Markers for Improved Evaluation of Intermediate Heart Risk

An analysis of 6 of the most novel risk factors for improvement in cardiovascular risk assessment found 4 markers that were independent predictors of incident coronary heart disease (CHD)/cardiovascular disease (CVD) in intermediate-risk individuals. The prospective cohort study was titled the Multi-Ethnic Study of Atherosclerosis (MESA); study findings were reported in the Journal of the American Medical Association [2012;308(8):788-795].

Practice guidelines for the prevention of CVD recommend classifying patients as high-, intermediate-, or low-risk for CVD using the Framingham Risk Score (FRS) or other similar CVD risk prediction models. However, there is increasing awareness of the imprecision of these classifications. For this study, researchers compared improvement in prediction of incident CHD/CVD using 6 risk markers within the intermediate-risk participants (estimated 10-year CHD risk of >5%-<20% based on the FRS) in MESA.

The 6 risk factors were: (1) carotid intima-media thickness (CIMT), (2) coronary artery calcium (CAC) scores, (3) brachial flow-mediated dilation (FMD), (4) ankle-brachial index (ABI), (5) high-sensitivity C-reactive protein (CRP), and (6) family history of CHD. Main outcome measures included incident CHD, defined as myocardial infarction, angina followed by revascularization, resuscitated cardiac arrest, or CHD death. Incident CVD also included stroke or CVD death.

A total of 6814 adults 45 to 84 years of age without known CVD were recruited from 6 US communities. Self-reported race/ethnicity was culled to explore the possible racial ethnic differences in the development and progression of atherosclerosis. Patients with diabetes were excluded because it is considered to be a CHD risk equivalent. Of the patients, 1330 were classified as intermediate risk, without diabetes, and had complete data on all 6 markers. Patients were recruited from July 2000 to September 2002, with follow-up through May 2011. The researchers used probability-weighted Cox proportional hazard models to estimate hazard ratios (HRs). Area under the curve and net reclassification improvement were used to compare incremental contributions of each marker when added to FRS, plus race/ethnicity.

After a 7.6-year median follow-up, 94 patients (7.1%) experienced a CHD event and 123 (9.2%) experienced a CVD event. The researchers found that CAC (HR=2.60; 95% confidence interval [CI], 1.94-3.50), ABI (HR=0.79; 95% CI, 0.66-0.95), high-sensitivity CRP (HR=1.28; 95% CI, 1.00-1.64), and family history (HR=2.18; 95% CI, 1.38-3.42) were independently linked to CHD in multivariable analyses. After adjusting for cofounders, CIMT (HR=1.17; 95% CI, 0.95-1.45) and brachial FMD (HR=0.93; 95% CI, 0.74-1.16) were not associated with incident CHD in the multivariable analyses.

For CHD/CVD events, the addition of each of the 6 risk markers to the baseline model improved the area under the curve. CIMT had the highest improvement (0.623 vs 0.784) while brachial FMD showed the least improvement (0.623 vs 0.639). For incident CHD, the net reclassification improvement with CIMT was 0.102, CAC was 0.659, brachial FMD was 0.024, ABI was 0.036, high-sensitivity CRP was 0.079, and family history was 0.160. Similar results were observed for CVD.

The researchers noted 2 study limitations. Analysis was limited to the subset of MESA participants with complete data on all 6 risk factors, which decreased the study’s sample size. In MESA, the investigators did not specifically define family history of CHD as premature (before the age of 55 for men and 65 for women), potentially influencing the association of family history with CHD and CVD.

“CAC, ABI, high-sensitivity CRP, and family history were independent predictors of incident CHD/CVD beyond traditional risk factors,” concluded the authors. “CAC had the highest improvement in both area under the curve and net reclassification improvement when added to the FRS.”