Coronary Artery Calcium Density and Risk of Cardiovascular Events: A Systematic Review and Meta-Analysis

Abstract

Background: There is increasing evidence that coronary artery calcium (CAC) density is inversely associated with plaque vulnerability and atherosclerotic cardiovascular disease risk.

Objectives: A systematic review and meta-analysis were performed to examine the predictive value of CAC density for future cardiovascular events in asymptomatic individuals undergoing noncontrast CAC scoring computed tomography.

Methods: Electronic databases were searched for studies reporting CAC density and subsequent cardiovascular disease (CVD) or coronary heart disease (CHD) events. Two independent reviewers performed data extraction. Random-effects models were used to estimate pooled HRs and 95% CIs. Subgroup analyses were performed with studies stratified by CVD vs CHD events and by statin use.

Results: Of 5,029 citations, 5 studies with 6 cohorts met inclusion criteria. In total, 1,309 (6.1%) cardiovascular events occurred in 21,346 participants with median follow-up ranging from 5.2 to 16.7 years. Higher CAC density was inversely associated with risk of cardiovascular events following adjustment for clinical risk factors and CAC volume (HR: 0.80 per SD of density [95% CI: 0.72-0.89]; P < 0.01; I² = 0%). There was no significant difference in the pooled HRs for CVD vs CHD events (HR: 0.80 per SD [95% CI: 0.71-0.90] vs 0.74 per SD [95% CI: 0.59-0.94] respectively; P = 0.59). The protective association between CAC density and event risk persisted among statin-naive patients (HR: 0.79 per SD [95% CI: 0.70-0.89]; P < 0.01) but not statin-treated patients (HR: 0.97 per SD [95% CI: 0.77-1.22]; P = 0.78); the test for interaction indicated no significant between-group differences (P = 0.12).

Conclusions: Higher CAC density is associated with a lower risk of cardiovascular events when adjusted for risk factors and CAC volume. Future work may expand the contribution of CAC density in CAC scoring, and enhance its role in CVD risk assessment, treatment, and prevention.

Keywords: atherosclerosis; cardiac computed tomography; cardiovascular risk; coronary artery calcium density; coronary artery calcium score.