Polygenic risk and subclinical atherosclerosis in asymptomatic middle-aged individuals. The ILERVAS study

Introduction and objectives: More than 50% of first cardiovascular events (CVE) occur in populations identified as at low or intermediate risk by the risk equations, so the inclusion of additional variables, such as polygenic risk scores (PRS), has been proposed to improve the predictive capacity of these equations. The aim of this study was to assess whether a PRS, independently or with clinical risk equations, is associated with the presence, severity and extent of subclinical atherosclerosis.

Methods: 109 subjects with atherosclerosis were selected from the ILERVAS cohort (primary prevention) and matched with 109 participants without atherosclerosis of the same age, sex and SCORE2 risk level. Atherosclerosis was assessed and quantified by arterial wall vascular ultrasound in 12 territories, and PRS was estimated using the Cardio inCode Score®. The predictive capacity of the presence of subclinical atherosclerosis was estimated, as well as the association between the extent and severity of atherosclerosis with PRS and clinical risk (SCORE2).

Results: PRS was similar between participants with or without atherosclerosis (P=0.525). We did not find an association between PRS and SCORE2 (r=-0.29, P=0.709), and the addition of PRS to SCORE2 did not improve the prediction of atherosclerosis [AUC (95% CI)=0.566 (0.477, 0.654), P=0.148]. The extent of atherosclerosis was related to SCORE2 (P=0.009), but not to PRS (P=0.709).

Conclusions: The Selected PRS is not associated with the presence of atherosclerosis or clinical risk, suggesting that its additional contribution to CVE risk would be mediated by mechanisms independent of the development of atherosclerosis. Additional biomarkers are needed to improve the prediction of subclinical atherosclerosis without using imaging tests as a first step in personalized assessment.