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

Abstract

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.

Keywords: atherosclerosis; calcium density; coronary artery calcium; noncontrast computed tomography.

FIGURE 1. Association of Peak and Mean Calcium Density With Biological Age Among Primary Prevention Patients With Prevalent CAC

Among more than 10,000 primary prevention patients with prevalent CAC in the CAC Consortium, peak calcium density and mean calcium density both positively associate age. Data from 10,373 primary prevention participants from the CAC Consortium with prevalent CAC. CAC = coronary artery calcium.

FIGURE 2. Independent Associations Between Traditional ASCVD Risk Factors and Calcium Density

In contrast to age, several upstream ASCVD risk factors, including body mass index and diabetes, may share inverse associations with calcium density. Diabetes appears to share the strongest inverse association with calcium density. Adapted with permission from Thomas et al. ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; HDL-C = high-density lipoprotein cholesterol; IL = interleukin; SBP = systolic blood pressure.

FIGURE 3. CAC Scoring With the Agatston Algorithm

The Agatston formula uses a quantized density weighting factor, assigning a weighting factor of 1 (130–199 HU), 2 (200–299 HU), 3 (300–399 HU), or 4 (>400 HU) depending on the peak density per atherosclerotic lesion. Abbreviation as in Figure 1.

FIGURE 4. Different Approaches for Measuring and Quantifying CAC Density

The current Agatston CAC scoring system could potentially be improved on by considering mean vs peak calcium density among individuals with low CAC burden and/or using different measures of calcium density variability. Abbreviations as in Figures 1 and 2.

FIGURE 5. Calcium Density and Plaque Vulnerability

Plaque vulnerability is associated with several unique characteristics on cardiac CT and CCTA, including spotty calcification, low calcium density, positive remodeling, and the napkin-ring sign. *Can be detected on both coronary CT and CCTA. †Better detected on CCTA. CT = computed tomography; CCTA = coronary computed tomography angiography.

CENTRAL ILLUSTRATION. The Evolving Role of Calcium Density in CAC Scoring

The current Agatston CAC scoring system could potentially be improved on by considering mean vs peak calcium density among individuals with low CAC burden, using different measures of calcium density variability, and further understanding the relationship between traditional ASCVD risk factors and calcium density phenotypes. ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; CAC = coronary artery calcium; HDL-C = high-density lipoprotein cholesterol; SBP = systolic blood pressure.