Development and Validation of a Coronary Artery Calcium Volume and Density Score

Coronary artery calcium (CAC) scoring is a useful tool for coronary heart disease (CHD) risk prediction. The current standard method, the Agatston score, weights plaque area upward by density. However, higher density is inversely associated with CHD. We aimed to develop and validate a CAC score accounting for the inverse association of density with CHD, and the nonlinear association between CAC volume and density in a prospective cohort study.

A CAC volume and density score was developed, which adjusts CAC volume for density based on whether the volume level was <130 mm³. We used data from the MESA (Multi-Ethnic Study of Atherosclerosis) to develop and assess the score, including all participants with CAC>0 and follow-up for CHD events. Score performance for CHD risk prediction was compared with the pooled cohort equations and the Agatston score using Cox proportional hazards models and Harrell C-index and continuous and categorical net reclassification improvement. Analyses were also stratified by Agatston score, age, sex, race/ethnicity, and statin use. Finally, performance was evaluated in 4 longitudinal cohorts for external validation.

The MESA cohort included 3360 individuals. CAC volume and density score improved the C-index for CHD to a greater degree over the pooled cohort equation (0.699 [95% CI, 0.675-0.723]) compared with the Agatston score (0.687 [95% CI, 0.663-0.711]) and resulted in greater continuous net reclassification improvement (0.54 [95% CI, 0.43-0.64]) compared with the Agatston score (0.45 [95% CI, 0.34-0.56]) when added to the pooled cohort equation. The greatest improvement in risk prediction was in those with lower burden of CAC (Agatston <300). Consistent results were seen in stratified analyses and external validation cohorts.

The CAC volume and density score, which adjusts CAC volume downward for higher density, and can be calculated from existing CAC reports, significantly improves risk discrimination and reclassification compared with the Agatston score.