Improving the CAC Score by Addition of Regional Measures of Calcium Distribution: Multi-Ethnic Study of Atherosclerosis

Abstract

Objectives: The aim of this study was to investigate whether inclusion of simple measures of calcified plaque distribution might improve the ability of the traditional Agatston coronary artery calcium (CAC) score to predict cardiovascular events.

Background: Agatston CAC scoring does not include information on the location and distributional pattern of detectable calcified plaque.

Methods: We studied 3,262 (50%) individuals with baseline CAC >0 from MESA (Multi-Ethnic Study of Atherosclerosis). Multivessel CAC was defined by the number of coronary vessels with CAC (scored 1 to 4, including the left main). The "diffusivity index" was calculated as: 1 - (CAC in most affected vessel/total CAC), and was used to group participants into concentrated and diffuse CAC patterns. Multivariable Cox proportional hazards regression, area under the curve, and net reclassification improvement analyses were performed for both coronary heart disease (CHD) and cardiovascular disease (CVD) events to assess whether measures of regional CAC distribution add to the traditional Agatston CAC score.

Results: Mean age of the population was 66 ± 10 years, with 42% women. Median follow-up was 10.0 (9.5 to 10.7) years and there were 368 CHD and 493 CVD events during follow-up. Considerable heterogeneity existed between CAC score group and number of vessels with CAC (p < 0.01). Addition of number of vessels with CAC significantly improved capacity to predict CHD and CVD events in survival analysis (hazard ratio: 1.9 to 3.5 for 4-vessel vs. 1-vessel CAC), area under the curve analysis (C-statistic improvement of 0.01 to 0.033), and net reclassification improvement analysis (category-less net reclassification improvement 0.10 to 0.45). Although a diffuse CAC pattern was associated with worse outcomes in participants with ≥2 vessels with CAC (hazard ratio: 1.33 to 1.41; p < 0.05), adding this variable to the Agatston CAC score and number of vessels with CAC did not further improve global risk prediction.

Conclusions: The number of coronary arteries with calcified plaque, indicating increasingly "diffuse" multivessel subclinical atherosclerosis, adds significantly to the traditional Agatston CAC score for the prediction of CHD and CVD events.

Keywords: cardiac computed tomography; risk prediction; risk stratification.

Figure 1. Heterogeneity Between CAC Score Groups and the Number of Vessels with CAC

There is heterogeneity between CAC score group and the number of vessels with CAC, particularly when CAC is intermediate (1-300). Nearly all participants with CAC>300 have at least 3 vessel CAC.

Figure 2. Relationship Between a More Diffuse CAC Pattern and CHD and CVD Events

(A,B): Within each CAC score group, there is a graded increase in CHD and CVD event rates with increasing number of vessels with CAC. (C, D) Within each CAC score group, there is a graded increase in CHD and CVD event rates progressing from a concentrated to a diffuse pattern of CAC distribution.

Figure 2. Relationship Between a More Diffuse CAC Pattern and CHD and CVD Events

(A,B): Within each CAC score group, there is a graded increase in CHD and CVD event rates with increasing number of vessels with CAC. (C, D) Within each CAC score group, there is a graded increase in CHD and CVD event rates progressing from a concentrated to a diffuse pattern of CAC distribution.

Figure 2. Relationship Between a More Diffuse CAC Pattern and CHD and CVD Events

(A,B): Within each CAC score group, there is a graded increase in CHD and CVD event rates with increasing number of vessels with CAC. (C, D) Within each CAC score group, there is a graded increase in CHD and CVD event rates progressing from a concentrated to a diffuse pattern of CAC distribution.

Figure 2. Relationship Between a More Diffuse CAC Pattern and CHD and CVD Events

(A,B): Within each CAC score group, there is a graded increase in CHD and CVD event rates with increasing number of vessels with CAC. (C, D) Within each CAC score group, there is a graded increase in CHD and CVD event rates progressing from a concentrated to a diffuse pattern of CAC distribution.

Figure 3. Illustration of More Diffuse Distribution of Coronary Artery Calcium

Both cases have an Agatston CAC score of 200. The first case involves only 1 vessel, and the diffusivity index cannot be calculated as this metric requires multi-vessel CAC. The second case has 3-vessel involvement, with CAC=100 in the left anterior descending, CAC=50 in the left circumflex, and CAC=50 in the right coronary artery. The diffusivity index is (1- [100/200]) = 0.50 or 50%, consistent with a diffuse multi-vessel CAC pattern. Adapted in part from Alluri et al(8).