Polygenic risk scores for prediction of subclinical coronary artery disease in persons with human immunodeficiency virus (HIV): The Swiss HIV Cohort Study. Clinical Infectious Disease
Schoepf et al. aimed to o investigate validated, coronary artery disease (CAD)-associated, intima-media thickness (IMT)-associated, and longevity-associated polygenic risk scores (PRSs) to subclinical coronary plaque in Swiss people with HIV (PWH), in the context of traditional and HIV-related risk factors including adverse antiretroviral exposures.
The authors 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 stud population’s coronary artery calcium (CAC) score, using noncontrast CT. They 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.
The study 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 they added CAD-PRS to nongenetic risk factors (SMHRP: 0.75 and 0.78, respectively; CAC: 0.80 and 0.83, respectively).
In conclusion, the study shows that an unfavorable individual polygenic risk score independently is associated with a 2.6-fold to 4-fold increased risk of nonc alcified (including high-risk) plaque and calcified plaque in PWH, respectively. It documents how PWH may have a significantly increased subclinical CAD risk because of genetic and/or nongenetic risk factors. The integration of genetic, traditional, HIV-related, and antiretroviral CAD risk factors helps explain interindividual variation and provides the best prediction of individual risk of subclinical and clinical CAD in PWH.
Additional comment Dominique Braun, Bernard Surial, Johannes Nemeth, Danièle Perraudin and Huldrych Günthard
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