Abstract

ObjectiveThe functionality of high-density lipoprotein (HDL) is impaired in chronic ischaemic heart failure (HF). However, the relationship between HDL functionality and outcomes in acute HF (AHF) has not been studied. The present study investigates whether the metrics of HDL functionality, including HDL cholesterol efflux capacity and HDL-associated paraoxonase (PON)-1 arylesterase (AE) activity are associated with hospital mortality in AHF patients.Methods and ResultsThe study was performed as a prospective, single-centre, observational research on 152 patients, defined and categorised according to the ESC and ACCF/AHA Guidelines for HF by time of onset, final clinical presentation and ejection fraction. The mean age of the included patients (52% female) was 75.2 years (SD 10.3) and hospital mortality was 14.5%. HDL cholesterol efflux capacity was examined by measuring the capacity of apoB depleted serum to remove tritium-labelled cholesterol from cultured macrophages. The AE activity of the HDL fraction was examined by a photometric assay. In a univariable regression analysis, low cholesterol efflux, but not AE activity, was significantly associated with hospital mortality [odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64–0.96, p = 0.019]. In multivariable analysis progressively adjusting for important clinical and laboratory parameters the association obtained for cholesterol efflux capacity and hospital mortality by univariable analysis, despite a stable OR, did not stay significant (p = 0.179).ConclusionOur results suggest that HDL cholesterol efflux capacity (but not AE activity) contributes to, but is not an independent risk factor for, hospital mortality in AHF patients. Larger studies are needed to draw firm conclusions.

Highlights

  • Clinical and epidemiological studies demonstrated an inverse relationship between high-density lipoprotein cholesterol (HDL-cholesterol) levels and cardiovascular disease (CVD) [1]

  • Our results suggest that HDL cholesterol efflux capacity contributes to, but is not an independent risk factor for, hospital mortality in acute HF (AHF) patients

  • In the present study we examined whether HDL-cholesterol efflux capacity and HDL-associated PON-1 AE activity are risk factors for hospital mortality in AHF patients

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Summary

Introduction

Clinical and epidemiological studies demonstrated an inverse relationship between high-density lipoprotein cholesterol (HDL-cholesterol) levels and cardiovascular disease (CVD) [1]. Recent studies provided evidence against HDL-cholesterol as a potential therapeutic target. Along these lines, a study using the Mendelian randomisation approach failed to reveal an association between genetic variants that raise HDL-cholesterol plasma concentrations and a lower risk of cardiovasuclar events [2]. Pharmacological interventions aimed at raising HDL-cholesterol levels failed to reduce cardiovascular events [3, 4]. Recent studies provided strong evidence that HDL-cholesterol efflux capacity, the first step in the process of reverse cholesterol transport, is inversely associated with incident coronary heart events, independent of established cardiovascular risk factors [13]

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