Polygenic Risk Scores for Prediction of Subclinical Coronary Artery Disease in Persons With Human Immunodeficiency Virus (HIV): The Swiss HIV Cohort Study.

Background: In people with human immunodeficiency virus (HIV) (PWH), individual polygenic risk scores (PRSs) are associated with coronary artery disease (CAD) events. Whether PRSs are associated with subclinical CAD is unknown.
Methods: In Swiss HIV Cohort Study participants of European descent, we defined subclinical CAD as presence of soft, mixed, or high-risk plaque (SMHRP) on coronary computed tomography (CT) angiography, or as participants in the top tertile of the study population's coronary artery calcium (CAC) score, using noncontrast CT. We obtained univariable and multivariable odds ratios (ORs) for subclinical CAD endpoints based on nongenetic risk factors, and validated genome-wide PRSs built from single nucleotide polymorphisms associated with CAD, carotid intima-media thickness (IMT), or longevity in the general population.
Results: We included 345 genotyped participants (median age, 53 years; 89% male; 96% suppressed HIV RNA); 172 and 127 participants had SMHRP and CAC, respectively. CAD-associated PRS and IMT-associated PRS were associated with SMHRP and CAC (all P < .01), but longevity PRS was not. Participants with unfavorable CAD-PRS (top quintile) had an adjusted SMHRP OR = 2.58 (95% confidence interval [CI], 1.18-5.67), and a CAC OR = 3.95 (95% CI, 1.45-10.77) vs. bottom quintile. Unfavorable nongenetic risk (top vs. bottom quintile) was associated with adjusted SMHRP OR = 24.01 (95% CI, 9.75-59.11), and a CAC-OR = 65.07 (95% CI, 18.48-229.15). Area under the receiver operating characteristic curve increased when we added CAD-PRS to nongenetic risk factors (SMHRP: 0.75 and 0.78, respectively; CAC: 0.80 and 0.83, respectively).
Conclusions: In Swiss PWH, subclinical CAD is independently associated with an individual CAD-associated PRS. Combining nongenetic and genetic cardiovascular risk factors provided the most powerful subclinical CAD prediction.
Competing Interests: Potential conflicts of interest. I. C. S.'s institution received a lecture fee from ViiV, outside the submitted work. P. E. T.'s institution reports grants, advisory fees, and support for educational activities from Gilead, ViiV, MSD, and Sankyo Daiichi, outside the submitted work. B. L. received personal fees from Kantonsspital Baselland, Liestal, Switzerland, during the conduct of the study, and reports personal fees from Gilead (for lectures), and ViiV (for participation on Advisory Board), outside the submitted work. R. R. B. reports speaker honoraria from Pfizer (personal <2000 CHF), Sanofi-Aventis (personal 2000 CHF), and GE Healthcare (personal <2000 CHF); support for attending meetings from Pfizer for Registration EAMN Congress 2021; and unpaid roles as Chair of the Nuclear Certification Sub-committee of the European Association of Cardiovascular Imaging and Programme committee member for the annual congress of the European Association of Cardiology; and Research contract with Department of Nuclear Medicine, University Hospital Zurich, Switzerland from GE Healthcare. D. L. B. reports honoraria for advisory boards, lectures and travel grants from AbbVie, Gilead, MSD, and ViiV; and consulting fees from ViiV, MSD, Gilead, Pfizer, and AstraZeneka. AC reports educational grants from AbbVie, MSD, Gilead, and ViiV healthcare; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or education events from Gilead Sciences (unrestricted), MSD, and ViiV healthcare (educational grant to institution). R. N. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events from Pfizer. P. A. K. reports payment for Advisory Board meeting (Date 02/05/21; Focus: myocardial perfusion tracer) from GE Healthcare; unpaid role as Vice Chair of the Swiss Society of Nucleaer Medicine; and research contract with Department of Nuclear Medicine, University Hospital Zurich, Switzerland from GE Healthcare. All other authors report no potential conflicts. All authors have prepared ICMJE forms for disclosure of potential conflicts of interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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