Reductions in the function of high-density lipoprotein (HDL) are associated with heart failure with reduced ejection fraction

Abstract Introduction Alterations in lipoprotein metabolism have been a focus of investigation in patients with heart failure (HF). Although evidence suggests that low levels of high-density lipoprotein (HDL) cholesterol are associated with worse HF prognosis, other functional properties of HDL should also be considered in this context. Purpose To investigate the rates of cholesterol transfers to high density lipoprotein (HDL) in the plasma, an important functional aspect of HDL metabolism, in patients with heart failure (HF) of ischemic or of nonischemic etiology. Methods This study included 101 patients, comprising 48 symptomatic HF patients (24 with ischemic and 24 with non-ischemic etiology) with NYHA(New York Heart Association) functional class II and III and left ventricular ejection fraction (LVEF) 40% and 53 patients without HF (26 with coronary atherosclerotic disease and 27 with only systemic arterial hypertension). Transfers of unesterified (UC) and esterified cholesterol (EC) to HDL were measured by an in vitro assay.. Additionally, plasma lipid levels, cholesterol ester transfer protein (CETP) concentration, HDL particle diameter, and paraoxonase-1 (PON-1) activity were measured. Results HDL-c, HDL size, PON-1 activity and CETP concentration were t different among the groups. However, transfer of EC was lower in the HF than in the non-HF groups (p0.05). Transfer of UC was lower exclusively inon patients with HF of non-ischemic etiology (p0.05). Correlation analysis showed that both EC and UC transfers to HDL positively correlated with LVEF, diastolic blood pressure and systolic blood pressure (p0.05) and negatively correlated with left ventricular end-diastolic diameter (p0.05) and B-type natriuretic peptide (p0.01). As an eventual finding, the study patients taking beta-blockers had lower EC and UC transfers, dose dependent. Conclusions The reduced transfer of EC to HDL observed in patients with HF, regardless of etiology, and its correlation with functional and anatomical parameters of cardiac remodeling suggest that this process may be linked to key factors in HF development or influenced by progression of this syndrome. These findings indicate the potencial emergence of a novel biomarker, offering new perspectives for further research. The finding of dose-dependent effects of beta-blockers on cholesterol transfer suggest that defects in HDL metabolism may be involved also in beta-blocker users.Beta-blockers and cholesterol transfer