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Published on: October 12, 2017
HDL function is impaired in acute myocardial infarction independent of plasma HDL cholesterol levels
Wijtske Annema1, Hendrik M Willemsen2, Jan Freark de Boer3
1Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Top Institute Food and Nutrition, Wageningen, The Netherlands.
Insights
High-density lipoprotein (HDL) functionality, specifically cholesterol efflux and anti-inflammatory properties, is impaired in ST-segment elevation myocardial infarction (STEMI) patients, independent of HDL cholesterol levels. Increased myeloperoxidase levels are linked to this reduced HDL function, highlighting a new mechanism in cardiovascular disease.
Area of Science:
- Cardiovascular Research
- Lipid Metabolism
- Immunology
Background:
- High-density lipoproteins (HDLs) are crucial in preventing atherosclerotic cardiovascular disease.
- HDL functionality is an emerging area of study in cardiovascular research.
Purpose of the Study:
- To investigate the association between HDL functionality and acute myocardial infarction (MI).
- To determine if HDL functionality is linked to MI independently of HDL-cholesterol plasma levels.
Main Methods:
- Compared HDL functionality in patients with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (non-STEMI), and non-MI controls.
- Assessed in vitro HDL capacity for cholesterol efflux, prevention of LDL oxidation, and inhibition of inflammatory molecule expression.
- Matched participants for age and plasma HDL cholesterol.
Main Results:
- HDL from STEMI patients showed reduced cholesterol efflux and anti-inflammatory functionality, but unaltered antioxidative properties.
- Cholesterol efflux capacity correlated with HDL's anti-inflammatory activity.
- Plasma myeloperoxidase levels, not C-reactive protein, were independently associated with impaired HDL function.
- Impaired HDL efflux and anti-inflammatory functionality were significantly associated with a higher odds ratio for MI.
Conclusions:
- Two key antiatherogenic HDL functionalities (cholesterol efflux, anti-inflammatory properties) are impaired in STEMI patients, irrespective of HDL cholesterol levels.
- Elevated myeloperoxidase levels may be a primary factor contributing to decreased HDL functionality in MI patients.
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.
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