Polygenic Risk Based Detection and Treatment of Subclinical Coronary Atherosclerosis in the PROACT Clinical Trials: A Genotype-First Precision Prevention Approach

Highlights

• PROACT trials demonstrate feasibility and effectiveness of genotype-first recruitment using polygenic risk scores (PRS) to identify individuals at high genetic risk for coronary artery disease (CAD) despite low conventional risk.
• Coronary computed tomographic angiography (CCTA) reveals a high prevalence of subclinical coronary atherosclerosis in asymptomatic, low-clinical-risk individuals stratified by high PRS.
• Engagement with prevention trials is facilitated by genotype-based callback, with factors such as specialty care engagement and proximity to study sites influencing participation.
• Findings highlight an actionable subset of “silent” CAD patients for whom early pharmacologic intervention (statins, colchicine) may prevent progression and clinical events, prompting reconsideration of risk assessment paradigms.