Why the study?
Aortic valve calcification is the primary process leading to aortic stenosis, but whether polygenic risk scores are associated with AVC beyond traditional atherosclerotic cardiovascular disease risk factors was unknown.
Are polygenic risk scores for traditional atherosclerotic cardiovascular disease risk factors associated with prevalent aortic valve calcification in individuals without known cardiovascular disease?
Are polygenic risk scores for traditional atherosclerotic cardiovascular disease risk factors associated with prevalent aortic valve calcification in individuals without known cardiovascular disease?
Polygenic risk scores for coronary artery disease, systolic blood pressure, LDL-C, and Lipoprotein(a) are significantly associated with prevalent aortic valve calcification, suggesting shared genetic pathways between CAD and AVC and highlighting systolic blood pressure as an underrecognized risk factor.
Should not alter current clinical risk assessment; leaves open independent prognostic utility of AVC>0 pending prospective validation.
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: <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.
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Whelton et al. (2026) studied this question.
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