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CLINICAL RESEARCH: CORONARY ARTERY DISEASE RISK

Serum Myeloperoxidase Levels Are Associated With the Future Risk of Coronary Artery Disease in Apparently Healthy Individuals

The EPIC-Norfolk Prospective Population Study

Marijn C. Meuwese, MD^_*, Erik S.G. Stroes, MD, PhD^_*, Stanley L. Hazen, MD, PhD, Joram N. van Miert, BSc^_*, Jan Albert Kuivenhoven, PhD^_*, Robert G. Schaub, PhD, Nicholas J. Wareham, MB, PhD^||, Robert Luben, BSc^#, John J.P. Kastelein, MD, PhD^_*, Kay-Tee Khaw, MBBChir^# and S. Matthijs Boekholdt, MD, PhD^_*,,_*

^_* Department of Vascular Medicine
Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands
Department of Cell Biology and the Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic Foundation, Cleveland, Ohio
Wyeth Research, Cambridge, Massachusetts
^|| MRC Epidemiology Unit, Cambridge, United Kingdom
^# Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, United Kingdom

Manuscript received November 27, 2006; revised manuscript received February 27, 2007, accepted March 2, 2007.

^_* Reprint requests and correspondence: Dr. S. Matthijs Boekholdt, Academic Medical Center, Department of Vascular Medicine (F4-159.2), Meibergdreef 9, P.O. Box 22660, 1100 DD Amsterdam, the Netherlands. (Email: s.m.boekholdt{at}amc.uva.nl).

Objectives: We evaluated whether serum myeloperoxidase (MPO) levels are associated with the risk of future development of coronary artery disease (CAD) in apparently healthy individuals.

Background: An enzyme of the innate immune system, MPO exhibits a wide array of proatherogenic effects. These include induction of oxidative damage to low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and promotion of plaque vulnerability. Recent studies revealed that MPO independently predicts adverse outcomes in patients with chest pain or suspected acute coronary syndrome.

Methods: Myeloperoxidase was measured in baseline samples of a case-control study nested in the prospective EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk population study. Case subjects (n = 1,138) were apparently healthy men and women who developed CAD during 8-year follow-up. Control subjects (n = 2,237), matched for age, gender, and enrollment time, remained free of CAD.

Results: The MPO levels were significantly higher in case subjects than in control subjects and correlated with C-reactive protein (CRP) ( = 0.25; p < 0.001) and white blood cell count ( = 0.33; p < 0.001). Risk of future CAD increased in consecutive quartiles of MPO concentration, with an odds ratio (OR) of 1.49 in the top versus bottom quartile (95% confidence interval [CI] 1.20 to 1.84; p < 0.001). After adjustment for traditional risk factors, the OR in the top quartile remained significant at 1.36 (95% CI 1.07 to 1.73). Elevated MPO levels (>728 pmol/l) similarly predicted increased risk of future CAD among participants with either LDL-cholesterol <130 mg/dl, HDL-cholesterol >50 mg/dl, or CRP <2.0 mg/l (OR 1.52 [95% CI 1.21 to 1.91], 1.59 [95% CI 1.24 to 2.05], and 1.42 [95% CI 1.14 to 1.77)], respectively).

Conclusion: Elevated MPO levels predict future risk of CAD in apparently healthy individuals. This study suggests that inflammatory activation precedes the onset of overt CAD by many years.

Abbreviations and Acronyms   ACS = acute coronary syndrome   BMI = body mass index   CAD = coronary artery disease   CRP = C-reactive protein   CVD = cardiovascular disease   HDL = high-density lipoprotein   LDL = low-density lipoprotein   MPO = myeloperoxidase   OR = odds ratio

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