Coronary artery calcium (CAC) provided superior discrimination and risk reclassification compared with other risk markers—ankle-brachial index, high-sensitivity C-reactive protein (CRP) and family history—all of which are independent predictors of incident coronary heart disease (CHD)/cardiovascular disease (CVD) in intermediate-risk individuals, according to a study in the Aug. 22/29 issue of the Archives of Internal Medicine.
Because the intermediate-risk group contains individuals in whom CVD might be managed with lifestyle changes alone, researchers have been motivated to identify markers that could offer greater discrimination of higher- and lower-risk patients within the intermediate-risk group.
Risk markers including CAC imaging, carotid intima–media thickness, ankle-brachial index, brachial flow-mediated dilation, CRP and family history of CHD have been reported to improve on the Framingham Risk Score (FRS) for prediction of CHD. But there are no direct comparisons of these markers for risk prediction in a single cohort, the study authors wrote.
To assess this population, Joseph Yeboah, MD, assistant professor of internal medicine-cardiology at Wake Forest Baptist Medical Center in Winston-Salem, N.C., and colleagues compared improvement in prediction of incident CHD/CVD of these six risk markers within intermediate-risk participants (with an FRS score of greater than 5 percent to less than 20 percent) in the Multi-Ethnic Study of Atherosclerosis (MESA).
A prospective cohort study, MESA investigated the prevalence, correlates and progression of subclinical CVD in individuals without known CVD at baseline. The full cohort includes 6,814 women and men age 45 to 84 years without known CVD, recruited from six U.S. communities (Baltimore; Chicago; Forsyth County, N.C.; Los Angeles; New York City; and St. Paul, Minn.).
For this analysis, the primary outcomes measures were incident CHD defined as MI, angina followed by revascularization, resuscitated cardiac arrest or CHD death. Incident CVD additionally included stroke or CVD death.
After 7.6-year median follow-up, 94 CHD and 123 CVD events occurred. The study authors reported that CAC, ankle-brachial index, high-sensitivity CRP and family history were independently associated with incident CHD in multivariable analyses.
However, carotid intima-media thickness and brachial flow-mediated dilation were not associated with incident CHD in multivariable analyses.
“Although addition of the markers individually to the FRS plus race/ethnicity improved AUC [area under the receiver operator characteristic curve], coronary artery calcium afforded the highest increment, while brachial flow-mediated dilation had the least,” the authors wrote.
For incident CHD, Yeboah et al noted that the net reclassification improvement with CAC was 0.659, brachial flow-mediated dilation was 0.024, ankle-brachial index was 0.036, carotid intima-media thickness was 0.102, family history was 0.160 and high-sensitivity CRP was 0.079. They discovered similar results for incident CVD.
“Even though our study indicates considerable superiority of CAC over several risk markers for risk prediction of CHD and CVD, several other factors should be considered before making broad recommendations about incorporation of CAC into primary prevention screening strategies,” according to the researchers. “One notable concern is that measurement of CAC exposes individuals to a small but nontrivial amount of ionizing radiation (approximately 0.9-1.1 mSv).”
As a result, the benefits and risks associated with incidental findings detected during CAC imaging “remain unclear,” they added.
Also, the researchers pointed to the direct financial costs of CAC imaging, which need to be weighed against the presumed benefits from better discrimination of participants at high risk for CHD and CVD events to best determine the role of CAC screening of intermediate-risk patients.
“Thus, the ultimate decision regarding the optimum test to order should not be based solely on improvement in risk prediction afforded by a test but also cost effectiveness, acceptability to patients, and the potential risk and benefits associated with the test,” concluded Yeboah et al.