Polygenic Risk Scores for Prediction of Subclinical Coronary Artery Disease in Persons Living with HIV: The Swiss HIV Cohort Study.
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BORIS DOI
Date of Publication
January 6, 2023
Publication Type
Article
Division/Institute
Contributor
Universitätsklinik für Viszerale Chirurgie und Medizin | |
Thorball, Christian W | |
Kovari, Helen | |
Ledergerber, Bruno | |
Buechel, Ronny R | |
Calmy, Alexandra | |
Weber, Rainer | |
Kaufmann, Philipp A | |
Nkoulou, René | |
Schwenke, Johannes M | |
Braun, Dominique L | |
Fellay, Jacques | |
Tarr, Philip E |
Subject(s)
Series
Clinical infectious diseases
ISSN or ISBN (if monograph)
1537-6591
Publisher
Oxford University Press
Language
en
Publisher DOI
PubMed ID
36097729
Uncontrolled Keywords
Description
BACKGROUND
In people living with HIV (PLWH), 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 CT angiography, or as participants in the top tertile of the study population's coronary artery calcium (CAC) score, using non-contrast CT. We obtained uni-/multivariable odds ratios (OR) for subclinical CAD endpoints based on non-genetic risk factors, and validated genome-wide PRSs built from single nucleotide polymorphisms (SNPs) 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 < 0.01), but longevity-PRS was not. Participants with unfavorable CAD-PRS (top quintile) had adjusted SMHRP-OR = 2.58 (95% confidence interval [CI], 1.18-5.67), and CAC-OR = 3.95 (95% CI, 1.45-10.77), vs. bottom quintile. Unfavorable non-genetic risk (top vs. bottom quintile) was associated with adjusted SMHRP-OR = 24.01 (95% CI, 9.75-59.11), and CAC-OR = 65.07 (95% CI, 18.48-229.15). Area under the ROC curve increased when we added CAD-PRS to non-genetic risk factors (SMHRP: 0.75, 0.78, respectively; CAC: 0.80, 0.83, respectively).
CONCLUSIONS
In Swiss PLWH, subclinical CAD is independently associated with an individual CAD-associated PRS. Combining non-genetic and genetic cardiovascular risk factors provided the most powerful subclinical CAD prediction.
In people living with HIV (PLWH), 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 CT angiography, or as participants in the top tertile of the study population's coronary artery calcium (CAC) score, using non-contrast CT. We obtained uni-/multivariable odds ratios (OR) for subclinical CAD endpoints based on non-genetic risk factors, and validated genome-wide PRSs built from single nucleotide polymorphisms (SNPs) 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 < 0.01), but longevity-PRS was not. Participants with unfavorable CAD-PRS (top quintile) had adjusted SMHRP-OR = 2.58 (95% confidence interval [CI], 1.18-5.67), and CAC-OR = 3.95 (95% CI, 1.45-10.77), vs. bottom quintile. Unfavorable non-genetic risk (top vs. bottom quintile) was associated with adjusted SMHRP-OR = 24.01 (95% CI, 9.75-59.11), and CAC-OR = 65.07 (95% CI, 18.48-229.15). Area under the ROC curve increased when we added CAD-PRS to non-genetic risk factors (SMHRP: 0.75, 0.78, respectively; CAC: 0.80, 0.83, respectively).
CONCLUSIONS
In Swiss PLWH, subclinical CAD is independently associated with an individual CAD-associated PRS. Combining non-genetic and genetic cardiovascular risk factors provided the most powerful subclinical CAD prediction.
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