Impaired High‐Density Lipoprotein Anti‐Oxidative Function Is Associated With Outcome in Patients With Chronic Heart Failure

BACKGROUND: Oxidative stress is mechanistically linked to the pathogenesis of chronic heart failure (CHF). Antioxidative functions of high-density lipoprotein (HDL) particles have been found impaired in patients with ischemic cardiomyopathy; however, the impact of antioxidative HDL capacities on clinical outcome in CHF patients is unknown. We therefore investigated the predictive value of antioxidative HDL function on mortality in a representative cohort of patients with CHF. METHODS AND RESULTS: We prospectively enrolled 320 consecutive patients admitted to our outpatient department for heart failure and determined antioxidative HDL function using the HDL oxidative index (HOI). During a median follow-up time of 2.8 (IQR: 1.8-4.9) years, 88 (27.5%) patients reached the combined cardiovascular endpoint defined as the combination of death due to cardiovascular events and heart transplantation. An HOI ≥1 was significantly associated with survival free of cardiovascular events in Cox regression analysis with a hazard ratio (HR) of 2.28 (95% CI 1.48-3.51, P<0.001). This association remained significant after comprehensive multivariable adjustment for potential confounders with an adjusted HR of 1.83 (95% CI 1.1-2.92, P=0.012). Determination of HOI significantly enhanced risk prediction beyond that achievable with N-terminal pro-B-type natriuretic peptide indicated by improvements in net reclassification index (32.4%, P=0.009) and integrated discrimination improvement (1.4%, P=0.04). CONCLUSIONS: Impaired antioxidative HDL function represents a strong and independent predictor of mortality in patients with CHF. Implementation of HOI leads to a substantial improvement of risk prediction in patients with CHF.