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CLINICAL RESEARCH: ACUTE MYOCARDIAL INFARCTION

Plasma Concentrations of Myeloperoxidase Predict Mortality After Myocardial Infarction

Tessa J. Mocatta, MSc^_*, Anna P. Pilbrow, PhD, Vicky A. Cameron, PhD, Revathy Senthilmohan, PhD, Chris M. Frampton, PhD, A. Mark Richards, MD, PhD and Christine C. Winterbourn, PhD^_*,_*

^_* Department of Pathology, Christchurch School of Medicine and Health Sciences, University of Otago, Christchurch, New Zealand
Department of Medicine, Christchurch School of Medicine and Health Sciences, University of Otago, Christchurch, New Zealand.

Manuscript received September 19, 2006; revised manuscript received February 9, 2007, accepted February 20, 2007.

^_* Reprint requests and correspondence: Dr. Christine C. Winterbourn, Department of Pathology, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch 8140, New Zealand. (Email: christine.winterbourn{at}chmeds.ac.nz).

Objectives: This study investigated relationships between plasma myeloperoxidase (MPO), protein oxidation markers, and clinical outcome retrospectively in patients after acute myocardial infarction (MI).

Background: Reactive oxidants are implicated in cardiovascular disease, and elevated plasma MPO is reported to predict adverse outcome in acute coronary syndromes.

Methods: Detailed demographic information, radionuclide ventriculography, neurohormone measurements, and clinical history were obtained for 512 acute MI patients at hospital admission. Plasma levels of MPO and protein carbonyls were measured in patients and 156 heart-healthy control subjects. 3-Chlorotyrosine was measured in selected patients. Patient mortality was followed for 5 years.

Results: Plasma MPO and protein carbonyl concentrations were higher in MI patients 24 h to 96 h after admission than in control subjects (medians: MPO 55 ng/ml vs. 39 ng/ml, and protein carbonyls 48 pmol/mg vs. 17 pmol/mg protein, p < 0.001 for each). Both markers were significantly correlated with each other and with cardiovascular hormone levels. Chlorotyrosine was not elevated in patients with high MPO or carbonyl levels. Above-median levels of MPO but not protein carbonyls were independently predictive of mortality (odds ratio 1.8, 95% confidence interval 1.0 to 3.0, p = 0.034). Patients with above-median MPO levels in combination with above-median plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) or below-median left ventricular ejection fraction (LVEF) had significantly greater mortality compared with other patients.

Conclusions: Myeloperoxidase and protein carbonyl levels are elevated in plasma after acute MI, apparently via independent mechanisms. High MPO is a risk factor for long-term mortality and adds prognostic value to LVEF and plasma NT-proBNP measurements.

Abbreviations and Acronyms   ANP = atrial natriuretic peptide   BNP = brain natriuretic peptide   IQR = interquartile range   LVEDV = left ventricular end-diastolic volume   LVEF = left ventricular ejection fraction   LVESV = left ventricular end-systolic volume   MI = myocardial infarction   MPO = myeloperoxidase   NT-proANP = amino-terminal pro-atrial natriuretic peptide   NT-proBNP = amino-terminal pro-brain natriuretic peptide   PTCA = percutaneous transluminal coronary angioplasty

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