Associations of Long-Term and Early Adult Atherosclerosis Risk Factors With Aortic and Mitral Valve Calcium

Objectives: To determine the association of long-term exposure to atherosclerosis risk factors with valvular calcification. Background: Traditional atherosclerosis risk factors have been associated with aortic and mitral valve calcium in cross-sectional studies, but long-term prospective data are lacking. Methods: This was a prospective, community-based cohort study with 27-year follow-up (median follow-up 26.9 years; range 23.1 to 29.6 years). Participants from the Framingham Offspring Study (n = 1,323, enrolled between 1971 and 1975, mean age at enrollment 34 ± 9 years; 52% women) underwent cardiac multidetector computed tomography assessment between 2002 and 2005. Associations between the long-term average of each cardiovascular risk factor and valve calcium were estimated using logistic regression. Results: Aortic valve calcium was present in 39% of participants and mitral valve calcium in 20%. In multivariable models, the odds ratio for aortic valve calcium associated with every SD increment in long-term mean total cholesterol was 1.74 (p < 0.0001); with every SD increment in high-density lipoprotein cholesterol, it was 0.77 (p = 0.002); and with every 9 cigarettes smoked per day, it was 1.23 (p = 0.002). Associations of similar magnitude were seen for mitral valve calcium. The mean of 3 serum C-reactive protein measurements was associated with mitral valve calcium (odds ratio: 1.29 per SD increment in C-reactive protein levels; p = 0.002). A higher Framingham risk score in early adulthood (40 years age or younger) was associated with increased prevalence and severity of aortic valve calcium measured 3 decades later. Conclusions: Exposure to multiple atherosclerotic risk factors starting in early to mid-adulthood is associated with aortic and mitral valve calcium. Studies evaluating early risk factor modification to reduce the burden of valve disease are warranted.