Calcium density of coronary artery plaque and risk of incident cardiovascular events.
Level 3 - non-randomized controlled study
Prospective observational cohort study evaluating prognostic markers for incident cardiovascular events
PubMed 24247483 · doi:10.1001/jama.2013.282535
What was done
Data were analyzed from 3,398 participants aged 45–84 years across four racial/ethnic groups (non-Hispanic white, African American, Hispanic, Chinese) in the prospective Multi-Ethnic Study of Atherosclerosis (MESA). All participants were free of known cardiovascular disease (CVD) at baseline and had a coronary artery calcium (CAC) score greater than 0 on baseline computed tomography (CT). Participants were followed for a median of 7.6 years through October 2010 to evaluate the independent associations of CAC volume and CAC density with incident coronary heart disease (CHD) and total CVD events.
What was found
During follow-up, 175 CHD events and 265 total CVD events occurred. In multivariable models including both volume and density, lnCAC volume was positively associated with incident CHD (hazard ratio [HR] 1.81, 95% CI 1.47–2.23 per 1 SD [1.6] increase; absolute risk increase 6.1 per 1,000 person-years) and CVD (HR 1.68, 95% CI 1.42–1.98 per SD increase; absolute risk increase 7.9 per 1,000 person-years). Conversely, CAC density was inversely associated with CHD (HR 0.73, 95% CI 0.58–0.91 per 1 SD [0.7] increase; absolute risk decrease 5.5 per 1,000 person-years) and CVD (HR 0.71, 95% CI 0.60–0.85 per SD increase; absolute risk decrease 8.2 per 1,000 person-years). Adding density to a model with volume improved the area under the receiver operating characteristic curve in the intermediate CVD risk group from 0.53 (95% CI 0.48–0.59) to 0.59 (95% CI 0.54–0.64, P = .02).
Why it matters
Standard Agatston CAC scoring weights upward for higher calcium density, but these findings indicate that denser calcification is protective after controlling for total volume. Decoupling calcium volume and density could substantially improve cardiovascular risk stratification.
Limits
The study included only individuals with baseline CAC > 0, limiting generalizability to those without detectable calcium. The observational design cannot establish causality or exclude residual confounding, and changes in clinical risk scoring would require altering existing automated CT measurement protocols.
Cited by
- context A coronary artery calcium score of 1,000 or above often indicates plaque stabilization and calcification associated with lower risk than lower scores with unstable plaque.