HDL function is impaired in acute myocardial infarction independent of plasma HDL cholesterol levels

J Clin Lipidol. 2016 Nov-Dec;10(6):1318-1328. doi: 10.1016/j.jacl.2016.08.003. Epub 2016 Aug 17.

Abstract

Background: High-density lipoproteins (HDLs) protect against the development of atherosclerotic cardiovascular disease. HDL function represents an emerging concept in cardiovascular research.

Objective: This study investigated the association between HDL functionality and acute myocardial infarction (MI) independent of HDL-cholesterol plasma levels.

Methods: Participants (non-ST-segment elevation MI, non-STEMI, n = 41; STEMI, n = 37; non-MI patients, n = 33) from a prospective follow-up study enrolling patients with acute chest pain were matched for age and plasma HDL cholesterol. The in vitro capacity of HDL to (1) mediate cholesterol efflux from macrophage foam cells, (2) prevent low-density lipoprotein oxidation, and (3) inhibit TNF-α-induced vascular adhesion molecule-1 expression in endothelial cells was determined.

Results: STEMI-HDL displayed reduced cholesterol efflux (P < .001) and anti-inflammatory functionality (P = .001), whereas the antioxidative properties were unaltered. Cholesterol efflux correlated with the anti-inflammatory HDL activity (P < .001). Not C-reactive protein levels, a marker of systemic inflammation, but specifically plasma myeloperoxidase levels were independently associated with impaired HDL function (efflux: P = .022; anti-inflammation: P < .001). Subjects in the higher risk quartile of efflux (odds ratio [OR], 5.66; 95% confidence interval [CI], 1.26-25.00; P = .024) as well as anti-inflammatory functionality of HDL (OR, 5.53; 95% CI, 1.83-16.73; P = .002) had a higher OR for MI vs those in the three lower risk quartiles combined.

Conclusion: Independent of plasma HDL cholesterol levels, 2 of 3 antiatherogenic HDL functionalities tested were significantly impaired in STEMI patients, namely cholesterol efflux and anti-inflammatory properties. Increased myeloperoxidase levels might represent a major contributing mechanism for decreased HDL functionality in MI patients.

Keywords: Acute coronary syndrome; Cholesterol; Cholesterol efflux; HDL function; Inflammation; Oxidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Amine Oxidase (Copper-Containing) / metabolism
  • C-Reactive Protein / analysis
  • Cell Adhesion Molecules / metabolism
  • Cholesterol, HDL / blood*
  • Creatine Kinase / blood
  • Creatine Kinase, MB Form / blood
  • Female
  • Follow-Up Studies
  • Gene Expression / drug effects
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Linear Models
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnosis*
  • Prospective Studies
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Cell Adhesion Molecules
  • Cholesterol, HDL
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • AOC3 protein, human
  • Amine Oxidase (Copper-Containing)
  • Creatine Kinase
  • Creatine Kinase, MB Form