Mean Versus Peak Coronary Calcium Density on Non-Contrast CT: Calcium Scoring and ASCVD Risk Prediction

Objectives: This study sought to assess the relationship between mean vs peak calcified plaque density and their impact on calculating coronary artery calcium (CAC) scores and to compare the corresponding differential prediction of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) mortality.

Background: The Agatston CAC score is quantified per lesion as the product of plaque area and a 4-level categorical peak calcium density factor. However, mean calcium density may more accurately measure the heterogenous mixture of lipid-rich, fibrous, and calcified plaque reflective of ASCVD risk.

Methods: We included 10,373 individuals from the CAC Consortium who had CAC >0 and per-vessel measurements of peak calcium density factor and mean calcium density. Area under the curve and continuous net reclassification improvement analyses were performed for CHD and ASCVD mortality to compare the predictive abilities of mean calcium density vs peak calcium density factor when calculating the Agatston CAC score.

Results: Participants were on average 53.4 years of age, 24.4% were women, and the median CAC score was 68 Agatston units. The average values for mean calcium density and peak calcium density factor were 210 ± 50 HU and 3.1 ± 0.5, respectively. Individuals younger than 50 years of age and/or those with a total plaque area <100 mm² had the largest differences between the peak and mean density measures. Among persons with CAC 1-99, the use of mean calcium density resulted in a larger improvement in ASCVD mortality net reclassification improvement (NRI) (NRI = 0.49; P < 0.001 vs. NRI = 0.18; P = 0.08) and CHD mortality discrimination (Δ area under the curve (AUC) = +0.169 vs +0.036; P < 0.001) compared with peak calcium density factor. Neither peak nor mean calcium density improved mortality prediction at CAC scores >100.

Conclusion: Mean and peak calcium density may differentially describe plaque composition early in the atherosclerotic process. Mean calcium density performs better than peak calcium density factor when combined with plaque area for ASCVD mortality prediction among persons with Agatston CAC 1-99.