Ten-year trajectory of coronary artery calcification and risk of cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis.

Background: Whether and how coronary artery calcium (CAC) progress contributes to cardiovascular outcomes has not been fully elucidated. The aim of this study was to identify different patterns of CAC change and evaluate the associations with different cardiovascular outcomes. Methods: Data from the Multi-Ethnic Study of Atherosclerosis study were analyzed. Participants with at least three CT measurements were included. The main study outcome is hard cardiovascular disease (CVD). CAC scores were determined as phantom-adjusted Agatston scores. A group-based trajectory model was used to identify latent groups and estimated the hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional regression models. Results: A total of 3,616 participants were finally enrolled [mean age 60.55 (SD 9.54) years, 47.76% men and 39.30% Caucasian]. Four distinct trajectories in CAC were identified: class 1, low-stable (24.17%); class 2, low-increasing (27.60%); class 3, moderate-increasing (30.56%); and class 4, elevated-increasing (17.67%). During 13.58 (SD 2.25) years of follow-up, 291 cases of hard CVD occurred. The event rates of hard CVD per 1,000 person-years were 2.23 (95% CI 1.53-3.25), 4.60 (95% CI 3.60-5.89), 7.67 (95% CI 6.38-9.21) and 10.37 (95% CI 8.41-12.80) for classes 1-4, respectively. Compared to participants assigned to class 1, the full-adjusted HRs of hard CVD for classes 2-4 were 2.10 (95% CI 1.33-3.01), 3.17 (95% CI 2.07-4.87), and 4.30 (95% CI 2.73-6.78), respectively. The graded positive associations with hard CVD were consistently observed in subgroups of age, sex, and race, with the presence or absence of hypertension or diabetes. By analyzing potential risk factors for distinctive CAC trajectories, risk factors for the onset and progression of CAC could possibly differ: age, male sex, history of hypertension, and diabetes are consistently associated with the low-, moderate-, and elevated-increasing trajectories. However, Caucasian race, cigarette smoking, and a higher body mass index was related only to risk of progression but not to incident CAC. Conclusion: In this multi-ethnic population-based cohort, four unique trajectories in CAC change over a 10-year span were identified. These findings signal an underlying high-risk population and may inspire future studies on risk management.