 Richter, Stefan P.001, P.002 Mulder, Paul O.26 Rio, Marc P.136 Murtada, Sae-Il O.27 Robertson, Andrew 0.6, P.141 Nabeel, P. M.P.095 Roca, Frederic P.123 Nadeau-Fredette, Annie-Claire O.10, P.045 Rodilla, Enrique O.22, P.042 Nandi, Manasi O.15 Roldan, Alicia O.22 Narang, Rajiv P.071 Roussel, Camille P.140 Natarajan, Satheesh P.062 Royaud, Isabelle O.7 Natour, Ehsan 0.11 Ruch, Aurelie P.132 Navarro, Adela O.21 Ruiz, Desire P.042 Nemcsik, Janos P.043 Ruiz, Fanny P.042 Nemcsik-Bencze, Zsofia P.043 Ruiz-Rodriguez, Maria Jesus O.1 Neuhauser, Hannelore O.13 Runciman, John P.066 Neutel, Cedric P.127 Ryliškytė, Ligita P.034 Neve, Gilles P.103 Sadaba, Rafael O.21 Artery Research Saez, Maria-Carmen O.22 Tian, Lei P.004 Salar, Luis P.042 Tisler, Andras P.043 Saller, Francois P.140 Tomiyama, Hirofumi O.20 Salvi, Paolo P.067 Tone, Caterina Maria P.004 Santha Chandran, Dinu P.095 Torella, Francesco O.9 Sarthou, Marie-Kergulen P.124 Torop, Liisi Anette P.055 Scalese, Marco P.014 Torzsa, Peter P.043 Scalise, Filippo P.067 Toupance, Simon P.130 Schalkwijk, Casper P.051 Tousoulis, Dimitrios P.081 Schalla, Simon 0.11 Triantafyllou, Areti O.14, O.23, P.015, P.151 Schellenberg, Celia P.131 Tsioufis, Konstantinos P.081 Schmidt-Trucksass, Arno O.13, P.103 Tuna, Bilge P.064 Schurgers, Leon P.061, 0.11 Tuna, Bilge Guvenc P.151 Schwartz, Martin A.O.1 Ung, Roth-Visal O.17 Sedzro, Josepha-Clara P.140 Vahi, Mare P.055 Segal, David P.097 Van De Velde, Gabrielle P.139 Segers, Patrick P.065, P.110 van der Bruggen, Myrthe M.P.032 Sharif, Isam O.4 van der Laan, Koen P.022, P.032, P.128 Shore, Angela C O.19 Van Loo, Cindy P.061, P.121 Siew, Keith O.4 van Mieghem, Nicolas P.091 Soderberg, Magnus P.070 Vassilenko, Valentina P.011 Soulat, Gilles P.021 Vaudo, Gaetano P.030 Soulez, Marie Shannon P.021 Vicente, Julio P.042 Spai, Sofia P.081 Vico, Julieta Anabela O.21 Spanneut, Theo P.058 Vion, Anne-Clemence P.136 Spronck, Bart O.27, P.001, P.002, P.022, P.032, P.061, P.067, P.092, P.121, Vlachopoulos, Charalambos P.081 P.128 Wagner, Jonathan P.103 Srivastava, Prachi P.095, P.122 Wahart, Amandine P.124 Stathi, Dimitra P.057 Wassertheurer, Siegfried O.10, P.033 Stauber, Alexander P.001, P.002 Weber, Thomas O.16, O.23, P.033 Stehouwer, Coen P.051 Wesley, Callan P.127 Stenvinkel, Peter P.070 Wessels, Hester P.097 Stephan, Yohan O.26 Wijnhoven, Renske P.091 Stergiopulos, Nikos P.065 Wildberger, Joachim Ernst 0.11 Stevens, Kailey P.121, P.141 Wilkinson, Ian O.4 Stohr, Eric P.068 Williams, Colin O.4 Stoner, Lee O.18 Wisniewski, Nathan P.005 Sunjic, Borna P.105 Wymann, Matthias P.124 Sutcliffe, Michael O.4 Yasmin, Y O.4 Tairi, Amira P.092, P.093 Young, Barnaby P.037 Tan, Isabella P.063 Zhao, Xiaofei P.051 Tanaka, Hirofumi O.18 Zilmer, Mihkel P.055 Terentes-Printzios, Dimitrios P.081, P.151 Zmuda, Louise P.123 Testa, Marisa P.151 Zografou, Ioanna O.14 Thomas, Arthur P.130 Thomas, Mireille O.3 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Artery Research Springer Journals

Selected Abstracts from Artery 22

Artery Research , Volume 29 (Suppl 1) – Feb 1, 2023

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Artery Research Artery Research https://doi.org/10.1007/s44200-022-00028-8 Open Access ABSTR AC T S Wednesday 19 – Saturday 22 October 2022, Centre de Congrès Prouvé, Nancy, France Oral presentations deterioration of elastic fibers and mechano-sensing appear to be pri- mary drivers of aberrant tissue remodeling and associated dilatation in the Marfan aorta, which is characterized by progressive stiffening. O.1 Microstructural deterioration drives progressive functional loss in Marfan syndrome aneurysms 1 1 2 3 Cristina Cavinato , David Lee , Marcos Latorre , Minghao Chen , 1 4 3,5 Dar Weiss , María Jesús Ruiz‑Rodríguez , Martin A. Schwartz , 1,5 Jay D. Humphrey Department of Biomedical Engineering, Yale University, New Haven, USA, Center for Research & Innovation in Bioengineering, Valencia Polytechnic University, Valencia, Spain, Cardiovascular Research Center, Yale School of Medicine, New Haven, USA, Centro Nacional de Investigaciones Car‑ diovasculares Carlos III, Madrid, Spain, Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, USA Background: Marfan Syndrome is a primary cause of thoracic aortic aneurysms; it arises from dysfunctional fibrillin-1, which normally sta- bilizes elastic fibers and promotes smooth muscle mechano-sensing of the matrix. Despite significant advancements, clear correlations between microstructural integrity and aortic functionality remain wanting. Biaxial stress-stretch curves (A) and circumferential stiffness vs. elastin Methods: Age-matched wild-type, Fbn1C1041G/ + [1], and Fbn1mgR/ porosity (B) for the ascending thoracic aorta of the analyzed Marfan mgR [2] mice represented three stages of disease severity. Experi- mice. Dilatation and circumferential stiffness from the G&R model (C). ments quantified specimen-specific thoracic aortopathy in terms of: (1) mechanical metrics from ex vivo biaxial testing that were described References by a four-fiber family hyperelastic model [3]; (2) microstructural met - [1] Milewicz DM, et al. Marfan syndrome. Nat Rev Dis Primers. 2021;7(1):64. rics[4] from ex  vivo multiphoton microscopy including elastin poros- [2] Pereira L, et al. Pathogenetic sequence for aneurysm revealed in mice ity, density, and engagement of collagen fibers and cells; (3) cardiac underexpressing fibrillin‑1. PNAS. 1999;96(7):3819–23. function from in  vivo ultrasound and µCT imaging. Material proper- [3] Judge DP, et al. Evidence for a critical contribution of haploinsufficiency ties were incorporated within a mechanobiologically equilibrated in the complex pathogenesis of Marfan syndrome. J Clin Invest. constrained mixture model of arterial growth and remodeling (G&R) 2004;114(2):172–81. [5]. The analysis assessed long-term impacts of locally compromised [4] Cavinato C, Chen M, Weiss D, Ruiz‑Rodríguez MJ, Schwartz MA, Humphrey elastin integrity, cellular mechanosensing and mechanoregulation, JD. Progressive Microstructural deterioration dictates evolving biome‑ collagen turnover, and endothelial function on disease progression chanical dysfunction in the Marfan aorta. Front Cardiovascular Medicine. through perturbations to the initial homeostatic state. 2021;8:1904. Results: Aortic dilatation correlated strongly with key mechanical met- [5] Latorre M, Humphrey JD. Numerical knockouts–In silico assessment of rics of compromised aortic functionality as well as with elastin defects, factors predisposing to thoracic aortic aneurysms. PLoS Comput Biol. collagen remodeling, and altered cellular function. Variable dilatations 2020;16(10). at a given age reflected a “pseudo-time” of progressive deterioration consistent with a progressive anoikis. The G&R model reproduces the Keywords: Marfan syndrome, Biaxial mechanics, Microstructure, same trends in aortic dilatation, stored energy, and circumferential Growth and remodeling, Aneurysms stiffness with increasing losses of elastic fiber integrity. The progressive © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Artery Research O.2 Methods: To address this need, we applied mechanical stimulations Impaired β2‑adrenergic endothelium‑dependent vasodilation on human aortic SMC in culture at passage 6–7, by using the Flex- is reversed by phosphodiesterase inhibition in patients previously cell tension system (Fig.  1A). We tried different durations of stimu- hospitalized with COVID‑19 lation (24  h, 48  h, 72  h, and 100  h) versus unstimulated control. We chose 7 genes, coding for contractile proteins of the cytoskeleton 1 1 1 1 Dr. Luca Faconti , Ms Bushra Farikh , Dr. Ryan J McNally , Dr Sally Brett , (Fbn1, ACTA2), extracellular matrix components (Coll1A1, LAMA5), or Prof. Philip J Chowienczyk involved in activation/regulation of traction forces (TGFBR1, MYLK), King’s College London, London, United Kingdom and in cell differentiation (TAGLN). The expression of these genes was quantified with qPCR analysis, relatively to a reference gene (HPRT) Background: Endothelial dysfunction may underlie many of the com- (Fig. 1B). plications of COVID-19 [1]. The pulse wave response to salbutamol Results: We observed that: 1. From 72 h of stimulation, the difference (PWRS)—change in the augmentation index, AIx- provides a means between stimulated and control groups is the most significant; 2. For to assess endothelial vasodilator function mediated through the nitric the majority of the genes, their expression decreases with the stimula- oxide-cyclic guanosine monophosphate pathway (NO-cGMP) [2,3]. tion; 3. The basal medium enhances α-SMA production. Nevertheless, Here we aim to determine whether PWRS is abnormal in patients due to the low quantity of RNA available, we had to repeat cell stimu- recovered from COVID-19. lation, and reach n = 3 repetitions for each group during the qPCR Methods: We examined PWRS in subjects previously hospitalized analysis for more accurate results. with COVID-19, those recovered from mild symptoms and seronega- Conclusions: We were able to quantify SMC mechanosensitivity and tive controls (absence of SARS-CoV-2-antibodies) with similar risk fac- mechanotransduction. AoSMC seem to modulate their gene expres- tors for cardiovascular disease. In a sub-sample, we also assessed the sion after 72 h of stimulation. As future work, we would like to investi- response in the presence and absence of the phosphodiesterase type gate the influence of intercellular signaling under stimulation. 5 inhibitor sildenafil which inhibits the breakdown of cGMP. Results: 101 subjects (60 men) aged 47.8 ± 14.1 (mean ± SD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Inhaled salbutamol reduced AIx in controls (n = 34) and those recov- ered from mild symptoms of COVID-19 (n = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] − 2.85 [− 5.52, − 0.188] %, − 2.32 [− 5.17, 0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symp- toms and those previously hospitalised respectively (P = 0.001). In a sub-sample (n = 22), sildenafil enhanced the response to salbutamol (change in AIx 0.05 [− 2.15, 2.24] vs. − 3.96 [− 7.01, − 2.18], P = 0.006) with no significant difference between hospitalized (n = 12) and non- hospitalized subjects (n = 10). Conclusions: In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function which can be ame- liorated by sildenafil. (A) Control group and stimulated group with Flexcell tension system. (B) Results of the qPCR analysis on all groups for 7 genes (cDNA quan- References tity, relatively to a reference gene (HPRT )). [1] Libby P, Lüscher T. COVID-19 is, in the end, an endothelial disease. Eur. Heart J. 2020;41:3038–3044. References [2] Chowienczyk PJ, Kelly RP, MacCallum H, Millasseau SC, Anders- 1. Michel J‑B, Jondeau G, Milewicz DM. From genetics to response to injury: son TLG, Gosling RG, Ritter JM, Änggård EE. Photoplethysmographic vascular smooth muscle cells in aneurysms and dissections of the assessment of pulse wave reflection: Blunted response to endothe - ascending aorta. Cardiovasc Res. 2018;114(4):578–89. lium-dependent beta2-adrenergic vasodilation in type II diabetes mel- 2. Milewicz DM, Trybus KM, Guo D, Sweeney HL, et al. Altered Smooth litus. J. Am. Coll. Cardiol. 1999;34:2007–2014. Muscle Cell Force Generation as a Driver of Thoracic Aortic Aneurysms [3] Wilkinson IB, Hall IR, Maccallum H, Mackenzie IS, Mceniery CM, and Dissections. Arteriosclerosis, Thrombosis, and Vascular Biology. Arend BJ Van Der, Shu Y, Mackay LS, Webb DJ, Cockcroft JR. Clinical 2016;116:303229. Evaluation of a Noninvasive, Widely Applicable Method for Assessing 3. Liu M, Gomez D. Smooth Muscle Cell Phenotypic Diversity. Arterioscler Endothelial Function. 2002; Thromb Vasc Biol. 2019;39(9):1715–1723. 4. Humphrey JD, Schwartz MA, Tellides G, Milewicz DM. Role of Mechanotrans‑ Keywords: COVID-19, Endothelium, AIx duction in Vascular Biology: Focus on Thoracic Aortic Aneurysms and Dissections. Circulation Research. 2015;116(8):1448–61. O.3 Keywords: Cell biomechanics, Epigenetics, Mechanical stimulation, How does mechanical stress affect gene expression in human qPC aortic smooth muscle cells? 1 1 2 Mme Claudie Petit , Amira Ben Hassine, Mireille Thomas , 2 1 Alain Guignandon , Pr. Stéphane Avril O.4 Pentosan polysulfate, an aggrecanase inhibitor modulates Mines Saint‑Etienne, Université de Lyon, INSERM, U 1059 SAINBIOSE, arterial stiffness in spontaneously hypertensive rats Saint‑Etienne, France, Université Jean Monnet, Université de Lyon, 1 2 3 INSERM, U 1059 SAINBIOSE, Saint‑Etienne, France Miss Aleksandra Klosinska , Dr Keith Siew , Mr Tao L uo , 4 1 5 5 Mrs Nichola Figg , Mrs Sarah Cleary , Dr Isam Sharif , Mr Colin Williams , Background: SMC modulate their phenotype in response to envi- 1 3 Professor Ian Wilkinson , Professor Michael Sutcliffe , Professor Kevin ronmental conditions, as in for instance ascending thoracic aortic 1 1 O’Shaughnessy , Dr Y Yasmin aneurysms (ATAA) (1–3). It was previously shown that missensing of University of Cambridge, Department of Medicine, EMIT Division, mechanical stimuli plays a major role in ATAA (2,4). Nevertheless, there Cambridge, United Kingdom, University College London, Department is a pressing need to better quantify the mechanobiological behaviour of Renal Medicine, London, United Kingdom, University of Cambridge, of SMCs. A rtery Research Department of Engineering, Cambridge, United Kingdom, University whether healthy adults (controls, n = 36) or patients with moderate of Cambridge, Department of Medicine, Cardiovascular Division, Cam‑ chronic kidney disease (CKD, n = 30) were analyzed respectively with bridge, United Kingdom, Covance CRS Limited, Huntingdon, United paired or independent samples t-tests. Kingdom Results: Despite similar cd-PWV and cr-PWV, rd-PWV at baseline was significantly lower in CKD than in controls (3.6 ± 1.4  m/s vs. Background: Arterial stiffness is an independent predictor of all-cause 4.5 ± 1.8  m/s, p = 0.024), but this difference faded (p = 0.145) after and cardiovascular mortality in many populations. Our recent research adjustment for age. Post NTG, brachial blood pressure decreased and showed that loss of aggrecan integrity associates with age-related heart rate increased similarly between groups. Rd-PWV increased in arterial stiffening (ARAS) in humans1, and others have shown that inhi- controls (from 4.62 ± 1.49 m/s to 5.94 ± 2.29 m/s, p < 0.001) and in CKD bition of ADAMTS/aggrecanase enzymes, which degrade aggrecan, (from 3.71 ± 1.60  m/s to 5.18 ± 2.12  m/s, p < 0.001), in a similar extent improves cardiac function 2. Currently, there are no drugs that specifi- (interaction p = 0.111). However, cd-PWV significantly increased post- cally target arterial stiffening in humans. We hypothesise that ADAMTS NTG only in the CKD group (p = 0.009). inhibitor, Pentosan Polysulfate (PPS), represents an attractive molecule Conclusions: This technique, adapted by our team for small conduit that can be repurposed as a first-in-class drug treatment for ARAS. arteries, may broaden our understanding of the consequences of the inversion of the stiffness gradient. Methods: We performed an in vivo pharmacological experiment using 15wk-old spontaneous hypertensive male rats (SHR) that were admin- References istered either PPS or vehicle control (n = 7 per group) subcutaneously 1. Obeid H, Fortier C, Garneau CA, Pare M, Boutouyrie P, Bruno RM, et al. 3 times per week for 4 weeks. Animals were sacrificed and fully intact Radial‑ digital pulse wave velocity: a noninvasive method for assess‑ aortae including blood, cartilage, etc. were harvested and stored at ing stiffness of small conduit arteries. Am J Physiol Heart Circ Physiol. − 800  °C. Arterial wall thickness, stress-strain and failures stress were 2021;320(4):H1361‑H9. measured, and tensile elasticity calculated ex vivo. 2. Fortier C, Garneau CA, Pare M, Obeid H, Cote N, Duval K, et al. Modulation of Results: Preliminary analysis showed that PPS significantly reduced Arterial Stiffness Gradient by Acute Administration of Nitroglycerin. Front aortic wall thickening normally associated with arterial stiffening in Physiol. 2021;12:774056. hypertension (Vehicle 225 ± 6 µm vs 204 ± 6  µm, p = 0.0143). PPS also decreased aortic stiffening significantly at supraphysiological pres- Keywords: Chronic kidney disease, Nitroglycerin, Arterial stiffness gra- sures in treated rats, and treated rats had a higher failure stress relative dient, Small conduit arteries to vehicle controls. Conclusions: This proof-of-principle study demonstrated that an O.6 aggrecanase inhibitor can modulate aortic stiffness markers in SHR, Characterization of internal jugular vein region‑specific but the short treatment period may not be adequate to reveal clini- distension during progressive volume loading cally significant differences. Further longitudinal studies are therefore, 1 1,2 2 needed to establish if longer exposure to PPS can reduce aortic stiff- Mr Jeremy N. Cohen , Mr Eric T. Hedge , Dr Danielle K. Greaves , 1,2 3 1 ness at clinically significant levels in older animals. Dr Andrew D. Robertson , Dr Lonnie G. Petersen , Dr Jason S. Au Department of Kinesiology and Health Sciences, University Of Waterloo, References Waterloo, Canada, Schlegel‑University of Waterloo Research Institute [1] Yasmin et al. The matrix proteins aggrecan and fibulin‑1 play a key role in for Aging, University of Waterloo, Waterloo, Canada, Department determining aortic stiffness. Sci Rep. 2018 Jun 4;8(1):8550. https:// doi. org/ of Aeronautics and Astronautics, Massachusetts Institute of Technology, 10. 1038/ s41598‑ 018‑ 25851‑5. Cambridge, United States of America [2] Vistnes M. et al. Penstisan polysulfate decreases myocardial expression of the extracellular matrixenzyme ADAMTS4 and improves cardiac function Background: The internal jugular vein (IJV) is highly compliant with in vivo rates subjected to pressure overload by aortoc banding. PLOS One roles in intracranial blood flow and pressure regulation. The dynamic and 2014: 9, e8923. https:// doi. org/ 10. 1371/ journ al. pone. 00896 21. variable nature of venous flow, especially during changes in gravitational stress, leads to non-linear geometry. However, the impact of this irregu- Keywords: Arterial stiffness, Aggrecan, Pentosan polysulfate, Sponta- lar anatomy on IJV distension during progressive volume loading is not neous hypertensive rats understood and may contribute to adverse flow profiles, a component of Virchow’s triad for thrombotic risk. We characterized IJV 3D shape and volume expansion during progressive head-down tilt (HDT), a micro- O.5 gravity analogue. Radial‑digital pulse wave velocity: stiffness of small conduit Methods: We recruited 5 healthy, young adults (2 females, 25 ± 4 year, arteries increases after nitroglycerin administration 168 ± 8  cm, 68 ± 15  kg). Using an ultrasound probe tracked in 3D 1,2 1 1 space, we captured right IJV cross-sectional area (CSA) from clavicle to Dr Catherine Fortier , Charles‑Antoine Garneau , Mathilde Paré , 1 1 1 2 mandible. Progressive cephalad fluid shift was achieved by HDT at 0°, Dr Hasan Obeid , Nadège Côté , Karine Duval , Dr Rémi Goupil , − 6°, − 15°, and − 30°, each held for 5 min. CSA were traced at 0.3 cm Dr Mohsen Agharazii intervals from caudal to cranial and vein volume calculated by cylindri- Chu De Québec Research Center ‑ Université Laval, Québec, Canada, cal CSA. CIUSSS NIM‑ Sacré Coeur de Montréal, Montréal, Canada Results: Progressive HDT significantly altered IJV distension, demon- 2 2 strating stepwise effects on average CSA (0.89 ± 0.4cm , 1.26 ± 0.6cm , Background: The alteration of the physiological stiffness gradient 2 2 2 1.68 ± 0.7cm , 2.02 ± 1cm ; P = 0.003, η = 0.67) and total volume within larger vessels would increase the transmission of greater pul- (4.0 ± 1.5  mL, 5.8 ± 3.3  mL, 7.6 ± 4.2  mL, 9.3 ± 5.4  mL; P = 0.007, satility to the microcirculation, thus explaining the damage to the η = 0.63) through HDT conditions 0°, − 6°, − 15°, − 30°, respectively. pressure-sensitive organs. We aimed to describe the response of small Caudal regions displayed greater distension capacity compared to cra- conduit arteries of the hand (radial-digital PWV, rd-PWV) (1) following nial across conditions (P < 0.001). the pharmacological alteration of the stiffness gradient using nitro - Conclusion: Our precise 3D volume measures demonstrate the IJV can glycerin. (2). accommodate significant fluid shifts through a large range in disten- Methods: Simultaneous application of piezoelectric sensors (Com- sion ability, beyond stimuli mimicking microgravity. Irregular expan- plior) at the level of the carotid (c), the radial artery (r) and the tip sion patterns in the caudal regions may lend to flow abnormalities and of the index finger (d) was used to calculate the rd-PWV, before and requires investigation to ascertain prognostic value of IJV geometry on 4  min after a sublingual administration of 0.4  mg of NTG. Changes in thrombotic risk. arterial stiffness pre-post NTG and comparisons between two groups Artery Research Reference Fayon A, Menu P & El Omar, R. Cellularized small‑ caliber tissue‑ engineered vascular grafts: looking for the ultimate gold standard. npj Regen Med. 2021 Aug (6), 46 Keywords: Tissue-engineered vascular graft, Human umbilical cord, Inside-out, Artery bypass models, Vascular Tissue Engineering O.8 Inhibition of atherosclerotic plaque calcification by Omega‑3 polyunsaturated fatty acids through the resolvin E1 receptor ChemR23 1 1 PhD Gonzalo Ar tiach , PhD Andres Laguna‑Fernandez , 1 1 1,2 PhD Miguel Carracedo , PhD Hildur Arnardottir , Prof. Magnus Bäck Department of Medicine, Karolinska Institutet, Stockholm, Sweden, Theme Heart and Vessels, Karolinska University Hospital, Stockholm, Sweden Fig. 1 Internal jugular vein cross‑sectional area from caudal to cranial Background: The immune cell response in atherosclerotic plaques is regions normalized to individual neck length (A) and total cylindrical vein characterized by an impaired resolution of inflammation (1). Resolvin E1 (RvE1), a specialized pro-resolving lipid mediator derived from volume during progressive head‑ down tilt (B) omega-3 polyunsaturated fatty acids (PUFA) has been shown to play Keywords: Microgravity, Venous, 3D a critical role in atherosclerosis by promoting the resolution of the inflammation (2). The aim of the present study was to unravel the role of omega-3 PUFA, RvE1 and the RvE1 receptor ChemR23 in the process O.7 of atherosclerotic plaque calcification. New approach in the design of a human tissue engineered Methods: Fat-1 transgene (Fat-1tg), which enables the endogenous pro- vascular graft and preliminary studies in arterial bypass models duction of n-3 PUFA, was inserted in apolipoprotein E (ApoE)-deficient in the pig mice, in combination or not with genetic deletion of ChemR23. Calcifi- 1 1 2 Dr Adrien Fayon , Mrs Deborah Helle , Dr Véronique R egnault , cation was assessed by Alizarin Red staining and macrophage markers 3 3 2,4 Dr Marc Ponçot , Pr Isabelle R oyaud , Pr Jean‑Pablo Maureira , were assessed by immunohistochemistry in aortic root sections. 4 5 1 1 Dr Dan Pan , Dr Caroline Gaucher , Pr Patrick M enu , Dr Reine El Omar Results: Our results show that 72  week old Fat-1tg × Apoe -/- mice 1 2 Université de Lorraine, CNRS, IMoPA, F‑54000 Nancy, France, Uni‑ developed less atherosclerotic plaque calcification compared with versité de Lorraine, Inserm, DCAC, F‑54000 Nancy, France, Université Apoe-/- mice (0–3% vs 4–8%, p < 0.001). Moreover, deletion of de Lorraine, CNRS, IJL, F‑54000 Nancy, France, Université de Lorraine, ChemR23 enhanced atherosclerotic plaque calcification (4–13% CHRU‑Nancy, Service de Chirurgie Cardiovasculaire, F‑54000 Nancy, vs. 4–8%, p < 0.001), and this effect was not reversed by the pres- France, Université de Lorraine, CITHEFOR, F‑54000 Nancy, France ence of Fat-1tg (4–14% vs. 4–8%, p < 0.001). Furthermore, the Fat- 1tg × Apoe-/- mice had significantly higher expression of the M2 Background: Arterial bypass surgery of small-caliber vessels using macrophage marker Arg1 compared with Apoe-/- mice (17.4 ± 2.5% synthetic vascular prostheses remains inefficient as they promote vs 5.1 ± 1.5%; p < 0.0001), which was reversed by genetic dele- thrombosis probably due to a low or non-functionalization of their tion of ChemR23 (5.0 ± 1.1% vs. 17.4 ± 2.5%; p < 0.0001 vs internal surface(1). As a potential therapeutic alternative, we have Fat-1tg × Apoe -/- mice). developed a human cellularized TEVG (tissue-engineered vascular Conclusion: These results suggest that the beneficial effects of Fat- graft) whose components are all derived from the umbilical cord. 1tg were mediated through ChemR23. Hence, omega-3 PUFA may Methods: Decellularized umbilical arteries were coated at their lumi- have a therapeutic potential for reducing atherosclerotic plaque cal- nal surface with an extracellular matrix extracted from Wharton’s cification through RvE1-signaling by means of ChemR23. jelly and then cellularized by mesenchymal stromal cells derived also from WJ. The luminal coating and cellularization were optimized by References an innovative "inside-out" method allowing easy access to the lumi- 1. Bäck M, Yurdagul A, Tabas I, Öörni K and Kovanen PT. Inflammation and its nal surface. TEVG hemocompatibility (Thrombin Generation Assay) resolution in atherosclerosis: mediators and therapeutic opportunities. and mechanical properties (burst pressure test, stress rupture test, Nat Rev Cardiol. 2019 Jul;16(7):389–406. dynamic mechanical analysis) were evaluated. Preliminary in  vivo 2. Carracedo M, Artiach G, Arnardottir H and Bäck M. The resolution of inflam‑ implantations were conducted in pigs for coronary or femoral arterial mation through omega‑3 fatty acids in atherosclerosis, intimal hyperpla‑ bypass. sia, and vascular calcification. Semin Immunopathol. 2019;41:757–766. Results: The “inside-out” method, which did not impact mechanical properties of the TEVG, allowed a homogeneous cellularization of Keywords: Atherosclerosis, Calcification, Omega-3, Resolvin arteries luminal surface confirming its adaptability to a vascular con- text. Hemocompatibility assays showed that the TEVG behaves as a native blood vessel due to full cell covering of the luminal surface. The TEVG was successfully implanted in a coronary artery bypass O.9 model (n = 1), and was well tolerated, colonized and remain pat- Reduced Micromechanical Stiffness of Large Diameter Abdominal ent for 2  weeks post-implantation in a femoral replacement model Aortic Aneurysm (AAA) Wall Tissue (n = 1). 2 2 2 1 Martin Hossack , Robert Fisher, Francesco Torella , Jillian Madine , Conclusion: Our TEVG is an allogeneic therapeutic solution offering Riaz Akhtar a ready-to-use graft that may supply a tissue bank and which can be 1 2 grafted by minimally invasive robotic techniques avoiding an invasive University of Liverpool, United Kingdom, Liverpool University Hospitals surgery, having beneficial societal and economic impacts. NHS Foundation Trust, United Kingdom A rtery Research Introduction: Use of a maximum diameter threshold as the sole O.10 indicator for aneurysm repair risks rupture during surveillance in Reservoir‑wave parameters and cardiovascular prediction: higher-risk cases, and unnecessary repair in others [1]. Here, we Analysis of the population‑based CARTaGENE cohort characterised the micromechanical properties of aneurysmal aortic 1,4 2,3 Dr Louis‑Charles Desbiens , Dr Catherine Fortier , Dr Annie‑Claire tissues with the aim of identifying high-risk cases and directing spe- 1,4 2,4 5 Nadeau‑Fredette , Dr François Madore , Dr Bernhard Hametner , cific management. 5 3,6 2,4 Dr Siegfried Wassertheurer , Dr Mohsen Agharazii , Dr Rémi Goupil Methods: Full thickness anterior aortic wall tissue samples were 1 2 Hôpital Maisonneuve‑Rosemont, Montréal, Canada, Hôpital du harvested from 16 patients undergoing repair of degenerative AAA. Sacré‑Coeur de Montréal, Montréal, Canada, CHU de Québec—Univer‑ Nanoindentation was used to determine the shear storage modulus sité Laval, Québec, Canada, Université de Montréal, Montréal, Canada, (G′). We performed indentations on tissue cross-sections in 3 lay- 5 6 AIT Austrian Institute of Technology, Vienna, Austria, Université Laval, ers (inner, middle, outer). At least 4 samples were tested from each Québec, Canada patient. In total, there were 102 samples (1269 indentations). We stratified micromechanical findings according to maximum trans- Background: The reservoir-wave concept hypothesizes that blood verse diameter (MTD), established through interrogation of pre- pressure is the sum of a reservoir and an excess pressure. Nevertheless, operative contrast-enhanced CT scans. the clinical association of reservoir-wave parameters with cardiovascu- Results & Discussion: Aortic wall tissue demonstrated a pattern lar outcomes remains controversial. of reducing stiffness from the inner to middle (median 31.5  kPa vs Methods: We studied individuals aged between 40 and 69 from the 24.4  kPa, P < 0.05) and middle to outer layers (24.4  kPa vs 13.1  kPa, CARTaGENE cohort (Canada). Radial waveforms were measured with P < 0.05). Wall stiffness increased as MTD increased from 50–59  mm aplanation tonometry (SphygmoCor). They were transformed to cen- to 60–69  mm (median 20.7  kPa vs 29.5  kPa, P < 0.05). At 70-79  mm, tral waveforms using generalized transfer functions and used to gen- wall stiffness reduced (median 22  kPa, NS), and reduced further erate reservoir parameters (Reservoir pressure [RP], Reservoir pressure as MTD exceeded 80  mm (median 19.6  kPa, P < 0.05) (Fig.  1). The integral [RPI], Excess pressure [XSP], Excess pressure integral [XSPI], mechanical properties of vascular tissues depend largely on the Systolic rate constant [SC], Diastolic rate constant [DC], Optimized extracellular matrix. A reduced G′, observed in larger diameter aneu- asymptotic pressure [PInf]). Major adverse atherosclerotic events rysms may indicate a failure in the collagen network, predisposing (MACE: cardiovascular death, stroke, myocardial infarction) during a to rupture. 10-year follow-up were obtained using medico-administrative data- Conclusion: At higher MTD, AAA wall loses stiffness at larger diam- bases. Associations of reservoir parameters with MACE were derived eters. The work can be translated to identify individuals with high- using crude and fully adjusted Cox models. Incremental predictive risk AAA. performance over the ASCVD score (atherosclerotic cardiovascular dis- ease score; using revised pooled cohort equations) for each reservoir parameter was displayed using c-statistic improvement and continu- ous net reclassification indexes (NRI). Results: From 17,629 individuals, 2327 had a MACE during the fol- low-up. All reservoir parameters were significantly higher in patients who experienced a MACE. After full adjustment, RP, XSPI and DC were associated with increased MACE incidence ( Table). Spline anal- ysis did not reveal any non-linear relationships between reservoir parameters and MACEs. When added to the ASCVD prediction score, XSP and DC significantly improved c-statistics while RP, XSPI, DC and PInf led to a significant net reclassification improvement. Conclusion: Reservoir parameters, especially the diastolic rate con- stant, improve cardiovascular prediction in a population-based cohort. Table Fig. 1 Shear storage modulus shown as a function of maximum trans‑ verse diameter Reference 1.Polzer, S., Gasser, T.C., Vlachovský, R., Kubíček, L., Lambert, L., Man, V., Novák, K., Slažanský, M., Burša, J. and Staffa, R., 2020. Biomechanical indices are more sensitive than diameter in predicting rupture of asympto‑ O.11 matic abdominal aortic aneurysms. Journal of vascular surgery, 71(2), Histomorphometric analysis of cell and matrix components pp.617–626. of ascending thoracic aortic aneurysm 1,2 3 4 2 Berta Ganizada , Shaiv Parikh , Mitch Ramaekers , Armand Jaminon , Keywords: abdominal aortic aneurysms, maximum diameter, biome- 2 1 5 Asim Cengiz Akbulut , Ehsan Natour , Ryan Accord , Joachim Ernst chanics, vascular Artery Research 4 1 1 3 1 Wildberger , Simon Schalla , Jos M aessen, Reesink , Elham Bidar , Age and weight are represented as mean ± SD and other values as Leon Schurgers. median with IQR [Q1-Q3]. Department of Cardiothoracic Surgery, Maastricht University Medical 2 References Centre + , Maastricht, The Netherlands, Department of Biochemistry, 1. Erbel R, Aboyans V, Boileau C, et al. 2014 ESC Guidelines on the diagnosis Cardiovascular Research Institute Maastricht, Maastricht University, 3 and treatment of aortic diseases: Document covering acute and chronic Maastricht, The Netherlands, Department of Biomedical Engineer‑ 4 aortic diseases of the thoracic and abdominal aorta of the adult. The Task ing, Maastricht University, Maastricht, The Netherlands, Department Force for the Diagnosis and Treatment of Aortic Diseases of the European of Radiology and Nuclear Medicine Cardiology, Maastricht University 5 Society of Cardiology (ESC) [published correction appears in Eur Heart J. Medical Centre + , Maastricht, The Netherlands, Department of Pediatric 2015 Nov 1;36(41):2779]. Eur Heart J. 2014;35(41):2873–2926. and Congenital Cardiothoracic Surgery, University Medical Center Gronin‑ 2. Cebull HL, Rayz VL, Goergen CJ. Recent Advances in Biomechanical Charac‑ gen, Groningen, The Netherlands. terization of Thoracic Aortic Aneurysms. Front Cardiovasc Med. 2020;7:75 Background: Current indication for ascending thoracic aortic aneu- Keywords: Ascending aorta, Aneurysms, ECM-VSMC, Arterial rysm (aTAA) surgery is based on aortic diameter of 5–5.5  cm or a remodeling growth rate of > 0.5 cm/year [1]. However, current screening surveil- lance and risk estimation simplifies the complexity of aTAA disease, which might lead to a high-risk open-chest cardiac surgery [2]. Our O.12 aim was to examine ex vivo histological features of aTAA specimens, C–C chemokine ligand 5 from subcutaneous adipose tissue to assess changes in extracellular matrix (ECM) content and vascular has a central role in vascular aging smooth muscle cell ( VSMC) properties. Laura Le Pelletier Methods: Surgical samples of the ventral aspect of the ascending UMRS938 Inserm Saint Antoine Research Center, Paris, France aorta were collected from patients suffering from aTAA (n = 20) and patients with non-aneurysmal coronary bypass or stenotic valve sur- Background: Adipose tissue (AT) has a critical role in cardiovascular gery which served as controls (n = 10). Medial cross-sectional thick- diseases – particularly through its secretory activity. Aging is associ- ness, collagen/elastin content, and VSMC number were determined ated with AT redistribution, senescence, and changes in the secretome by quantitative histomorphometry. In addition, immunohistochemi- (1,2). We have previously shown that human adipose stromal cells cal markers of VSMC phenotype, α-smooth muscle actin (α-SMA), (ASCs) from the subcutaneous AT (SCAT) of aged women display calponin-1 (CNN1), and S100 calcium binding protein A4 (S100A4) senescence and oxidative stress (3). We hypothesized that the ASC were assessed. Image quantification analysis was performed using secretome contributes to the onset of endothelial dysfunction, an QuPath. early stage in vascular aging. Results: Aneurysmal aortas showed increased elastin fragmentation Methods: Conditioned media were prepared from ASCs isolated and regionally more dense collagen I/III confirming medial degenera- from SCAT of healthy young (< 25y) or aged (> 60y) women. ASCs’ tion. This resulted in a marked rise in collagen-to-elastin ratio (Table 1). secretome were added to human coronary artery endothelial cells. Medial cross-sectional thickness and number of VSMCs were increased C–C-chemokine-ligand-5 (CCL5) was identified by an adipokine array. in aneurysmal aortas (Table  1). Expression of α-SMA and CNN1 The expression of CCL5 in SCAT from men with coronary disease was decreased significantly, whilst S100A4 expression was not different evaluated. The effect of a CCL5 receptor antagonist, maraviroc, was between the groups (Table 1). investigate in peripheral blood mononuclear cells (PBMCs) in HIV- Conclusions: Our preliminary results support the notion of an infected individuals from two studies. imbalanced interaction between ECM-VSMCs that may play a cru- Results: The secretome of aged-donor ASCs induced endothelial cial role in arterial remodeling cascade, leading to aTAA formation. cell dysfunction and senescence. We showed that CCL5 was respon- Further research is needed with the ultimate aim to guide clinical sible for these effects and corroborate in experiments with recom- management. binant protein and maraviroc. We observed that CCL5 expression in SCAT of patients with coronary heart disease was strongly associated with blood pressure. Moreover, maraviroc prevented endothelial cell dysfunction in  vitro and reverted PBMC senescence in HIV-infected individuals. Conclusions: Our results highlighted the ability of the CCL5 secreted by aged ASCs from SCAT to induce endothelial dysfunction and senes- cence—both of which are early steps in vascular aging—and a poten- tial link between these phenomena and hypertension. References 1.Stout MB, Justice JN, Nicklas BJ, Kirkland JL. Physiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty. Physiol Bethesda Md. janv 2017;32(1):9‑19. 2.Liu Z, Wu KKL, Jiang X, Xu A, Cheng KKY. The role of adipose tissue senes‑ cence in obesity‑ and ageing‑related metabolic disorders. Clin Sci Lond Engl 1979. 31 janv 2020;134(2):315‑30. 3.Le Pelletier L, Mantecon M, Gorwood J, Auclair M, Foresti R, Motterlini R, et al. Metformin alleviates stress‑induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction. eLife. 21 sept 2021;10:e62635. Keywords: Aging, adipose tissue, endothelial dysfunction, adipose stromal cells A rtery Research O.13 (PeriCam PSI NR System, Perimed). Post-occlusive reactive hyper- Cardiovascular risk in adolescents translates into lower carotid emia (PORH) was assessed following a standardized protocol and intima‑media thickness and better distensibility in young data were analyzed with a signal processing software (PIMSoft, Per- adults—The KiGGS2‑cohort imed). The amplitude of PORH responses was expressed as a per- 1,2,3 2,3 1 centage increase between peak and baseline perfusion (%). Karsten Königstein , Julia Büschges , Arno SchmidtT ‑ rucksäss , 2,3 Results: Twenty-nine individuals (14 patients with prediabetes and Hannelore Neuhauser 15 controls) were studied. There wasn’t any statistically significant 1 2 University of Basel, Basel, Switzerland, Robert‑Koch Institute, Berlin, difference regarding age, sex, body mass index and blood pres- Germany, DZHK (German Centre for Cardiovascular Research), Berlin, sure levels between the two groups. At baseline, skin microvascu- Germany lar perfusion was significantly higher in patients with prediabetes compared to controls (50.9 ± 11.5 vs. 39.2 ± 8.7, p = 0.006) while Background: Lifestyle-associated cardiovascular risk may be elevated during occlusion, perfusion was similarly reduced in both groups. already during adolescence translating into an increased disease Post occlusion reperfusion was significantly lower in the prediabetes burden in adulthood. The KiGGS cohort characterizes cardiovascular group as compared to the controls (145.0 ± 42.8 vs. 195.2 ± 47.3% aging from childhood until young adulthood in the German general respectively, p = 0.007). population. This study analyzes the effects of increased cardiovascular Conclusions: We showed, for the first time, that individuals with risk during adolescence on carotid properties in young adults. prediabetes demonstrated skin microvascular dysfunction, that may Methods: 1,545 participants of the representative healthy popula- reflect a more generalized microvascular damage. tion sample of the national KiGGS-0 cohort (10–17  years of age) had carotid ultrasound-assessment 10 years later at the KiGGS-2 follow-up References (20–28 years of age). A cardiovascular risk score (CV-R) was calculated 1. Lamparter J, Raum P, Pfeiffer N, Peto T, Höhn R, et al. Prevalence and associa‑ at KiGGS-0 including variables of arterial hypertension, obesity, dyslipi- tions of diabetic retinopathy in a large cohort of prediabetic subjects: The demia and smoking. Carotid intima-media thickness (CIMT) and dis- Gutenberg Health Study. J Diabetes Complications. 2014;28(4):482–7. tensibility (DC) at KiGGS-2 were associated with CV-R. 2. Friedman A, Marrero D, Ma Y, Ackermann R, Narayan KMV, et al. Value of Results: Unfavorable alterations of all components of CV-R were urinary albumin‑to ‑ creatinine ratio as a predictor of type 2 diabetes in associated with higher CIMT and/or reduced DC. Relative risks for pre‑ diabetic individuals. Diabetes Care. 2008;31(12):2344–8. pathologically elevated CIMT ≥ 90th percentile and/or decreased 3. de Matheus AS, Clemente ELS, de Lourdes RM, Torres VDC, Gomes MB, et al. DC ≤ 10th percentile were elevated in participants with ‘intermedi- Assessment of microvascular endothelial function in type 1 diabetes ate’ (RRCIMT = 1.89 [1.23–2.91], p < 0.05; RRDC = 1.27 [0.79–2.06]) or using laser speckle contrast imaging. J Diabetes Complications. 2017, ‘high’ risk (RRCIMT = 1.83 [0.95–3.52], p < 0.1; RRDC = 1.76 [0.93–3.32], 31(4):753–7. p < 0.1) according to CV-R. Conclusions: If an intermediate or high cardiovascular risk according Keywords: prediabetes, microcirculation dysfunction, LASCA to CV-R is apparent in adolescence, signs of early vascular aging may occur at a very young age. The promotion of a favorable lifestyle to reduce risk factor burden even in the overall healthy general popula- tion at a young age seems to be crucial for primary prevention of car- O.15 diovascular diseases. Arterial Stiffness Assessment by Pulse Arrival Time: An In Silico Proof of Concept. Keywords: carotid intima-media thickness (cIMT ), primary prevention, 1 2 1 Jingyuan Hong , Manasi Nandi , Jordi Alastruey. cardiovascular risk, adolescents School of Biomedical Engineering & Imaging Sciences, King’s College London, London, UK, School of Cancer & Pharmaceutical Sciences, King’s O.14 College London, London, UK Evaluation of skin microvascular dysfunction with Laser Speckle Contrast Analysis in prediabetes Arterial stiffness (AS) is one of the primary symptoms of vascu- 1 1 2 lar ageing (1). Stiffer arteries lead to increased pulse wave velocity Stamatina Lamprou , Nikolaos Koletsos , Ioanna Zografou , 3 1 (PWV ) and decreased pulse transit time (PTT ). PWV is considered the Gesthimani Mintziori , Konstantinos Mastrogiannis , 2 1 1 clinical gold standard for the diagnosis of AS, but direct measure- Michael Doumas , Eugenia Gkaliagkousi , Areti Triantafyllou. ment in daily life is challenging (2). Pulse arrival time (PAT), which Third Department of Internal Medicine, Papageorgiou General Hospital, consists of the pre-ejection period (PEP) and PTT, is defined as the Aristotle University of Thessaloniki, Thessaloniki, Greece, Second Prope‑ time interval between the R-peak of electrocardiogram (ECG) and deutic Department of Internal Medicine, Hippokration General Hospital, a characteristic point of photoplethysmogram (PPG) (3,4). Since Aristotle University of Thessaloniki, Thessaloniki, Greece, Unit of Repro‑ most standard wearable devices can capture PPG and ECG signals, ductive Endocrinology, 1st Department of Obstetrics and Gynecology, and PAT correlates highly with vascular properties, such as vascu- Papageorgiou General Hospital, Aristotle University of Thessaloniki, lar tone, PAT extracted from wearable signals has the potential to Thessaloniki, Greece indicate cardiovascular health (5). The study used a database of in silico pulse wave signals for 4,374 virtual subjects to calculate aor- Objectives: Prediabetes is recognized as a significant metabolic tic PWV (aPWV), aortic-radial PTT (arPTT ), and PEP (6). The strength status, being a key factor in the occurrence of diabetes mellitus of the correlation between PAT and aPWV was assessed using the (DM). There is increasing evidence concerning microvascular com- correlation coefficient (R2). Relative sensitivity analysis was used to plications in prediabetes most commonly in skin, kidneys and ret- investigate the effects of cardiac and vascular properties on PAT. The ina (1,2). Laser speckle contrast analysis (LASCA) is a non-invasive R2 value between PAT and aPWV was 0.84. The inverse relationship technique that can be used to evaluate skin microvascular func- between PAT and aPWV illustrates that stiffer arteries resulted in tion. Previous studies have shown skin microvascular dysfunction in decreased PAT, even when considering specific age groups. Accord- patients with DM (3). However, to our knowledge, no previous study ing to the relative sensitivity analysis, PAT is mainly affected by has evaluated skin microcirculation, using LASCA, in patients with stroke volume and PWV. Our in silico study suggests that PAT has the prediabetes. potential to be used as a marker for assessing the arterial stiffening Methods: In all subjects, forearm skin blood flow was recorded component of vascular ageing. under standardized conditions using a laser speckle contrast imager Artery Research Results: In the overall population (n = 7924, 54.2% women, age 18–82  years), the prevalence of HVA/NVA/EVA was 7.8/68.1/24.1%, respectively, with EVA prevalence increasing in older age. NVA and EVA, as compared to HVA, were independently associated with anthropometric (BMI), metabolic (HbA1c), psychosocial (family sta- tus) and lifestyle (pack years, alcohol intake) factors, on top of age, gender, and blood pressure (Figure). Additional associations with VA categories were found in younger and older age (level of education), in middle age (income), and in older age (lack of physical activity). Conclusions: In this large population-based study we found a high percentage of early vascular aging, with a significant increase with increasing age. Psychosocial and lifestyle factors seem to play an independent role. Schematic representation of the definition of pulse arrival time (Back - ground), the extraction method of pulse transit time and pre-ejection period (Methodology), and arterial stiffness analysis of pulse arrival time (Result). References 1. Olsen MH, Angell SY, Asma S, Boutouyrie P, et al. The Lancet. 2016 Nov;388(10060):2665–712. 2. Willum Hansen T, Staessen JA, Torp‑Pedersen C, Rasmussen S, et al. Circula‑ Keywords: Vascular aging tion. 2006 Feb;113(5):664–70. 3. Zhang G, Gao M, Xu D, Olivier NB, Mukkamala R. Journal of Applied Physiol‑ ogy. 2011 Dec;111(6):1681–6. 4. Zheng YL, Ding XR, Poon CCY, Lo BPL, et al. IEEE Trans Biomed Eng. 2014 O.17 May;61(5):1538–54. Hydrochlorothiazide, but not chlortalidone nor furosemide, 5. Zheng YL, Yan BP, Zhang Y T, Poon CCY. Ann Biomed Eng. 2015 enhances vascular calcification in CKD rats with mineral bone Sep;43(9):2242–52. disorder 6. Charlton PH, Mariscal Harana J, Vennin S, Li Y, Chowienczyk P, Alastruey J. 1 1 1 1 Mohsen Agharazii , Richard Larivière , Roth‑Visal Ung , Sylvain Picard , Am. J. Physiol.‑Heart Circ. Physiol. 2019 Nov;H1062–85. 1 1 1 Dailson N. de Souza , Darren E. Richard , Fabrice Mac‑Way Chu De Québec‑université Laval, Québec, Canada Keywords: Vascular ageing, Arterial stiffness, Pulse arrival time, Pulse wave velocity, Wearable signals Background: Previously, we reported that hydrochlorothiazide (HCTZ)-based regimen aggravated arterial calcification and stiff- O.16 ness in a rat model of chronic kidney disease (CKD) with mineral and Prevalence and determinants of vascular aging: the LEAD study. bone disorder (MBD). In this study, we investigated if all diuretic- 1 2 2 based treatments aggravate of arterial stiffness and calcification in Kathrin Danninger , Otto Burghuber , Marie‑Kathrin Breyer , 2 2 2 CKD-MBD rats. Patricia Puchhammer , Alina Ofenheimer , Robab Breyer‑Kohansal , 3 2 1 Methods: In rats with renal mass ablation-induced CKD, MBD Christoph Kaufmann , Sylvia Hartl, Thomas Weber was generated by a Ca/P-rich diet and calcitriol. The animals were Klinikum Wels‑Grieskirchen, Department of Cardiology, Linz, Austria, divided into four groups; (1) CKD-MBD control; (2) CKD-MBD + HC TZ 2 3 Ludwig‑Boltzmann‑Institute for Lung Diseases, Vienna, Austria, Klinikum (thiazide diuretic, 5  mg/kg/d); (3) CKD-MBD + Chlor thalidone (thi- Ottakring, Department of Cardiology, Vienna, Vienna azide-like diuretic, 5  mg/kg/d), and; (4) CKD-MBD + Furosemide (loop diuretics, 10  mg/kg/d). At week 6, systolic and mean blood Background: Vascular aging (VA) is an important and prognostically pressure (SBP and MBP), pulse pressure (PP) and pulse wave velocity relevant aspect of biological aging. Its determinants are incompletely (PWV) were determined invaisively. Thoracic aorta calcification was understood, and a holistic view is missing. assessed by von Kossa staining. Methods: The LEAD (Lung, Heart, Social, Body) study is an ongoing, Results: SBP was reduced by all types of diuretics. Contrary to chlo- longitudinal, population-based observational study, which started rtalidone and furosemide, HCTZ treatment led to a reduction of in 2011 in Vienna and six villages from Lower Austria. As part of the MBP, but an increase in PP and PWV in CKD-MBD rats (p < 0.05). As study, cfPWV was measured non-invasively using applanation tonom- expected from these hemodynamic changes, medial calcification in etry (SphygmoCor device, Atcor medical). In a predefined healthy nor - the thoracic aorta was significantly greater in CKD-MBD rats treated mal population (non-smokers without known hypertension, diabetes, with HCTZ as compared to all the other groups of rats (p < 0.05). hyperlipidemia, or cardiovascular disease, free from antihypertensive Conclusions: In rats with CKD-MBD, HCTZ, but not other types of and lipid-lowering medication, blood pressure of < 130/85  mmHg), diuretic, exacerbated arterial stiffness and vascular calcification age-specific Z-scores for cfPWV were calculated. Healthy VA (HVA), nor - despite a reduction in SBP. The deleterious effect of HCTZ in CKD- mal (NVA) and early (EVA) VA was defined as cfPWV value < 10th, 10th- MBD rats may have major clinical impact as this diuretic is widely 90th, and > 90th percentile, respectively. use in patients with CKD that often develop MBD. A rtery Research The figures shows blood pressure (systolic, mean, diastolic, pulse pres- sure), and aortic stiffness by pulse wave velocity (PWV), and aortic calcifi- cation by von Kossa staining. Keywords: Chronic kidney disease, mineral bone disease, vascular calcification O.18 Results are adjusted for age, race-study center, body mass index, dia- Relationships between excessive daytime sleepiness, arterial betes, heart rate, mean arterial pressure, and blood-pressure medica- stiffness, and physical activity. The Atherosclerosis Risk tion use. AHA: American Heart Association: T: tertile. in Communities (ARIC) Study References Michael A Newton, Rachael Hamm, Emma Barinas‑Mitchell, Pamela L 1. Blachier M, Dauvilliers Y, Jaussent I et al. Excessive daytime sleepiness and Lutsey, Hirofumi Tanaka, Kapuaola Gellert, Lee Stoner, Michelle Meyer vascular events: the Three City Study. Ann Neurol. 2012;71(5):661–7. University of North Carolina at Chapel Hill, Chapel Hill, United States, 2. Lee CH, Ng WY, Hau W et al. Excessive daytime sleepiness is associated with University of North Carolina at Chapel Hill, Chapel Hill, United States, longer culprit lesion and adverse outcomes in patients with coronary 3 4 University of Pittsburgh, Pittsburgh, United States, University of Minne‑ artery disease. J Clin Sleep Med. 2013;9(12):1267–72. sota Twin Cities, Minneapolis, United States, University of Texas at Austin, 3. Li J, Covassin N, Bock JM et al. Excessive Daytime Sleepiness and Cardiovas‑ Austin, United States, University of Hawaii, Honolulu, United States, cular Mortality in US Adults: A NHANES 2005–2008 Follow‑Up Study. Nat University of North Carolina at Chapel Hill, Chapel Hill, United States, Sci Sleep. 2021;13:1049–59. University of North Carolina at Chapel Hill, Chapel Hill, United States Keywords: Arterial stiffness, sleep, physical activity, older adults Background: Excessive Daytime Sleepiness (EDS) is associated with higher risk of cardiovascular disease (CVD) events (1,2) and mortal- ity (3). However, the association between EDS and subclinical CVD, O.19 such as arterial stiffness, is not fully understood nor is the role of Greater intrinsic arterial wall stiffness and its unfavourable physical activity (PA) in this association. We examined the relation- trajectory over time in type 2 diabetes ship between EDS and arterial stiffness, measured using carotid- 1 1 1 Kunihiko Aizawa , Phillip E Gates , David M Mawson , femoral pulse wave velocity (cfPWV), with PA as a potential effect 1 1 1 2,3 Francesco Casanova , Kim M Gooding , Suzy V Hope , Isabel Goncalves , modifier. 2 4 5 6 Jan Nilsson , Faisel Kahn , Helen M Colhoun , Andrea Natali , Carlo Methods: A cross-sectional analysis of ARIC Study participants 7 1 Palombo , Angela C Shore (n = 2349, mean age: 79.6, 57.2% female, 19.2% black adults) who underwent cfPWV measures (VP-1000 Plus, Omron Co., Kyoto, 1 NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Japan) and completed the Epworth Sleep Scale (ESS) and Baecke 2 Exeter, United Kingdom, Department of Clinical Sciences, Lund Univer‑ questionnaires in 2016–2019. EDS was defined as ESS ≥ 11. We 3 sity, Malmö, Sweden, Department of Cardiology, Skåne University Hospi‑ calculated moderate-vigorous PA (min/week) and categorized PA 4 tal, Malmö, Sweden, Division of Systems Medicine, University of Dundee, based on the distribution and guidelines. We used multivariable 5 Dundee, UK, Centre for Genomic and Experimental Medicine, University linear regression to estimate the association between ESS, EDS, 6 of Edinburgh, Edinburgh, UK, Department of Clinical and Experimental and cfPWV, and evaluated effect modification by PA. Results are 7 Medicine, University of Pisa, Pisa, Italy, Department of Surgical, Medical, presented as beta coefficients (β) and 95% confidence intervals Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy (CI). Results: A total of 14.4% participants reported EDS. The association Background: A greater central artery stiffness is observed in people of ESS and EDS with cfPWV differed by PA level. The association of ESS with type 2 diabetes (T2DM). However, it is unclear about intrinsic arte- (Figure A) and EDS (Figure B) with cfPWV became more negative with rial wall stiffness in these patients. We aimed to determine the utility higher PA levels, although the associations with EDS were not statistically of β cross-sectionally and longitudinally in T2DM. METHODS: We stud- significant. ied 753 adults with T2DM (DM+: 67.5 ± 8.3 years, 227F) and 436 adults Conclusion: A negative association was observed between ESS without T2DM (DM−: 67.0 ± 9.2 years, 159F) cross-sectionally (Phase 1), and cfPWV at the most intense level of PA in older adults. In and subsequently studied 310 adults in DM + (68.6 ± 7.6 years, 104F) those not meeting PA guidelines, other adverse life and partici- and 210 adults in DM− (67.6 ± 8.5 years, 83F) over three years longitu- pant characteristics could outweigh the effects of ESS and EDS on dinally (Phase 2). Carotid-femoral pulse wave velocity was measured, cfPWV. and its data were used to calculate β as previously described . o Artery Research 1 1 1 1 Results: In Phase 1, β was significantly greater in DM+ than DM− Garcia‑Peña , Amaya Fernández‑Celis , Alicia Gainza , Virginia Álvarez , 1 1 1 after adjusting for age and sex [27.5 (26.6–28.3) vs 23.6 (22.4–24.8) Rafael Sádaba , Natalia López‑Andrés , Eva Jover García au, p < 0.001]. Partial correlation analyses after adjusting for age and 1 Cardiovascular Translational Research, Navarrabiomed, Hospital Univer‑ sex found that β was significantly associated with HbA1c (r = 0.15 sitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, p < 0.001) and heart rate (r = 0.23 p < 0.001) in DM+. I Phase 2, percent- Pamplona, Spain, Pamplona, Spain age changes in β were significantly greater in DM + than DM− [19.5 (14.9–24.0) vs 5.0 (− 0.6–10.6) %, p < 0.001] after adjusting for age, sex Background: The pathophysiological role of angiogenesis and lym- and baseline β . Multivariable linear regression analyses revealed that phangiogenesis in aortic stenosis (AS) remains unknown. Valve the percentage changes in β were independently associated with avascularity is seemly abrogated in AS and neovascularization is well- percentage changes in heart rate in DM + (overall R = 0.19). correlated with the disease(1,2). We study sex-related differences in Conclusion: β was greater in DM + than DM−. Furthermore, β angiogenesis and lymphangiogenesis in aortic valves (AVs) and valve o o changed over three years with ageing but it changed much more in interstitial cells (VICs) from AS patients. DM + than DM−. These data suggest that intrinsic arterial wall stiff- Methods: 226 patients recruited (60.6% men) with severe AS undergo- ness may be a useful target for therapeutic intervention. ing surgical valve replacement. Results: The density of total neovessels was higher in AVs from men Reference versus women’s. Small and medium neovessels were more abundant Spronck et al. J Hypertens 2017;35:98–104. in men’s AVs. Male AVs exhibited enhanced CD31 and VE-cadherin expressions. Levels of the pro-angiogenic markers [vascular endothe- Keywords: Ageing, Aorta, Blood pressure, Heart rate lial growth factor (VEGF)-A, VEGF receptor (VEGFR)1, VEGFR2, insu- lin-like growth factor-binding protein-2 (IGFBP-2), interleukin (IL)-8, chemerin and fibroblast growth factor (FGF)-7] were increased in O.20 men’s AVs. Transforming growth factor-β expression was higher in The bidirectional longitudinal relationships between arterial male AVs. Expression of antiangiogenic molecules [thrombospondin stiffness and hypertension and those between arterial stiffness (Tsp)-1, endostatin and CD36] was upregulated in male AVs, although and diabetes mellitus the levels of Tsp-2, IL-4, IL-12p70 and chondromodulin-1 were similar Professor Hirofumi Tomiyama between sexes. The number of lymphatic vessels and the expression of the lymphangiogenic markers Lyve-1 and D2-40 was enhanced in Japan, Suginami, Japabn men’s AV also VEGF-C, VEGF-D and VEGFR3. VICs isolated from men’s Background: Hypertension and diabetes mellitus frequently coex- AVs secreted higher amounts of pro-angiogenic (VEGF-A, VEGFR1, ist; however, it has not yet been clarified if the bidirectional longi- IGFBP-2 and FGF-7) and pro-lymphangiogenic factors (VEGF-C, VEGF- tudinal relationships between arterial stiffness and hypertension D and VEGFR3) than women’s without changes in antiangiogenic are independent of those between arterial stiffness and diabetes markers. mellitus. Conclusions: We show that aberrant angiogenic and lymphangio- Methods: In this 16-year prospective observational study, 3960 genic cues are over-represented in male AVs. VICs are a relevant source middle-aged employees of a Japanese construction company with- of multiple morphogens involved in angiogenesis and lymphangi- out hypertension/diabetes mellitus at the study baseline underwent ogenesis likely endowing the AV of men with the predominant calcific annual repeated measurements of the blood pressure, serum glyco- AS phenotypes (3,4). sylated hemoglobin A1c level (HbA1c), and brachial-ankle pulse wave velocity (baPWV ). References Results: By the end of the study period, 664, 779, 154, and 406 1. Collett GD, Canfield AE. Angiogenesis and pericytes in the initiation of subjects developed hypertension, prehypertension, diabetes ectopic calcification. Circ Res. 2005;96(9):930–8. mellitus, and prediabetes, respectively. Increased baPWV at the 2.Rajamannan NM, et al. Calcified rheumatic valve neoangiogenesis is associ‑ baseline was associated with a significant odds ratio (per 1 stand- ated with vascular endothelial growth factor expression and osteoblast‑ ard deviation increase) for new onset of prehypertension/hyper- like bone formation. Circulation. 2005;111(24):3296–301. tension with (2.45/3.28, P < 0.01) or without (2.49/2.76, P < 0.01) 3.Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N. VEGF couples coexisting prediabetes/diabetes mellitus, but not for new onset hypertrophic cartilage remodeling, ossification and angiogenesis during of prediabetes/diabetes mellitus without coexisting hypertension. endochondral bone formation. Nat Med. 1999;5(6):623–8. Analyses using the latent growth curve model confirmed the bi- 4.Nelson V, Patil V, Simon LR, Schmidt K, McCoy CM, Masters KS. Angiogenic directional relationships between baPWV and hypertension, but Secretion Profile of Valvular Interstitial Cells Varies With Cellular Sex and no such relationship was observed between baPWV and abnormal Phenotype. Front Cardiovasc Med. 2021;8:736303. glucose metabolism. Conclusions: In middle-aged Japanese subjects in contrast to the Keywords: Aortic-stenosis, sex, angiogenesis, lymphangiogenesis bi-directional relationships that exist between arterial stiffness and hypertension, increased arterial stiffness preceding the development of diabetes mellitus may represent that associated with the develop- O.22 ment of hypertension, as it is observed only in cases of diabetes mel- Arterial stiffness predicts sustained hypertension in patients litus coexisting with hypertension. Therefore, arterial stiffness may be with high normal blood pressure/grade 1 hypertension associated to a greater degree with the development of hypertension 1,2 1 1 Dr. Enrique Rodilla , Dr. Andrea Mendizábal , Dr. Iratxe Jiménez , than with the development of diabetes mellitus. 1 1 1 Dr. Leticia Pérez , Dr. Sergio Canales , Dr. Alicia Roldán , Dr. Santiago Keywords: arterial stiffness; hypertension 1 1 1 2 Pintos , Dr. Marta Catalán , Dr. María‑Carmen Sáez , Dr. José Chordá , Dr. José‑Antonio Costa O.21 1 2 Hospital Universitario de Sagunto, Puerto De Sagunto, Spain, Universi‑ Characterization of the sex‑specific pattern of angiogenesis dad Cardenal Herrera‑CEU, CEU Universities, Moncada, Spain and lymphangiogenesis in aortic stenosis 1 1 Background: 2018 ESC-ESH Guidelines for the Management of Arte- Lara Matilla Cuenca , Ernesto Martín‑Núñez , Mattie Garaikoetxea 1 1 1 1 rial Hypertension recommend pharmacological treatment if patients Zubillaga , Adela Navarro , Julieta Anabela Vico, Vanessa Arrieta , Amaia A rtery Research with grade 1 HTN at low-moderate risk remain hypertensive after a period of lifestyle intervention. Our objective was to assess the pre- dictive value of early vascular aging (EVA) to identifying patients who developed sustained HTN after baseline diagnosis. Methods: Retrospective, descriptive, longitudinal study including all consecutive patients referred to a HTN Unit with suspected naïve HTN without prior pharmacological treatment. EVA was defined accord- ing to estimated pulse wave velocity (brachial oscillometry, Mobil- O-Graph (IEM ) in seven age-groups(1). Standard clinical tests were performed at baseline and after 12 months. Results: Since 2010, 335 consecutive patients entered the study, with 201 women (60%), a mean age of 46,4 years (± 13), mean office BP of 130/76 (± 12/9), and ambulatory BP of 122/78 (± 8/7) mmHg. Distri- bution of BP was 155 (46.3%) patients with high-normal BP, 28 (8,4%) with white-coat HTN, 108 (32.2%) with masked HTN and 44 (13.1%) with established HTN. At baseline, 57% of patients showed EVA, after a mean time of 1.1 year, 65% of participants presented elevated ABPM. A selection of Survey Results In univariate analysis, baseline stiffness (EVA) was associated with ele - vated ABPM-values in the follow-up visit (OR: 2.0; IC 1.3–3.1; p = 0.003). Keywords: Survey, Knowledge, Awareness, Vascular age After adjustment for age, gender and pulse pressure, baseline EVA kept its significant predictive value (OR:2.6; IC 1.6–4.2; p = 0.001). O.25 Conclusions: Arterial damage characterized as EVA according to esti- Early vascular aging associated with sympathetic hyperactivity mated PWV by brachial oscillometry doubles the probability of sustained in obese hypertensive individuals with moderate to severe HTN one year after initial assessment in naïve patients with high-normal obstructive sleep apnea BP/grade 1 HTN at low-moderate risk. 1 1 1 Samanta Mattos , Michelle Rabello Cunha , Marcia Regina Simas Klein , Reference Mario Neves Nunan D, Fleming S, Hametner B, Wassertheurer S. Performance of pulse wave State University of Rio de Janeiro, Rio de Janeiro, Brazil velocity measured using a brachial cuff in a community setting. Blood Press Monit. 2014;19:315–9. Background: Obstructive sleep apnea (OSA) is an independent cardi- ovascular risk (CVR) factor. The objective was to evaluate sympathetic Keywords: Early vascular aging (EVA), risk stratification, pulse wave tone and vascular disease in obese hypertensive with moderate and velocity, high-normal blood pressure severe OSA. Methods: Individuals of both sexes, aged 40–70  years and body mass index (BMI) ≥ 30 and < 40  kg/m2, submitted to assessment of O.23 heart rate variability (HRV), central parameters by Mobil-O-Graph and Awareness and perceptions of health care providers carotid ultrasound. Sleep study was performed through a portable and researchers on vascular ageing: Quantitative Survey Results. home sleep test device (WatchPAT ). 1 2 5 4 Chloe Park , Andrie Panayiotou, Thomas Weber , Christopher Mayer , Results: Patients (n = 49) were divided into two groups based on 3 6 Areti Triantafyllou , Rachel Climie the apnea–hypopnea index (AHI): absent-mild (AM) group (AHI < 15 MRC Unit for lifelong Health and Ageing at UCL, London, United King‑ events/h, n = 17) and moderate-severe (MS) group (AHI ≥ 15 dom, Cyprus International Institute for Environmental and Public Health, events/h, n = 32). The mean BMI was similar (35 ± 3 vs 34 ± 2  kg/ Cyprus University of Technology, Limassol, Cyprus, Medical School, m2, p = 0.248). Systolic blood pressure (120 ± 15 vs 131 ± 14  mmHg, Aristoteleio University Thessaloniki, Thessaloniki, Greece, AIT Austrian p = 0.003), pulse pressure (43 ± 9 vs 49 ± 8  mmHg, p = 0.011), CVR Institute of Technology GmbH, Vienna, Austria, Cardiology Department, (6.8 ± 4.1 vs 14.4 ± 10.7%, p = 0.003) and cardiometabolic age Klinikum Wels‑Grieskirchen, Wels, Austria, Menzies Institute for Medical (48 ± 6 vs 52 ± 8  years, p = 0.034) were higher in the MS group. The Research, University of Tasmania, Hobart, Australia same group presented higher low frequency/high frequency (LF/ HF) ratio (0.83 ± 0.56 vs 1.91 ± 1.98, p = 0.017), pulse wave veloc- Introduction: Vascular Age (VA) can assess cardiovascular disease risk, ity (PWV) (7.1 ± 0.7 vs 8.0 ± 1.2  m/s, p = 0.003), vascular age (50 ± 6 independently of chronological age, however it is not yet widely applied vs 56 ± 8  years, p = 0.014) and carotid intima-media thickness in routine clinical practice. A quantitative questionnaire was developed (0.58 ± 0.09 vs 0.70 ± 0.12  mm, p = 0.001). PWV was significantly cor - to assess current knowledge gaps related to VA and barriers to imple- related with LF/HF ratio (r = 0.609, p < 0.001) only in the MS group. mentation in routine practice in both research and clinical settings. Conclusion: In this sample of obese hypertensive patients, moderate Methods: Using a stepwise mixed-methods approach, a quantitative to severe OSA was associated with sympathetic hyperactivity and evi- questionnaire was constructed. The 22-item anonymous survey was dence of early vascular aging with increased arterial stiffness and sub - based on a previous qualitative analysis including 80 participants with clinical atherosclerosis. multiple scientific backgrounds, and included questions on perceptions/ beliefs, knowledge, and implementation of VA. The survey was dissemi- Reference nated to clinicians and researchers world-wide, via social media and tar- Bironneau V, Tamisier R, Trzepizur W, et al. Sleep apnoea and endothelial dys‑ geted emails from well-known societies (including Artery, ESH, ISH, ESC). function: An individual patient data meta‑analysis. Sleep Med Rev. 2020 Results: 276 (50% female) completed the questionnaire, 46% were clini- Aug;52:101–309. cians, 33% researchers, 10% students. Clinical specialties included cardi- ology (36%), internal medicine (22%) and General Practice (10%). While Keywords: Hypertension; Sleep apnea; Obesity; Arterial stiffness 84% of clinicians and researchers rate VA importance as high or very high (Table), only 11% of clinicians measure VA in clinical settings. Limiting factors include cost, lack of guidelines and lack of knowledge. Discussion: These results show that implementation of VA is very low in clinical settings and awareness of VA needs to be improved via planned targeted awareness strategies and educational material. Artery Research O.26 pressure-diameter tests were performed at 95/100/105% of Acute vasopressin neutralization with the aptamer NOX‑F37 the < i > in vivo < /i > axial stretch and axial force –length tests at improves immediately cardiac but not peripheral endothelial 10/60/100/140  mmHg. Data were fit using a nonlinear constitutive dysfunction in rats with chronic heart failure model [1]. 1 1 1 1 Results: Figure (bar char ts, < i > n < /i > = 4–8 per group) shows pas- Yohan Stephan , Marina Hamrouche , Lise Charrier , Lionel Nicol , 2 2 1 1 sive metrics calculated at < i > in vivo < /i > axial stretch and group- Marie‑Laure Ozoux , Philip Janiak , Jeremy Bellien , Paul Mulder specific systolic blood pressures [2]. AngII caused larger increases in 1 2 Inserm U1096, Rouen, France, Corteria Pharmaceuticals, Paris, France wall thickness than NE. Both NE and AngII led to significant struc - tural arterial stiffening, driven by a combination of wall thickening Background: Vasopressin is one of the leading pathophysiologi- and stiffening of the wall material. Figure also shows correlation of cal drivers of chronic heart failure (CHF) acting via V1a-, V1b- and V2 wall thickness with contractility (scatter plots, < i > n < /i > = 4–7 per receptors. Selective V2 and dual V1a-V2 receptor antagonists amelio- group; symbols represent individual aortas). The stronger an individ- rate plasma sodium levels, but fail to reduce mortality in clinical stud- ual aorta was able to contract (larger absolute stress change; to the ies. Vasopressin neutralization is an original alterative for receptor left on < i > x < /i > -axis), the weaker its remodelling response. blockers but its effect in CHF is unknown. For this purpose, we sought Conclusions: NE- and AngII-induced hypertension elicit distinct investigated the short-term cardiac and vascular effects of the vaso - aortic remodelling responses. However, independent of the hyper- pressin neutralizing aptamer NOX-F37. tensive stimulus, aortic contractile capacity emerged as protective Methods: Left ventricular (LV) function (hemodynamics by LV cath- against hypertensive arterial remodelling. erization) and LV tissue perfusion (MRI) as well as mesenteric artery endothelium function (flow mediated dilation by arteriograph) were determined 2  h after NOX-F37 administration (80  nM/kg; IP) to rats with well-established CHF induced by coronary artery ligation. Results: Two hours after administration, NOX-F37 significantly improved LV systolic function, illustrated by the significant increase in LV end-systolic pressure volume relation (CHF: 20.2 ± 0.0.7; CHF + NOX: 23.3 ± 1.0  mmHg/RVU) and diastolic function, illustrated by the sig- nificant decrease in LV end-diastolic pressure volume relation (CHF: 4.03 ± 0.48; CHF + NOX: 2.06 ± 0.21  mmHg/RVU), which were associ- ated with a significant increase in LV tissue perfusion (CHF: 6.12 ± 0.24; CHF + NOX: 10.10 ± 0.26  ml/min/g LV tissue). However, mesenteric artery flow-induced dilatation was not modified and remained impaired (% dilatation at 150 µl/min; CHF: 10 ± 7; CHF + NOX: 9 ± 8). Conclusions: These results illustrate the immediate protective effects on cardiovascular function of vasopressin neutralization in chronic heart failure confirming the existence of a deleterious vaso - pressinergic tone in chronic heart failure. Whether these beneficial cardiac effects persist with chronic vasopressin neutralization needs to be confirmed. Keywords: Heart failure; pharmacology; vasopressin O.27 Hypertensive aortic remodelling as induced by adrenergic receptor activation vrsus renin–angiotensin–aldosterone system activation in mice 1,2,3 2 2 Bart Spronck , Alexander W. Caulk , Abhay B. Ramachandra , Sae‑Il 2 2,4 Murtada , Jay D. Humphrey Dept. of Biomedical Engineering, Maastricht University, Maastricht, The Netherlands, Dept. of Biomedical Engineering, Yale University, New Haven, United States, Macquarie Medical School, Macquarie University, Sydney, Australia, Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, United States Background: Hypertension causes the aorta to remodel and poten- tially stiffen. We aimed to compare the aortic remodelling response to hypertension as induced by adrenergic receptor activation versus renin–angiotensin–aldosterone system activation. Methods: Adult male C57BL/6 J mice were studied under seven con- ditions: untreated, and after 7/14/28-day subcutaneous infusion of 3880  ng/kg/min norepinephrine (NE) or 1000  ng/kg/min angioten- sin II (AngII). After euthanasia, ascending/descending thoracic (ATA/ Whiskers: standard errors, overbars: < i > p < /i > < 0.05 (Bonferroni). Sys- DTA) and infrarenal abdominal (IAA) aortas were dissected, placed tolic/diastolic blood pressures: 120/80 mmHg (WT); 154/103, 162/108, within a computer-controlled biaxial testing device, and subjected 154/103  mmHg (7/14/28d NE); 150/100, 159/106, 177/118  mmHg to isobaric (90 mmHg) vasoreactivity experiments to, among others, (7/14/28d AngII). Lines/grey areas: multilevel regressions/95% confi- 1  µM phenylephrine + 1  mM L-NAME [1]. Under passive conditions, dence intervals. A rtery Research References Basic [1] Spronck B, Latorre M, Wang M, Mehta S, Caulk AW, Ren P, et al. Excessive adventitial stress drives inflammation‑mediated fibrosis in hyperten‑ P.001 sive aortic remodelling in mice. J R Soc Interface 2021; 18:20,210,336. Variability of invasive aortic pulse wave velocity measured [2] Owens AP, 3rd, Subramanian V, Moorleghen JJ, Guo Z, McNamara CA, Cassis by catheter pull‑back method and implications for pulse wave LA, Daugherty A. Angiotensin II induces a region‑specific hyperplasia of velocity device validation the ascending aorta through regulation of inhibitor of differentiation 3. 1 2,7 2,8 Alexander Stäuber , Bart Spronck , Alessandro Giudici , Cornelia Circ Res 2010; 106:611–619. 3 3 4 5 Piper , Siegfried Eckert , Stefan Richter , Marc‑Alexander Ohlow , Johannes Baulmann Keywords: Angiotensin II; arterial mechanics; norepinephrine; vasoconstriction Professorship of Sports Medicine / Sports Biology, Chemnitz University of Technology, Chemnitz, Germany, Department of Biomedical Engineer‑ O.28 ing, CARIM School for Cardiovascular Diseases, Maastricht University, Raised arterial stiffness at 24–26 weeks of gestation is associated Maastricht, The Netherlands, Klinik für Allgemeine und Interventionelle with the development of hypertension in pregnancy Kardiologie/Angiologie, Herz‑ und Diabeteszentrum NRW, Univer ‑ sitätsklink der Ruhr‑Universität Bochum, Bad Oeynhausen, Germany, 1 1 1 1 Pritika Dutta, Tarang Gupta , Rajesh Kumari, Vidushi Kulshrestha , Department of Cardiology, Zentralklinik Bad Berka GmbH, Herzzentrum, 1 1 1 Ashok Kumar Jaryal , Kishore Kumar Deepak , Garima Kachhawa. Department of Cardiology, Bad Berka, Germany, Department of Cardiol‑ 1 6 All India Institute of Medical Sciences, New Delhi, India ogy, SRH Wald‑Klinikum, Gera, Germany, Praxis Dres. Gille/Baulmann, Rheinbach, Germany, Macquarie Medical School, Faculty of Medicine, Background: Increase in arterial stiffness in third trimester is pro - 8 Health and Human Sciences, Macquarie University, Australia, GROW posed to be involved in the pathogenesis of hypertensive disorders School for Oncology and Reproduction, Maastricht, The Netherlands of pregnancy. The present study was conducted to evaluate arte- rial stiffness in pregnant women at 24–26 + 6  weeks of gestation. Background: The invasive method of catheter pullback from ascending They were grouped into healthy pregnancy (HP), preeclampsia aorta (asc) to iliac bifurcation (bifu) is gold standard for aortic pulse wave (PE) or gestational hypertension (GHTN) depending upon maternal velocity (aPWV) and the reference standard for validation of non-invasive outcome. devices that estimate aPWV [1]. In this work, we examine aPWV variability Methods: Arterial stiffness was measured using applanation tonom- in invasive recordings of patients undergoing cardiac catheterization. etry. Central arterial stiffness was quantified by augmentation index Methods: Invasive measurements were performed in 56 patients (57% normalized to heart rate 75 beats/minutes (AIx@75) and carotid- male, 67 ± 13  years, mean ± standard deviation (SD)) with a femoral femoral pulse wave velocity (cfPWV), peripheral arterial stiffness catheter access. Catheter pullback method was used to measure aortic was quantified by carotid-radial pulse wave velocity (crPWV) using pulse transit time (aPTT ) from asc to bifu. Pulse wave analysis using the SphgmoCor CVMS CPVH device. intersecting tangent method (Sirius, Redwave Medical GmbH, Jena, Results: Out of 313 women, PE developed in 3.51% (n = 11), GHTN Germany) provided the diastolic foot points for each recording site in 5.11% (n = 16) and 22.04% (n = 69) remained healthy preg- (asc, bifu) and recorded heartbeat (number of beats, asc: 86 ± 42, bifu: nant without any obstetrical or medical factors. The mean age in 82 ± 43). From the respective time difference with the R-wave of the years, BMI in kilograms/metre2 and MAP in mmHg between the time-synchronised electrocardiogram, the pulse transit time for the groups were [(30.0 ± 1.6 vs 28.81 ± 4.8 vs 27.70 ± 4.0, p = 0.094), corresponding recording site (PTTasc, PTTbifu) was derived for each {27.41(25.10–33.09) vs 28.51(24.29–31.84) vs 27.01(25.39–28.40), heartbeat. aPTT was then determined from the difference of the aver - p = 0.529}, (99.09 ± 7.58 vs 95.88 ± 9.09 vs 85.99 ± 9.64, p < 0.0001)] aged PTTbifu and PTTasc. Based on aPTT, the known catheter pullback respectively. AIx@75 was found to be increased (PE:22.82 ± 14.65%, length and the estimated SD of aPTT, SD_aPTT = √(SD_PTTasc + SD_ GHTN:19.47 ± 10.60%, HP:10.35 ± 12.14%, p = 0.001) in women devel- PTTbifu ), the SD of the corresponding aPWV was calculated as SD_ oping hypertension in pregnancy than normotensive healthy preg- aPWV = aPWV × SD_aPTT/aPTT for each patient. nancy. Similarly cfPWV (PE:7.21 ± 1.24  m/s, GHTN:6.64 ± 1.22  m/s, HP: Results: aPTT was 44.01 ± 12.89 ms; aPWV was 9.7 ± 3.1 m/s. SD_aPT T 6.19 ± 1.06  m/s, p = 0.013) was also significantly higher in pregnant was 3.72 ± 1.73 ms, resulting in an SD_aPWV of 1.0 ± 0.8 m/s. women with PE and GHTN. The crPWV were comparable among PE, Conclusions: Our data indicate a substantial beat-to-beat SD in inva- GHTN and healthy pregnant. sively determined aPWV by catheter pull-back method. The issue of Conclusion: Raised central arterial stiffness is observed before the aPWV variability in the invasive reference needs to be addressed in clinical onset of disease in women destined to develop PE later in validation protocols for non-invasive estimation of aPWV. pregnancy. AIx@75 and cfPWV could be used as a putative prognos- tic marker of hypertensive disorders of pregnancy. Reference [1] Wilkinson IB, McEniery CM, Schillaci G, Boutouyrie P, Segers P, Donald A, References Chowienczyk PJ (2010). ARTERY Society guidelines for validation of non‑ 1.Garg P, Jaryal AK, Kachhawa G, Kriplani A, Deepak KK. Sequential profile of invasive haemodynamic measurement devices: Part 1, arterial pulse wave endothelial functions and arterial stiffness in preeclampsia during the velocity. Artery Research, 4(2), 34–40. course of pregnancy. Pregnancy Hypertens. 2019; 18: 88–95. 2.Franzi MB, Burgmann M, Neubauer A, Zeisleri H, Sanani R, Gottsauner‑ Wolf Keywords: PWV, PTT, variability M et al. Augmentation index and pulse wave velocity in normotensive and pre‑ eclamptic pregnancies. Acta. Obstet. Gynecol. Scand. 2013; 92: 960–66. P.002 3. Tomiyama H, Yamashina A. Non‑invasive vascular function tests: Their patho ‑ Multiple linear regression analysis of age, gender, anthropometric physiological background and clinical application. Circ. J. 2010; 74: 24–33. and haemodynamic factors to predict variability in aortic pulse transit time determined by the catheter pull‑back method Keywords: Arterial stiffness, augmentation index, pulse wave velocity, 1 2,7 2,8 Alexander Stäuber , Bart Spronck , Alessandro Giudici , Cornelia hypertensive disorders of pregnancy 3 3 4 5 Piper , Siegfried Eckert , Stefan Richter , Marc‑Alexander Ohlow , Posters Johannes Baulmann. Artery Research Professorship of Sports Medicine/Sports Biology, Chemnitz University mice survival. qPCR analysis indicated the altered expression of cir- of Technology, Chemnitz, Germany, Department of Biomedical Engineer‑ cadian-related genes such as genes of Bmal and ciart. ing, CARIM School for Cardiovascular Diseases, Maastricht University, Conclusions: Our data indicate the primary effect of Bcl11b inacti- Maastricht, The Netherlands, Klinik für Allgemeine und Interventionelle vation on cell death, probably by necroptosis. Kardiologie/Angiologie, Herz‑ und Diabeteszentrum NRW, Univer ‑ sitätsklink der Ruhr‑Universität Bochum, Bad Oeynhausen, Germany, Department of Cardiology, Zentralklinik Bad Berka GmbH, Herzzentrum, Department of Cardiology, Bad Berka, Germany, Department of Cardiol‑ ogy, SRH Wald‑Klinikum, Gera, Germany, Praxis Dres. Gille/Baulmann, Rheinbach, Germany, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Australia, GROW School for Oncology and Reproduction, Maastricht, The Netherlands Background: Aortic pulse transit time (aPTT) is not constant but fluc - tuates, which affects the accurate determination of aortic pulse wave velocity (aPWV). In this work, we investigate the influence of age, gen- der, anthropometric and haemodynamic parameters on aPTT variabil- ity determined by the catheter pull-back method. Methods: aPTT could be analysed in 69 patients (61% male, 68 ± 13 years) with femoral catheter access. A stepwise multiple linear regression analysis was performed with aPTT variability as dependent variable and age, gender, BMI, heart rate, aortic systolic blood pressure (aSBP), aortic diastolic blood pressure (aDBP) and variability of aSBP (aSBPV ) and aDBP (aDBPV ) as predictors. For the dependent haemody- namic variables, only data from the ascending aorta were used. Results: The regression model with the factors heart rate, aSBP, aSBPV, aDBPV achieved the highest goodness of fit of 0.49 (adjusted R-squared). aSBPV and heart rate proved to be the strongest factors (standardised regression coefficient beta 0.397 and 0.301, respec - tively) followed by 0.258 for aDBPV and -0.199 for aSBP (all p < 0.05). Photos showing thoracic aorta from control (A) and mutant mice (B) at The unstandardised regression coefficients B were 0.489 for aSBPV, 7 days after the injection of tamoxifen to 3 month-old mice. 0.322 for aDBPV, -0.020 for aSBP and 0.047 for heart rate. Conclusions: Our data show the influence of aortic systolic and diastolic References blood pressure variations, heart rate and aSBP on aPTT variability whereas Mitchell GF, Verwoert GC, Tarasov KV et al., Common genetic variation in the age, gender, and BMI had no significant influence. However, the adjusted 3’‑BCL11B gene desert is associated with carotid‑femoral pulse wave R-squared of the model suggests that a considerable part of aPTT variability velocity and excess cardiovascular disease risk: the AortaGen Consortium. cannot be explained by the independent variables included in the model. Circ Cardiovasc Genet. 2012;5(1):81–90. Valisno JAC, May J, Singh K, Helm EY, Venegas L, Budbazar E, Goodman JB, Keywords: PTT variability, PWV variability Nicholson CJ, Avram D, Cohen RA, Mitchell GF, Morgan KG, Seta F. BCL11B Regulates Arterial Stiffness and Related Target Organ Damage. Circ Res. 2021;128(6):755–768. P.003 Keywords: Cell death, CTIP2/Bcl11b, hemorrhage Smooth muscle cell‑specific knock‑out of CTIP2 gene results in aortic hemorrhage 1,2,3 1,2,3 1,2,3 P.004 Ara Parlakian , Jocelyne Blanc , Jacqueline GAO‑Li , Véronique 4 1,2,3 4 1,2,3 Smooth muscle integrin αv contributes to the regulation of cell Regnault , Onnik A gbulut , Patrick Lacolle y , Zhenlin Li stiffness 1 2 Sorbonne Universite, Paris, France, CNRS UMR8256, Paris, France, 1 2 3 3 4Alexandre Raoul , Ekaterina Belozertseva, Lei Tian , Xiao Liu , INSERM ERL U1164, Paris, France, INSERM—U1116, Nancy, France 3 2 2 4 Caterina Maria Tone , Jocelyne Blanc , Dario Coletti , Daniel Henrion , 1 1 3 Background: Ctip2/Bcl11b is a transcription factor with dual action Véronique Regnault , Patrick Lacolley , Emmanuelle Lacaze , Pascal 5 2 (repression/activation) that couples epigenetic regulation to gene Challande , Dr Zhenlin Li transcription in a variety of physiological responses under healthy 1 2 INSERM1116, Vandoeuvre‑lès‑nancy, France, CNRS8256, Paris, France, and pathological conditions of various tissues. Single nucleotide 3 4 CNRS7588, Paris, France, INSERM1083 – CNRS6214, Angers, France, polymorphisms of Ctip2/Bcl11b gene are associated with a higher CNRS7190, Paris, France susceptibility for aortic stiffness (1). although Ctip2/Bcl11b has been proposed as a crucial regulator of aortic smooth muscle func- Background: Integrin αv is a receptor for adhesion proteins expressed tion (2), its mechanism of action in smooth muscle cells is still to be at high density in vascular smooth muscle cells (VSMC) whose pheno- uncovered. typic modulation plays a crucial role in arterial ageing. Methods: Morphological, cellular and molecular analysis were car- Objectives: To define the arterial phenotype in mice conditionally ried out on the arteries of smooth muscle cell-specific Ctip2-knock - inactivated for the integrin αv subunit in VSMC and the role of this out (KO) mice at 3, 7, 28 days after tamoxifen injections. integrin in angiotensin II (Ang II)-induced arterial and VSMC stiffness. Results: There is no difference between control and mutant mice Methods and results: We used a VSMC specific knock-out αv mouse at the macroscopic level 3  days after Ctip2 KO induction, however, model induced in adult mice by injection of tamoxifen. Trangenic 7 day after Bcl11b inactivation, 65% of the Ctip2-SMKO mice showed mice (αvSMKO) and control littermates (Ctrl) were infused with Ang II signs of hemorrhage in the distal part of the thoracic aorta near the (1.5 mg/kg/day) for 4 weeks. The pressure effect of Ang II was similar in abdominal aorta. The histological examination of thoracic aorta at 7 Ctrl and αvSMKO mice. The carotid distensibility/pressure and elastic indicated the presence of “bumpy region” in the mutant aorta. These modulus/wall stress curves were similar in control and αvSMKO mice, areas is covered by a thicker layer of extracellular matrix and the indicating comparable arterial stiffness. Ang II treatment resulted in presence of IgG positive cells, indicating that cell death is occurring. increased carotid stiffness in both groups without changes in vascu- However, the hemorrhages is contained over time, do not impact lar reactivity and myogenic tone. Electronic microscopy revealed less A rtery Research vesicles containing fiber-like materials in the SMCs of Ang II-treated cardiovascular pathologies [2]. In the current project, we explore the αvSMKO carotids Elastic modulus of cultured VSMCs determined using impact of an AT biased agonist (TRV027) on the regulation of the cer- atomic force microscopy was higher after Ang II treatment in cells from ebral circulation. both groups. At baseline and after treatment, elastic modulus was Methods: We evaluated the TRV027 signaling on HEK293-cells higher in cells from αvSMKO mice than in cells from Ctrl mice.overexpressing AT using bioluminescence resonance energy Conclusion: Inactivation of αv-containing integrins on VSMCs transfer (NanoBRET) and calcium mobilization assays. In parallel, con- increases cell stiffness. The general mechanism involves a cross-talk centration–response curves to TRV027 were built on an ex vivo model between extracellular matrix, αv integrins and cytoskeletal complex. of isolated and perfused middle cerebral arteries (MCA) by measuring The lack of distensibility changes suggests additional changes at the changes in internal diameter. level of αv-mediated dynamics of focal adhesion. Results: BRET results show that TRV027 induces an activation of the β-arrestin pathway with a maximal increase of BRET ratio of 0.08 while Keywords: Integrin αv, vascular smooth muscle cells, cell stiffness inactivating the Gq pathway. Calcium mobilization assays confirm this Gq inactivation. As expected, results obtained in MCA show no effect of TRV027 on arterial diameter. P.005 Discussion: Tracking the A T receptor using specific fluorescent tools Estrogen modulates phenotypic state of male vascular smooth to follow its internalization (confocal microscopy) is currently under muscle cells exposed to flow conditions development. 1 1 1 1 The next step will be to assess in vivo the potential beneficial and pro - Enzo Lecoq , Nathan Wisniewski , Leo Jannot , Eva Feigerlova tective effects of TRV027 in cerebrovascular pathologies, in collabora- INSERM UMR_S 1116—DCAC Université de Lorraine, Nancy, France tion with Maastricht University. Although an estrogen-mediated vasculoprotective effect is widely References accepted in premenopausal women, literature data indicate that 1. Violin JD, Lefkowitz RJ. β‑Arrestin‑biased ligands at seven‑transmembrane estrogen therapy in transgender women confer an increased risk of receptors. Trends Pharmacol Sci. août 2007;28(8):416‑22. cardiovascular events. Vascular smooth muscle cell (VSMC) reside in a 2. Boerrigter G, Soergel DG, Lark MW, Burnett JC. TRV120027, a Novel Beta‑ 3-dimensional environment and are not normally exposed directly to Arrestin Biased Ligand at the Angiotensin II Type I Receptor, Unloads the shear stresses of flowing blood in the vascular system, because the the Heart and Maintains Renal Function When Added to Furosemide in endothelial cell layer provides the contacting surface for blood flow. Experimental Heart Failure. J Card Fail. août 2011;17(8):S63‑4. However, in cases of endothelial injury, the superficial layer of SMCs is exposed directly to blood flow shear stresses. We hypothesized that Keywords: AT receptor; cerebral circulation; β-arrestin; biased agonist treatment of male VSMCs with estrogens alters cell behavior. Our aim was to study the effect of shear stress on male VSMCs in a 2D Imaging technologies environment under flow model. Cells were treated with 17-β-estradiol and cultured in the Ibidi chamber under laminar flow and shear stress −2 of 1–2 dyn.cm . The cell orientation and morphology and phenotypic P.011 changes were analyzed. Non‑contact Method for Fast Localization of Perforator Arteries Results: We observed an increased expression of MYH10 exposed to 1,2 1 3,4 Valentina Vassilenko , Anna Poplavska , Diogo Casal , Edivaldo shear stress. The expression of MYH10 seems to be correlated with the 1,4 Junior orientation of VSMCs. The orientation of VSMCs treated with estrogens is parallel to the culture medium flow. Our preliminary results further Nova School Of Science And Technology—Nova University Of Lisbon, suggest an increased expression of the MMP-2 under estrogen treat- Campus FCT UNL, Portugal, Iberian Network on Arterial Structure, ment under flow conditions in the 2D model. Central Hemodynamics and Neurocognition,, Portugal, Plastic Conclusion: The differential effects of laminar flow and shear stress and Reconstructive Surgery Department and Burn Unit, Centro Hospitalar flow may be due to the different phenotypic state of the VSMCs. de Lisboa Central, Lisbon, Portugal, Anatomy Department, Nova Medical School—Nova University of Lisbon, Lisbon, Portugal Keywords: Sex hormones, Laminar flow and shear stress flow, Vascular Recently an extensive clinical experience in flap surgery has con- smooth muscle cell firmed that its success depends on the correct identification of vital perforator vessels [1]. Unfortunately, the perforator vessels frequently have a variable location. So, the knowledge about perforator anatomy Brain during preoperative planning is one of the most critical factors. In this work, we present the method and experimental results for non- P.006 contact and fast localization of the cutaneous perforators using Infra- Physiological effects of a biased angiotensin II type 1 receptor red Thermography (IRT ). This imaging technique can provide real-time agonist on cerebral circulation information on skin perfusion by measuring body surface tempera- 1,4 1 2 3 Mélissa Colin , Céline D elaitre , Sandra L ecat , Samir Acherar , ture. Validation of the method was performed against the ultrasound 4 1 1 Sébastien Foulquier , Isabelle Lartaud , François Dupuis. technology realized in the hand-held Doppler flowmeter, which is 1 2 widely used in most hospitals and is an essential tool where a rapid Université de Lorraine, CITHEFOR, Vandoeuvre‑lès‑Nancy, France, Uni‑ analysis of the vascular status of a patient is routine. versité de Strasbourg, CNRS, Biotechnologie et Signalisation Cellulaire, 3 Both technics were applied in this work for the identification of forearm Illkirch‑Graffenstaden, France, Université de Lorraine, CNRS, LCPM, Nancy, 4 cutaneous perforator vessels. The reflection of sound waves, predomi- France, Maastricht University, School for Mental Health and Neurosci‑ nantly from intravascular blood flow of the forearm, was registered by a ence, Maastricht, The Netherlands hand-held BT-200  V Vascular Doppler pan. The infrared images were Background: The angiotensin II type 1 (AT ) receptor has a relevant obtained by two cameras: FLIR E6 with temperature sensitivity < 0.06 °C role in the physiology and pathophysiology of the cerebrovascular and (320 × 240)-pixel display resolution, and Thermal Expert with sensitiv- system. Its vasoconstrictor effect, consecutive to Gq protein activa- ity < 0.05  °C and array format 640 × 480. Perforator mapping of the fore- tion, reduces cerebral perfusion during stroke. In addition, A T recep- arm area ware compared for accuracy, timing, and the operator’s skills. tor activity is directly regulated by the β-arrestin pathway, involved Obtained results show that IRT images provide valuable real-time in receptor internalization [1]. Recently, the development of biased information on the hemodynamic quality of perforators and their agonists, able to selectively activate the β-arrestin pathway without accurate location. Its potential to reveal underlying perforator vessels Gq activation appears to be a promising new therapeutic strategy in may also be used for postoperative monitoring of flap perfusion [2]. Artery Research References Methods: 49 runners (A) trained for 8.5 ± 8.9  years, 3.9 ± 1.4  days/ [1] D. Casal et al., “A Model of Free Tissue Transfer: The Rat Epigastric Free Flap,” week and 15 sedentary (S) subjects matched by sex, age, BMI, baseline J. Vis. Exp., no. 119, pp. 14–16, 2017. brachial pressures and heart rate underwent ultrasound semi-auto- [2] T. Sjøberg, J. B. Mercer, S. Weum, and L. de Weerd, “The Value of Dynamic matic assessment of the vascular system (arterial mean diameters, MD, Infrared Thermography in Pedicled Thoracodorsal Artery Perforator Flap and distensibility, DC, of abdominal aorta, common carotid, common Surgery,” Plast. Reconstr. Surg. – Glob. Open, vol. 8, no. 7, 2020. femoral, brachial artery) and of cardiac parameters. Central pressure- based (applanation tonometry) hemodynamic properties according to Keywords: Cutaneous Perforator Vessels (CPVs), Infrared Thermogra- the reservoir theory were derived. phy (IRT ), hand-held Doppler devices (HHDD), perforator mapping Results: Cardiac parameters related to dimensions, mass and vol- umes showed significantly higher values in A compared to S (A/S: Left Ventricular Internal diameter, 29 ± 3  mm/27 ± 3  mm; Left Ventricular P.013 Mass, 161 ± 31  g/141 ± 25  g; Aortic root size 30 ± 3  mm/27 ± 2  mm; Radial artery phenotyping in systemic sclerosis Stroke Volume, 76 ± 13  mL/69 ± 16  mL; Arterial Elastance, 7 ± 1  mm through ultra‑high frequency ultrasound: a radiomic approach –1 –1 HgmL /6 ± 1 mm HgmL ). 1 2 3 1,3 Federica Poli , Goncalo Boleto , Hakim Khettab , Pierre Bout ouyrie , MD was greater in each large arterial site in A than in S reporting a 2 1,3 Yannick Allanore , Rosa Maria Bruno trend in the carotid and significant differences in aorta and femoral artery (aorta: 16 ± 2  mm/13 ± 1  mm; femoral: 10 ± 1  mm/9 ± 1  mm). Paris Cardiovascular Research Center (PARCC)‑INSERM UMR‑970, Paris, DC evidenced a lowering trend in A for each arterial site except for the France, Department of Rheumatology, Université de Paris, Cochin Hospi‑ brachial artery. Hemodynamic parameters showed higher reservoir tal, Paris, France, AP‑HP, Hopital Européen Georges Pompidou, Université pressure in A compared to S (Pressure reservoir integral, 14 ± 4/11 ± 3). de Paris, Paris, France Conclusions: Strenuous exercise induced a well-known cardiac Background: Systemic sclerosis (SSc) is a disorder characterized by a remodeling which can be hypothesized to be slower in the arte- massive vascular involvement. Imaging biomarkers of vascular involve- rial tree because of highly differentiated and complex mechanism ment in SSc may have potential clinical implications for prediction of aiming to heart protection. Accordingly, the increased reservoir the pathogenesis of vascular complications [1]. This study is aimed at pressure in runners could be interpreted as sentinel parameter of identifying possible patterns of vascular wall disarray and remodeling vascular “fatigue”. in radial arteries of SSc patients, by means of ultrahigh frequency ultra- sound (UHFUS). References Methods: 5 end-diastolic frames of the right radial arteries of 41 1. Heffernan KS, Yoon ES, Sharman JE, Davies JE, Shih Y T, Chen CH, et al. patients with SSc and 41 healthy controls were obtained by VevoMD Resistance exercise training reduces arterial reservoir pressure in (70  MHz probe, FUJIFILM, VisualSonics, Toronto, Canada). 74 radiomic older adults with prehypertension and hypertension. Hypertens Res. features and 4 engineered parameters were extracted: inner and outer 2013;36(5):422–7. layer thickness, and presence of adjunctive acoustic interfaces (triple 2. Ramos JS, Ramos M V., Dalleck LC, Borrani F, Walker KB, Fassett RG, et al. signal). A feature selection algorithm was applied to reduce the num- Fitness Is Independently Associated with Central Hemodynamics in ber of features. The selected features were used to train classification Metabolic Syndrome. Med Sci Sports Exerc. 2016;48(8):1539–47. model, using Linear Support Vector Machine (SVM). 3. Ujka K, Bruno RM, Bastiani L, Bernardi E, Sdringola P, Dikic N, et al. Results: The SVM classification model showed good performance Relationship between occupational physical activity and subclinical (sensitivity = 0.63, specificity = 0.88, accuracy = 0.75, AUC = 0.75) to vascular damage in moderate‑altitude dwellers. High Alt Med Biol. discriminate SSc patients from controls using sixteen selected fea- 2017;18(3):249–57. tures. Inner layer (208 ± 61 vs 179 ± 47  µm, p = 0.04) and outer layer thickness (104 ± 22 vs 120 ± 36  µm, p = 0.03) were significantly higher Keywords: Cardiovascular adaptation, exercise, ultrasound in SSc than in controls, triple signal pattern more frequent in patients (p = 0.002). Conclusions: Wall ultrastructure of radial arteries of SSc patients is P.015 altered: inner and outer layer thickened, showing frequently a triple Sex‑related differences in skin microvascular function of healthy signal pattern. Radiomic approach allow to distinguish between radial normotensive individuals as assessed with laser speckle contrast images from SSc patients and controls with a 75% accuracy. imaging 1 1 1 Reference Antonios Lazaridis , Konstantinos Mastrogiannis , Anastasia Malliora , 1 1 1 1. Allanore Y, Distler O, Matucci‑ Cerinic M, Denton CP. Review: Defining a Stamatina Lamprou , Nikolaos Koletsos , Barbara Nikolaidou , Panagiotis 1 1 1 Unified Vascular Phenotype in Systemic Sclerosis. Arthritis Rheumatol Dolgyras, Areti Triantafyllou , Eugenia Gkaliagkousi Hoboken NJ. febbraio 2018;70(2):162–70. 3rd Department of Internal Medicine, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Keywords: UHFUS, radial arteries, radiomic analysis, machine learning Background: Skin microcirculation is considered a window to assess generalized microvascular function. Changes in skin micro- P.014 Cardiovascular adaptation to strenuous exercise: exploring vascular function (SMF) have been identified in several cardiovas- the complexity of the arterial protective role for the heart cular disease states. However, scarce data exists regarding SMF in 1 1 1 Maria Raffaella Martina , Elisabetta Bianchini , Marco Scalese , Nicole healthy adults and the impact of gender on it [1,2]. In this study, we 1 2 1 Di Lascio , Rosa Maria Bruno , Lorenza Pratali. assessed SMF in healthy individuals with the dynamic technique Lase Speckle Contrast Imaging (LSCI). Institute of Clinical Physiology—Italian National Research Council Methods: Healthy normotensives were included in the study. Office (CNR‑IFC), Pisa, Italy, Université Paris Cité, Inserm, PARCC, F‑75015, Paris, blood pressure (BP) was measured according to standard guidelines. France SMF was assessed with LSCI (PeriCam PSI NR, Perimed, Sweden) cou- pled with post-occlusive reactive hyperemia (PORH). Results were Background: The intense exercise effect evaluation on the cardiovas- expressed as perfusion during baseline, occlusion and peak period cular system can help to profile and reduce the risks (1–3). This work (arbitrary Perfusion Units,PUs), time until maximal perfusion (sec), the aims at assessing cardiovascular adaptation in runners by a multi-site percentage increase of perfusion between baseline and peak period non-invasive approach. A rtery Research (%) and PORH amplitude calculated as peak cutaneous vascular con- ductance (CVC) – baseline CVC. CVC was calculated as mean perfu- sion during each PORH period divided by mean BP (LSPUs/mmHg). Results: We studied 86 healthy normotensives including 50 women and 36 age-matched men. Body mass index, creatinine, office sys- tolic BP (SBP) and diastolic BP (DBP) were significantly higher in men compared to women. Regarding SMF, perfusion during baseline and occlusion, baseline CVC, peak CVC and PORH amplitude (0.89 ± 0.21 vs 0.75 ± 0.19, p < 0.01) were significantly higher in females compared to males. In addition, PORH was negatively associated with office SBP (r = − 0.258, p < 0.05). Conclusions: Healthy females present significantly higher SMF param- eters compared to age-matched males. Further research is needed to clarify the impact of gender on microvascular function and its further implications. References (a): AA longitudinal (white) and radial (red) strain from sagittal MRI [1] Stupin A, Stupin M, Baric L, Matic A, Kolar L and Drenjancevic I. Sex‑related (b): Dist-axial (left), DistR-sagittal (middle) and DistL-sagittal (right) differences in forearm skin microvascular reactivity of young healthy according to subject group: HV < 40  years, HV ≥ 40  years and AVS subjects. Clin Hemorheol Microcirc. 2019;72(4):339–351. patients. [2] Hodges G, Sharp L, Clements R, Goldspink R, George K, and Cable N. Influ‑ ence of age, sex, and aerobic capacity on forearm and skin blood flow References and vascular conductance. Eur J Appl Physiol. 2010;109(6):1009–15. [1] Lamy J, Soulat G, Evin M, Huber A, de Cesare A, Giron A, et al. Scan‑rescan reproducibility of ventricular and atrial MRI feature tracking strain. Com‑ Keywords: Microcirculation, laser speckle contrast imaging, perfusion, put Biol Med. 2018; 92:197–203. https:// doi. org/ 10. 1016/j. compb iomed. skin microvascular function 2017. 11. 015. [2] Redheuil A, Yu WC, Wu CO, Mousseaux E, de Cesare A, Yan R, Kachenoura P.021 N, Bluemke D, Lima JA. Reduced ascending aortic strain and distensibil‑ Longitudinal and radial distensibility of the ascending aorta ity: earliest manifestations of vascular aging in humans. Hypertension. in aging and aortic valve stenosis using MRI feature tracking 2010 Feb;55(2):319–26. https:// doi. org/ 10. 1161/ HYPER TENSI ONAHA. 109. 1,2 3 1 141275. Marie Shannon Soulez , Jérôme Lam y, Vincent Nguyen , Umit 4 4 4 1 Gencer , Gilles Soulat , Elie Mousseaux , Emilie Bollache , Nadjia 1 Keywords: MRI, Aortic strain, Aging, Aortic valve stenosis Kachenoura Sorbonne Université, CNRS, INSERM, Laboratoire d’Imagerie Biomédicale, Hypertension 2 3 LIB, Paris, France, Université Paris‑Est Créteil, Creteil, France, Department of Radiology and Biomedical Imaging, Yale University, New Haven, USA, P.022 PARCC, Université de Paris, Inserm/AP‑HP, Hôpital Européen Georges Exploring strain‑dependent collagen degradation as a driver Pompidou, Paris, France of hypertension‑induced arterial remodelling in lean ZSF1 rats: Background: We aimed to test the feasibility of MRI-based feature a pilot study tracking (FT) to measure longitudinal strain and radial motion frac- 1,2 1,2 3,4 Koen van der Laan , Koen Reesink , Sara Lambrichts , Laura van der tion of the proximal ascending aorta (AA) and to investigate how these 1,3 1 1,2 1,3,4 Taelen , Nicole Bitsch, Tammo Delhaas , Sebastien Foulquier , Bart measures are affected by aging and by the presence of calcified aortic 1,2,5 Spronck valve stenosis (AVS). 1 2 Methods: Twenty healthy volunteers (HV ) < 40 years (29 ± 1.6 years, 10 Carim, University Maastricht, Maastricht, Netherlands, Department males), 20 HV ≥ 40 years (58 ± 1.5 years, 10 males) and 31 patients with of Biomedical Engineering, Maastricht University medical centre, AVS (73 ± 1.6 years, 20 males) underwent 2D cine thoracic aortic MRI in Maastricht, Netherlands, Department of Pharmacology & Toxicology, sagittal and axial views immediately followed by carotid artery appla- Maastricht University, Maastricht, Netherlands, MHENS School for Mental nation tonometry. AA anterior wall (Figure a) was semi-automatically Health and Neuroscience, Maastricht University, Maastricht, Netherlands, tracked on sagittal images throughout the cardiac cycle to estimate Macquarie Medical School, Faculty of Medicine, Health and Human Sci‑ longitudinal strain and radial motion fraction peaks, while using cus- ences, Macquarie University, Sydney, Australia. tom FT software [1], which was previously dedicated to multi-chamber Background: Hypertension-induced arterial remodelling involves e.g., strain evaluation in the heart. Conventional global AA strain was also increased wall thickness, changes in collagen structure and increased measured on axial views based on cross-sectional area [2]. Finally, dis- collagen content [1]. Normally, collagen is degraded and deposited in tensibility was derived as strain/central pulse pressure. 8–10 week turn-over cycles [2]. Collagen fibre strain significantly influ- Results: Axial (Dist-axial: R = − 0.82, p < 0.0001) and sagittal (radial ences enzymatic degradation efficiency, where straightened but not DistR-sagittal: R = − 0.54, p = 0.0004, longitudinal DistL-sagittal: overstretched fibres experience minimum degradation (Fig. A) [3]. In R = − 0.37, p = 0.02) distensibility measures decreased significantly a homeostatic situation where collagen experiences minimum deg- with age and even more in the presence of AVS (Figure b). When inves- radation at mean arterial pressure, fibres would be optimally strained tigating the ability of distensibility measures to discriminate HV from [4]. The onset of hypertension overstretches collagen (1 in Fig. B), patients, newly proposed DistR-sagittal (0.84) and DistL-sagittal (0.92) demonstrated higher area under the ROC curve than Dist-axial (0.81). Conclusions: MRI FT revealed that age has a stronger impact on AA axial distensibility, while longitudinal distensibility could be more sen- sitive to the effect of AVS probably because of valvular calcifications that limit this longitudinal motion specifically. Artery Research accelerating collagen degradation [4]. We hypothesise that optimally P.024 strained fibres will gradually make up the bulk of collagen during Eec ff ts of Nitroglycerin Induced Vasodilation on Elastic hypertension, as overstrained collagen degrades faster. This implies versus Muscular Artery Stiffness in Older Veterans that, as collagen returns to the optimal level of strain, increased colla- 1 1 2 1 Ryan Pewowaruk , Amy Hein , Claudiq Korcarz , Adam Gepner. gen content is required to maintain luminal diameter and avoid dilata- William S. Middleton Memorial Veterans Hospital, Madison, United tion (2 in Fig. B). We evaluated this hypothesis, expecting hypertensive States, University of Wisconsin School of Medicine and Public Health, rat aorta to exhibit less collagen strain under normotensive conditions Madison, United States compared to normotensive control (3 in Fig. B). Methods: One normotensive (NT, Wistar) and one hypertensive (HT, Background: Vascular smooth muscle tone may play an important ZSF1 lean [5]) 22-week-old rat abdominal aorta were stretched to role in the physiology of increased arterial stiffness that occurs with in  vivo-like length and pressurised to 100  mmHg. Three-dimensional aging. This study evaluated the impact of smooth muscle tone on collagen structure was then imaged by second harmonic generation arterial stiffness in older individuals following nitroglycerin induced using a two-photon microscope. vasodilation in elastic and muscular arteries. Results: At 100 mmHg, the HT artery visibly displayed a thicker colla- Methods: 40 older Veterans (> 60 years old), without known cardio- gen layer and curlier collagen fibres than the NT artery (Fig. C-F), sug- vascular disease, were included in this study. 20 were hypertensive gesting lower collagen fibre strain at normotensive pressures (3 in Fig. (70.8 ± 6.6  years, 10 female) and 20 were normotensive controls B). (72.0 ± 9.3  years, 8 female). Nitroglycerin (NTG) induced changes in Conclusions: Strain-dependent collagen degradation may be a key arterial stiffness were measured locally with vascular ultrasound in process driving hypertension-induced arterial remodelling. the carotid and brachial arteries, and regionally by carotid-femoral pulse wave velocity (cfPWV ) by tonometry. Results: With NTG, both hypertensive and normotensive control Vet- erans showed increased carotid PWV (6.4 ± 1.3 m/s to 7.2 ± 1.4  m/s, Δ 0.8 ± 1.1  m/s, p = 0.007) and cfPWV (8.6 ± 1.9 m/s to 9.5 ± 2.4  m/s, Δ 0.9 ± 2.3  m/s, p = 0.020) but did not change brachial PWV (11.2 ± 2.4  m/s to 11.1 ± 2.2  m/s, Δ − 0.2 ± 2.5  m/s, p = 0.72). The carotid artery dilated more in control participants than hypertensive Veterans (Δ 0.54 ± 0.19  mm vs 0.42 ± 0.12  mm, p = 0.022). Brachial artery dilation was similar, (Δ 0.55 ± 0.26  mm vs 0.51 ± 0.20  mm, p = 0.46). Conclusion: In older Veterans, without known cardiovascular dis- ease, NTG induced vasodilation increased elastic artery stiffness and did not change muscular artery stiffness. Increased central arterial stiffness and reduction in the arterial stiffness gradient could offset some of the benefits of lowering blood pressure in older patients who are prescribed vasodilators as an antihypertensive therapy. Elastic artery stiffening with vasodilation warrants further investiga- tion as it may be important for antihypertensive medication selec- tion and influence CVD development. A: Straight-but-not-overstretched collagen experiences minimal degradation [3]. B: Diameter maintenance in hypertension requires additional collagen at minimum-degradation strain. More and curlier collagen in hypertension (E–F) than normotension (C-D). References 1. Intengan and Schiffrin. Vascular remodeling in hypertension. Hypertension. 2001;38:581–587. 2. Nissen et al. Increased turnover of arterial collagen in hypertensive rats. Proc Natl Acad Sci USA. 1978;75:451–453. 3. Gaul et al. Strain mediated enzymatic degradation of arterial tissue. Acta Biomater. 2018;77:301–310. 4. Gaul et al. Pressure‑induced collagen degradation in arterial tissue as a potential mechanism for degenerative arterial disease progression. J Mech Behav Biomed Mater. 2020;109:103,771. Graphic abstract overviewing 1. research question, 2. methods, 3. 5. Hamdani et al. Myocardial titin hypophosphorylation importantly contrib‑ results, and 4. clinical implications of findings utes to heart failure with preserved ejection fraction in a rat metabolic risk model. Circ Heart Fail. 2013;6:1239–1249. Reference Pewowaruk RJ, Gepner AD. Smooth muscle tone alters arterial stiffness: the Keywords: Remoddeling strain collagen degradation importance of the extracellular matrix to vascular smooth muscle stiff‑ ness ratio. J Hypertens. 2022 Mar 1;40(3):512–519. Keywords: Vascular stiffness, hypertension, vasodilation, smooth muscle A rtery Research P.025 arterial elastance, Ea, and end-systolic elastance, Ees were computed ® ® Performance of  pOpmetre versus  SphygmoCor to detect central during rest, exercise, and recovery. arterial stiffness using central aortic pressures Results: At rest, subjects with Ipc-PH or No PH tended to have lower 1 2 2 3 ZC and Ea than those with PAH (Fig.  1A&C); all Ees values were simi- Mathilde Laime , Hasan Obeid , Imad Abi‑Nasr , Hakim Khettab , Magid 2 3 4,5 lar (Fig.  1b). During exercise, Zc decreased in the subject with No PH, Hallab , Pierre Bout ouyrie , Loukman Omarjee whereas it increased in those with Ipc-PH and did not change in those University Bretagne Occidentale, Laboratoire ORPHY, Brest, France, with PAH. During exercise, both Ees and Ea increased for all subjects 2 3 Clinique Bizet, Cardiology unit, Paris, France, Pharmacology department, but the increase in Ea was larger than the increase in Ees for both the European Georges Pompidou Hospital and Assistance Publique Hôpitaux PAH and Ipc-PH groups, suggesting RV:PA uncoupling. Interestingly, de Paris, Paris Cardiovascular Research Center (PARCC), Paris, France, Univ the changes in ZC and Ees/Ea were inversely related in Ipc-PH during Rennes, CHU Rennes, INSERM CIC1414, Vascular Medicine Department, exercise. Rennes, France, Vascular Medicine Department, Redon Hospital, 35600, Conclusions: With the limitation that the sample size is small, our find- Redon, Redon, France ings suggest that analysis of pulsatile pulmonary hemodynamics and RV:PA coupling with exercise can reveal distinctive PH phenotypes and Central arterial stiffness is an independent predictor of cardiovascular have diagnostic value. and total mortality. It can be diagnose directly by aortic pulse wave velocity (aPWV ) or indirectly by central aortic pressures (CAP). SphygmoCor , a non-invasive device using applanation tonometry, is the gold standard to measure CAP. However, its complexity limits its use in clinical practice. The aim of this study is to evaluate the accuracy of a novel non- invasive device, pOpmètre (Axelife SAS, Saint-Nicolas de Redon, France), to measure CAP in suspected peripheral arterial disease (PAD) patients. Systolic, diastolic and central pulse pressures measured with pOpmè- ® ® tre are compared with those measured with SphygmoCor . In this pilot, monocentric, prospective study, 53 suspected PAD patients were included. Among them: i) 26 patients (age: 69 ± 10y; 65% men) were diagnosed with peripheral arterial obstructive disease (PAOD) defined by a toe-brachial index ≤ 0.7 and/or an ankle-brachial index (ABI) ≤ 0.9; ii) 10 patients (age: 74 ± 9y; 70% men) were diag- nosed with peripheral arterial stiffness (mediacalcosis) defined by an ABI > 1.4; iii) 20 patients (age: 55 ± 16; 40% men) without PAD diagno- sis. There was a significant correlation between systolic, diastolic and central pulse pressures measured by pOpmètre compared with those measured by SphygmoCor in PAD patients (respectively, R2 = [0.94, 1.00, 0.84]; p = [10e − 16, 10e − 16, 10e − 11]), peripheral arterial stiffness patients (respectively, R2 = [0.96, 1.00, 0.84]; p = [10e − 8, 10e − 13, 10e − 7]) and no PAD patients (R2 = [0.98, 1.00, 0.97]]; p = [10e − 12, 10e − 16, 10e − 8]). CAP assessed by pOpmètre could be used in clinical practice to References: detect central arterial stiffness in suspected PAD patients. [1] Rosenkranz, S et al., Circulation, 141(8):678–693, 2020. Reference [2] Al‑ Omary, MS et al., Hypertension, 75(6):1397–1408, 2020. McEniery CM, Cockcroft JR, Roman MJ, Franklin SS, Wilkinson IB. Central blood [3] Vanderpool, RR et al., Annals of Biomedical Engineering, 38(5):1854–1861, pressure: current evidence and clinical importance. Eur Heart J. 7 juill 2010. 2014;35(26):1719‑25. [4] Sabbahi, A et al., Expert Review of Respiratory Medicine, 14(3):317–327, Keywords: Central aortic pressure, Peripheral arterial disease Keywords: Impedance, Coupling, Hypertension, Exercise. P.027 Obesity, metabolic disorders and cardiovascular disease Analyses of pulsatile pulmonary hemodynamics and right ventricular function during exercise P.030 1 1 1 Christopher Lechuga , Farhan Raza , Mitchel J. Colebank , Naomi C. Relationship between aortic and carotid stiffness with measures Chesler. of adiposity in adolescents. The maciste study University of California, Irvine, Irvine, United States 1,2 3 3 Giacomo Pucci , Mariella Martina , Elisabetta Bianchini , Vincenzo 3 1,2 1,2 4 Gemignani , Marco D’Abbondanza , Rosa Curcio , Francesca Battista , Background: Pulmonary hypertension (PH) leads to a mismatched 5 1,2 Fabio Anastasio, Gaetano Vaudo right ventricular (RV)-pulmonary arterial (PA) relationship (uncou- pling), which increases mortality [1]. Current diagnostic strategies 1 Department of Medicine and Surgery—University of Perugia, Perugia, utilize pulmonary vascular resistance (PVR) [2] but disregard the oppo- 2 3 Italy, "Santa Maria" University Hospital, Terni, Italy, Institute of Clinical sition to pulsatile flow as well as response to exercise [3,4]. We hypoth- 4 Physiology—National Council of Research, Pisa, Italy, Sports Medicine— esize that pulsatile pulmonary hemodynamics during exercise and 5 University of Padua, Padua, Italy, Cardiology Division—Mondovì Hospital, their relationship to RV-PA coupling can differentiate PH phenotypes Cuneo, Italy and refine diagnoses. Methods: 13 adult subjects with precapillary PH (PAH; n = 5), isolated Background: We evaluated the differential association between arte - postcapillary PH (Ipc-PH; n = 5), or no PH (No PH; n = 1) performed rial stiffness, taken at different arterial segments (aortic and carotid), invasive cardiopulmonary exercise testing with echocardiography- with global and local measures of adiposity, accounting for BP as a based pulmonary vascular pressure-flow and catheter-based RV pres- mediator of the relationship between fat accumulation and increased sure–volume data collection. Characteristic impedance ZC, effective arterial stiffness. Artery Research Bessa LR, Cruz LAB, Lima RLS, Presta MCLF, Alves Filho AAO, Cunha, RCA, et al. Methods: 322 healthy Italian adolescents from the MACISTE Study Correlation between Neck Circumference and Pulse Wave Velocity: A (Metabolic and Cardiovascular Investigation at School, TErni), were Population‑based Study. Rev Artery Research 2020. evaluated. BMI, waist, hip and neck circumferences (NC) were taken Instituto Brasileiro de Geografia e Estatística (IBGE). CensoIBGE 2010. Brazil: as measures of adiposity. Laboratory measures of adiposity were also IBGE; 2010. collected. Arterial stiffness was measured through carotid-femoral pulse wave velocity (applanation tonometry, SphygmoCor), and at the Keywords: Obesity, Pulse wave speed, Arterial stiffness carotid level (Cardiovascular suite, Quipu, Italy). Results: Mean age 17 ± 1.4 years, 56% boys, 40 (12%) with overweight. All central and peripheral measures of BP were higher in overweight vs normoweight (all p < 0.01) excluding peripheral and central DBPs, P.032 which were lower in overweight. The aortic-to-brachial pulse pressure In vivo measurement of blood pressure and pulse wave velocity amplification was reduced in overweight vs normoweight (1.51 ± 0.13 in streptozotocin‑induced type 1 diabetes in mice vs 1.58 ± 0,13, p < 0.01). Carotid and aortic stiffness were positively cor - 1,2 1,3 3,4 related with anthropometric and laboratory measures of adiposity. Margarita G. Pencheva , Eline Berends , Peter Leenders , Myrthe M. 1,2 2 2,5 After adjustment for MAP, only NC remained associated with carotid van der Bruggen , Koen W.F. van der Laan , Alessandro Giudici , Koen 2 3 2,6 1 (β = 0.24, p < 0.01) and aortic stiffness (β = 0.16, p = 0.02). After adjust- D. Reesink , Sébastien Foulquier , Bart Spronck , Casper G. Schalkwijk ment for central PP, only carotid (β = 0.15, p = 0.04), but not aortic stiff- Depatrment of Internal Medicine, CARIM School for Cardiovascular ness (β = 0.12, p = 0.07) was associated with NC. Diseases, Maastricht University, Maastricht, The Netherlands, Dept. Conclusions: Arterial stiffness, when assessed at different levels of of Biomedical Engineering, CARIM School for Cardiovascular Diseases, central arteries, showed site-specific associations with measures of Maastricht University, Maastricht, The Netherlands, Dept. of Pharmacol‑ body fat adiposity. NC was the only measure of adiposity to show a ogy and Toxicology, CARIM School for Cardiovascular Diseases, Maastricht BP-independent association with carotid stiffness. Carotid stiffness is University, Maastricht, The Netherlands, Dept. of Biochemistry, CARIM a promising marker of pressure-independent vascular damage pro- School for Cardiovascular Diseases, Maastricht University, Maastricht, The moted by overweight status. Netherlands, GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands, Macquarie Medical School, Keywords: Adolescents, adiposity, carotid stiffness, blood pressure Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia P.031 Background: In humans, type 1 diabetes (T1D) is associated with Obesity and Cardiovascular Risk Factors in the Outcome arterial stiffening as assessed by carotid-femoral pulse wave velocity of Arterial Stiffness (cfPWV) [1]. To experimentally study the underlying mechanism of this 1 1 1 Gabriela Portugal , Mariana Mendes , Laysa Rebouças , Lucelia stiffening, we investigated blood pressure (BP) and cfPWV in strepto - Magalhães zotocin (STZ)-induced diabetes in mice. Methods: Twenty-four 9-week-old male C57BL/6  J mice were divided Uniftc, Salvador, Brazil equally among diabetic (induced through once-daily 50  mg/kg STZ Obesity is one of the biggest health problems in the world. It is injections for five days) and control (sham injections using citrate constituted as the second most important risk factor for the devel- buffer) groups, and were kept to an age of 24  weeks. Fasting glucose opment of chronic non-communicable diseases. In this sense, it is was measured every 4–5  weeks via tail blood collection with levels assumed that the increase in arterial stiffness is on the path between of 15  mmol/L and higher considered diabetic. Non-invasive tono- obesity and cardiovascular diseases. The objective of this study was metric cfPWV was measured in anaesthetised animals (1% isoflurane) to evaluate the correlation between obesity and cardiovascular risk 24  h prior to euthanasia; tail-cuff BP was measured directly prior to factors with arterial stiffness in patients treated at a teaching clinic euthanasia. in the university center, Salvador-Ba, in 2022. This is an observa- Results: Diabetic mice exhibited higher fasting glucose than controls tional, cross-sectional and analytical study. The studied population (p < 0.0001, two-way ANOVA with Tukey post-hoc test; Fig. A). There comprised individuals residing in the Valley of Ogunjá neighbor- was no difference in systolic BP (110 ± 4 vs. 104 ± 3  mmHg, p = 0.26, hood, Acupe in Brotas, both sexes, over 18  years of age and obese. mean ± SE, unpaired t-test) and cfPWV (2.60 ± 0.14 vs. 2.55 ± 0.11 m/s, The indicators of obesity were: waist circumference (women > 88 cm p = 0.80) between diabetic and control mice (Fig. B-C). and men > 90 cm), cervical (> 34 cm in women and > 37 cm in men), Discussion: In the popular animal model of STZ-induced T1D, existing waist-hip ratio (> 0.80 in women and > 0.95 in men), body mass literature on systolic BP is not consistent [2,3]. Literature about cfPWV index (BMI) (> 30 kg/m ) and evaluation of the carotid-femoral pulse is limited: in contrast to our data, one report showed an STZ-induced wave velocity (PWV ) (> 10 m/s). The results obtained denote a direct increase in ultrasound-derived cfPWV [4]. Discrepancies between stud- to statistically significant linear correlation: waist circumference indi- ies could be due to different methods of measuring BP and cfPWV [5]; cator associated with PWV (p value 0.055), waist-hip ratio (p-value the choice of measurement methods therefore needs critical appraisal. 0.003), cervical circumference (p-value 0.004). Only the BMI indicator Conclusion: In the murine model of STZ-induced T1D, we did not find associated with PWV (p value 0.584) was not statistically significant. elevated BP or increased arterial stiffness. It is concluded that the indicators of abdominal and cervical circum- ference and waist-hip ratio obtained statistical significance when attributed to PWV and can be used as indicators of arterial stiffness. References Associação Brasileira para o Estudo da Obesidade e Síndrome Metabólica. Mapa da Obesidade [internet]. Higienópolis: 2021 [citied: Out 24 2021]. Available from: https:// abeso. org. br/ obesi dade‑e‑ sindr ome‑ metab olica/ mapa da‑ obesidade/. Brasil. Saúde prepara ações para controle do excesso de peso e da obesidade Despite clearly increased fasting blood glucose (A), streptozotocin- [Internet]. Brasília: Ministério da Saúde,2020 [cited: Out 24 2021]. Available induced diabetic mice did not show increased blood pressure (B) from: https:// aps. saude. gov. br/ notic ia/ 10137#: ~: text=O% 20Min ist% C3% or arterial stiffness (C). Shown are mean ± SE; ****p < 0.0001; ns, not A9rio% 20da% 20Sa% C3% BAde% 20ir% C3% A1,de% 20pro mo% C3% A7% significant. C3% A3o% 20de% 20da% 20sa% C3% BAde. A rtery Research References: LVET (left) and iLVET (right) against EF Simpson, effect direction 1. Tougaard NH, Theilade S, Winther SA, Tofte N, Ahluwalia TS, Hansen TW, et al. between second and first visit. Gray arrows show individual meas- J Am Heart Assoc. 2020;9:e017165. urements, the blue arrow shows the mean effect over 37 subjects. 2. Gurley SB, Clare SE, Snow KP, Hu A, Meyer TW, Coffman TM. Am J Physiol Renal Physiol. 2010;298:F788‑795. References 3. Zhong F, Chen H, Wei C, Zhang W, Li Z, Jain MK, et al. Kidney Int. [1] A. Haiden, B. Eber, and T. Weber, ‘U‑Shaped Relationship of Left Ventricu‑ 2015;87:382–395. lar Ejection Time Index and All‑ Cause Mortality’, American Journal of 4. Heath JM, Sun Y, Yuan K, Bradley WE, Litovsky S, Dell’Italia LJ, et al. Circ Res. Hypertension, vol. 27, no. 5, pp. 702–709, Mai 2014, https:// doi. org/ 10. 2014;114:1094–1102. 1093/ ajh/ hpt185. 5. Leloup AJ, Fransen P, Van Hove CE, Demolder M, De Keulenaer GW, Schrijvers [2] A. Bauer, B. Hametner, T. Weber, and S. Wassertheurer, ‘Method Comparison DM. Hypertension. 2014;64:195–200. and Validation of the Determination of Ejection Duration from Oscillo‑ metric Measurements’, IFAC‑PapersOnLine, vol. 51, no. 2, pp. 343–348, Jan. Keywords: Diabetes, streptozotocin, blood pressure, pulse wave 2018, https:// doi. org/ 10. 1016/j. ifacol. 2018. 03. 059. velocity [3] Lewis R P, Rittogers S E, Froester W F, and Boudoulas H, ‘A critical review of the systolic time intervals.’, Circulation, vol. 56, no. 2, pp. 146–158, Aug. 1977, https:// doi. org/ 10. 1161/ 01. CIR. 56.2. 146. P.033 Pulse waveform analysis for monitoring of left ventricular function in patients with severely reduced ejection fraction P.034 Sex‑specific association between the metabolic score for insulin 1,4 1 1 Stefan Orter , Bernhard Hametner, Siegfried Wassertheurer , Kathrin resistance and arterial stiffness in middle‑aged adults 2 3 3 4 Danninger , Antonis Ar gyris , Athanase Protogerou , Eugenijus K aniusas , with metabolic syndrome 2 2 Ronald Binder, Thomas Weber 1 2,3 3 Jurgita Mikolaitytė , Agnė Laučytė‑Cibulskienė , Ligita Ryliškytė , Center for Health & Bioresources, AIT Austrian Institute of Technology, 1,3 Jolita Badarienė Vienna, Austria, Cardiology Department, Klinikum Wels‑Grieskirchen, 3 1 Wels, Austria, Cardiovascular Prevention and Research Unit, Laiko Hospi‑ State Research Institute Centre for Innovative Medicine, Vilnius, Lithu‑ 4 2 tal, Athens, Greece, Institute of Biomedical Electronics, Vienna University ania, Department of Nephrology, Lund University, Malmö, Sweden, of Technology, Vienna, Austria Faculty of Medicine, Vilnius University, Vilnius, Lithuania Background: Impaired systolic function of the left ventricle leads to Background: The Metabolic Score for Insulin Resistance (METS-IR) is shortening of the left ventricular ejection time (LVET ) and heart rate a non-insulin-based metabolic index used as a substitution marker of adjusted LVET (iLVET)[1]. The aim of this study is the investigation insulin resistance and cardiometabolic risk. Previous studies have sug- of the improvement in left ventricular function using radial pulse gested that insulin resistance is significantly related to the develop - waveforms compared to improvement assessed by ejection fraction ment and progression of coronary atherosclerosis and adverse plaque (EF). characteristics. The main objective of this study was to evaluate the Methods: 37 patients (7 females) with heart failure (HF) with reduced sex-specific relationship between METS-IR and arterial parameters in ejection fraction (HFrEF) were treated according to HF guidelines. EF the middle-aged Lithuanian population with metabolic syndrome. and its changes under treatment were monitored with echocardiogra- Methods: A total of 2064 subjects (1136 women and 928 men). phy (EPIQ, Philips, Simpson method with apical 4-chamber view), and Anthropometric, laboratory testing, and cardiovascular risk factors LVET was monitored with tonometry (SphygmoCor, AtCor Medical, along with arterial parameters (carotid-radial pulse wave velocity method based on numerical derivatives)[2]. Furthermore, LVET was (crPWV ), carotid-femoral pulse wave velocity (cfPWV ), carotid intima- adjusted for heart rate[3]. Visualization of differences between first media thickness (CIMT), ankle-brachial index (ABI), cardio-ankle vas- and second visit was done by 4-quadrant plots (Fig.  1) and concord- cular index (CAVI) and atherosclerotic plaques) were evaluated. ance rate was calculated. Results: After stratifying subjects into sex-specific METS-IR quartiles, Results: Patients mean age and body height were 54  years, and we observed statistically significant differences in all arterial param- 174 cm respectively. Their average weight decreased from 89 to 88 kg. eters among METS-IR quartiles, except for crPWV in men (p = 0.533). Measured basic parameters on first and second visit were HR (68BPM Differences between men and women in the METS-IR quartiles were vs. 60BPM), SBP (128  mmHg vs. 128  mmHg), DBP (81  mmHg vs. observed only in cfPWV (p < 0.05), CAVI (p < 0.05), and CIMT (p < 0.001). 76 mmHg), EF (25% vs. 42%), LVET (0.266 s vs. 0.289 s), iLVET (0.380 vs. In a fully adjusted linear regression analysis, METS-IR was associated 0.389), percentage of patients with betablocker intake (76% vs. 97%), with CAVI in both men (p = 0.005) and women (p < 0.001). However, and percentage of patients with ACE-I/ARB/ARNI intake (92% vs. 97%). ABI—only in men (p = 0.040), and CIMT – in women (p = 0.025). The mean timespan between first and second measurements was Conclusion: Insulin resistance measured by METS-IR is associated with 100  days. A concordance rate of 0.84 for LVET and 0.65 for iLVET was CAVI in both men and women in the middle-aged Lithuanian popula- observed. tion with metabolic syndrome. Additionally, in men, it is also associ- Conclusions: Automatically measured LVET and iLVET from radial ated with ABI, whereas in women – with CIMT. pressure waveforms is suitable for monitoring the improvement of EF with medical treatment in HFrEF. Keywords: Arterial stiffness, cardio-ankle vascular index, carotid intima-media thickness, ankle-brachial index, Metabolic Score for Insu- lin Resistance P.036 The effects of different types of calorie restriction on atherosclerosis‑related miRNAs in mice 1 2 2 Dilara Buse Durdabak , Nazim Arda Keles , Soner Dogan , Bilge Guvenc Tuna Department of Biophysics, School of Medicine, Yeditepe University, Istanbul, Turkey, Department of Medical Biology, School of Medicine, Yeditepe University, Istanbul, Turkey Artery Research Atherosclerosis is a chronic inflammatory blood vessel disease.Stud- Pulse-Wave-velocity (cfPWV), central pulse pressure (CPP) (Sphyg- ies highlight the importance of epigenetic modifications specifically mocor); 6. Autofluorescence- Advanced glycation end-products miRNAs in the development and progression of atherosclerosis.Calo- (AGE-Reader); 7. Carotid intima-media thickness (CIMT). We per- rie restriction(CR) is one of the best-known interventions to prolong formed one-way ANOVA to compare differences in the three groups. lifespan and impact lowering the risk of atherosclerosis.In the present Results: Demographics and anthropometry (BMI and waist circum- study, the effects of different types of CR on atherosclerosis-related ference) were comparable in all three groups. When compared to miRNA were studied. Groups 2 and 3, In Group 1: Troponin and the red cell distribution width (RDW) was higher (p < 0.05); Sphygmocor based cfPWV & Female mice were enrolled into three groups; ad-libitum (AL), Chronic- CPP, was higher (p < 0.001); RHI-EndoPAT based AI (@75) was higher CR (CCR, 15% CR), and Intermittent-CR (ICR) which 60% CR was applied and HRV(SDNN) was lower (p < 0.05); AGE was higher (p < 0.01) (see for one week (ICR-R, restricted) followed by three weeks of AL feed- Fig. 1). ing (ICR-RF, refeed).Blood and brain samples were collected at week Conclusion: Measures of arterial-stiffness (cf-PWV & AI@75) and HRV 49/50 to measure miRNA expression levels using Affymetrix GeneChip are more significantly impaired in DM when compared to hyper - miRNA 4.1 Array.The targets of differentially expressed(DE) miRNAs tension/hyperlipidemia, one year post COVID-19 recovery. These that are enriched in atherosclerosis-related molecular pathways were measures are higher when compared to similar matched diabe- analyzed. tes patients with no history of COVID-19 infection. COVID-19 DM In blood, a total of 12 miRNAs were DE among dietary groups.There patients need to be followed up to study long-term impact on vas- were common miRNAs that differ in dietary regimes when compared cular complications and autonomic neuropathy. to the AL group; miR-709(17,09-fold higher), miR-30b-5p(7,12-fold lower), and miR-19b-3p(5,72-fold lower) in CCR.The overexpression of miR-709 is shown to have a cardioprotective effect , while miR- 2 3 30b-5p and miR-19b-3p are considered pro-atherosclerotic.GO- KEGG analyses revealed that targets of atherosclerosis-related miRNAs that were affected with CR were also enriched in aging and cancer- related molecular pathways.In the brain, a total of 6 miRNAs were dif- ferentially expressed.Interestingly, there was no significant change in atherosclerosis-related miRNAs between blood and brain. In conclusion, even though CR has different effects on blood and brain tissues, some common miRNAs might have protective effects on ath- erosclerosis, suggesting the link between the brain and vascular axis. References 1. Li M, Chen H, Chen L, Chen Y, Liu X, Mo D. miR‑709 modulates LPS‑induced inflammatory response through targeting GSK ‑3β. Int Immunopharma‑ col. 2016 Jul;36:333–8. 2. Qi X, Wang H, Xia L, Lin R, Li T, Guan C, et al. miR‑30b ‑5p releases HMGB1 Table showing various vascular measures and figure showing box via UBE2D2/KAT2B/HMGB1 pathway to promote pro‑inflammatory plot on the pulse-wave-velocity in the three groups polarization and recruitment of macrophages. Atherosclerosis. 2021 May;324:38–45. 3. Wang J, Xu X, Li P, Zhang B, Zhang J. HDAC3 protects against atherosclerosis through inhibition of inflammation via the microRNA‑19b/PPARγ/NF‑κB axis. Atherosclerosis. 2021 Apr;323:1–12. Keywords: Atherosclerosis, calorie restrictions, miRNA P.037 Diabetes Mellitus is associated with relatively higher arterial stiffness when compared to hypertension or hyperlipidemia post‑recovery from COVID‑19 1,2 2,3 2,3 2 Rinkoo Dalan, Barnaby Young , David Lye , Bernhard Boehm. 1 2 Tan Tock Seng Hospital, Singapore, Singapore, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore, National Centre for infectious diseases, Singapore, Singapore Background: COVID-19, is associated with vascular dysfunction, arte- rial stiffness and worse outcomes in diabetes mellitus (DM) (1). We hypothesise that longer-term impact in COVID-19 DM patients will be worse when compared to other metabolic conditions, 1  year after recovery from COVID-19. Reference Methods: We recruited 63 patients belonging to the three groups: 1. Zota IM, Stătescu C, Sascău RA, et al. Acute and Long‑ Term Consequences group 1 – recovered COVID-19 DM-type 2, n = 14; Group 2- recov- of COVID‑19 on Arterial Stiffness‑A Narrative Review. Life (Basel). ered COVID-19, non-diabetes hypertension or hyperlipidemia, 2022;12(6):781. n = 29 and Group 3- non-COVID-19 DM, n = 14. Data collected: 1. Demographics, 2. Anthropometry, 3. Metabolic profile, 4. Reac - Keywords: COVID-19; arterial-stiffness, pulse-wave-velocity, tive Hyperaemia index (LnRHI), Augmentation index (AI@75), diabetes Heart Rate variability (HRV) (RHI-EndoPAT), 5. Carotid-femoral A rtery Research P.038 Clinical aspects Large artery stiffness using Sphgymocor technology shows higher augmentation index in pre‑diabetes and diabetes in multi‑ethnic P.042 Singapore Estimating pulse wave velocity in Community Pharmacies improves CV‑risk stratification compared to SCORE Ying Jie Chee , Rinkoo Dalan 1,2 3 3 3 Enrique Rodilla , Manuel Adell, Vicente Baixauli , Otón Bellver , Lidón Tan Tock Seng Hospital, Singapore, Singapore 3 3 3 3 Castillo , Santiago Centelles , Edelmira Córcoles , Rosario Hernández , 3 3 3 3 Background: The Sphygmocor technology uses applanation tonometry Sara Martínez , Zeneida Perseguer , Rosa Prats , Javier Reig , Desiré 3 3 2,3 2 2 to measure large artery stiffness. Although the carotid-femoral pulse Ruiz , Fanny Ruiz , Luis Salar , José‑Antonio Costa , José Chordá , Julio 1 1 3 wave velocity (cfPWV) is higher in diabetes, an association with pre-dia- Vicente , Ana Gómez , Maite Climent betes has not been observed.(1,2) There is limited data on augmentation 1 2 Hospital Universitario de Sagunto, Puerto De Sagunto, Spain, Universi‑ index (AIx). We aimed to study the correlation of arterial stiffness among dad Cardenal Herrera‑CEU, CEU Universities, Moncada ( Valencia), Spain, healthy, pre-diabetes, or diabetes in multi-ethnic Singapore. Sociedad Española de Farmacia Familiar y Comunitaria (SEFAC‑Valencia), Methods: Population: n = 130; Age = 44.8 (9.6) years; Male = 41 (31%), Valencia, Spain Chinese = 93, Indians = 12, Malays = 15, Others = 10. All participants underwent a standard 75 g oral glucose tolerance test and applanation Background: Arterial stiffness is considered to be an intermediate tonometry to assess cfPWV, central pulse pressure (CPP) and AIx. One- marker of CV risk with independent prognostic value. The objective of way ANOVA was done to study the differences in the arterial measure - this study is to assess whether the estimation of arterial stiffness can ments based on diabetes status. improve CV risk stratification compared to SCORE in patients at Commu- Results: Healthy (n = 81), Prediabetes (n = 27), Diabetes (n = 22). While nity Pharmacies. cfPWV was higher in diabetes (mean (SD): 7.2(1.6)) compared to absence Methods: Observational prospective epidemiological study in which of diabetes (6.5(1.0)); p < 0.01), there was no difference between healthy consecutive individuals entering a participating Community Pharmacy 6.5(1.1) and pre-diabetes (6.4(1.0)); p > 0.01. An increasing trend was are offered a voluntary measurement of blood pressure and estimation seen in AIx, healthy (mean (SD): 9.5(4.3)) < pre-diabetes (mean (SD): of pulse wave velocity by oscillometry (AGEDIO, IEM ) to stratify their 11.1(5.4)) < diabetes (mean (SD):13.1(7.0)); p < 0.01. No statistically signifi- CV risk according to SCORE compared to the use of arterial stiffness. cant difference was seen in CPP (p > 0.01). Results: After nine months of recruitment, data from 923 patients Discussion: AIx may reflect early markers of impaired glucose tolerance (173 women, 102 men) were collected. 16/122 (13.1%) patients under or pre-diabetes. Moreover, as AIx is determined by the properties of the 40 years and 72/364 (19.8%) over 65 years of age presented pathologi- distal vasculature, it may be used as an early marker of distal circulatory cal stiffness and could be classified as high-risk, even though being dysfunction involving the small arterioles, which precede abnormalities out of the age-range of SCORE. Of the 437 (47.3%) patients who were in pulse wave velocities. AIx can be a valuable marker of early vascular susceptible to calculating SCORE, 42/437 patients (9.6%) presented dysfunction, especially among individuals with pre-diabetes. Further pathological arterial stiffness. Cholesterol values were available in 281 studies are needed to understand the mechanistic basis of this trend. patients (64.3%). Among them, according to SCORE, only 6 (2.1%) fell into the high-risk category. Conclusions: More than half of the subjects who randomly enter a community pharmacy had ages that make it impossible to calculate the CV risk by SCORE. Among them, arterial damage was detected in 18.1%. Of the other half, 9.6% presented arterial damage and, there- fore, high CV risk, when SCORE only detected it in 2.1%. Therefore, esti- mating arterial stiffness in community pharmacies markedly improves detection of high CV risk compared to SCORE. Fig. 1 (A) augmentation index and (B) pulse wave velocity in healthy, pre‑ diabetes and diabetes References 1. Henry RM, Kostense PJ, Spijkerman AM, Dekker JM, Nijpels G, Heine RJ, et al. Arterial stiffness increases with deteriorating glucose tolerance status: the Hoorn Study. Circulation. 2003 Apr;107(16):2089–95. https:// doi. org/ 10. 1161/ 01. CIR. 00000 65222. 34933. FC. 2. Prenner SB, Chirinos JA. Arterial stiffness in diabetes mellitus. Atherosclerosis. 2015 Feb;238(2):370–9. https:// doi. org/ 10. 1016/j. ather oscle rosis. 2014. 12. Keywords: Arterial stiffness, augmentation index, pre-diabetes, diabetes Artery Research References Background: Remote ischemic preconditioning (RIPC) is a phenom- ‑ Rodilla Sala E, Adell Alegre M, Giner Galvañ V, Perseguer Torregrosa Z, Pascual enon in which short episodes of ischemia are applied to distant organs Izuel JM, Climent Catalá MT, et al. Arterial stiffness in normotensive and to prepare target organs for more prolonged ischemia and induce hypertensive subjects: frequency in community pharmacies. Med Clin protection against ischemia–reperfusion injury [1]. The aim of this (Barc) 2017;149:469–76 [Article in English, Spanish]. study was to evaluate whether preoperatively performed RIPC affects ‑ Nunan D, Fleming S, Hametner B, Wassertheurer S. Performance of pulse metabolome following vascular surgery and assess if metabolomic wave velocity measured using a brachial cuff in a community setting. changes correlate with heart and kidney injury markers. Blood Press Monit. 2014;19:315–9. Methods: A randomized-controlled, double-blinded trial was con- ducted in the Tartu University Hospital. Patients undergoing open Keywords: Pulse wave velocity, brachial oscillometry, risk stratifica- surgical repair of abdominal aortic aneurysm, surgical lower limb tion, pharmacies revascularization, and carotid endarterectomy were recruited. A RIPC consisting of four cycles of 5 min of ischemia followed by 5 min of rep- erfusion was applied before the operation. The blood was collected P.043 preoperatively and approximately 24  h postoperatively. The metabo- Evaluation of office and ambulatory central blood pressure lome was analyzed with the AbsoluteIDQ p180 Kit. by two methods and their changes after lifestyle or medical Results: The final analysis included 45 patients from the RIPC and 47 interventions in hypertension from the sham group. Baseline characteristics and values of metabo- 1 2 1 3 János Nemcsik , Helga Gyöngyösi , Dóra Batta , Andrea László , Dr. lites were statistically similar between groups. RIPC did not cause sta- 1 1 4 5 Péter Torzsa , Beáta Kőrösi , Zsófia Nemcsik‑Bencze , Orsolya Cseprekál , tistically significant changes in metabolites 24 h postoperatively. There András Tislér was a significant positive correlation between the change Kynure - nine/Tryptophan ratio and the changes of hs-Troponin T (r = 0.570, p Semmelweis University, Department Of Family Medicine, Budapest, Hun‑ ˂0.001), NT-proBNP (r = 0.552, p ˂0.001), Cystatin C (r = 0.534, p ˂0.001) gary, Semmelweis University, Faculty of Medicine, Budapest, Hungary, 3 4 and Beta-2-Microglobulin (r = 0.504, p ˂0.001). Norisana‑ MVZ Rosenau, Nuremberg, Germany, Semmelweis University, Conclusions: Preoperatively performed RIPC did not significantly Department of Neuroradiology, Budapest, Hungary, Semmelweis Univer‑ affect metabolome 24  h after vascular surgery. The positive linear sity, Department of Transplantation and Surgery, Budapest, Hungary, correlation between Kynurenine/Tryptophan ratio and heart and Semmelweis University, Department of Internal Medicine and Oncology, kidney injury markers suggests that the Kynurenine-Tryptophan Budapest, Hungary pathway can play a role in RIPC-associated cardio- and nephropro- Background: Central systolic blood pressure (cSBP) can be evaluated tective effects. in office and also in ambulatory condition, during 24-h monitoring. The aim of our study was to measure office brachial systolic BP (bSBP) Reference and cSBP in the office and brachial SBP and cSBP in 24-h setting