Coronary artery disease
Mortality in Individuals Without Known Coronary Artery Disease but With Discordance Between the Framingham Risk Score and Coronary Artery Calcium

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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.

Section snippets

Methods

The study population consisted of 730 consecutive veterans with suspected CAD but without previous known CAD who underwent CAC scanning. Subjects with established cardiovascular disease, stroke, diabetic retinopathy, end-stage renal disease, Raynaud syndrome, infection, cancer, immunosuppression, systemic inflammation status, or end-stage liver disease were excluded.

Conventional cardiovascular risk factors were assessed according to the FRS.6 Medical information was obtained from the Veterans

Results

The study population consisted of 730 consecutive subjects; 86.7% were men and the mean age was 61 ± 10 years. Demographic and conventional risk factors are presented in Table 1. In total 21.8% had intermediate likelihood of coronary heart disease but no symptoms, 31.5% had atypical chest pain, 32.1% had typical chest pain, 12.4% had abnormal treadmill test result, and 2.2% had syncope. There was no significant association between presence of symptoms and clinical outcome in the DLR and DHR

Discussion

The FRS predicts future cardiovascular outcomes and mortality in patients without previous known CAD.9 Although used commonly, this method is not well studied for symptomatic patients or for those with high suspicion for CAD but without previous known CAD or cardiac symptoms. These may include asymptomatic patients with an abnormal electrocardiogram or echocardiogram or an indeterminate stress test result or those with atypical chest pain or even syncope. Many of our current diagnostic tools

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