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ISA2018 Abstract Volaume XVIIIth International Symposium on Atherosclerosis June 9–12, 2018 TORONTO CANADA ABSTRACT VOLUME Abstracts, XVIII International Symposium on Atherosclerosis, Toronto, Canada, June 9 - 12, 2018 Table of Contents Oral Presentations C1-1 NLA - CSATVB Joint Session – Familial Hypercholesterolemia . .1 C1-3 NAVBO - CSATVB Joint Session: The Aging Vasculature . .2 C1-4 JAS - CSATVB Joint Session: Endothelial Dysfunction, Aging and Atherosclerosis . 5. C1-5 CIHR – IAPH/ICRH/IG Joint Session: From Molecules to Communities – The Complexities of Indigenous Heart and Brain Health . 8. C1-10 Lipoprotein(a): More Fascinating Than Ever . 9. C1-11 Smooth Muscle Cells: the Workhorse of the Vasculature . 12. C1-12 Pediatric Familial Hypercholesterolemia: Early Origins of Disease . .15 C1-13 Mazankowski Alberta Heart Institute Session: The pros-and-cons of Atherosclerosis Imaging for Drug Development . .17 C1-14 JAS - CSATVB Joint Session: Endothelial Dysfunction, Aging and Atherosclerosis . 19. C2-1 Lipid Therapy: What’s New and What’s Next? . .22 C2-2 Journal of Lipid Research Session: Genetics of Dyslipidemias – the Complexity Intensifies . 25. C2-3 IAS/ International Chair on Cardiometabolic Risk (ICCR) Joint Session – Obesity: The Weight of Evidence . 28. C2-4 Macrophages: Agents Provocateurs in Atherosclerosis . .30 C2-5 PCSK9: Exciting Times for Therapeutic Interventions . .34 C2-6 IAS – EAS Joint Session: Atherosclerosis: From Plaque Biology to Clinical Practice . .37 C2-7 Optimal Medical Treatment for ASCVD: Theory or Reality . .39 C2-8 NLA - CSATVB: Triglyceride Rich Lipoproteins and non-HDL: Residual Risk Embodied . 40. C2-10 Diet and Lifestyle: Turning the Tide Without Drugs . 43. C2-11 Statin Intolerance: a Barrier to Treatment . 47. C2-12 Frontiers in Vascular Biology . 49. C2-13 Inflammation: Dousing the Flames . .52 C2-14 JAS - CSATVB Joint Session: miRNAs in Cardiovascular and Metabolic Disease . .54 C3-1 High Density Lipoproteins: the Coming Renaissance? . 57. C3-2 Diabetes Strategic Patient Oriented Research (SPOR) Network . .58 C3-3 Hypertension . 61. C3-4 Nutraceuticals: New Directions . 65. C3-5 Late Breaking Clinical Trials . .69 C3-6 CIHR-ICRH Distinguished Lecturer / Stars of CSATVB . .76 i Abstracts, XVIII International Symposium on Atherosclerosis, Toronto, Canada, June 9 - 12, 2018 C3-9 HDL and Reverse Cholesterol Transport: Does it Still Matter? . 78 C3-10 Type 2 Diabetes: A Persistent Challenge . .80 C3-11 Widening Impact of Thrombosis Treatment . .83 C3-12 Developmental Determinants of Atherosclerosis . .87 C3-13 CETP: Agonism Versus Antagonism for CV Prevention . .91 Poster Presentations P1: Dyslipidemia: Lipids, Lipoproteins and Apolipoproteins . .92 P2: Epidemiology: Risk Factors . .202 P3: Pathogenesis: Endothelium, Macrophages, Thrombosis, Inflammation, Immunity, Microbiome . 258. P4: Prevention: Lifestyle Measures and Pharmacological Intervention . .389 P5: Therapeutics: Pharmacologic Intervention, New Treatment Modalities, Late Breaking Clinical Trials . 420. ii Abstracts, XVIII International Symposium on Atherosclerosis, Toronto, Canada, June 9 - 12, 2018 Oral Presentations C1-1 NLA - CSATVB Joint Session – Familial Hypercholesterolemia C1-1.05 Preliminary Results from an International Registry on LDL-Apheresis in Children with Homozygous Hypercholesterolemia Ilse K . Luirink1, Eric Bruckert2, Eldad J . Dann3, Susanne Greber-Platzer4, Barbara A . Hutten1, Daiana Ibarretxe5, John J . Kastelein1, Luis Masana5, Martin Mäser6, Rosa M . Sanchez Hernández7, Christina Taylan8, Albert Wieg- man1, Jaap W . Groothoff1 1. AMC, Amsterdam, Netherlands, 2. Hôpital Pitié-Salpêtrière, Paris, France, 3. Rambam Health Care Campus, Haifa, Israel, 4. Department of Pediatrics, University of Vienna, Vienna, Austria, 5. Unitat de Medicina Vascular i Metabolisme, Sant Joan University Hospital, Reus, Spain, 6. Akademisches Lehrkrankenhaus Feldkirch, Feld- kirch, Austria, 7. Hospital Insular de Gran Canaria, Las Palmas, Spain, 8. Children’s and Adolescents’ Hospital, University Hospital of Cologne, Cologne, Germany Objective: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severe- ly elevated low-density lipoprotein cholesterol (LDL-C) levels . If left untreated, patients are at extremely high risk of progressive atherosclerotic cardiovascular disease from early childhood onwards . As HoFH patients hardly respond to diet and modestly to statins there is an urgent need for additional treatment options, of which Lipoprotein Apheresis (LA) is most commonly used . However, the efficacy, safety and optimal way of performing LA are only evaluated in small case series and no consensus exists on its performance and monitoring . We therefore established an international registry in order to obtain information on execution and out- comes of LA in a large group of HoFH children . Methods: Worldwide centres that treated HoFH children (0-18 years) with LA were invited to participate . Of each participating child we collected information on demographics, diagnosis, lipid profile, treatment characteristics and medical history at time of diagnosis and entry into the registry . Follow-up data will be collected every year . Results: We included 26 children (3-18 years) from 7 different countries with molecularly proven HoFH or com- pound heterozygous FH . Most children received apheresis either weekly (40%) or biweekly (40%) and 8 different systems for LA where used . LDL-C at diagnosis ranged from 7 .8–27 .4 mmol/L (mean 19 .3 mmol/L), and after medication from 6 .3–19 .2 mmol/L (mean 13 .8 mmol/L) . On LA, LDL-C further decreased to a mean of 4 .2 mmol/L . Mean LDL-C reduction per session was 70% but only 30% of the children reached their age-specific target levels . Side-effects of LA were minor and occurred in 9 (32%) children with a stomach ache being reported most frequently (14%) . Conclusions: This international registry describes the most comprehensive cohort of living children on apheresis to date and patient inclusion will continue . Results so far show large heterogeneity in the way LA is performed . Ef- ficacy in lowering LDL-C levels is evident and LA is generally well tolerated . Efficacy on long-term cardiovascular outcome is yet to be established using the prospective part of this registry . Our findings will ultimately help clinicians to improve management of these high-risk patients . 1 Abstracts, XVIII International Symposium on Atherosclerosis, Toronto, Canada, June 9 - 12, 2018 C1-3 NAVBO - CSATVB Joint Session: The Aging Vasculature C1-3.04 Sex Difference in the Association of Androgens with Aortic Calcification Tsuyoshi Hashizume, Bo-Kyung Son, Taro Kojima, Michiko Nanao-Hamai, Yusuke Asari, Yumi Umeda-Kame- yama, Sumito Ogawa, Masahiro Akishita Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan Objective: Aortic calcification is a significant pathological phenotype of vascular aging that increases with age and is associated with advanced risk of cardiovascular event . Age-related decline of plasma testosterone and estrogen has been reported to be related to the extent of aortic calcification in men and women, respectively . To further characterize sex difference for the association of sex hormone with aortic calcification, in the present study, we examined the relationship between testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estrogen and aortic calcification both in Japanese men and women . Methods: Subjects in this study were 254 male (mean age ± SD = 54±18 years) and 362 female (mean age ± SD = 66±13 years) outpatients who monitored for cardiovascular disease or risks . Aortic arch calcification (AAC) was examined by postero-anterior plain chest X-ray and its extent was divided into four grades (0 to 3) . Plasma total testosterone, DHEA-S, and estradiol levels were assessed after 12-hour fast in the morning . Results: In men, total testosterone and DHEA-S were significantly correlated with AAC grade (r=-0 .450 and -0 .422, respectively; p<0 .001), while estradiol was not . On the other hand, in women, all of total testosterone, DHEA-S and estradiol were significantly correlated with AAC grade (r=-0 .270, -0 .414 and -0 .203, respectively; p<0 .001) . Multiple regression analysis revealed that total testosterone in men and DHEA-S in women were related to AAC grade independent of age, body mass index, hypertension, dyslipidemia, diabetes mellitus and smoking (β=-0.294, p<0.01; β=-0.346, p<0.05, respectively). DHEA-S and estradiol in men and total testosterone and estradiol in women were not significantly related to AAC grade on multivariate analysis . Conclusions: Total testosterone in men and DHEA-S in women were associated with aortic calcification in- dependent of other risk factors, suggesting sex difference in the association of androgens with aortic calcification . 2 Abstracts, XVIII International Symposium on Atherosclerosis, Toronto, Canada, June 9 - 12, 2018 C1-3.05 The Discoidin Domain Receptor-1 Acts as a Mechanotransducer in Vascular Smooth Muscle Cells to Promote Atherosclerotic Vascular Calcification David Ngai1, 2, Michelle Bendeck1, 2 1. University of Toronto, Toronto, ON, Canada, 2. Ted Rogers Centre for Heart Research, Toronto, ON, Canada Objective: To investigate the hypothesis that DDR1 allows vascular smooth muscle cells (VSMCs) to respond to increases in matrix stiffness during the pathogenesis of atherosclerosis, which promotes VSMC transdifferentia- tion and calcification . Methods: Ddr1+/+ (WT)
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