Language
English
Publication Date
5-19-2026
Journal
Journal of the American Heart Association
DOI
10.1161/JAHA.124.040064
PMID
42089167
PMCID
PMC13279466
PubMedCentral® Posted Date
5-6-2026
PubMedCentral® Full Text Version
Post-print
Abstract
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 (P< 0.05), whereas the systolic blood pressure PRS was borderline significant for women (HR, 1.10 [95% CI, 0.97-1.25]) and significant for men (HR, 1.11 [95% CI 1.00-1.24]).
Conclusions: Our results confirm the role of atherogenic lipids in the pathogenesis of AVC and suggest that systolic blood pressure and the genetic risk factors for CAD are also important risk factors. The lack of association for the coronary artery calcium PRS with AVC >0 strongly suggests significant differences exist in the calcification pathways for AVC and coronary artery calcium.
Keywords
Humans, Female, Male, Aortic Valve, Calcinosis, Genetic Risk Score, Aged, Middle Aged, Risk Factors, Aortic Valve Stenosis, Cross-Sectional Studies, United States, Genetic Predisposition to Disease, Risk Assessment, Atherosclerosis, Coronary Artery Disease, Blood Pressure, Tomography, X-Ray Computed, Aged, 80 and over, aortic stenosis, aortic valve calcium, polygenic risk score
Published Open-Access
yes
Recommended Citation
Whelton, Seamus P; Yao, Jie; Clish, Clary; et al., "Association of Polygenic Risk Scores With Aortic Valve Calcium: The Multi-Ethnic Study of Atherosclerosis" (2026). Faculty, Staff and Students Publications. 7736.
https://digitalcommons.library.tmc.edu/baylor_docs/7736