American Journal of Preventive Cardiology
Utility of a coronary artery disease polygenic risk score in a low-risk primary prevention cohort
Par John H. Bertot, Giorgio E.M. Melloni, James Pirruccello et 6 autres.
Contenu en anglais
Résumé
Aims
To evaluate whether a coronary artery disease (CAD) polygenic risk score (PRS) identifies clinically low-risk individuals at elevated atherosclerotic cardiovascular disease (ASCVD) risk.
Methods
We conducted a longitudinal cohort study within the UK Biobank including adults aged 40–74 years, free of ASCVD and diabetes, not on lipid-lowering therapy, and with baseline LDL <190 mg/dL. Participants were enrolled from 2006 to 2010 and followed through 2021. Ten-year ASCVD risk was estimated using pooled cohort equations. A CAD PRS derived from 2.3 million genome-wide variants was categorized as top 1%, 5%, 20%, 50%, and bottom 50%. Lipoprotein(a) and high-sensitivity C-reactive protein were similarly stratified. The primary endpoint was a composite of myocardial infarction, ischemic stroke, or cardiovascular death. Cox proportional hazards models estimated adjusted hazard ratios (HRs) for 10-year ASCVD events, and net reclassification improvement (NRI) was assessed at 5% and 7.5% risk thresholds.