Biomarkers collected through blood sampling are helpful for identifying patients with severe coronary artery disease (CAD), a study found. Along with male sex and previous percutaneous coronary intervention (PCI), the levels of midkine, adiponectin, apolipoprotein C-I, and kidney injury molecule (KIM)-1 were incorporated into a risk model which investigators found had an area under the curve of 0.87 for finding coronary stenosis over 70% (P<0.001). In the paper online in the Journal of the American College of Cardiology, higher scores corresponded with more severe angiographic stenosis and predicted acute myocardial infarction over follow-up (HR 2.39, P<0.001). The score was a strong predictor of severe CAD across all subgroups analyzed (OR 9.74, 95% CI 6.05-16.1), reported James L. Januzzi, Jr., MD, director of the Dennis and Marilyn Barry Fellowship in Cardiology Research at Massachusetts General Hospital in Boston, and colleagues. The optimal cutoff point for detecting severe CAD yielded 77% sensitivity, 84% specificity, a 90% positive predictive value, and a 67% negative predictive value. “This scoring has the potential to avoid the high cost of stress tests or coronary angiography, because in comparison, the cost of biomarker testing is generally considerably lower,” the team wrote. “Advantages of such a reliable clinical and biomarker score include the fact that such a technology can be widely disseminated in a cost-effective manner, is easily interpreted, and might be associated with a well-defined sequence of therapeutic steps to reduce the risk for CAD-related complications, such as antiplatelet or lipid-lowering therapy.” Writing in an accompanying editorial, Robert A. Vogel, MD, of the Veterans Affairs Medical Center at the University of Colorado in Denver, noted that midkine and KIM-1 have not previously been linked to CAD. “It is interesting that none of the biomarkers identified is a marker of inflammation, as would be expected if the goal had been determining unstable disease,” Vogel said. “To date, there seems to be little consensus on useful protein biomarkers for coronary atherosclerosis. The lack of consensus might be due to the characteristics of the populations studied, an important consideration for the development of any screening test. “Discriminatory clinical and blood biomarkers were determined in the training group and then retested in the similar validation group,” he noted of the analysis by Januzzi and colleagues. “Validation of the scoring system in an independent population selected with more varied inclusion criterion would give the current study more certainty — a criticism acknowledged by the investigators.” Indeed, the training cohort (n=649) and validation cohort (n=278) for the study were plucked from the same prospective registry of patients referred for coronary angiography. Participants had 15 ml of blood collected before and after angiography, and were followed for an average of 3.6 years. “There are plans to validate this score in an external cohort in the future,” the authors wrote. Another limitation of the study, they acknowledged, was that it included mostly white and male patients. “This study begs the question of whether high-grade coronary disease is associated with unique biomarkers apart from those associated with coronary atherosclerosis in general,” Vogel said. “It did not answer this question because it did not provide the performance of the selected biomarkers in separating those patients with and without any disease. Assigning patients to the ‘nonsignificant’ category of coronary disease, as opposed to ‘no angiographic disease,’ is a disservice to patients because they have almost the same risk for major coronary events, and secondary preventive measures are usually not suggested with the same vigor as for those with significant disease.” Vogel also emphasized the importance of collaborative efforts such as the Emerging Risk Factors Collaboration in the development of universally applicable biomarker screening tests for both early and severe CAD. Disclosures The study was supported by Prevencio. Januzzi is supported in part by the Hutter Family Professorship in Cardiology and has financial relationships with Siemens, Singulex, Prevencio, Roche Diagnostics, Critical Diagnostics, Sphingotec, Phillips, Novartis; he also disclosed participating in clinical endpoint committees/data safety monitoring boards for Novartis, Amgen, Janssen, and Boehringer Ingelheim.