High Serum Level of Pentosidine, an Advanced Glycation End Product (AGE), is a Risk Factor of Patients with Heart Failure

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Background: Pentosidine, one of the advanced glycation end products (AGE), is generated by nonenzymatic glycation and oxidation of proteins. The receptor of AGE (RAGE) is expressed in a variety of tissue, and interaction of AGE with RAGE induces oxidative stress and activation of intracellular signaling causing production of cytokines and mediators of inflammation. We investigated whether serum pentosidine is a risk factor for heart failure. Methods: Serum pentosidine concentration was measured in 141 patients with heart failure and 18 control subjects by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 479 days with endpoints of cardiac death or re-hospitalization. Results: Serum concentration of pentosidine was significantly higher in NYHA class III/IV patients than in NYHA class I/II patients (P < 0.0001). Serum pentosidine was also higher in patients with cardiac events than in event free patients (P < 0.001). In the univariate Cox proportional hazard analysis, age, NYHA class, pentosidine, creatinine, uric acid, B-type natriuretic peptide, left ventricular end-systolic volume and left ventricular mass were significant risk factors to predict cardiac events. In the multivariate Cox analysis, serum pentosidine concentration was an independent risk factor for cardiac events (hazard ratio 1.88, 95% confidence interval 1.23 . 2.69, P = 0.002). Patients were divided into 4 groups based on the serum pentosidine levels. The highest 4th quartile of pentosidine was associated with the highest risk of cardiac events (4.52-fold). Conclusions: Serum pentosidine concentration is an independent prognostic factor for heart failure, and this new marker may be useful for risk stratification of patients with heart failure.