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.
Vita
Joseph A
JA
Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass, USA.
Brennan
Marie-Luise
ML
Gokce
Noyan
N
Mann
Shirley A
SA
Goormastic
Marlene
M
Shishehbor
Mehdi H
MH
Penn
Marc S
MS
Keaney
John F
JF
Hazen
Stanley L
SL
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