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.