Circulating receptor for advanced glycation end products (RAGE) is a risk factor for developing heart failure

Abstract

Aim: RAGE amplifies inflammation and oxidative stress and may represent a novel mechanism in the development of heart failure (HF). Soluble RAGE (sRAGE) is a prognostic factor in patients with chronic HF. We sought to examine the role of circulating RAGE in predicting future HF events in patients at increased cardiovascular risk. Methods: We recruited 421 patients attending the cardiac catheterisation laboratory and measured sRAGE and endogenous secretory RAGE (esRAGE) in serum using an ELISA. All patients were prospectively followed for 12 months and HF admissions were recorded. Kaplan-Meier and multivariable Cox regression analysis were performed to determine the predictors of HF. The highest quartiles of RAGE were compared with all others. Results: Within the 12-month follow-up period, 18 patients presented with HF. Mean age was 72±12 years in patients with HF and 64±11 years in event-free patients. Kaplan-Meier analysis showed a significant difference in the freedom from HF according to quartiles of serum RAGE (shown below). Univariable predictors of HF events were serum RAGE, age, NYHA class, prior HF and LVEF<50%. In a multivariable model, independent predictors of HF events were sRAGE (HR 3.7, 95%CIs 1.4,9.7, p=0.009), esRAGE (HR 3.8, 95%CIs 1.3, 10.8, p= 0.01) and age. When patients with prior HF were excluded, sRAGE (6.4, 95%CIs 1.9, 21.1, p= 0.003) and esRAGE (HR 7.1, 95%CIs 2.1, 23.5, p= 0.001) independently predicted new HF. Conclusions: Circulating RAGE independently predicts future HF events and may represent a useful biomarker and therapeutic target in HF.