PRS predict baseline risk but not statin or ACEi effects

Background Statins and ACE inhibitors (ACEIs) are cornerstones of primary prevention. Genetic factors may influence drug response, but their clinical relevance is uncertain. We aimed to investigate whether Polygenic Risk Scores (PRS) of LDL cholesterol, systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels interact with statins and ACEi on the levels of these risk factors in the general adult population of Catalonia. Methods We analysed data from 7,594 participants in the REGICOR population cohort (Catalonia, Spain) linked to electronic pharmacy and hospital records from 2008–2023. We constructed PRS for LDL cholesterol, SBP, and DBP from large recent GWAS and tested their association with respective biomarkers. We used linear regression models adjusted for age, sex, and genetic principal components to evaluate PRS–drug interactions. Results All three PRS were strongly associated with their corresponding traits. Each one standard deviation increase in the LDL cholesterol PRS was associated with +13 mg/dL in LDL cholesterol, while PRS for SBP and DBP were associated with +3.97 and +2.33 mmHg, respectively (Figure 1). No significant PRS×treatment interactions were observed for statins or ACEIs (Figure 2). The associations between PRS and biomarkers were consistent across adherence levels and sexes. Conclusions PRS for LDL cholesterol and blood pressure robustly predict baseline biomarker levels but do not modify the pharmacological response to statins or ACEIs. These findings support the use of PRS for risk stratification rather than for guiding treatment intensity in cardiovascular prevention.PRS performanceFor image description, please refer to the figure legend and surrounding text. PRS interactionFor image description, please refer to the figure legend and surrounding text.