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Coronary Artery Disease: HELP
Articles from University of Pennsylvania
Based on 222 articles published since 2010
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These are the 222 published articles about Coronary Artery Disease that originated from University of Pennsylvania during 2010-2020.
 
+ Citations + Abstracts
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51 Review Porcine models of accelerated coronary atherosclerosis: role of diabetes mellitus and hypercholesterolemia. 2013

Hamamdzic, Damir / Wilensky, Robert L. ·Cardiovascular Division, Hospital of the University of Pennsylvania and Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. ·J Diabetes Res · Pubmed #23844374.

ABSTRACT: Animal models of atherosclerosis have proven to be an invaluable asset in understanding the pathogenesis of the disease. However, large animal models may be needed in order to assess novel therapeutic approaches to the treatment of atherosclerosis. Porcine models of coronary and peripheral atherosclerosis offer several advantages over rodent models, including similar anatomical size to humans, as well as genetic expression and development of high-risk atherosclerotic lesions which are similar to humans. Here we review the four models of porcine atherosclerosis, including the diabetic/hypercholesterolemic model, Rapacz-familial hypercholesterolemia pig, the (PCSK9) gain-of-function mutant pig model, and the Ossabaw miniature pig model of metabolic syndrome. All four models reliably represent features of human vascular disease.

52 Review Coronary and cardiac computed tomography in the emergency room: current status and future directions. 2013

Cook, Tessa S / Galperin-Aizenberg, Maya / Litt, Harold I. ·Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ·J Thorac Imaging · Pubmed #23744126.

ABSTRACT: In the United States, chest pain is the second leading reason for patients to present to an emergency department (ED). Previously, those patients suspected to have acute coronary syndrome were monitored for 24 hours to determine the presence of serum biomarkers consistent with myocardial injury. However, more recently, imaging has been used to more efficiently triage these individuals and even discharge them directly from the ED. There are multiple cardiac imaging modalities; however, cardiac computed tomography now plays a significant role in the evaluation of patients with suspected acute coronary syndrome who present to the ED. In this review, we discuss the available state-of-the-art techniques for evaluating this cohort of patients, including clinical evaluation, serum biomarkers, and imaging options. Further, we analyze in detail evidence for the use of coronary computed tomography angiography to determine whether these patients can safely be discharged from the ED. Finally, we review some of the related future techniques that may become part of the accepted clinical management of these patients in the future.

53 Review Magnetocardiography for the diagnosis of coronary artery disease: a systematic review and meta-analysis. 2012

Agarwal, Rajender / Saini, Abhimanyu / Alyousef, Tareq / Umscheid, Craig A. ·Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. ·Ann Noninvasive Electrocardiol · Pubmed #23094875.

ABSTRACT: BACKGROUND: Coronary artery disease (CAD) has a significant disease burden making early diagnosis and management imperative. Magnetocardiography (MCG) is a relatively new noninvasive technique that allows diagnosis of CAD by recording the magnetic fields generated by the electrical activity of the heart. METHODS: We searched MEDLINE and the Cochrane Central Register of Controlled Trials for prospective studies that evaluated the test characteristics (e.g., sensitivity, specificity, likelihood ratios) of MCG for detection of CAD. Studies were included if they evaluated either patients with stable CAD documented by angiogram or patients presenting initially with acute coronary syndrome and subsequently diagnosed with CAD. The quality of included studies was assessed using an adaptation of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. We performed meta-analyses of sensitivity, specificity and positive and negative likelihood ratios using Meta-DiSc software. RESULTS: Screening of titles and abstracts followed by full-text review yielded seven studies that met our inclusion criteria. Meta-analyses yielded a pooled sensitivity of 83% (95% confidence interval [CI] 80% to 86%) and a specificity of 77% (95% CI 73% to 81%). The pooled positive likelihood ratio was 3.92 (95% CI 2.30 to 6.66) and negative likelihood ratio was 0.20 (95% CI 0.12 to 0.35). Significant heterogeneity was present in all meta-analyses. CONCLUSIONS: The pooled test characteristics for MCG are similar to those of existing noninvasive modalities for diagnosing CAD. Our results suggest that MCG is a potential complementary or alternative tool for noninvasive detection of CAD.

54 Review Effect of interleukin 1β inhibition in cardiovascular disease. 2012

Qamar, Arman / Rader, Daniel J. ·Cardiovascular Institute, Institute for Translational Medicine and Therapeutics, and Department of Medicine, Perelman School of Medicine at University of Pennsylvania, Philadelphia, Pennsylvania, USA. ·Curr Opin Lipidol · Pubmed #23069985.

ABSTRACT: PURPOSE OF REVIEW: Atherosclerosis is greatly influenced by inflammatory mediators at all phases. Recent studies have suggested a causal role of one such mediator, interleukin 1β (IL-1β), in the development of atherosclerotic vascular disease. This review highlights recent investigation of the role of IL-1β in atherosclerosis and the potential of its inhibition as a promising therapeutic strategy for the treatment of atherosclerotic vascular disease. RECENT FINDINGS: Studies in animals have generally shown decreased atherosclerotic plaque burden in atherosclerosis-prone mice deficient in IL-1β and increased plaque in mice exposed to excess IL-1β. In humans, IL-1β was found in greater concentrations in atherosclerotic human coronary arteries compared with normal coronary arteries. Preclinical and clinical studies of IL-1β inhibition have shown efficacy in the treatment of several inflammatory disorders, suggesting that IL-1β may be a novel therapeutic target for anti-inflammatory therapy in atherosclerosis, such as coronary artery disease (CAD). SUMMARY: IL-1β inhibition offers an interesting and biology-based opportunity to test the potential beneficial effects of an anti-inflammatory therapeutic strategy in patients with CAD. A large clinical trial evaluating the impact of IL-1β inhibition in CAD is ongoing and will be an important test of the inflammation hypothesis in CAD.

55 Review Genetic basis of atherosclerosis: insights from mice and humans. 2012

Stylianou, Ioannis M / Bauer, Robert C / Reilly, Muredach P / Rader, Daniel J. ·Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, 654 BRBII/III Labs, 421 Curie Boulevard, Philadelphia, Pennsylvania, 19104-6160, USA. ·Circ Res · Pubmed #22267839.

ABSTRACT: Atherosclerosis is a complex and heritable disease involving multiple cell types and the interactions of many different molecular pathways. The genetic and molecular mechanisms of atherosclerosis have, in part, been elucidated by mouse models; at least 100 different genes have been shown to influence atherosclerosis in mice. Importantly, unbiased genome-wide association studies have recently identified a number of novel loci robustly associated with atherosclerotic coronary artery disease. Here, we review the genetic data elucidated from mouse models of atherosclerosis, as well as significant associations for human coronary artery disease. Furthermore, we discuss in greater detail some of these novel human coronary artery disease loci. The combination of mouse and human genetics has the potential to identify and validate novel genes that influence atherosclerosis, some of which may be candidates for new therapeutic approaches.

56 Review The year in Cardiothoracic and Vascular Anesthesia: selected highlights from 2011. 2012

Patel, Prakash A / Ramakrishna, Harish / Andritsos, Michael / Wyckoff, Tygh / Riha, Hynek / Augoustides, John G T. ·Cardiovascular and Thoracic Section, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. ·J Cardiothorac Vasc Anesth · Pubmed #22221506.

ABSTRACT: There have been rapid advances in oral anticoagulation. The oral factor Xa inhibitors rivaroxaban and apixaban and the oral direct thrombin inhibitor dabigatran recently have been rigorously evaluated. These novel anticoagulants will usher in a new paradigm for perioperative anticoagulation. Perioperative blood conservation in cardiac surgery recently has been highlighted in the updated guidelines by the Society of Cardiovascular Anesthesiologists and the Society of Thoracic Surgeons. These recommendations reflect a comprehensive evaluation of the recent evidence to optimize transfusion practice. Transcatheter mitral valve repair continues to mature. Transcatheter aortic valve implantation for aortic stenosis has entered the clinical mainstream, with randomized trials showing its superiority over medical management and its equivalency to surgical valve replacement in high-risk patients. This transformational technology represents a major leadership opportunity for the cardiac anesthesiologist. Minimally invasive valve surgery has shown effectiveness in high-risk patients. Radial access is equivalent to femoral access for percutaneous coronary intervention in acute coronary syndromes but significantly reduces the risk of local vascular complications. Recent trials have further clarified the roles of medical therapy, percutaneous coronary intervention, and coronary artery bypass surgery in patients with significant coronary artery disease and left ventricular dysfunction. The past year has witnessed major advances in cardiovascular practice with new drugs, new devices, and new guidelines. The coming year most likely will advance these achievements to enhance the care of patients.

57 Review The novel atherosclerosis locus at 10q11 regulates plasma CXCL12 levels. 2011

Mehta, Nehal N / Li, Mingyao / William, Dilusha / Khera, Amit V / DerOhannessian, Stephanie / Qu, Liming / Ferguson, Jane F / McLaughlin, Catherine / Shaikh, Lalarukh Haris / Shah, Rhia / Patel, Parth N / Bradfield, Jonathan P / He, Jing / Stylianou, Ioannis M / Hakonarson, Hakon / Rader, Daniel J / Reilly, Muredach P. ·Penn Cardiovascular Institute, University of Pennsylvania School of Medicine, Penn Tower, 6th Floor, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA. nehal.mehta@uphs.upenn.edu ·Eur Heart J · Pubmed #21415067.

ABSTRACT: AIMS: Two single-nucleotide polymorphisms (SNPs), rs1746048 and rs501120, from genome wide association studies of coronary artery disease (CAD) map to chromosome 10q11 ∼80 kb downstream of chemokine CXCL12. Therefore, we examined the relationship between these two SNPs and plasma CXCL12 levels. METHODS AND RESULTS: We tested the association of two SNPs with plasma CXCL12 levels in a two-stage study (n= 2939): first in PennCath (n= 1182), a Caucasian, angiographic CAD case-control study, and second in PennCAC (n= 1757), a community-based study of CAD risk factors. Plasma CXCL12 levels increased with age and did not vary by gender. There was no linkage disequilibrium between these two SNPs and SNPs within CXCL12 gene. However, CAD risk alleles at rs1746048 (C allele, P= 0.034; CC 2.33 ± 0.49, CT 2.27 ± 0.46, and TT 2.21 ± 0.52 ng/mL) and rs501120 (T allele, P= 0.041; TT 2.34 ± 0.49, CT 2.28 ± 0.46, and CC 2.23 ± 0.53 ng/mL) were associated with higher plasma levels of CXCL12 in age and gender adjusted models. In Stage 2, we confirmed this association (rs501120, T allele, P= 0.007), and meta-analysis strengthened this finding (n= 2939, P= 6.0 × 10(-4)). Finally, in exploratory analysis, the rs1746048 risk allele tended to have higher transcript levels of CXCL12 in human natural killer cells and the liver. CONCLUSION: Coronary artery disease risk alleles downstream of CXCL12 are associated with plasma protein levels of CXCL12 and appear to be related to CXCL12 transcript levels in two human cell lines. This implicates CXCL12 as potentially causal and supports CXCL12 as a potential therapeutic target for CAD.

58 Review Local drug delivery for treatment of coronary and peripheral artery disease. 2011

Gertz, Zachary M / Wilensky, Robert L. ·Cardiovascular Division, Hospital of the University of Pennsylvania, and Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA. ·Cardiovasc Ther · Pubmed #20553281.

ABSTRACT: Local drug delivery (LDD), the direct application of a therapeutic agent to a focal location, has been used in cardiovascular interventions to prophylactically reduce neointimal hyperplasia and relieve clot burden. LDD allows targeted use of drugs whose toxicities inhibit their systemic use while stent delivery allows for consistent and prolonged delivery. Stents eluting limus family drugs or paclitaxel inhibit vascular smooth muscle cell hyperplasia and migration and clinical use of such stents have reduced restenosis rates after percutaneous coronary procedures. However, associated with the increased efficacy is an increased rate of late stent thrombosis associated with death and myocardial infarction. Recent innovations, including bioabsorbable polymers and completely bioabsorbable stents may expand the use of drug-eluting stents. In this review, we discuss the development, the clinical use, and the effects of LDD from balloon and stent-based platforms in the treatment of restenosis and thrombus.

59 Review CXCL12: a new player in coronary disease identified through human genetics. 2010

Farouk, Samira S / Rader, Daniel J / Reilly, Muredach P / Mehta, Nehal N. ·Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104-6160, USA. ·Trends Cardiovasc Med · Pubmed #22137643.

ABSTRACT: Genome-wide association studies (GWAS) of more than 100,000 people have revealed novel loci associated with coronary artery disease and myocardial infarction that present exciting opportunities to discover novel disease pathways. One such recently identified locus is on chromosome 10q11, near the gene for the chemokine CXCL12, which has been implicated in cardiovascular disease in both mouse and human studies. These GWAS demonstrate that CXCL12 may emerge as a potential therapeutic target for atherosclerosis and thrombosis.

60 Clinical Trial Associations of Lipoprotein(a) Levels With Incident Atrial Fibrillation and Ischemic Stroke: The ARIC (Atherosclerosis Risk in Communities) Study. 2017

Aronis, Konstantinos N / Zhao, Di / Hoogeveen, Ron C / Alonso, Alvaro / Ballantyne, Christie M / Guallar, Eliseo / Jones, Steven R / Martin, Seth S / Nazarian, Saman / Steffen, Brian T / Virani, Salim S / Michos, Erin D. ·Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. · Division of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX. · Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA. · Division of Cardiology, University of Pennsylvania Medical System University of Pennsylvania School of Medicine, Philadelphia, PA. · Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN. · Michael E. DeBakey Veterans Affairs Medical Center and Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX. · Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD edonnell@jhmi.edu. ·J Am Heart Assoc · Pubmed #29246963.

ABSTRACT: BACKGROUND: Lipoprotein(a) (Lp[a]) is proatherosclerotic and prothrombotic, causally related to coronary disease, and associated with other cardiovascular diseases. The association of Lp(a) with incident atrial fibrillation (AF) and with ischemic stroke among individuals with AF remains to be elucidated. METHODS AND RESULTS: In the community-based ARIC (Atherosclerosis Risk in Communities) study cohort, Lp(a) levels were measured by a Denka Seiken assay at visit 4 (1996-1998). We used multivariable-adjusted Cox models to compare AF and ischemic stroke risk across Lp(a) levels. First, we evaluated incident AF in 9908 participants free of AF at baseline. AF was ascertained by electrocardiography at study visits, hospital CONCLUSIONS: High Lp(a) levels were not associated with incident AF. Lp(a) levels were associated with increased ischemic stroke risk, primarily among individuals without AF but not in those with AF.

61 Clinical Trial Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease. 2017

Dewey, Frederick E / Gusarova, Viktoria / Dunbar, Richard L / O'Dushlaine, Colm / Schurmann, Claudia / Gottesman, Omri / McCarthy, Shane / Van Hout, Cristopher V / Bruse, Shannon / Dansky, Hayes M / Leader, Joseph B / Murray, Michael F / Ritchie, Marylyn D / Kirchner, H Lester / Habegger, Lukas / Lopez, Alex / Penn, John / Zhao, An / Shao, Weiping / Stahl, Neil / Murphy, Andrew J / Hamon, Sara / Bouzelmat, Aurelie / Zhang, Rick / Shumel, Brad / Pordy, Robert / Gipe, Daniel / Herman, Gary A / Sheu, Wayne H H / Lee, I-Te / Liang, Kae-Woei / Guo, Xiuqing / Rotter, Jerome I / Chen, Yii-Der I / Kraus, William E / Shah, Svati H / Damrauer, Scott / Small, Aeron / Rader, Daniel J / Wulff, Anders Berg / Nordestgaard, Børge G / Tybjærg-Hansen, Anne / van den Hoek, Anita M / Princen, Hans M G / Ledbetter, David H / Carey, David J / Overton, John D / Reid, Jeffrey G / Sasiela, William J / Banerjee, Poulabi / Shuldiner, Alan R / Borecki, Ingrid B / Teslovich, Tanya M / Yancopoulos, George D / Mellis, Scott J / Gromada, Jesper / Baras, Aris. ·From Regeneron Genetics Center (F.E.D., C.O., C.S., O.G., S.M., C.V.V.H., S.B., L.H., A.L., J.P., N.S., A.J.M., J.D.O., J.G.R., A.R.S., I.B.B., T.M.T., G.D.Y., S.J.M., A. Baras) and Regeneron Pharmaceuticals (V.G., H.M.D., A.Z., W.S., N.S., A.J.M., S.H., A. Bouzelmat, R.Z., B.S., R.P., D.G., G.A.H., W.J.S., P.B., G.D.Y., S.J.M., J.G.) Tarrytown, NY · the Department of Medicine, Division of Translational Medicine and Human Genetics (R.L.D.), and Departments of Surgery (S.D.) and Genetics and Medicine (A.S., D.J.R.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, and Geisinger Health System, Danville (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.) - both in Pennsylvania · the Division of Endocrinology and Metabolism, Department of Internal Medicine (W.H.H.S., I.-T.L.) and Cardiovascular Center (K.-W.L.), Taichung Veterans General Hospital, Institute of Medical Technology, National Chung-Hsing University (W.H.H.S.), School of Medicine, Chung Shan Medical University (I.-T.L.), and the Department of Medicine, China Medical University (K.-W.L.), Taichung, and School of Medicine, National Yang-Ming University (W.H.H.S., I.-T.L., K.-W.L.), and School of Medicine, National Defense Medical Center (W.H.H.S.), Taipei - all in Taiwan · Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (X.G., J.I.R., Y.-D.I.C.) · the Division of Cardiology, Department of Medicine, Molecular Physiology Institute, School of Medicine, Duke University, Durham, NC (W.E.K., S.H.S.) · the Department of Clinical Biochemistry, Rigshospitalet (A.B.W., B.G.N., A.T.-H.), the Copenhagen General Population Study (B.G.N., A.T.-H.) and Department of Clinical Biochemistry (B.G.N.), Herlev and Gentofte Hospital, and the Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, and Faculty of Health and Medical Sciences, University of Copenhagen (B.G.N., A.T.-H.) - all in Copenhagen · and TNO Metabolic Health Research, Gaubius Laboratory, Leiden, the Netherlands (A.M.H., H.M.G.P.). ·N Engl J Med · Pubmed #28538136.

ABSTRACT: BACKGROUND: Loss-of-function variants in the angiopoietin-like 3 gene (ANGPTL3) have been associated with decreased plasma levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. It is not known whether such variants or therapeutic antagonism of ANGPTL3 are associated with a reduced risk of atherosclerotic cardiovascular disease. METHODS: We sequenced the exons of ANGPTL3 in 58,335 participants in the DiscovEHR human genetics study. We performed tests of association for loss-of-function variants in ANGPTL3 with lipid levels and with coronary artery disease in 13,102 case patients and 40,430 controls from the DiscovEHR study, with follow-up studies involving 23,317 case patients and 107,166 controls from four population studies. We also tested the effects of a human monoclonal antibody, evinacumab, against Angptl3 in dyslipidemic mice and against ANGPTL3 in healthy human volunteers with elevated levels of triglycerides or LDL cholesterol. RESULTS: In the DiscovEHR study, participants with heterozygous loss-of-function variants in ANGPTL3 had significantly lower serum levels of triglycerides, HDL cholesterol, and LDL cholesterol than participants without these variants. Loss-of-function variants were found in 0.33% of case patients with coronary artery disease and in 0.45% of controls (adjusted odds ratio, 0.59; 95% confidence interval, 0.41 to 0.85; P=0.004). These results were confirmed in the follow-up studies. In dyslipidemic mice, inhibition of Angptl3 with evinacumab resulted in a greater decrease in atherosclerotic lesion area and necrotic content than a control antibody. In humans, evinacumab caused a dose-dependent placebo-adjusted reduction in fasting triglyceride levels of up to 76% and LDL cholesterol levels of up to 23%. CONCLUSIONS: Genetic and therapeutic antagonism of ANGPTL3 in humans and of Angptl3 in mice was associated with decreased levels of all three major lipid fractions and decreased odds of atherosclerotic cardiovascular disease. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT01749878 .).

62 Clinical Trial Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: Rationale and design of the ACCELERATE trial. 2015

Nicholls, Stephen J / Lincoff, A Michael / Barter, Philip J / Brewer, H Bryan / Fox, Keith A A / Gibson, C Michael / Grainger, Christopher / Menon, Venugopal / Montalescot, Gilles / Rader, Daniel / Tall, Alan R / McErlean, Ellen / Riesmeyer, Jeffrey / Vangerow, Burkhard / Ruotolo, Giacomo / Weerakkody, Govinda J / Nissen, Steven E. ·South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia. · Cleveland Clinic Coordinating Center for Clinical Research and Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH. · University of New South Wales, Sydney, Australia. · Medstar Research Institute, Hyattsville, MD. · University of Edinburgh, Edinburgh, Scotland. · Harvard Medical School, Boston, MA. · Duke Clinical Research Institute, Durham, NC. · Pitie-Salpetriere University Hospital, Paris, France. · University of Pennsylvania, Philadelphia, PA. · Columbia University, New York City, NY. · Eli Lilly and Company, Indianapolis, IN. ·Am Heart J · Pubmed #26678626.

ABSTRACT: BACKGROUND: Potent pharmacologic inhibition of cholesteryl ester transferase protein by the investigational agent evacetrapib increases high-density lipoprotein cholesterol by 54% to 129%, reduces low-density lipoprotein cholesterol by 14% to 36%, and enhances cellular cholesterol efflux capacity. The ACCELERATE trial examines whether the addition of evacetrapib to standard medical therapy reduces the risk of cardiovascular (CV) morbidity and mortality in patients with high-risk vascular disease. STUDY DESIGN: ACCELERATE is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients qualified for enrollment if they have experienced an acute coronary syndrome within the prior 30 to 365 days, cerebrovascular accident, or transient ischemic attack; if they have peripheral vascular disease; or they have diabetes with coronary artery disease. A total of 12,092 patients were randomized to evacetrapib 130 mg or placebo daily in addition to standard medical therapy. The primary efficacy end point is time to first event of CV death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Treatment will continue until 1,670 patients reached the primary end point; at least 700 patients reach the key secondary efficacy end point of CV death, myocardial infarction, and stroke, and the last patient randomized has been followed up for at least 1.5 years. CONCLUSIONS: ACCELERATE will establish whether the cholesteryl ester transfer protein inhibition by evacetrapib improves CV outcomes in patients with high-risk vascular disease.

63 Clinical Trial Infusion of Reconstituted High-Density Lipoprotein, CSL112, in Patients With Atherosclerosis: Safety and Pharmacokinetic Results From a Phase 2a Randomized Clinical Trial. 2015

Tricoci, Pierluigi / D'Andrea, Denise M / Gurbel, Paul A / Yao, Zhenling / Cuchel, Marina / Winston, Brion / Schott, Robert / Weiss, Robert / Blazing, Michael A / Cannon, Louis / Bailey, Alison / Angiolillo, Dominick J / Gille, Andreas / Shear, Charles L / Wright, Samuel D / Alexander, John H. ·Duke Clinical Research Institute, Durham, NC (P.T., M.A.B., J.H.A.). · CSL Behring, King of Prussia, PA (D.M.A., Z.Y., C.L.S., S.D.W.). · Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore and Johns Hopkins University School of Medicine, Baltimore, MD (P.A.G.). · University of Pennsylvania, Philadelphia, PA (M.C.). · Black Hills Cardiovascular Research, Rapid City, SD (B.W.). · diaDexus, Inc., San Francisco, CA (R.S.). · Maine Research Associates, Auburn, ME (R.W.). · Cardiac and Vascular Research Center of Northern Michigan, Petoskey, MI (L.C.). · Gill Heart Institute, University of Kentucky, Lexington, KY (A.B.). · University of Florida College of Medicine-Jacksonville, Jacksonville, FL (D.J.A.). · CSL Limited, Parkville, Victoria, Australia (A.G.). ·J Am Heart Assoc · Pubmed #26307570.

ABSTRACT: BACKGROUND: CSL112 is a new formulation of human apolipoprotein A-I (apoA-I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double-blind, multicenter, dose-ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease. METHODS AND RESULTS: Patients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2-hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations >3× upper limits of normal and study drug-related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA-I plasma concentration and measures of the ability of serum to promote cholesterol efflux from cells ex vivo. Of 45 patients randomized, 7, 12, and 14 received 1.7-, 3.4-, and 6.8-g CSL112, respectively, and 11 received placebo. There were no clinically significant elevations (>3× upper limit of normal) in alanine aminotransferase or aspartate aminotransferase. Adverse events were nonserious and mild and occurred in 5 (71%), 5 (41%), and 6 (43%) patients in the CSL112 1.7-, 3.4-, and 6.8-g groups, respectively, compared with 3 (27%) placebo patients. The imbalance in adverse events was attributable to vessel puncture/infusion-site bruising. CSL112 resulted in rapid (T(max)≈2 hours) and dose-dependent increases in apoA-I (145% increase in the 6.8-g group) and total cholesterol efflux (up to 3.1-fold higher than placebo) (P<0.001). CONCLUSIONS: CSL112 infusion was well tolerated in patients with stable atherosclerotic disease. CSL112 immediately raised apoA-I levels and caused a rapid and marked increase in the capacity of serum to efflux cholesterol. This potential novel approach for the treatment of atherosclerosis warrants further investigation. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01499420.

64 Clinical Trial Non-cancer endpoints in BRCA1/2 carriers after risk-reducing salpingo-oophorectomy. 2012

Cohen, J V / Chiel, L / Boghossian, L / Jones, M / Stopfer, J E / Powers, J / Rebbeck, T R / Nathanson, K L / Domchek, S M. ·Pennsylvania Hospital, Philadelphia, PA, USA. ·Fam Cancer · Pubmed #21898151.

ABSTRACT: Risk-reducing salpingo-oophorectomy (RRSO) significantly reduces the risk of ovarian cancer and breast cancer in pre-menopausal women with BRCA1 and BRCA2 (B1/2) mutations. Despite its clear benefits, little is known about non-cancer endpoints in this population. Medical records were examined in 226 B1/2 mutation carriers, who had previously undergone RRSO with a focus on bone health as well as the frequency of hypertension, hyperlipidemia, coronary artery disease (CAD), myocardial infarction (MI), diabetes, hypothyroidism and depression. From the medical records, DEXA scans, medications and medical conditions were recorded. Of the 226 patient records examined, 16% (36/226) had hypertension, 17% (39/226) hyperlipidemia, 2% (5/226) CAD or MI, 2% (4/226) diabetes, 13% (29/226) hypothyroidism and 14% (31/226) depression. DEXA results were available in 152 women. Of those DEXA scans, 71% (108/152) were abnormal (57% osteopenia and 14% osteoporosis). Among women who underwent RRSO prior to age 50, 71% (62/88) had osteopenia/osteoporosis. Although there was no difference in osteopenia/osteoporosis in women with RRSO prior to age 50 compared to those RRSO > 50, the age at follow up in these two groups differs greatly (mean age 44.7 vs. 60.6), suggesting that both current age and age at RRSO contribute to bone health assessment. In summary, here, we report the prevalence of non-cancer endpoints in a cohort of B1/2 mutation carriers and note a particularly high rate of osteopenia and osteoporosis in B1/2 with breast cancer undergoing RRSO prior to 50. Despite the risk reduction RRSO offers, attention should be paid to non-cancer endpoints, particularly bone health, in this population.

65 Article Predictive Utility of Polygenic Risk Scores for Coronary Heart Disease in Three Major Racial and Ethnic Groups. 2020

Dikilitas, Ozan / Schaid, Daniel J / Kosel, Matthew L / Carroll, Robert J / Chute, Christopher G / Denny, Joshua A / Fedotov, Alex / Feng, QiPing / Hakonarson, Hakon / Jarvik, Gail P / Lee, Ming Ta Michael / Pacheco, Jennifer A / Rowley, Robb / Sleiman, Patrick M / Stein, C Michael / Sturm, Amy C / Wei, Wei-Qi / Wiesner, Georgia L / Williams, Marc S / Zhang, Yanfei / Manolio, Teri A / Kullo, Iftikhar J. ·Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. · Department of Biomedical Informatics, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37212, USA. · Schools of Medicine, Public Health, and Nursing, Johns Hopkins University, Baltimore, MD 21205, USA. · Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY 10032, USA. · Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37212, USA. · Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. · Department of Medicine, University of Washington, Seattle, WA 98195, USA. · Geisinger, Danville, PA 17822, USA. · Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. · National Human Genome Research Institute, Bethesda, MD 20892, USA. · Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37212, USA. · Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: kullo.iftikhar@mayo.edu. ·Am J Hum Genet · Pubmed #32386537.

ABSTRACT: Because polygenic risk scores (PRSs) for coronary heart disease (CHD) are derived from mainly European ancestry (EA) cohorts, their validity in African ancestry (AA) and Hispanic ethnicity (HE) individuals is unclear. We investigated associations of "restricted" and genome-wide PRSs with CHD in three major racial and ethnic groups in the U.S. The eMERGE cohort (mean age 48 ± 14 years, 58% female) included 45,645 EA, 7,597 AA, and 2,493 HE individuals. We assessed two restricted PRSs (PRS

66 Article Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. 2020

Shah, Sonia / Henry, Albert / Roselli, Carolina / Lin, Honghuang / Sveinbjörnsson, Garðar / Fatemifar, Ghazaleh / Hedman, Åsa K / Wilk, Jemma B / Morley, Michael P / Chaffin, Mark D / Helgadottir, Anna / Verweij, Niek / Dehghan, Abbas / Almgren, Peter / Andersson, Charlotte / Aragam, Krishna G / Ärnlöv, Johan / Backman, Joshua D / Biggs, Mary L / Bloom, Heather L / Brandimarto, Jeffrey / Brown, Michael R / Buckbinder, Leonard / Carey, David J / Chasman, Daniel I / Chen, Xing / Chen, Xu / Chung, Jonathan / Chutkow, William / Cook, James P / Delgado, Graciela E / Denaxas, Spiros / Doney, Alexander S / Dörr, Marcus / Dudley, Samuel C / Dunn, Michael E / Engström, Gunnar / Esko, Tõnu / Felix, Stephan B / Finan, Chris / Ford, Ian / Ghanbari, Mohsen / Ghasemi, Sahar / Giedraitis, Vilmantas / Giulianini, Franco / Gottdiener, John S / Gross, Stefan / Guðbjartsson, Daníel F / Gutmann, Rebecca / Haggerty, Christopher M / van der Harst, Pim / Hyde, Craig L / Ingelsson, Erik / Jukema, J Wouter / Kavousi, Maryam / Khaw, Kay-Tee / Kleber, Marcus E / Køber, Lars / Koekemoer, Andrea / Langenberg, Claudia / Lind, Lars / Lindgren, Cecilia M / London, Barry / Lotta, Luca A / Lovering, Ruth C / Luan, Jian'an / Magnusson, Patrik / Mahajan, Anubha / Margulies, Kenneth B / März, Winfried / Melander, Olle / Mordi, Ify R / Morgan, Thomas / Morris, Andrew D / Morris, Andrew P / Morrison, Alanna C / Nagle, Michael W / Nelson, Christopher P / Niessner, Alexander / Niiranen, Teemu / O'Donoghue, Michelle L / Owens, Anjali T / Palmer, Colin N A / Parry, Helen M / Perola, Markus / Portilla-Fernandez, Eliana / Psaty, Bruce M / Anonymous2011141 / Rice, Kenneth M / Ridker, Paul M / Romaine, Simon P R / Rotter, Jerome I / Salo, Perttu / Salomaa, Veikko / van Setten, Jessica / Shalaby, Alaa A / Smelser, Diane T / Smith, Nicholas L / Stender, Steen / Stott, David J / Svensson, Per / Tammesoo, Mari-Liis / Taylor, Kent D / Teder-Laving, Maris / Teumer, Alexander / Thorgeirsson, Guðmundur / Thorsteinsdottir, Unnur / Torp-Pedersen, Christian / Trompet, Stella / Tyl, Benoit / Uitterlinden, Andre G / Veluchamy, Abirami / Völker, Uwe / Voors, Adriaan A / Wang, Xiaosong / Wareham, Nicholas J / Waterworth, Dawn / Weeke, Peter E / Weiss, Raul / Wiggins, Kerri L / Xing, Heming / Yerges-Armstrong, Laura M / Yu, Bing / Zannad, Faiez / Zhao, Jing Hua / Hemingway, Harry / Samani, Nilesh J / McMurray, John J V / Yang, Jian / Visscher, Peter M / Newton-Cheh, Christopher / Malarstig, Anders / Holm, Hilma / Lubitz, Steven A / Sattar, Naveed / Holmes, Michael V / Cappola, Thomas P / Asselbergs, Folkert W / Hingorani, Aroon D / Kuchenbaecker, Karoline / Ellinor, Patrick T / Lang, Chim C / Stefansson, Kari / Smith, J Gustav / Vasan, Ramachandran S / Swerdlow, Daniel I / Lumbers, R Thomas. ·Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia. · Institute of Cardiovascular Science, University College London, London, UK. · British Heart Foundation Research Accelerator, University College London, London, UK. · Institute of Health Informatics, University College London, London, UK. · Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA. · Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. · Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. · National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA. · deCODE genetics/Amgen Inc., Sturlugata 8, 101, Reykjavik, Iceland. · Health Data Research UK London, University College London, London, UK. · Cardiovascular Medicine unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden. · Pfizer Worldwide Research & Development, 1 Portland St, Cambridge, MA, USA. · Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, London, W2 1PG, UK. · MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, London, W2 1PG, UK. · Department of Clinical Sciences, Lund University, Malmö, Sweden. · Department of Cardiology, Herlev Gentofte Hospital, Herlev Ringvej 57, 2650, Herlev, Denmark. · Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. · Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA. · Department of Neurobiology, Care Sciences and Society/ Section of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden. · School of Health and Social Sciences, Dalarna University, Falun, Sweden. · Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA. · Department of Biostatistics, University of Washington, Seattle, WA, USA. · Department of Medicine, University of Washington, Seattle, WA, USA. · Division of Cardiology, Department of Medicine, Emory University Medical Center, Atlanta, GA, USA. · Department of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas, USA. · Department of Molecular and Functional Genomics, Geisinger, Danville, PA, USA. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA. · Harvard Medical School, Boston, MA, 02115, USA. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Novartis Institutes for Biomedical Research, Cambridge, MA, USA. · Department of Biostatistics, University of Liverpool, Liverpool, UK. · Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Germany. · The National Institute for Health Research University College London Hospitals Biomedical Research Centre, University College London, London, UK. · The Alan Turing Institute, London, United Kingdom. · Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK. · Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany. · DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany. · Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN, USA. · Regeneron Pharmaceuticals, Cardiovascular Research, 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA. · Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, 51010, Estonia. · Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. · Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, 75185, Sweden. · Department of Medicine, Division of Cardiology, University of Maryland School of Medicine, Baltimore, MD, USA. · School of Engineering and Natural Sciences, University of Iceland, 101, Reykjavik, Iceland. · Division of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA. · Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. · Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands. · Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA. · Stanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA. · Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. · Stanford Diabetes Research Center, Stanford University, Stanford, CA, 94305, USA. · Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. · Einthoven Laboratory for Experimental Vascular Medicine, LUMC, Leiden, The Netherlands. · Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB2 0QQ, UK. · Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. · Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK. · MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, UK. · Department of Medical Sciences, Uppsala University, Uppsala, Sweden. · Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. · Division of Cardiovascular Medicine and Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA, USA. · Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany. · Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. · Department of Internal Medicine, Clinical Sciences, Lund University and Skåne University Hospital, Malmö, Sweden. · Vanderbilt University School of Medicine, Nashville, TN, USA. · Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom. · Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria. · National Institute for Health and Welfare, Helsinki, Finland. · Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland. · TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA. · Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. · Department of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA. · Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA, USA. · The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA. · Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands. · Division of Cardiology, Department of Medicine, University of Pittsburgh Medical Center and VA Pittsburgh HCS, Pittsburgh, PA, USA. · Department of Epidemiology, University of Washington, Seattle, WA, USA. · Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research & Development, Seattle, WA, USA. · Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte, København, Denmark. · Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. · Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden. · Department of Cardiology, Södersjukhuset, Stockholm, Sweden. · Institute for Translational Genomics and Population Sciences, LABiomed and Departments of Pediatrics at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA. · Division of Cardiology, Department of Internal Medicine, Landspitali, National University Hospital of Iceland, Hringbraut, 101, Reykjavik, Iceland. · Faculty of Medicine, Department of Medicine, University of Iceland, Saemundargata 2, 101, Reykjavik, Iceland. · Department of Epidemiology and Biostatistics, Aalborg University Hospital, Aalborg, Denmark. · Department of Health, Science and Technology, Aalborg University Hospital, Aalborg, Denmark. · Departments of Cardiology, Aalborg University Hospital, Aalborg, Denmark. · Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands. · Translational and Clinical Research, Servier Cardiovascular Center for Therapeutic Innovation, 50 rue Carnot, 92284, Suresnes, France. · Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. · Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. · Human Genetics, GlaxoSmithKline, Collegeville, PA, USA. · Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, OH, USA. · Université de Lorraine, CHU de Nancy, Inserm and INI-CRCT (F-CRIN), Institut Lorrain du Coeur et des Vaisseaux, 54500, Vandoeuvre Lès, Nancy, France. · BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. · Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia. · Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA. · Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA. · Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, UK. · Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Big Data Institute, University of Oxford, Oxford, UK. · National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital, Oxford, UK. · Division of Psychiatry, University College of London, London, W1T 7NF, UK. · UCL Genetics Institute, University College London, London, WC1E 6BT, UK. · Department of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden. · Wallenberg Center for Molecular Medicine and Lund University Diabetes Center, Lund University, Lund, Sweden. · Sections of Cardiology, Preventive Medicine and Epidemiology, Department of Medicine, Boston University Schools of Medicine and Public Health, Boston, MA, USA. · British Heart Foundation Research Accelerator, University College London, London, UK. t.lumbers@ucl.ac.uk. · Institute of Health Informatics, University College London, London, UK. t.lumbers@ucl.ac.uk. · Health Data Research UK London, University College London, London, UK. t.lumbers@ucl.ac.uk. · Bart's Heart Centre, St. Bartholomew's Hospital, London, UK. t.lumbers@ucl.ac.uk. ·Nat Commun · Pubmed #31919418.

ABSTRACT: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

67 Article Biomarkers and Noncalcified Coronary Artery Plaque Progression in Older Men Treated With Testosterone. 2020

Shaikh, Kashif / Ellenberg, Susan S / Nakanishi, Rine / Snyder, Peter J / Lee, Juhwan / Wenger, Nanette K / Lewis, Cora E / Swerdloff, Ronald S / Preston, Peter / Hamal, Sajad / Stephens-Sheilds, Alisa / Bhasin, Shalender / Cherukuri, Lavanya / Cauley, Jane A / Crandall, Jill P / Cunningham, Glenn R / Ensrud, Kristine E / Matsumoto, Alvin M / Molich, Mark E / Alla, Venkata M / Birudaraju, Divya / Nezarat, Negin / Rai, Kelash / Almeida, Shone / Roy, Sion K / Sheikh, Mohammad / Trad, George / Budoff, Mathew J. ·Division of Cardiology, Lundquist Institute of Biomedical Innovation, Harbor-University of California at Los Angeles Medical Center, Torrance, California. · Division of Cardiovascular Diseases, Creighton University School of Medicine, Omaha, Nebraska. · Department of Biostatistics and Epidemiology, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania. · Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Medicine, Division of Cardiology, Emory Heart and Vascular Center Emory University School of Medicine, Atlanta, Georgia. · Division of Preventive Medicine, University of Alabama at Birmingham, Alabama. · Division of Endocrinology, Lundquist Institute of Biomedical Innovation, Harbor-University of California at Los Angeles Medical Center, Torrance, California. · Department of Family and Preventive Medicine, Division of Epidemiology, University of California, San Diego School of Medicine, La Jolla, California. · Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, Pennsylvania. · Divisions of Endocrinology and Geriatrics, Albert Einstein College of Medicine, Bronx, New York. · Departments of Medicine and Molecular & Cellular Biology, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine and Baylor St. Luke's Medical Center, Houston, Texas. · Department of Medicine, Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, Minnesota. · Minneapolis VA Health Care System, Minneapolis, Minnesota. · Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs, Puget Sound Health System, and Division of Gerontology and Geriatric Medicine, Department of Internal Medicine, University of Washington School of Medicine, Seattle, Washington. · Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. ·J Clin Endocrinol Metab · Pubmed #31784747.

ABSTRACT: OBJECTIVE: Recent results from the Cardiovascular Trial of the Testosterone Trials showed that testosterone treatment of older men with low testosterone was associated with greater progression of noncalcified plaque (NCP). We evaluated the effect of anthropometric measures and cardiovascular biomarkers on plaque progression in individuals in the Testosterone Trial. METHODS: The Cardiovascular part of the trial included 170 men aged 65 years or older with low testosterone. Participants received testosterone gel or placebo gel for 12 months. The primary outcome was change in NCP volume from baseline to 12 months, as determined by coronary computed tomography angiography (CCTA). We assayed several markers of cardiovascular risk and analyzed each marker individually in a model as predictive variables and change in NCP as the dependent variable. RESULTS: Of 170 enrollees, 138 (73 testosterone, 65 placebo) completed the study and were available for the primary analysis. Of 10 markers evaluated, none showed a significant association with the change in NCP volume, but a significant interaction between treatment assignment and waist-hip ratio (WHR) (P = 0.0014) indicated that this variable impacted the testosterone effect on NCP volume. The statistical model indicated that for every 0.1 change in the WHR, the testosterone-induced 12-month change in NCP volume increased by 26.96 mm3 (95% confidence interval, 7.72-46.20). CONCLUSION: Among older men with low testosterone treated for 1 year, greater WHR was associated with greater NCP progression, as measured by CCTA. Other biomarkers and anthropometric measures did not show statistically significant association with plaque progression.

68 Article None 2019

Sorci, Olivia / Batzdorf, Alexandra S / Mayer, Michael / Rhodes, Sylvia / Peng, Matthew / Jankelovits, Amanda R / Hornyak, Julia N / Gerke, Oke / Høilund-Carlsen, Poul Flemming / Alavi, Abass / Rajapakse, Chamith S. ·Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA. · Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark. · Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA. chamith@pennmedicine.upenn.edu. · Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, USA. chamith@pennmedicine.upenn.edu. · MRI Education Center, 1 Founders Building, 3400 Spruce St., Philadelphia, PA, 19104, USA. chamith@pennmedicine.upenn.edu. ·Eur J Nucl Med Mol Imaging · Pubmed #31734781.

ABSTRACT: AIMS: To investigate the benefit of utilizing METHODS AND RESULTS: This retrospective study included 136 participants (ages 21-75, BMI 18-43 kg/m CONCLUSION: Unlike calcium scores, NaF PET/CT-derived values differed between patients and controls. Framingham risk score patterns echoed those of SUV TRIAL REGISTRATION: ClinicalTrials.gov (NCT01724749).

69 Article Application of machine learning to determine top predictors of noncalcified coronary burden in psoriasis: An observational cohort study. 2019

Munger, Eric / Choi, Harry / Dey, Amit K / Elnabawi, Youssef A / Groenendyk, Jacob W / Rodante, Justin / Keel, Andrew / Aksentijevich, Milena / Reddy, Aarthi S / Khalil, Noor / Argueta-Amaya, Jenis / Playford, Martin P / Erb-Alvarez, Julie / Tian, Xin / Wu, Colin / Gudjonsson, Johann E / Tsoi, Lam C / Jafri, Mohsin Saleet / Sandfort, Veit / Chen, Marcus Y / Shah, Sanjiv J / Bluemke, David A / Lockshin, Benjamin / Hasan, Ahmed / Gelfand, Joel M / Mehta, Nehal N. ·George Mason University, Fairfax, Virginia. · National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. · University of Michigan, Ann Arbor, Michigan. · Northwestern University, Chicago, Illinois. · University of Wisconsin, Madison, Wisconsin. · DermAssociates, Silver Spring, Maryland. · University of Pennsylvania, Philadelphia, Pennsylvania. · National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: nehal.mehta@nih.gov. ·J Am Acad Dermatol · Pubmed #31678339.

ABSTRACT: BACKGROUND: Psoriasis is associated with elevated risk of heart attack and increased accumulation of subclinical noncalcified coronary burden by coronary computed tomography angiography (CCTA). Machine learning algorithms have been shown to effectively analyze well-characterized data sets. OBJECTIVE: In this study, we used machine learning algorithms to determine the top predictors of noncalcified coronary burden by CCTA in psoriasis. METHODS: The analysis included 263 consecutive patients with 63 available variables from the Psoriasis Atherosclerosis Cardiometabolic Initiative. The random forest algorithm was used to determine the top predictors of noncalcified coronary burden by CCTA. We evaluated our results using linear regression models. RESULTS: Using the random forest algorithm, we found that the top 10 predictors of noncalcified coronary burden were body mass index, visceral adiposity, total adiposity, apolipoprotein A1, high-density lipoprotein, erythrocyte sedimentation rate, subcutaneous adiposity, small low-density lipoprotein particle, cholesterol efflux capacity and the absolute granulocyte count. Linear regression of noncalcified coronary burden yielded results consistent with our machine learning output. LIMITATION: We were unable to provide external validation and did not study cardiovascular events. CONCLUSION: Machine learning methods identified the top predictors of noncalcified coronary burden in psoriasis. These factors were related to obesity, dyslipidemia, and inflammation, showing that these are important targets when treating comorbidities in psoriasis.

70 Article Powerful three-sample genome-wide design and robust statistical inference in summary-data Mendelian randomization. 2019

Zhao, Qingyuan / Chen, Yang / Wang, Jingshu / Small, Dylan S. ·Department of Statistics, Wharton School, University of Pennsylvania, Philadelphia, PA, USA. · Department of Statistics, University of Michigan, Ann Arbor, MI, USA. ·Int J Epidemiol · Pubmed #31298269.

ABSTRACT: BACKGROUND: Summary-data Mendelian randomization (MR) has become a popular research design to estimate the causal effect of risk exposures. With the sample size of GWAS continuing to increase, it is now possible to use genetic instruments that are only weakly associated with the exposure. DEVELOPMENT: We propose a three-sample genome-wide design where typically 1000 independent genetic instruments across the whole genome are used. We develop an empirical partially Bayes statistical analysis approach where instruments are weighted according to their strength; thus weak instruments bring less variation to the estimator. The estimator is highly efficient with many weak genetic instruments and is robust to balanced and/or sparse pleiotropy. APPLICATION: We apply our method to estimate the causal effect of body mass index (BMI) and major blood lipids on cardiovascular disease outcomes, and obtain substantially shorter confidence intervals (CIs). In particular, the estimated causal odds ratio of BMI on ischaemic stroke is 1.19 (95% CI: 1.07-1.32, P-value <0.001); the estimated causal odds ratio of high-density lipoprotein cholesterol (HDL-C) on coronary artery disease (CAD) is 0.78 (95% CI: 0.73-0.84, P-value <0.001). However, the estimated effect of HDL-C attenuates and become statistically non-significant when we only use strong instruments. CONCLUSIONS: A genome-wide design can greatly improve the statistical power of MR studies. Robust statistical methods may alleviate but not solve the problem of horizontal pleiotropy. Our empirical results suggest that the relationship between HDL-C and CAD is heterogeneous, and it may be too soon to completely dismiss the HDL hypothesis.

71 Article Genome-wide association analysis of HDL-C in a Lebanese cohort. 2019

Deek, Rebecca / Nasser, Jason / Ghanem, Anthony / Mardelli, Marc / Khazen, Georges / Salloum, Angelique K / Abchee, Antoine / Ghassibe-Sabbagh, Michella / Zalloua, Pierre. ·Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America. · School of Medicine, Lebanese American University, Beirut, Lebanon. · Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon. · Department of Internal Medicine, American University of Beirut, Beirut, Lebanon. · Harvard School of Public Health, Boston, MA, United States of America. ·PLoS One · Pubmed #31211820.

ABSTRACT: Low serum levels of high-density lipoprotein cholesterol (HDL-C) have been shown to be a risk factor for coronary artery disease independent of low-density lipoprotein cholesterol (LDL-C) in different populations. In this study, we investigated genetic variants through genome-wide association studies to determine their association with HDL-C levels in a sample of 2,700 patients. We identified several SNPs associated with HDL-C levels in the Lebanese population using unadjusted and adjusted by biological factors models. We replicated the association of rs3764261 within CETP with HDL-C levels in the study population, and found other previously unidentified SNPs to be significant at the suggestive level, in both previously identified and unidentified genes. This paper reports the first genome-wide analysis of HDL-C in the Lebanese, Middle Eastern, population and supports the importance of genome-wide association studies across different and minor ethnicities to understand better the etiology of complex human diseases.

72 Article Association of serum androgens and coronary artery calcium scores in women. 2019

Penn, Courtney A / Chan, Jessica / Mesaros, Clementina / Snyder, Nathaniel W / Rader, Daniel J / Sammel, Mary D / Dokras, Anuja. ·Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. · Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. · A. J. Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania. · Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania. · Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: adokras@obgyn.upenn.edu. ·Fertil Steril · Pubmed #31200968.

ABSTRACT: OBJECTIVE: To determine the association between serum androgens measured by high-resolution liquid chromatography-mass spectrometry and coronary artery calcium (CAC) scores. DESIGN: Cross-sectional study. SETTING: Academic institution. PATIENT(S): A total of 239 women, aged 40-75 years, with CAC testing and complete cardiovascular disease risk evaluation. Total T, DHEA, and androstenedione were measured using high-resolution liquid chromatography-mass spectrometry, whereas E INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Independent associations between CAC scores and sex steroids. RESULT(S): Overall, 164 subjects had a CAC score < 10, 48 had a CAC score between 10 and 100, and 27 had a score > 100. There were no differences in sex hormone levels between women with CAC scores > 10 vs. CAC scores ≤ 10. In multivariable models adjusting for age, body mass index, and low-density lipoprotein cholesterol, a higher T/E CONCLUSION(S): In the general population, there are mixed reports regarding the relationship between serum androgens and risk factors for cardiovascular disease, and limited information on the relationship between androgens and subclinical atherosclerosis. Our study shows that increased androgens relative to estrogens may have a weak but independent association with subclinical atherosclerosis, as measured by CAC scores.

73 Article Etiologies, trends, and predictors of readmission in ST-elevation myocardial infarction patients undergoing multivessel percutaneous coronary intervention. 2019

Tripathi, Byomesh / Yeh, Robert W / Bavishi, Chirag P / Sardar, Partha / Atti, Varunsiri / Mukherjee, Debabrata / Bashir, Riyaz / Abbott, Jinnette Dawn / Giri, Jay / Chatterjee, Saurav. ·Division of Cardiology, Banner University Medical Center, University of Arizona, Phoenix, Arizona. · Division of Cardiovascular Medicine, Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. · Division of Cardiology, Cardiovascular Institute, Warren Alpert Medical School at Brown University, Providence, Rhode Island. · Department of Medicine, Michigan State University, East Lansing, Michigan. · Division of Cardiology, Texas Tech University Health Sciences Center, El Paso, Texas. · Division of Cardiology, Temple University Hospital, Philadelphia, Pennsylvania. · Cardiovascular Medicine Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Division of Cardiovascular Medicine, Hoffman Heart Institute, Saint Francis Hospital, Teaching Affiliate of the University of Connecticut School of Medicine, Hartford, Connecticut. ·Catheter Cardiovasc Interv · Pubmed #31165573.

ABSTRACT: BACKGROUND: Recent trials have shown benefits with percutaneous coronary intervention (PCI) on nonculprit coronary vessels in select ST-elevation myocardial infarction (STEMI) patients with multivessel coronary artery disease (CAD). However, readmission rates and causes in this high-risk group are unknown. Objective of this study is to explore pattern, causes and factors associated with 30-day readmission after multivessel PCI in STEMI patients. METHODS AND RESULTS: Nationwide Readmissions Data (NRD) between 2010 and 2014 was utilized to identify multivessel PCI cases in STEMI patients using appropriate ICD-9 codes. We evaluated 30-day readmission rate and factors associated with 30-day readmission. Hierarchical logistic regression model was used to identify factors associated with 30-day readmission. Among 22,257 STEMI patients who survived to discharge after multivessel PCI, 2,302 (10.3%) were readmitted within 30-days. Subsequent unresolved/aggravated cardiac issues most commonly triggered readmission (62.66%). Among cardiac causes, heart failure and ischemic heart disease were most frequent etiologies. Advancing age (OR: 1.073, 95%CI: 1.026 to 1.122, p = .002), female sex (OR: 1.36, 95%CI: 1.23 to 1.50, p < .001), comorbid conditions like chronic kidney disease (CKD; OR: 1.35, 95%CI: 1.17 to 1.57, p = .001), congestive heart failure (CHF; OR: 1.40, 95%CI: 1.24 to 1.57, p = .04), anemia (OR: 1.16, 95%CI: 1.002 to 1.34, p = .04), and utilization of a mechanical circulatory support (MCS) device (OR: 1.45, 95%CI: 1.19 to 1.77, p < .001) during the index procedure were predictive of subsequent readmission within 30 days. CONCLUSION: In this large nationally representative study, nearly one in 10 patients were readmitted within 30 days from discharge after index admission for multivessel PCI in STEMI, most commonly for cardiac causes.

74 Article Serum Calcification Propensity and Coronary Artery Calcification Among Patients With CKD: The CRIC (Chronic Renal Insufficiency Cohort) Study. 2019

Bundy, Joshua D / Cai, Xuan / Scialla, Julia J / Dobre, Mirela A / Chen, Jing / Hsu, Chi-Yuan / Leonard, Mary B / Go, Alan S / Rao, Panduranga S / Lash, James P / Townsend, Raymond R / Feldman, Harold I / de Boer, Ian H / Block, Geoffrey A / Wolf, Myles / Smith, Edward R / Pasch, Andreas / Isakova, Tamara / Anonymous1471185. ·Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. Electronic address: jdbundy@northwestern.edu. · Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. · Department of Medicine, Duke Clinical Research Institute, Duke University, Durham, NC. · Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH. · Department of Medicine, Tulane University School of Medicine, New Orleans, LA. · Department of Medicine, University of California San Francisco School of Medicine, San Francisco, CA. · Department of Pediatrics, Stanford University School of Medicine, Palo Alto. · Comprehensive Clinical Research Unit, Kaiser Permanente Northern California Division of Research, Oakland, CA. · Department of Medicine, University of Michigan Health System, Ann Arbor, MI. · Department of Medicine, University of Illinois College of Medicine at Chicago, Chicago, IL. · Departments of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. · Departments of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. · Department of Medicine, University of Washington, Seattle, WA. · Colorado Kidney Care, Denver, CO. · Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia. · Calciscon AG, Biel-Nidau, Switzerland. · Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. Electronic address: tamara.isakova@northwestern.edu. ·Am J Kidney Dis · Pubmed #30935773.

ABSTRACT: RATIONALE & OBJECTIVE: Coronary artery calcification (CAC) is prevalent among patients with chronic kidney disease (CKD) and increases risks for cardiovascular disease events and mortality. We hypothesized that a novel serum measure of calcification propensity is associated with CAC among patients with CKD stages 2 to 4. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Participants from the Chronic Renal Insufficiency Cohort (CRIC) Study with baseline (n=1,274) and follow-up (n=780) CAC measurements. PREDICTORS: Calcification propensity, quantified as transformation time (T OUTCOMES: CAC prevalence, severity, incidence, and progression. ANALYTICAL APPROACH: Multivariable-adjusted generalized linear models. RESULTS: At baseline, 824 (65%) participants had prevalent CAC. After multivariable adjustment, T LIMITATIONS: Potential selection bias in follow-up analyses; inability to distinguish intimal from medial calcification. CONCLUSIONS: Among patients with CKD stages 2 to 4, higher serum calcification propensity is associated with more severe CAC and CAC progression.

75 Article The role of ventricular-arterial coupling in cardiac disease and heart failure: assessment, clinical implications and therapeutic interventions. A consensus document of the European Society of Cardiology Working Group on Aorta & Peripheral Vascular Diseases, European Association of Cardiovascular Imaging, and Heart Failure Association. 2019

Ikonomidis, Ignatios / Aboyans, Victor / Blacher, Jacque / Brodmann, Marianne / Brutsaert, Dirk L / Chirinos, Julio A / De Carlo, Marco / Delgado, Victoria / Lancellotti, Patrizio / Lekakis, John / Mohty, Dania / Nihoyannopoulos, Petros / Parissis, John / Rizzoni, Damiano / Ruschitzka, Frank / Seferovic, Petar / Stabile, Eugenio / Tousoulis, Dimitrios / Vinereanu, Dragos / Vlachopoulos, Charalambos / Vlastos, Dimitrios / Xaplanteris, Panagiotis / Zimlichman, Reuven / Metra, Marco. ·Second Cardiology Department, Echocardiography Department and Laboratory of Preventive Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece. · Department of Cardiology, Dupuytren University Hospital, Limoges, France. · Inserm 1094, Limoges School of Medicine, Limoges, France. · Diagnosis and Therapeutic Center, Hypertension and Cardiovascular Prevention Unit, Paris-Descartes University, Hôtel-Dieu Hospital, AP-HP, Paris, France. · Division of Angiology, Department of Internal Medicine, Medical University Graz, Graz, Austria. · Department of Cardiology, University Hospital Antwerp, Edegem, Belgium. · Perelman School of Medicine and Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, PA, USA. · Cardiac Catheterization Laboratory, Cardiothoracic and Vascular Department, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. · Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands. · Department of Cardiology, University of Liège Hospital, GIGA Cardiovascular Sciences, CHU SantTilman, Liège, Belgium. · Gruppo Villa Maria Care and Research, Anthea Hospital, Bari, Italy. · NHLI - National Heart and Lung Institute, Imperial College London, London, UK. · 1st Department of Cardiology, Hippokration Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece. · Heart Failure Unit, School of Medicine and Department of Cardiology, National and Kapodistrian University of Athens, Athens University Hospital Attikon, Athens, Greece. · Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. · Department of Cardiology, University Hospital, Zurich, University Heart Center, Zurich, Switzerland. · Cardiology Department, Clinical Centre Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia. · Department of Advanced Biomedical Sciences, 'Federico II' University, Naples, Italy. · University of Medicine and Pharmacy 'Carol Davila', and Department of Cardiology, University and Emergency Hospital, Bucharest, Romania. · Department of Medicine and Hypertension Institute, Brunner Institute for Cardiovascular Research, Sackler Faculty of Medicine, The E. Wolfson Medical Center, Institute for Quality in Medicine, Israeli Medical Association, Tel Aviv University, Tel Aviv, Israel. · Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy. ·Eur J Heart Fail · Pubmed #30859669.

ABSTRACT: Ventricular-arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent diagnostic and prognostic value and may be used to refine riskstratification and monitor therapeutic interventions. Traditionally, VAC is assessed by the non-invasive measurement of the ratio of arterial (Ea) to ventricular end-systolic elastance (Ees). With disease progression, both Ea and Ees may become abnormal and the Ea/Ees ratio may approximate its normal values. Therefore, the measurement of each component of this ratio or of novel more sensitive markers of myocardial (e.g. global longitudinal strain) and arterial function (e.g. pulse wave velocity) may better characterize VAC. In valvular heart disease, systemic arterial compliance and valvulo-arterial impedance have an established diagnostic and prognostic value and may monitor the effects of valve replacement on vascular and cardiac function. Treatment guided to improve VAC through improvement of both or each one of its components may delay incidence of heart failure and possibly improve prognosis in heart failure. In this consensus document, we describe the pathophysiology, the methods of assessment as well as the clinical implications of VAC in cardiac diseases and heart failure. Finally, we focus on interventions that may improve VAC and thus modify prognosis.

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