Beyond the Agatston calcium score: role of calcium density and other calcified plaque markers for cardiovascular disease prediction

Purpose of review To review the current evidence and highlight future strategies regarding consideration of coronary artery calcium (CAC) density in cardiovascular disease (CVD) risk stratification. Recent findings Expressed as the product of plaque area and a peak calcium density weighting factor, the Agatston method is the gold-standard for measuring CAC on noncontrast cardiac computed tomography. Over the last decade, observational data have suggested that calcium density is inversely associated with CVD events and confers additional prognostic information independent of traditional risk factors and Agatston CAC scores. Specific density measures have been assessed including peak calcium density, mean CAC density, and CAC area-density discordance. Beyond calcium density, the number of affected arteries and regional distribution of CAC which may be correlated with CAC density have also improved the predictive utility of the Agatston score. Summary Calcium density is inversely associated with CVD risk after considering plaque area and/or volume. Calcium markers including density, vessel involvement, and regional distribution confer additional prognostic information for the prediction of incident CVD among those with prevalent subclinical atherosclerosis. A future area of study includes calcium radiomics (’calcium-omics’) and whether the artificial intelligence-derived automated measurement of calcium markers beyond the Agatston score may be of value in CVD risk stratification among individuals with early to advanced subclinical atherosclerosis.