In a comparison of novel cardiovascular risk markers, coronary artery calcium, ankle-brachial index, high-sensitivity C-reactive protein, and family history were independent predictors of coronary heart disease/cardiovascular disease in intermediate-risk individuals beyond traditional risk factors, with coronary artery calcium providing superior discrimination and risk reclassification compared with other risk markers, according to a study in the August 22/29 issue of JAMA.

“Current trends in primary prevention of cardiovascular disease (CVD) emphasize the need to treat individuals based on their global cardiovascular risk. Accordingly, practice guidelines recommend approaches to classify individuals as high, intermediate, or low risk using the Framingham Risk Score (FRS) or other similar CVD risk prediction models. However, there is increasing recognition of the imprecision of these classifications such that the intermediate-risk group actually represents a composite of higher-risk individuals for whom more aggressive (i.e., drug) therapy might be indicated. The intermediate-risk group also contains lower-risk individuals in whom CVD might be managed with lifestyle measures alone. This recognition has motivated researchers to identify markers that could offer greater discrimination of higher- and lower-risk patients within the intermediate-risk group,” according to background information in the article.

“Risk markers including coronary artery calcium (CAC), carotid intima-media thickness (CIMT), ankle-brachial index (ABI), brachial flow-mediated dilation (FMD), high-sensitivity C-reactive protein (CRP), and family history of coronary heart disease (CHD) have been reported to improve on the Framingham Risk Score for prediction of CHD, but there are no direct comparisons of these markers for risk prediction in a single cohort,” the authors write.

Joseph Yeboah, M.D., M.S., of the Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues assessed the improvements in CHD/CVD prediction accuracy and reclassification to high- and low-risk categories using CIMT, CAC, FMD, ABI, high-sensitivity CRP, and family history of CHD in asymptomatic adults classified as intermediate risk who participated in the Multi-Ethnic Study of Atherosclerosis (MESA). Of 6,814 MESA participants from 6 U.S. field centers, 1,330 were intermediate risk, without diabetes mellitus, and had complete data on all 6 markers. Recruitment spanned July 2000 to September 2002, with follow-up through May 2011. Analysis was conducted to compare incremental contributions of each marker when added to the FRS, plus race/ethnicity. Incident CHD was defined as heart attack, angina followed by revascularization, resuscitated cardiac arrest, or CHD death. Incident CVD additionally included stroke or CVD death.

After a median (midpoint) follow-up of 7.6 years, 94 participants (7.1 percent) experienced a CHD event and 123 (9.2 percent) experienced a CVD event. After analyses, the researchers found that each of the novel risk markers was associated with incident CHD; however, after adjusting for confounders, the associations with CIMT and FMD were no longer significant. Among all of the risk markers, CAC had the strongest association. Similarly, for incident CVD, each of the markers was associated with events except high-sensitivity CRP. However, after adjusting for confounders, the associations between CIMT and FMD were no longer significant. CAC also had the strongest association in the multivariable models for CVD.

“The current study shows that among 6 of the most promising novel risk markers, CAC provides the highest improvement in discrimination over the FRS and Reynolds score (RS) in individuals classified as intermediate risk. The present study provides additional support for the use of CAC as a tool for refining cardiovascular risk prediction in individuals classified as intermediate risk by the FRS or the RS,” the authors write. “Additional research is warranted to explore further both the costs and benefits of CAC screening in intermediate-risk individuals.”

(JAMA. 2012;308[8]:788-795. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Cardiovascular Risk Assessment in the 21st Century

In an accompanying editorial, J. Michael Gaziano, M.D., M.P.H., of the Boston VA Healthcare System, Brigham and Women’s Hospital, Harvard Medical School, Boston, (and Contributing Editor, JAMA), and Peter W. F. Wilson, M.D., of the Atlanta VA Medical Center and Emory Clinical Cardiovascular Research Institute, comment on the two studies in this issue of JAMA on assessing cardiovascular risk.

“These reports illustrate the means by which the enhancement of a given model such as FRS with additional data is evaluated. Area under the receiver operating characteristic curve has been used for many diagnostic tests. A clinically useful approach describes the proportion of individuals who are reclassified, known as the net reclassification index. However, not all reclassifications are created equally. Refining risk estimation at the low or high end of the risk spectrum is not helpful because it will not likely alter management. On the other hand, reclassification can assist in decision making for patients who are near clinical decision boundaries. For this reason, both studies provided information on the reclassification that occurred among those at 5 percent to 20 percent risk. In this intermediate range, risk estimates inform clinical decisions about certain interventions.”

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Marguerite Beck
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