Serum myeloperoxidase levels independently predict endothelial dysfunction in humans

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.

Figures

Fully adjusted models for markers of inflammation and risk for endothelial dysfunction. Displayed are ORs for each quartile compared with first quartile of myeloperoxidase (MPO; left) or C-reactive protein (CRP; right) with endothelial dysfunction defined as flow-mediated dilation less than median. Models include Framingham Risk Score, prevalent cardiovascular disease, cardiovascular medications, and alternative marker of inflammation (C-reactive protein or myeloperoxidase). Myeloperoxidase predicts endothelial dysfunction (P=0.001 for trend), whereas C-reactive protein does not (P=0.87 for trend). *OR, 2.1 (95% CI, 1.02 to 4.5; P=0.04). †OR, 6.4; 95% CI, 2.6 to 16; P<0.001).