Differential Performance of Polygenic Score for Coronary Artery Disease Based on Coronary Artery Calcium Between Men Living With and Without HIV

Background Individuals with HIV have increased risk for coronary artery disease (CAD). However, the utility of the polygenic risk score (PRS) for estimating CAD risk (PRS CAD ) is unknown in people living with HIV (PLWH). We evaluated the performance of PRS CAD on coronary artery calcium (CAC), a measure of subclinical atherosclerosis, by HIV serostatus. Methods A PRS CAD was applied to 1071 men ( PLWH , n=659; people living without HIV [ PWOH ], n=412) within MACS (Multicenter AIDS Cohort Study), then stratified by non‐Hispanic White or Black race and genetic similarity to references ( non‐Hispanic White /genetically similar to European reference group, n=731; non‐Hispanic Black /genetically similar to African reference group, n=340). PRS CAD performance for CAC , estimated by Agatston score ( AS ) from cardiac computed tomography scans, was evaluated independently and jointly with the American College of Cardiology/American Heart Association Pooled Cohort Equations by HIV serostatus using adjusted R 2 for log‐transformed CAC and area under the curve ( AUC ) for binary outcomes (absence/presence of CAC , absence of CAC [ AS =0] versus low CAC [ AS =1–100] or high CAC [ AS >100]). Results Predicting the presence/absence of CAC in non‐Hispanic White /genetically similar to European reference group adding PRS CAD significantly improved the performance compared with the base model ( AUC PLWH =0.738, AUC PWOH =0.759; P =0.015) but not the Pooled Cohort Equations ( AUC PLWH =0.722, AUC PWOH =0.736; P =0.26). Performance was lower in PLWH than PWOH among outcomes, especially comparing high with absent AS ( AUC PLWH =0.785, AUC PWOH =0.865; P =0.025). Joint modeling of PRS CAD and Pooled Cohort Equations decreased these gaps by HIV serostatus. PRS CAD performed worse in non‐Hispanic Black /genetically similar to African reference groups compared with non‐Hispanic White /genetically similar to European reference groups, with lower performance in PLWH ( AUC PLWH =0.671, AUC PWOH =0.769; P =0.22). Conclusions The application of a PRS CAD to CAC showed lower performance for PLWH than PWOH men. Further research is needed to develop accurate risk prediction models with clinical utility in all patients. </ja