Evolving Role of Calcium Density in Coronary Artery Calcium Scoring and Atherosclerotic Cardiovascular Disease Risk

Coronary artery calcium (CAC) is a specific marker of coronary atherosclerosis that can be used to measure calcified subclinical atherosclerotic burden. The Agatston method is the most widely used scoring algorithm for quantifying CAC and is expressed as the product of total calcium area and a quantized peak calcium density weighting factor defined by the calcification attenuation in HU on noncontrast computed tomography. Calcium density has emerged as an important area of inquiry because the Agatston score is upweighted based on the assumption that peak calcium density and atherosclerotic cardiovascular disease (ASCVD) risk are positively correlated. However, recent evidence demonstrates that calcium density is inversely associated with lesion vulnerability and ASCVD risk in population-based cohorts when accounting for age and plaque area. Here, we review calcium density by focusing on 3 main areas: 1) CAC scan acquisition parameters; 2) pathophysiology of calcified plaques; and 3) epidemiologic evidence relating calcium density to ASCVD outcomes. Through this process, we hope to provide further insight into the evolution of CAC scoring on noncontrast computed tomography. [Display omitted] •Coronary artery calcium is expressed as the product of calcium area and a quantized peak calcium density weighting factor.•Calcium density strongly and positively associates with age, which may correspond with the biological framework and natural progression of atherosclerosis.•Calcium density is inversely associated with lesion vulnerability and atherosclerotic cardiovascular disease risk in population-based cohorts when accounting for age and plaque area.•The presence of a calcium density >1,000 HU (1K plaque) is associated with a lower risk of acute coronary syndrome independent of traditional risk factors.•Mean calcium density performs better than peak calcium density factor when combined with plaque area for atherosclerotic cardiovascular disease mortality prediction among persons with limited coronary artery calcium burden.