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)
Key Words
aortic sclerosis
aortic valve calcium
atherosclerosis
cardiovascular death
cardiovascular events
computed tomography
coronary artery calcium
coronary events
Abbreviations and Acronyms
AVC
aortic valve calcium
CAC
coronary artery calcium
CI
confidence interval
CRP
C-reactive protein
CT
computed tomography
HR
hazard ratio
MI
myocardial infarction
Cited by (0)
This research was supported by R01-HL-63963-01A1 and by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI). The NHLBI participated in the design and conduct of MESA, but did not take part in manuscript preparation or the decision to submit for publication. The NHLBI did not review this manuscript before submission. Dr. Owens had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr. Budoff has received speaking honoraria from General Electric. Dr. O'Brien has received speaking honoraria from AstraZeneca and Merck. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. Shavelle is currently affiliated with the Department of Medicine, University of Southern California, Los Angeles, California.
