Serum myeloperoxidase levels independently predict endothelial dysfunction in humans.
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.


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.
Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass, USA.
Joseph A
JA
Vita
Marie-Luise
ML
Brennan
Noyan
N
Gokce
Shirley A
SA
Mann
Marlene
M
Goormastic
Mehdi H
MH
Shishehbor
Marc S
MS
Penn
John F
JF
Keaney
Stanley L
SL
Hazen
D000328:Adult; D000368:Aged; D015415:Biomarkers; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D018384:Oxidative Stress; D009195:Peroxidase / Q000097:blood*; D011237:Predictive Value of Tests; D012306:Risk; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
D015415:Biomarkers; D008055:Lipids; D002097:C-Reactive Protein; D009195:Peroxidase; D005996:Nitroglycerin