Serum myeloperoxidase levels independently predict endothelial dysfunction in humans

Circulation. 2004 Aug 31;110(9):1134-9. doi: 10.1161/01.CIR.0000140262.20831.8F. Epub 2004 Aug 23.

Abstract

Background: In vitro and animal studies demonstrate that myeloperoxidase catalytically consumes nitric oxide as a substrate, limiting its bioavailability and function. We therefore hypothesized that circulating levels of myeloperoxidase would predict risk of endothelial dysfunction in human subjects.

Methods and results: Serum myeloperoxidase was measured by enzyme-linked immunoassay, and brachial artery flow-mediated dilation and nitroglycerin-mediated dilation were determined by ultrasound in a hospital-based population of 298 subjects participating in an ongoing study of the clinical correlates of endothelial dysfunction (age, 51+/-16; 61% men, 51% with cardiovascular disease). A strong inverse relation between brachial artery flow-mediated dilation and increasing quartile of serum myeloperoxidase level was observed (11.0+/-6.0%, 9.4+/-5.3%, 8.6+/-5.8%, and 6.4+/-4.5% for quartiles 1 through 4, respectively; P<0.001 for trend). Using the median as a cut point to define endothelial dysfunction, increasing quartile of myeloperoxidase predicted endothelial dysfunction after adjustment for classic cardiovascular disease risk factors, C-reactive protein levels, prevalence of cardiovascular disease, and ongoing treatment with cardiovascular medications (OR, 6.4; 95% CI, 2.6 to 16; P=0.001 for highest versus lowest quartile).

Conclusions: Serum myeloperoxidase levels serve as a strong and independent predictor of endothelial dysfunction in human subjects. Myeloperoxidase-mediated endothelial dysfunction may be an important mechanistic link between oxidation, inflammation, and cardiovascular disease.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Brachial Artery / diagnostic imaging
  • Brachial Artery / drug effects
  • C-Reactive Protein / analysis
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / physiopathology
  • Endothelium, Vascular / physiopathology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Inflammation
  • Lipids / blood
  • Male
  • Middle Aged
  • Nitroglycerin / pharmacology
  • Oxidative Stress
  • Peroxidase / blood*
  • Predictive Value of Tests
  • Risk
  • Ultrasonography
  • Vasodilation / drug effects

Substances

  • Biomarkers
  • Lipids
  • C-Reactive Protein
  • Peroxidase
  • Nitroglycerin

Grant support