Progression of coronary artery calcium predicts all-cause mortality

Objectives: This study examined a large cohort to assess whether progression of coronary artery calcium (CAC) was associated with all-cause mortality, and which among 3 different methods to assess CAC progression provided the best estimate of risk.

Background: Serial assessment of CAC scores has been proposed as a method to follow progression of coronary artery disease, and it has been suggested that excessive CAC progression may be a useful noninvasive predictor of the patient's risk of future events. However, the optimal method to measure calcium progression has not been well established.

Methods: The study sample consisted of 4,609 consecutive asymptomatic individuals referred by primary physicians for CAC measurement with electron beam tomography, who underwent repeat screening. Three general statistical approaches were taken: 1) the absolute difference between follow-up and baseline CAC score; 2) percent annualized differences between follow-up and baseline CAC score; and 3) difference between square root of baseline and square root of follow-up CAC score >2.5 (the "SQRT method").

Results: The average interscan time was 3.1 years, and there were 288 deaths. Progression of CAC was significantly associated with mortality regardless of the method used to assess progression (p < 0.0001). After adjusting for baseline score, age, sex, and time between scans, the best CAC progression model to predict mortality was the SQRT method (hazard ratio [HR]: 3.34; 95% confidence interval [CI]: 2.65 to 4.21; p < 0.0001), followed by a >15% yearly increase (HR: 2.98; 95% CI: 2.20 to 4.95; p < 0.0001). Progression was very limited and did not predict mortality in patients with baseline CAC = 0.

Conclusions: The CAC progression added incremental value in predicting all-cause mortality over baseline score, time between scans, demographics, and cardiovascular risk factors. Serial assessment may have clinical value in assessing plaque progression and future cardiovascular risk.