Novel risk markers – CT looks strong

The primary prevention of cardiovascular disease involves classifying individuals according to their global cardiovascular risk. However, those at intermediate risk represent a particular challenge; while some may require aggressive treatment, others may be best managed by lifestyle measures alone. Biomarkers that have shown promise in improving risk discrimination include carotid intima-media thickness (CIMT), coronary artery calcium (CAC) scoring, brachial flow-mediated dilation (FMD), ankle-brachial index (ABI), high-sensitivity C-reactive protein (CRP) and, in addition, having a family history of coronary heart disease (CHD). Determining whether – and by how much – risk prediction can be improved by various markers could help to determine the most efficient strategy for the use of primary prevention drugs.

1330 intermediate risk participants (Framingham risk score of >5% and <20% for a coronary event within the next ten years) in the Multi-Ethnic Study of Atherosclerosis (MESA) were followed up for a mean of 7.6 years. The area under the receiver operator characteristic curve (AUC) and net relassification improvement were used to compare the incremental contributions of each marker when added to Framingham risk score, plus race/ethnicity.

94 coronary heart disease (CHD) and 123 cardiovascular (CVD) events occurred overall. Coronary artery calcium, ankle-brachial index, high-sensitivity CRP, and family history were independently associated with incident CHD in multivariable analysis, but carotid intima-media thickness and brachial flow-mediated dilation were not. Although addition of each of the markers individually to the Framingham risk score improved the AUC, coronary artery calcium afforded the highest increment, and brachial flow-mediated dilation the least. Similarly, the net reclassification improvement for incident CHD was highest for coronary artery calcium. Similar results were obtained for incident CVD.


In this study of patients at intermediate risk for cardiovascular disease, coronary artery calcium provided superior discrimination and risk reclassification when compared to other novel risk markers.

• Yeboah J, McClelland RL, Polonsky TS et al. Comparison of Novel Risk Markers for Improvement in Cardiovascular Risk Assessment in Intermediate-Risk Individuals. JAMA 2012;308:788-795.