Soluble Receptor for Advanced Glycation End Products (RAGE) is a Prognostic Factor for Heart Failure

Background: We recently reported that serum levels of pentosidine, one of the well defined advanced glycation end products (AGE), was an independent prognostic factor for heart failure. Receptor for AGEs (RAGE) is expressed in a variety of tissues, and RAGE has a C-truncated secretory isoform of the receptor protein, termed soluble RAGE. In the present study, we measured serum soluble RAGE levels in patients and examined whether serum soluble RAGE predicts prognosis in patients with heart failure. Methods and Results: Serum soluble RAGE concentration was measured in 160 patients with heart failure by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 872 days with endpoints of cardiac death or re-hospitalization. Serum soluble RAGE level increased with advancing NYHA functional class. Serum soluble RAGE level was also higher in patients with cardiac events than in event free patients. From the receiver operating characteristic (ROC) curve analysis, the cut-off value of serum soluble RAGE level was determined as 1220 pg/ml. Kaplan-Meier analysis clearly demonstrated that the high soluble RAGE group had a significantly higher incidence of cardiac events than occurred in the low serum soluble RAGE group (P = 0.0004). In the multivariate Cox proportional hazard analysis, soluble RAGE and serum pentosidine were independent risk factors for cardiac events (soluble RAGE: HR 1.90, 95% CI 1.16 . 3.09, P = 0.010; pentosidine: HR 1.59, 95% CI 1.11 . 2.29, P = 0.012). Conclusions: Serum soluble RAGE level is an independent prognostic factor for heart failure, and this novel marker may be useful for risk stratification of patients with heart failure