Particle size and cholesterol content of circulating HDL correlate with cardiovascular death in chronic heart failure

Albert Teis,Josep Lupón ,Núria Amigó ,Júlia Aranyó ,Dı́dac Mauricio ,Elena Ferrer-Sistach ,Jf Andres-Cordon ,Josep Julve ,Germán Cediel ,Nuria Garatachea Vallejo ,Gladys Juncà ,Carlos Puig-Jové ,Jorge López-Ayerbe ,Esmeralda Castelblanco ,Marta De Antonio ,Núria Alonso ,Pau Codina ,Mar Domingo ,Francisco Gual-Capllonch ,Evelyn Santiago‐Vacas ,Antoni Bayés‐Genís

doi:10.1038/s41598-021-82861-6

Abstract

Evidence regarding any association of HDL-particle (HDL-P) derangements and HDL-cholesterol content with cardiovascular (CV) death in chronic heart failure (HF) is lacking. To investigate the prognostic value of HDL-P size (HDL-Sz) and the number of cholesterol molecules per HDL-P for CV death in HF patients. Outpatient chronic HF patients were enrolled. Baseline HDL-P number, subfractions and HDL-Sz were measured using 1H-NMR spectroscopy. The HDL-C/P ratio was calculated as HDL-cholesterol over HDL-P. Endpoint was CV death, with non-CV death as the competing event. 422 patients were included and followed-up during a median of 4.1 (0–8) years. CV death occurred in 120 (30.5%) patients. Mean HDL-Sz was higher in CV dead as compared with survivors (8.39 nm vs. 8.31 nm, p < 0.001). This change in size was due to a reduction in the percentage of small HDL-P (54.6% vs. 60% for CV-death vs. alive; p < 0.001). HDL-C/P ratio was higher in the CV-death group (51.0 vs. 48.3, p < 0.001). HDL-Sz and HDL-C/P ratio were significantly associated with CV death after multivariable regression analysis (HR 1.22 [95% CI 1.01–1.47], p = 0.041 and HR 1.04 [95% CI 1.01–1.07], p = 0.008 respectively). HDL-Sz and HDL-C/P ratio are independent predictors of CV death in chronic HF patients.

Highlights

Epidemiological and clinical studies have consistently demonstrated that lower levels of high-density lipoprotein (HDL) cholesterol (HDL-C) are independently associated with coronary heart disease (CHD)[1,2]
To date no data has been reported regarding the association of HDL particles (HDL-P) concentration, HDL size, HDL-P subfraction distribution, or the HDL-C/P ratio with CV death in chronic heart failure (HF)
We investigate the prognostic value of HDL-P, mean normalized HDL size (HDL-Sz), and the HDL-C/P ratio for CV death in patients with ambulatory chronic HF

Summary

Introduction

Epidemiological and clinical studies have consistently demonstrated that lower levels of high-density lipoprotein (HDL) cholesterol (HDL-C) are independently associated with coronary heart disease (CHD)[1,2]. A recently published report describe an inverse gradation of small HDL-P levels across no-HF, HF with preserved, and HF with reduced ejection fraction patients and its correlation with all-cause mortality and coronary artery disease events in a catheterization lab-based p opulation[24]. As estimated by the ratio of HDL-C to HDL-P (HDL-C/P ratio), it was associated with increased progression of carotid atherosclerosis in a community-based p opulation[16] Despite these studies, to date no data has been reported regarding the association of HDL-P concentration, HDL size, HDL-P subfraction distribution, or the HDL-C/P ratio with CV death in chronic HF. We investigate the prognostic value of HDL-P, mean normalized HDL size (HDL-Sz), and the HDL-C/P ratio for CV death in patients with ambulatory chronic HF

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Conclusion