Incidence and progression of aortic valve calcium in the Multi-ethnic Study of Atherosclerosis (MESA)

Abstract

Aortic valve calcium (AVC) is common among older adults and shares epidemiologic and histopathologic similarities to atherosclerosis. However, prospective studies have failed to identify meaningful risk associations with incident ("new") AVC or its progression. In the present study, AVC was quantified from serial computed tomographic images from 5,880 participants (aged 45 to 84 years) in the Multi-Ethnic Study of Atherosclerosis, using the Agatston method. Multivariate backward selection modeling was used to identify the risk factors for incident AVC and AVC progression. During a mean follow-up of 2.4 +/- 0.9 years, 210 subjects (4.1%) developed incident AVC. The incidence rate (mean 1.7%/year) increased significantly with age (p <0.001). The risk factors for incident AVC included age, male gender, body mass index, current smoking, and the use of lipid-lowering and antihypertensive medications. Among those with AVC at baseline, the median rate of AVC progression was 2 Agatston units/year (interquartile range -21 to 37). The baseline Agatston score was a strong, independent predictor of progression, especially among those with high calcium scores at baseline. In conclusion, in this ethnically diverse, preclinical cohort, the rate of incident AVC increased significantly with age. The incident AVC risk was associated with several traditional cardiovascular risk factors, specifically age, male gender, body mass index, current smoking, and the use of both antihypertensive and lipid-lowering medications. AVC progression risk was associated with male gender and the baseline Agatston score. Additional research is needed to determine whether age- and stage-specific mechanisms underlie the risk of AVC progression.

Figure 1

Flow diagram for MESA participants, categorized by aortic valve calcification status.

Figure 2. Average incidence rate of AVC (% per year) by yearly age-increments, among those free of AVC at baseline (n=5,142), for both men (squares) and women (circles)

The size of the scatter points is weighted for number at risk at each age category, and non-linear Lowess smooth curves are displayed for the full cohort (solid), women (dotted) and men (dashed). There is a marked increase in AVC incidence rate with advancing age.

Figure 3

Figure 3a. Mean annualized rate of AVC progression (Agatston units/year) by yearly age increments, among those with detectable AVC at baseline (n=738). The size of the scatter points is weighted for number at risk at each age category, and a non-linear Lowess smooth curve (solid) is displayed. Figure 3b. Mean annualized rate of AVC progression (Agatston units/year) grouped by baseline Agatston scores, among those with detectable AVC at baseline (n=738). Baseline Agatston scores are log-transformed to reduce skew.