Reactive oxygen metabolites are closely associated with the diagnosis and prognosis of coronary artery disease

Abstract

BACKGROUND: Reactive oxygen species (ROS) are associated with development of coronary artery disease (CAD). However, there's no useful biomarker of ROS in CAD. METHODS AND RESULTS: We recruited 395 consecutive CAD patients who were performed coronary angiography (262 male and 133 female, age 70.2±10), and we measured serum derivatives of reactive oxidative metabolites (DROM) were measured. Two hundred twenty-seven non-CAD patients were also enrolled. We performed follow-up study in these 395 CAD patients and case-control study after risk factor and 1:1 pair matching (both, n=163). As subgroup analysis, DROM were also measured at the aortic root and the coronary sinus in 59 CAD patients. DROM were significantly higher in CAD patients (n=163, median [inter-quartile range, IQR]=338 [302 to 386]) than in risk factor-matched non-CAD patients (n=163, 311 [282 to 352.5], effect size=0.33, P<0.001). During a mean follow-up period of 20 months of 395 CAD patients, 83 cardiovascular events were recorded. Kaplan-Meier analysis showed a higher probability of cardiovascular events in the high-DROM group (>346 U.CARR) than in the low-DROM group (≤346 U.CARR) (P=0.001 [log-rank test]). Multivariate Cox hazard analysis identified ln-DROM as an independent predictor for cardiovascular events (hazard ratio: 10.8, 95% confidence interval: 2.76 to 42.4, P=0.001). The transcardiac gradient of DROM was significantly higher in CAD patients than in non-CAD patients (-2.0 [-9.0 to 9.0] versus 8 [-8.0 to 28.3], effect size=0.21, P=0.04), indicating that DROM production in coronary circulation is associated with development of CAD. CONCLUSION: DROM are increased in CAD patients and associated with future cardiovascular events. DROM might provide clinical benefits for risk stratification of CAD. CLINICAL TRIAL REGISTRATION URL: http://www.umin.ac.jp/ctr/. Unique identifier: UMIN000012990.