Abstract Body (Do not enter title and authors here): Background: Aortic valve calcification (AVC) is the primary underlying process leading to aortic stenosis. Whether polygenic risk scores (PRS) are associated with AVC beyond traditional atherosclerotic cardiovascular disease risk factors (ASCVD) is unknown.

Methods: This study included 6,812 Multi-Ethnic Study of Atherosclerosis participants who had AVC measured via CT at Visit 1 and single-nucleotide polymorphism (SNP) genotype data. Using previously published PRS for coronary artery disease (CAD), coronary artery calcium (CAC), and ASCVD risk factors we calculated a weighted PRS for each participant that was standardized within each ancestry group. The cross-sectional association of the individual PRS with AVC >0 was examined using multivariable logistic regression modeling with Bonferroni correction.

Results: The mean age was 62 years old, 53% were women, and 913 (13.4%) of participants had AVC >0 at baseline. The PRS for CAD (HR 1.17, 95% CI 1.07-1.26), SBP (HR 1.13, 95% CI 1.04-1.24), LDL-C (HR 1.16, 95% CI 1.07-1.26), and lipoprotein(a) [Lp(a)] (HR 1.11, 95% CI 1.02-1.20) were significantly associated with AVC, while the other PRS including CAC (HR 1.02, 95% CI 0.94-1.10) and CRP (HR 0.97, 95% CI 0.89-1.05) were not (Table). In sex stratified analyses, the PRS for CAD, LDL-C, and Lp(a) were significantly associated with AVC >0 for both women and men (p<0.05), while the SBP PRS for women was HR 1.14, 95% CI 0.99-1.32 and for men was HR 1.11, 95% CI 0.99-1.25.

Conclusions: Our results further confirm the role of atherogenic lipids in the pathogenesis of AVC and suggest that SBP may also be an important risk factor for AVC, while also suggesting that inflammation may not be an independent risk factor for AVC >0. Additionally, the lack of association for the CAC PRS with AVC >0 demonstrates that significant differences exist in the calcification pathways for AVC and CAC.