Abstract

Background: It is known that oxidative stress is increased in patients with heart failure. Advanced glycation end products (AGE) are generated nonenzymatically by glycation and oxidation of proteins. We have recently reported that serum level AGE is an independent prognostic factor for heart failure. Receptor for AGE (RAGE) has a secretory isoform of the receptor protein, termed soluble RAGE. In the present study, we measured serum soluble RAGE levels in patients with heart failure. Methods: Serum soluble RAGE level was measured in 160 patients with heart failure and 40 control subjects. Patients were prospectively followed with endpoints of cardiac death or re-hospitalization. Results: Serum soluble RAGE level was increased with advancing NYHA functional class (figure 1 ). We determined the cut-off value of serum soluble RAGE level to predict cardiac events from ROC curve analysis as 1220 pg/ml (sensitivity 0.60, specificity 0.69). As shown in figure 2 , high serum soluble RAGE groups (>1220 pg/ml) had a significantly lower cardiac event-free rate (P = 0.0004) than low serum soluble RAGE groups (≥ 1220 pg/ml). In the univariate Cox proportional hazard analysis, serum soluble RAGE, age, NYHA functional class, creatinine, B-type natriuretic peptide (BNP), left ventricular end-diastolic diameter (LVEDD) were significantly associated with cardiac events. In the multivariate Cox proportional hazard analysis, serum soluble RAGE and plasma BNP were independent risk factors for cardiac events (soluble RAGE: HR 2.22, 95% CI 1.08 - 4.53, P = 0.029; BNP: HR 2.86, 95% CI 1.11 - 7.37, P = 0.029). Conclusions: Serum soluble RAGE level is a novel independent prognostic factor for heart failure.

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