Aortic valve calcium independently predicts coronary and cardiovascular events in a primary prevention population

Abstract

Objectives: This study sought to test whether aortic valve calcium (AVC) is independently associated with coronary and cardiovascular events in a primary-prevention population.

Background: Aortic sclerosis is associated with increased cardiovascular morbidity and mortality among the elderly, but the mechanisms underlying this association remain controversial. Also, it is unknown whether this association extends to younger individuals.

Methods: We performed a prospective analysis of 6,685 participants in MESA (Multi-Ethnic Study of Atherosclerosis). All subjects, ages 45 to 84 years and free of clinical cardiovascular disease at baseline, underwent computed tomography for AVC and coronary artery calcium scoring. The primary, pre-specified combined endpoint of cardiovascular events included myocardial infarctions, fatal and nonfatal strokes, resuscitated cardiac arrest, and cardiovascular death, whereas a secondary combined endpoint of coronary events excluded strokes. The association between AVC and clinical events was assessed using Cox proportional hazards regression with incremental adjustments for demographics, cardiovascular risk factors, inflammatory biomarkers, and subclinical coronary atherosclerosis.

Results: Over a median follow-up of 5.8 years (interquartile range: 5.6 to 5.9 years), adjusting for demographics and cardiovascular risk factors, subjects with AVC (n = 894, 13.4%) had higher risks of cardiovascular (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.10 to 2.03) and coronary (HR: 1.72; 95% CI: 1.19 to 2.49) events compared with those without AVC. Adjustments for inflammatory biomarkers did not alter these associations, but adjustment for coronary artery calcium substantially attenuated both cardiovascular (HR: 1.32; 95% CI: 0.98 to 1.78) and coronary (HR: 1.41; 95% CI: 0.98 to 2.02) event risk. AVC remained predictive of cardiovascular mortality even after full adjustment (HR: 2.51; 95% CI: 1.22 to 5.21).

Conclusions: In this MESA cohort, free of clinical cardiovascular disease, AVC predicts cardiovascular and coronary event risk independent of traditional risk factors and inflammatory biomarkers, likely due to the strong correlation between AVC and subclinical atherosclerosis. The association of AVC with excess cardiovascular mortality beyond coronary atherosclerosis risk merits further investigation. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Figure 1. Distribution of Coronary Artery Calcium Scores, Stratified by Presence of Aortic Valve Calcium

The prevalence of coronary artery calcium (CAC) categories (CAC score = 0; <100; 100-300; and >300) among MESA participants with (n=894) and without (n=5791) aortic valve calcium (AVC) at baseline. Participants with baseline AVC had a higher prevalence of CAC (87.1% vs. 45.1%, p<0.0001) compared to those without AVC, with skewing of the distribution of CAC scores towards more severe calcification.

Figure 2. Kaplan-Meier Event Curves for Primary and Secondary Outcomes

Unadjusted Kaplan-Meier cumulative event curves depicting the Cardiovascular (Figure 2A) and Coronary (Figure 2B) events rates among participants with (red curve) and without (blue curve) aortic valve calcium (AVC) at baseline. At the median 5.8 years of follow up, participants with AVC had higher unadjusted rates of both Cardiovascular (3.2% vs. 10.2%, p<0.0001) and Coronary (1.9% vs. 6.9%, p<0.0001) events compared to participants without AVC.

Figure 2. Kaplan-Meier Event Curves for Primary and Secondary Outcomes

Unadjusted Kaplan-Meier cumulative event curves depicting the Cardiovascular (Figure 2A) and Coronary (Figure 2B) events rates among participants with (red curve) and without (blue curve) aortic valve calcium (AVC) at baseline. At the median 5.8 years of follow up, participants with AVC had higher unadjusted rates of both Cardiovascular (3.2% vs. 10.2%, p<0.0001) and Coronary (1.9% vs. 6.9%, p<0.0001) events compared to participants without AVC.

Figure 3. Kaplan Meier Event Curves for Cardiovascular Mortality

Unadjusted Kaplan-Meier cumulative event curves for the combined endpoint of cardiovascular (CV) death or resuscitated cardiac arrest (RCA), stratified by tertiles of baseline aortic valve calcium (AVC) score. At the median 5.8 years of follow up, the unadjusted event rate for participants without baseline AVC was 0.5%, compared with event rates of 2.1% (tertile 1), 3.2% (tertile 2), and 3.7% (tertile 3) for those with increasing severity of baseline AVC. After full adjustment for age, sex, cardiovascular risk factors, renal function and coronary artery calcium scores, there remained a 1.48-fold (95% CI: 1.14, 1.95; p=0.004) increase in risk of CV death or RCA per tertile-increase in AVC score.