Risk Refinement, Reclassification, and Treatment Thresholds in Primary Prevention of Cardiovascular Disease

JAMA Coronary Artery Calcium Score and Risk Classification for Coronary Heart Disease Prediction Tamar S. Polonsky, MD; Robyn L. McClelland, PhD; Neal W. Jorgensen, BS; Diane E. Bild, MD, MPH; Gregory L. Burke, MD, MSc; Alan D. Guerci, MD; Philip Greenland, MD Context: The coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear. Objective: To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk. Design, Setting, and Participants: CACS was measured by computed tomography in 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded from the primary analysis. Five-year risk estimates for incident CHD were categorized as 0% to less than 3%, 3% to less than 10%, and 10% or more using Cox proportional hazards models. Model 1 used age, sex, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement and compared the distribution of risk using model 2 vs model 1. Main Outcome Measures: Incident CHD events. Results: During a median of 5.8 years of follow-up among a final cohort of 5878, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared with model 1 (net reclassification improvement = 0.25; 95% confidence interval, 0.16-0.34;P < .001). In model 1, 69% of the cohort was classified in the highest or lowest risk categories compared with 77% in model 2. An additional 23% of those who experienced events were reclassified as high risk, and an additional 13% without events were reclassified as low risk using model 2. Conclusion: In this multi-ethnic cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories. JAMA. 2010;303(16):1610-1616..