Polygenic Risk Is Associated With Long-Term Coronary Plaque Progression and High-Risk Plaque

Nick S. Nurmohamed, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Division of Cardiology, The George Washington University School of Medicine, Washington, DC, USA.
Injeong Shim, Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Department of Digital Health, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of South Korea.
Emilie L. Gaillard, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Shirin Ibrahim, Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Michiel J. Bom, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
James P. Earls, Cleerly Inc, Denver, Colorado, USA.
James K. Min, Cleerly Inc, Denver, Colorado, USA.
R Nils Planken, Department of Radiology and Nuclear Medicine, Amsterdam UMC, Universiteit van Amsterdam, Amsterdam, the Netherlands.
Andrew D. Choi, Division of Cardiology, The George Washington University School of Medicine, Washington, DC, USA.
Pradeep Natarajan, Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Erik S. Stroes, Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Paul Knaapen, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Laurens F. Reeskamp, Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: l.f.reeskamp@amsterdamumc.nl.
Akl C. Fahed, Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: afahed@mgh.harvard.edu.

Document Type

Journal Article

Publication Date

8-2-2024

Journal

JACC. Cardiovascular imaging

DOI

10.1016/j.jcmg.2024.06.015

Keywords

atherosclerosis; atherosclerosis imaging; atherosclerotic cardiovascular disease; coronary CT angiography; coronary artery disease; polygenic risk score; quantitative computed tomography

Abstract

BACKGROUND: The longitudinal relation between coronary artery disease (CAD) polygenic risk score (PRS) and long-term plaque progression and high-risk plaque (HRP) features is unknown. OBJECTIVES: The goal of this study was to investigate the impact of CAD PRS on long-term coronary plaque progression and HRP. METHODS: Patients underwent CAD PRS measurement and prospective serial coronary computed tomography angiography (CTA) imaging. Coronary CTA scans were analyzed with a previously validated artificial intelligence-based algorithm (atherosclerosis imaging-quantitative computed tomography imaging). The relationship between CAD PRS and change in percent atheroma volume (PAV), percent noncalcified plaque progression, and HRP prevalence was investigated in linear mixed-effect models adjusted for baseline plaque volume and conventional risk factors. RESULTS: A total of 288 subjects (mean age 58 ± 7 years; 60% male) were included in this study with a median scan interval of 10.2 years. At baseline, patients with a high CAD PRS had a more than 5-fold higher PAV than those with a low CAD PRS (10.4% vs 1.9%; P < 0.001). Per 10 years of follow-up, a 1 SD increase in CAD PRS was associated with a 0.69% increase in PAV progression in the multivariable adjusted model. CAD PRS provided additional discriminatory benefit for above-median noncalcified plaque progression during follow-up when added to a model with conventional risk factors (AUC: 0.73 vs 0.69; P = 0.039). Patients with high CAD PRS had an OR of 2.85 (95% CI: 1.14-7.14; P = 0.026) and 6.16 (95% CI: 2.55-14.91; P < 0.001) for having HRP at baseline and follow-up compared with those with low CAD PRS. CONCLUSIONS: Polygenic risk is strongly associated with future long-term plaque progression and HRP in patients suspected of having CAD.

Department

Medicine

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