Abstract 12549: Circulating Irisin is a Novel Biomarker Providing Prognostic Information in Patients With Heart Failure With Reduced Ejection Fraction

Abstract

Introduction: Reduced skeletal muscle function link to poor prognosis in patients with chronic heart failure (HF). Irisin is a newly identified muscle-derived protein found in human serum. The gene expression of irisin precursor fibronectin domain containing protein 5 in skeletal muscle is associated with exercise tolerance in HF patients. Hypothesis: Irisin could be a useful biomarker for disease severity and future adverse cardiovascular events in patients with HF with reduced ejection fraction (HFrEF). Methods and results: We measured serum irisin levels in 84 patients with HFrEF. HFrEF was defined as left ventricular ejection fraction≦50% and meet the Framingham criteria of HF. Serum irisin concentrations were measured by ELISA. The endpoint of this study was a composite of total mortality, cardiovascular hospitalization and coronary revascularization. Serum irisin levels were negatively correlated with serum high sensitive troponin T levels (r=-0.24, p=0.048). Right heart catheterization revealed that serum irisin levels had significant negative correlation with pulmonary capillary wedge pressure (r=-0.23, p=0.044). In receiver operating characteristic (ROC) analysis, cut-off values of irisin and BNP for prediction of one-year events were 55.548 ng/mL and 324.8 pg/mL, respectively. Kaplan Meier curve demonstrated that the event-free rate was decreased in the low irisin (≦cut-off value) group (log-rank test p=0.024). The combination of low irisin and high BNP (≧cut-off value) identified patients with a significantly higher probability of adverse events (p=0.008). Multivariate Cox hazard analysis identified low levels of irisin (≦cut-off value) (hazard ratio [HR]: 3.08; 95% confidence interval [CI]: 1.31-7.21, p=0.01) and ischemic etiology (HR: 3.32; 95% CI: 1.50-7.35, p=0.003) as independent predictors of mortality and cardiovascular events. ROC analysis revealed that irisin achieved an area under the curve (AUC) of 0.67 for one-year events (p=0.031), and that the AUC increased when irisin was added to BNP level (alone: 0.64, BNP+irisin: 0.74). Conclusions: Irisin could be a useful biomarker for evaluating disease severity and providing incremental prognostic information in patients with HFrEF.