Patients with coronary endothelial dysfunction have impaired cholesterol efflux capacity and reduced HDL particle concentration

Jeffrey S. Monette, Patrick M. Hutchins, Graziella E. Ronsein, Jake Wimberger, Angela D. Irwin, Chongren Tang, Jaskanwal D. Sara, Baohai Shao, Tomas Vaisar, Amir Lerman, Jay W. Heinecke

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Rationale: Coronary endothelial dysfunction (ED) - an early marker of atherosclerosis - increases the risk of cardiovascular events. Objective: We tested the hypothesis that cholesterol efflux capacity and high-density lipoprotein (HDL) particle concentration predict coronary ED better than HDL-cholesterol (HDL-C). Methods and Results: We studied 80 subjects with nonobstructive (<30% stenosis) coronary artery disease. ED was defined as <50% change in coronary blood flow in response to intracoronary infusions of acetylcholine during diagnostic coronary angiography. Cholesterol efflux capacity and HDL particle concentration (HDL-P IMA) were assessed with validated assays. Cholesterol efflux capacity and HDL-P IMA were both strong, inverse predictors of ED (P<0.001 and 0.005, respectively). In contrast, HDL-C and other traditional lipid risk factors did not differ significantly between control and ED subjects. Large HDL particles were markedly decreased in ED subjects (33%; P=0.005). After correction for HDL-C, both efflux capacity and HDL-P IMA remained significant predictors of ED status. HDL-P IMA explained cholesterol efflux capacity more effectively than HDL-C (r=0.54 and 0.36, respectively). The efflux capacities of isolated HDL and serum HDL correlated strongly (r=0.49). Conclusions: Cholesterol efflux capacity and HDL-P IMA are reduced in subjects with coronary ED, independently of HDL-C. Alterations in HDL-P IMA and HDL itself account for a much larger fraction of the variation in cholesterol efflux capacity than does HDL-C. A selective decrease in large HDL particles may contribute to impaired cholesterol efflux capacity in ED subjects. These observations support a role for HDL size, concentration, and function as markers - and perhaps mediators - of coronary atherosclerosis in humans.

Original languageEnglish (US)
Pages (from-to)83-90
Number of pages8
JournalCirculation research
Volume119
Issue number1
DOIs
StatePublished - Jun 24 2016

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Keywords

  • apolipoproteins
  • atherosclerosis
  • cardiovascular diseases
  • cholesterol
  • lipoproteins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Monette, J. S., Hutchins, P. M., Ronsein, G. E., Wimberger, J., Irwin, A. D., Tang, C., Sara, J. D., Shao, B., Vaisar, T., Lerman, A., & Heinecke, J. W. (2016). Patients with coronary endothelial dysfunction have impaired cholesterol efflux capacity and reduced HDL particle concentration. Circulation research, 119(1), 83-90. https://doi.org/10.1161/CIRCRESAHA.116.308357