Association of Polygenic Risk Scores With Aortic Valve Calcium: The Multi‐Ethnic Study of Atherosclerosis

Background Aortic valve calcification (AVC) is the primary process leading to aortic stenosis. We examined whether polygenic risk scores (PRS) are associated with AVC beyond traditional atherosclerotic cardiovascular disease risk factors. Methods We included 6812 participants in MESA (Multi‐Ethnic Study of Atherosclerosis) with computed tomography‐measured AVC at Visit 1. Using previously published PRS we calculated weighted PRS, standardized within each ancestry group. The cross‐sectional association per 1 SD higher PRS with AVC >0 was examined using multivariable logistic regression modeling with Bonferroni correction. The mean age was 62 years old, 53% were female, and 913 (13.4%) had AVC >0 at baseline. Results The PRS for coronary artery disease (hazard ratio [HR], 1.16 [95% CI, 1.07–1.26]), systolic blood pressure (HR, 1.1 [95% CI, 1.020–1.2]), low‐density lipoprotein cholesterol (HR, 1.16 [95% CI, 1.06–1.25]), and lipoprotein(a) (HR, 1.11 [95% CI, 1.02–1.20]) were significantly associated with AVC, whereas the other PRS including coronary artery calcium (HR, 1.02 [95% CI, 0.94–1.10]) and C‐reactive protein (HR, 0.97 [95% CI, 0.89–1.05]) were not. In sex‐stratified analyses, the PRS for coronary artery disease, low‐density lipoprotein cholesterol, and lipoprotein(a) were significantly associated with AVC >0 for both sexes (P0 strongly suggests significant differences exist in the calcification pathways for AVC and coronary artery calcium.