Impact of polygenic risk score on the use of lipid-lowering therapy in primary prevention for coronary artery disease

Background/Synopsis

Polygenic risk scores (PRS) for coronary artery disease (CAD) aggregate the effects of multiple common genetic variants to quantify an individual's inherited risk of cardiovascular disease. Early data suggest PRS enhances traditional risk models by incorporating genetic predisposition, particularly in younger patients or those with borderline-to-intermediate risk, prior to the development of clinical risk factors for CAD. As PRS becomes further validated across diverse populations, its clinical integration may enhance primary prevention and guide early interventions, such as lipid-lowering therapy.

Objective/Purpose

We aimed to evaluate how PRS influences the use of lipid-lowering therapy in primary prevention for CAD.

Methods

A single-center retrospective study was conducted over one year at a Preventive Cardiology clinic. All consecutive patients without known cardiovascular disease who consented for PRS testing were included. CAD PRS testing was performed by Allelica, Inc. High genetic risk was defined as a PRS ≥ 90% percentile. Pre- and post-PRS data were collected, including lipid profiles, advanced lipid biomarkers, and lipid-lowering therapy (LLT) regimens. Lipid-lowering therapy included statins, ezetimibe, PCSK9 inhibitors, bempedoic acid, and icosapent ethyl.

Results

A total of 107 patients who underwent PRS testing were evaluated (median age 51 years; 37.2% Female; 82.2% White). Of the total patients, 20.6% had a high-risk PRS. A change in LLT was observed in 54.5% of high-risk patients, which corresponded to a 36.4% initiation and a 18.2% intensification of prescriptions. High-risk patients had an 18.2% increase in statin prescriptions (RR 1.25; 95% CI: 0.94–1.67; p=0.13) and 22.7% increase in non-statin prescriptions (RR 1.63; 95% CI: 0.85–3.12; p=0.15) after PRS testing. Furthermore, high-risk PRS patients were more likely to be prescribed statins compared to low-risk PRS patients (RR 1.36; 95% CI: 1.11–1.65; p<0.01).

Conclusions

Polygenic risk scoring revealed that one-fifth of the patient population had a high genetic risk for CAD, highlighting the residual cardiovascular risk in these individuals. More than half of the high-risk PRS patients had a change in LLT, with a signal toward increased statin and non-statin prescriptions after testing. Lastly, a significantly greater proportion of high-risk PRS patients were prescribed statin therapy compared to low-risk PRS patients, despite a higher rate of pre-PRS prescriptions. While our findings suggest PRS influences LLT for primary prevention of CAD, further investigation is needed to demonstrate statistically robust correlations between PRS and clinical decision-making.