DOI: 10.18521/ktd.1882189 ISSN: 1309-3878

Beyond Risk Prediction: Polygenic Risk Scores for Coronary Artery Disease and the Realities of Primary Care

Nevena Ivanova
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Cardiovascular diseases remain the leading global cause of morbidity and mortality, with coronary artery disease (CAD) accounting for the largest share of cardiovascular deaths. In routine practice, preventive decisions are guided by conventional risk factors and multivariable prediction models emphasizing short-term absolute risk and age. Consequently, lifetime risk may be underestimated in younger individuals and those with inherited susceptibility, potentially delaying preventive interventions. Polygenic risk scores (PRS), derived from genome-wide association studies, aggregating numerous common variants, offer a lifelong measure of genetic predisposition, enabling earlier identification of individuals at elevated CAD risk.This review synthesizes the genetic basis of CAD and critically evaluates evidence supporting PRS for CAD in primary care. CAD exhibits a predominantly polygenic architecture, with common variants explaining much of heritable risk, while monogenic causes account for a minority of cases at the population level. Contemporary genome-wide PRS can identify a subset of individuals with risk comparable to rare monogenic mutations. High genetic risk is not deterministic and may be attenuated by favourable lifestyle patterns and lipid-lowering therapy.Despite robust associations in population-based studies, primary care implementation remains constrained by limited outcome evidence, lack of standardized thresholds for action, challenges communicating probabilistic risk, and inequitable performance across ancestries. Available data suggest that PRS may influence clinical decisions and support shared decision-making, although behavioural effects remain modest.PRS for CAD should be regarded as adjunctive and investigational tools. Future research should prioritize primary-care implementation trials, decision-support strategies, equity-focused validation, and consensus standards for PRS development, reporting and updating.

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