Soluble receptor for advanced glycation end products and the risk for incident heart failure: The Atherosclerosis Risk in Communities Study

Background Experimental studies in animals suggest that circulating soluble receptor for advanced glycation end products (sRAGE) decrease oxidative stress, inflammation, and fibrosis. The association between sRAGE and incident heart failure has not been systematically examined in a prospective study. Methods We conducted a prospective analysis of a subsample of 1,086 participants from the Atherosclerosis Risk in Communities Study who attended visit 2 (1990-1992) without a history of coronary heart disease, stroke, or heart failure and with measured plasma sRAGE levels. Incident heart failure was defined as death from heart failure or hospitalization due to heart failure during a median of 20 years of follow-up. Results In this sample of a community-based population (mean age 63 years, 60% women, 78% white), there were 126 incident cases of heart failure. Lower levels of sRAGE were significantly associated with an increased risk of heart failure; the adjusted hazard ratios (95% CIs) of heart failure were 1.0 (reference), 1.81 (0.94-3.49), 1.57 (0.80-3.08), and 3.37 (1.75-6.50), for fourth, third, second, and first quartiles, respectively (P for trend = .001). We did not observe significant interactions by diabetes status or by race or obesity status. Conclusions Lower circulating levels of sRAGE are independently associated with the development of heart failure in a community-based population. Our results add to the growing evidence that sRAGE is a valuable predictor of cardiovascular disease.