Mortality in individuals without known coronary artery disease but with discordance between the Framingham risk score and coronary artery calcium

A risk-management approach based on the Framingham risk score (FRS), although useful in preventing future coronary artery disease (CAD) events, is unable to identify a considerable portion of patients with CAD who need aggressive medical management. Coronary artery calcium (CAC), an anatomic marker of atherosclerosis, correlates well with presence and extent of CAD. This study investigated mortality risk associated with CAC score and FRS in subjects classified as "low risk" versus "high risk" based on FRS. In total 730 veterans without known CAD (61 ± 10 years old, 12.8% women) underwent measurement of their FRS and CAC. Subjects were classified as "discordant low risk" (DLR) if their FRS was <10% and CAC score was ≥ 100 (n = 108, 14.8%) or "discordant high risk" (DHR) if their FRS was ≥ 20% and CAC score was 0 (n = 104, 14.2%). Survival analysis was used to compare mortality rates associated with FRS and CAC in DLR versus DHR subjects. Mortality rate during the mean 48-month follow-up was 7.3% (n = 53) including 18.5% (n = 20) in the DLR group and 7.7% (n = 8) in the DHR group, respectively. Adjusted relative risks of mortality were 5.46 (95% confidence interval [CI] 2.44 to 12.20, p = 0.0001) in subjects with CAC score ≥ 100 compared to CAC score 0 and 1.35 (95% CI 1.01 to 4.32, p = 0.04) in subjects with FRS ≥ 20% compared to FRS <10%. Adjusted relative risk of mortality was 3.6 (95% CI 1.57 to 8.34, p = 0.003) for DLR compared to DHR. Areas under the receiver operator curve to predict mortality were 0.72 for FRS, 0.82 for CAC score, and 0.92 for the combination. In conclusion, the prognostic value of CAC to predict future mortality is superior to the FRS. Addition of CAC score to FRS significantly improves the identification and prognostication of patients without known CAD.