The role of advanced glycation end-products and their receptor on outcome in heart failure patients with preserved and reduced ejection fraction

Introduction Advanced glycation end products (AGEs) are increased in patients with heart failure (HF). We studied the predictive value of plasma AGEs N-E-(carboxymethyl) lysine (CML), pentosidine, and the soluble form of its receptor (sRAGE) in a large HF population. Methods In 580 patients hospitalized with HF, plasma AGEs were measured before discharge when patients were clinically stable. Patients were followed for a period of 18 months. Primary end point was a composite of death and HF admissions. CML was determined by liquid chromatography mass spectrometry, pentosidine by high-performance liquid chromatography and sRAGE by sequential sandwich immunoassay. Results Mean age was 71 +/- 11 years, 62% were men, and mean left ventricular ejection fraction was 0.32 +/- 0.14. At baseline, mean CML level was 2.16 +/- 0.73 mu mol/L, median pentosidine was 0.043 (0.030-0.074) mu mol/L, and median sRAGE level was 2.92 (1.90-4.59) ng/mL. CML and pentosidine levels were independently related to the composite end-point (HR, 1.20 per SD; 95% CI, 1.05-1.37; P = .01 and HR, 1.15 per SD; 95% CI, 1.00-1.31; P = .045, respectively) and HF hospitalization (HR, 1.27 per SD; 95% CI, 1.10-1.48; P = .001 and HR, 1.27 per SD; 95% CI, 1.10-1.47; P = .001, respectively). Furthermore, CML levels were independently related to increased mortality (P = .006). Whereas sRAGE levels were univariately predictive for outcome, in multivariate models sRAGE did not reach statistical significance. Discussion In HF patients, both CML and pentosidine predict HF hospitalization and the combined primary end-point (mortality or HF-hospitalization), whereas sRAGE did not predict events. In addition, CML was significantly and independently associated with a higher risk for mortality. (Am Heart J 2012;164:742-749.e3.)