Relative value of multiple plasma biomarkers as risk factors for coronary artery disease and death in an angiography cohort.

BACKGROUND: Although elevated levels of C-reactive protein (CRP), interleukin (IL)-6, serum amyloid A protein (SAA) and total homocysteine (tHcy) have been associated with the increased likelihood of cardiovascular events, the relative or combined utility of these biomarkers in predicting atherosclerosis and death in an angiography cohort is unknown. METHODS: A cohort of 1117 consecutive patients (797 men and 320 women), referred to 2 Vancouver teaching hospitals for selective coronary angiography, was recruited between 1993 and 1995. Angiography results were obtained for 1019 patients. In 2004 we determined that of 1050 patients who could be traced, 231 had died, 95 of CAD-related causes. We compared the relative utility of baseline measurements of CRP, IL-6, SAA and tHcy as well as of lipids for predicting angiographic CAD and all-cause and CAD-related death. RESULTS: The risk of death increased across quartiles for CRP, IL-6, SAA and tHcy. When comparing the highest and lowest quartiles, the greatest hazard ratios were associated with IL-6 (2.57, 95% confidence interval [CI] 1.62-4.09) and tHcy (2.36, 95% CI 1.53-3.65). A Cox regression model containing all plasma biomarkers and traditional risk factors indicated that age, angiographic CAD and baseline plasma levels of IL-6 and tHcy remained independent predictors of CAD-related death, whereas age, sex, smoking, diabetes and apolipoprotein B levels were independent predictors of angiographic CAD. Kaplan-Meier survival curves indicated a utility in combining measures of CRP, SAA, IL-6 and tHcy for predicting risk of all-cause and CAD-related death. INTERPRETATION: A comparison of elevated levels of CRP, IL-6, SAA and tHcy with traditional CAD risk factors indicated that IL-6 and tHcy were the strongest independent biomarkers for CAD-related death. Elevated levels of multiple biomarkers were associated with an increasing rate of all-cause and CAD-related death.