Genetic predisposition remains a powerful determinant of coronary risk—even beyond traditional disease classifications. A large multinational analysis, published in the European Journal of Preventive Cardiology, investigated how CAD polygenic risk scores (PRS) relate to future coronary events across varying ASCVD status.

The study included 59,905 participants (mean age 66 years; 71% men) genotyped from six cardiovascular outcome trials. Individuals were stratified by PRS into low, intermediate, or high genetic risk categories and grouped by ASCVD status: prior ischemic event, ASCVD without event, or no ASCVD.

Compared with low genetic risk, major coronary events were more than twice as frequent among those with high PRS (HR 2.06; 95% CI 1.88–2.24; p < 0.001). The relative genetic association was strongest in those without ASCVD (HR 4.63) but remained significant across all categories. Despite similar absolute risk differences of 5–7% over three years, PRS refined prediction beyond conventional risk factors.

These findings underscore the role of genetic profiling in enhancing cardiovascular risk stratification and support integrating PRS into preventive cardiology frameworks.