Impaired HDL antioxidant and anti-inflammatory functions are linked to increased mortality in acute heart failure patients

Abstract

Acute heart failure (AHF) is typified by inflammatory and oxidative stress responses, which are associated with unfavorable patient outcomes. Given the anti-inflammatory and antioxidant properties of high-density lipoprotein (HDL), this study sought to examine the relationship between impaired HDL function and mortality in AHF patients. The complex interplay between various HDL-related biomarkers and clinical outcomes remains poorly understood. HDL subclass distribution was quantified by nuclear magnetic resonance spectroscopy. Lecithin–cholesterol acyltransferase (LCAT) activity, cholesterol ester transfer protein (CETP) activity, and paraoxonase (PON-1) activity were assessed using fluorometric assays. HDL-cholesterol efflux capacity (CEC) was assessed in a validated assay using [3H]-cholesterol-labeled J774 macrophages. Among the study participants, 74 (23.5 %) out of 315 died within three months after hospitalization due to AHF. These patients exhibited lower activities of the anti-oxidant enzymes PON1 and LCAT, impaired CEC, and lower concentration of small HDL subclasses, which remained significant after accounting for potential confounding factors. Smaller HDL particles, particularly HDL3 and HDL4, exhibited a strong association with CEC, PON1 activity, and LCAT activity. In patients with AHF, impaired HDL CEC, HDL antioxidant and anti-inflammatory function, and impaired HDL metabolism are associated with increased mortality. Assessment of HDL function and subclass distribution could provide valuable clinical information and help identify patients at high risk. Impaired HDL function and metabolism are associated with an increased risk of mortality in patients with AHF. Evaluating HDL function, subclass distribution, and metabolism may offer valuable clinical insights for predicting prognosis in AHF patients. A total of 315 patients hospitalized due to AHF were evaluated at baseline. Serum HDL subclass levels were measured by nuclear magnetic resonance (NMR) spectroscopy. HDL cholesterol efflux capacity (CEC), paraoxonase 1 (PON1) activity, lecithin-cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. After accounting for potential confounding factors, lower levels of HDL-CEC, PON1 activity, LCAT activity, and smaller HDL subclasses remained significantly associated with an increased risk of death within three months. • HDL function, structure and metabolism in hospitalized AHF patients significantly differ between survivors and non-survivors. • HDL function markers PON1, LCAT activity, CEC, and small HDL particles predict 3-month mortality as effectively as NT-proBNP • NMR analysis of HDL subclasses reveals insights into HDL function, with potential for clinical use and targeted therapies.

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