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Polygenic Scores and Preclinical Cardiovascular Disease in Individuals With HIV: Insights From the REPRIEVE Trial
Roger S Zou1,2,3, Yunfeng Ruan2, Buu Truong2
1Department of Medicine Massachusetts General Hospital Boston MA USA.
Insights
Polygenic risk scores (PRS) for coronary artery disease (CAD) predict subclinical atherosclerosis in people with HIV. This finding supports the use of PRS in assessing cardiovascular risk for this population.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Infectious Diseases
Background:
- Coronary artery disease (CAD) is a major cause of death in people with HIV globally.
- The generalizability of cardiovascular polygenic risk scores (PRSs) from non-HIV populations to people with HIV is not well understood.
Purpose of the Study:
- To evaluate the utility of externally developed cardiovascular PRSs in a global cohort of people with HIV.
- To assess the association of PRSs with subclinical atherosclerosis in people with HIV.
Main Methods:
- Calculated PRSs for CAD (GPSMult) and lipid traits in 4495 genotyped participants with HIV from the REPRIEVE trial.
- Assessed PRS association with subclinical CAD (plaque presence, stenosis >50%, vulnerable plaque) in 662 participants using coronary computed tomography angiography.
- Examined the incremental predictive value of GPSMult when added to established risk factors.
Main Results:
- GPSMult was significantly associated with plaque presence (OR, 1.42), stenosis >50% (OR, 2.39), and vulnerable plaque (OR, 1.45) in people with HIV.
- These associations remained consistent across subgroups of age, sex, risk, ancestry, and CD4 count.
- Adding GPSMult improved the prediction of plaque presence (C-statistic from 0.718 to 0.734).
- A PRS for low-density lipoprotein cholesterol was also associated with plaque presence (OR, 1.21).
Conclusions:
- An externally developed CAD PRS is predictive of subclinical atherosclerosis in people with HIV on antiretroviral therapy.
- A PRS for low-density lipoprotein cholesterol also showed an association with subclinical atherosclerosis.
- These findings support the role of PRS in assessing cardiovascular risk and highlight the importance of lipid management in HIV-associated CAD.
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 (GPSMult) 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), GPSMult was associated with plaque presence with odds ratio (OR) per SD in GPSMult 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 GPSMult 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.
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