Interleukin-6, fibrin D-dimer, and coagulation factors VII and XIIa in prediction of coronary heart disease.

OBJECTIVE Activated inflammation and activated blood coagulation are believed to increase the risk of coronary thrombosis and are related. We therefore compared plasma IL-6 (a key cytokine in the inflammatory process), fibrin D-dimer (a marker of fibrin turnover), and coagulation factors VII and XIIa (initiators of extrinsic and intrinsic blood coagulation, respectively) as predictors of coronary risk in the West of Scotland Coronary Prevention Study of pravastatin in men with hypercholesterolemia. METHODS AND RESULTS 485 men who had had a coronary event (nonfatal myocardial infarction, death from coronary heart disease, or revascularization) were matched for age and smoking status with 934 controls. Baseline IL-6 and D-dimer were strong univariate predictors of coronary risk (relative risk in the highest quintile approximately twice that in the lowest quintile) and were associated with each other and with C-reactive protein. On multivariate analyses, D-dimer retained a significant association with coronary risk (relative risk, 1.86; 95% CI, 1.24 to 2.80), whereas IL-6 (1.47; 0.95 to 2.28) and C-reactive protein (1.33; 0.85 to 2.08) did not. Neither factor VII nor factor XIIa antigens were predictors of coronary events. CONCLUSIONS Fibrin D-dimer may be a stronger predictor of coronary risk than inflammatory markers, perhaps through its ability to stimulate monocyte release of IL-6.