Affiliation:
1. Department of Medicine Massachusetts General Hospital Boston MA USA
2. Cardiovascular Disease Initiative Broad Institute of MIT and Harvard Cambridge MA USA
3. Harvard Medical School Boston MA USA
4. Division of Cardiology, Department of Medicine, Center for Genomic Medicine Massachusetts General Hospital Boston MA USA
5. Cardiovascular Imaging Research Center Massachusetts General Hospital and Harvard Medical School Boston MA USA
6. Metabolism Unit Massachusetts General Hospital Boston MS USA
7. Department of Biostatistics, Center for Biostatistics in AIDS Research Harvard TH Chan School of Public Health Boston MA USA
8. Duke Clinical Research Institute, Duke University School of Medicine Durham NC USA
Abstract
Background
Coronary artery disease (CAD) is a leading cause of death among the 38.4 million people with HIV globally. The extent to which cardiovascular polygenic risk scores (PRSs) derived in non‐HIV populations generalize to people with HIV is not well understood.
Methods and Results
PRSs for CAD (GPS
Mult
) and lipid traits were calculated in a global cohort of people with HIV treated with antiretroviral therapy with low‐to‐moderate atherosclerotic cardiovascular disease risk enrolled in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV). The PRSs were associated with baseline lipid traits in 4495 genotyped participants, and with subclinical CAD in a subset of 662 who underwent coronary computed tomography angiography. Among participants who underwent coronary computed tomography angiography (mean age, 50.9 [SD, 5.8] years; 16.1% women; 41.8% African, 57.3% European, 1.1% Asian), GPS
Mult
was associated with plaque presence with odds ratio (OR) per SD in GPS
Mult
of 1.42 (95% CI, 1.20–1.68;
P
=3.8×10
−5
), stenosis >50% (OR, 2.39 [95% CI, 1.48–3.85];
P
=3.4×10
−4
), and noncalcified/vulnerable plaque (OR, 1.45 [95% CI, 1.23–1.72];
P
=9.6×10
−6
). Effects were consistent in subgroups of age, sex, 10‐year atherosclerotic cardiovascular disease risk, ancestry, and CD4 count. Adding GPS
Mult
to established risk factors increased the C‐statistic for predicting plaque presence from 0.718 to 0.734 (
P
=0.02). Furthermore, a PRS for low‐density lipoprotein cholesterol was associated with plaque presence with OR of 1.21 (95% CI, 1.01–1.44;
P
=0.04), and partially calcified plaque with OR of 1.21 (95% CI, 1.01–1.45;
P
=0.04) per SD.
Conclusions
Among people with HIV treated with antiretroviral therapy without documented atherosclerotic cardiovascular disease and at low‐to‐moderate calculated risk in REPRIEVE, an externally developed CAD PRS was predictive of subclinical atherosclerosis. PRS for low‐density lipoprotein cholesterol was also associated with subclinical atherosclerosis, supporting a role for low‐density lipoprotein cholesterol in HIV‐associated CAD.
Registration
URL:
https://www.reprievetrial.org
; Unique identifier: NCT02344290.
Publisher
Ovid Technologies (Wolters Kluwer Health)