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

Abstract

BackgroundOxidative 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 ResultsWe 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).ConclusionsImpaired 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.

Proteomic diversity of high‐density lipoprotein explains its association with clinical outcome in patients with heart failure

“…Previous studies investigating the HDL proteome in HF observed differences in proteome profiles between healthy subjects and HF patients and proteome profiles in HF patients associated with immune response . Additionally, diminished anti‐inflammatory, antioxidant activity, and cholesterol efflux capacity of HDL have been implicated in HF and predicted adverse events. The present study is the first to investigate differences in HDL proteome profiles related to clinical outcome in HF in a larger, well‐characterised HF patient population with well‐matched subgroups, utilising state‐of‐the‐art nanoscale liquid chromatography‐coupled mass spectrometry and powerful informatics to analyse the data.…”

Extracellular Fluid Excess Is Significantly Associated With Coronary Artery Calcification in Patients With Chronic Kidney Disease

“…We also showed the association of ECF status with CAC in graphical format (cubic spline curves). The predictive value of ECF status for the presence of CAC was determined using receiver operating characteristic curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI), as previously described 19. Risk categories for the categorical NRI were set as 0% to 10% (low), 10% to 20% (middle), and >20% (high) because the patients with coronary artery calcification were 14.4%.…”

Polyunsaturated fatty acids supplementation impairs anti‐oxidant high‐density lipoprotein function in heart failure

“…In accordance with previous studies, apolipoprotein B‐depleted plasma, which includes HDL, apo‐A1, apo‐A2 and HDL‐associated particles, was used. The analyses were performed in all patients with available plasma samples as previously described …”

“…All samples were plated in duplicate. To calculate the HDL inflammatory index (HII), the fluorescence signal of DCF alone was subtracted from that of DCF incubated with apolipoprotein B depleted patient plasma and log‐transformed before analysis . Therefore, a higher HII indicates a poorer anti‐oxidant function.…”

“…It has become apparent that quality and function of HDL may relate more to outcome in CV diseases than serum levels . Particularly, the anti‐oxidant capacity of HDL was found associated with HF and clinical outcome, emphasizing the pivotal role of oxidative stress in the pathogenesis of HF. Whether supplementation with n3‐PUFA might modulate the anti‐oxidant function of HDL has not been analysed yet.…”