Cardiovascular Event Prediction and Risk Reclassification by Coronary, Aortic, and Valvular Calcification in the Framingham Heart Study

Abstract

BACKGROUND: We determined whether vascular and valvular calcification predicted incident major coronary heart disease, cardiovascular disease (CVD), and all-cause mortality independent of Framingham risk factors in the community-based Framingham Heart Study. METHODS AND RESULTS: Coronary artery calcium (CAC), thoracic and abdominal aortic calcium, and mitral or aortic valve calcium were measured by cardiac computed tomography in participants free of CVD. Participants were followed for a median of 8 years. Multivariate Cox proportional hazards models were used to determine association of CAC, thoracic and abdominal aortic calcium, and mitral and aortic valve calcium with end points. Improvement in discrimination beyond risk factors was tested via the C-statistic and net reclassification index. In this cohort of 3486 participants (mean age 50±10 years; 51% female), CAC was most strongly associated with major coronary heart disease, followed by major CVD, and all-cause mortality independent of Framingham risk factors. Among noncoronary calcifications, mitral valve calcium was associated with major CVD and all-cause mortality independent of Framingham risk factors and CAC. CAC significantly improved discriminatory value beyond risk factors for coronary heart disease (area under the curve 0.78-0.82; net reclassification index 32%, 95% CI 11-53) but not for CVD. CAC accurately reclassified 85% of the 261 patients who were at intermediate (5-10%) 10-year risk for coronary heart disease based on Framingham risk factors to either low risk (n=172; no events observed) or high risk (n=53; observed event rate 8%). CONCLUSIONS: CAC improves discrimination and risk reclassification for major coronary heart disease and CVD beyond risk factors in asymptomatic community-dwelling persons and accurately reclassifies two-thirds of the intermediate-risk population.