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Serum Myeloperoxidase Levels Independently Predict Endothelial Dysfunction in Humans

Serum Myeloperoxidase Levels Independently Predict Endothelial Dysfunction in Humans,Joseph A. Vita,Marie-Luise Brennan,Noyan Gokce,Shirley A. Mann,Ma

Serum Myeloperoxidase Levels Independently Predict Endothelial Dysfunction in Humans   (Citations: 39)
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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, 5116; 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 (11.06.0%, 9.45.3%, 8.65.8%, and 6.44.5% for quartiles 1 through 4, respectively; P0.001 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; P0.001 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. (Circulation. 2004;110:1134-1139.)
Published in 2011.
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    • ...The present study is the first to report a long-term post-ACS multimarker risk prediction model for which biomarkers are selected on the basis of adjustment for baseline clinical patient characteristics as well as adjustment for all other analysed biomarkers. The results add to the growing body of evidence that novel biomarkers reflecting atherosclerotic burden or disease activity independently predict the long-term risk of death and non-fatal infarction in patients with an ACS. Elevated baseline levels of placental growth factor, myeloperoxidase and low levels of the anti-inflammatory cytokine IL-10 were independently associated with adverse long-term outcomes in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). These findings support the pathophysiological concept of a chronic (vascular) inflammatory basis of atherosclerosis,...

    R M Oemrawsinghet al. Multimarker risk model containing troponin-T, interleukin 10, myeloper...

    • ...The ROC curve analysis of our study showed a higher area under the curve for MPO, and the mean values are also significantly elevated in ACS patients. No studies have carried out an ROC curve analysis in the South Indian population to arrive at a diagnostic cut-off value and shown a significant difference between NCCP and STEMI, NSTEMI and UA. Relatively higher MPO levels were observed in STEMI than in NSTEMI and UA. This may be due to elevated WBC levels in this group. MPO is pivotally involved in the pathogenesis of atherosclerosis. Apart from its major role in microbicidal activity, it also oxidises LDL, initiates lipid peroxidation, consumes nitric oxide as a substrate and also promotes endothelial dysfunction....

    P Gururajanet al. Serum myeloperoxidase: a novel biomarker for evaluation of patients wi...

    • ...Additionally, it has been found in in vivo studies that MPO can be localized during inflammation in vascular endothelial cells and sub-endothelial spaces where it may modulate NO availability (23-25)...

    Brett A. Wagneret al. Inactivation of Anthracyclines by Serum Heme Proteins

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