Serum Myeloperoxidase Levels Are Associated With the Future Risk of Coronary Artery Disease in Apparently Healthy Individuals: The EPIC-Norfolk Prospective Population Study

doi:10.1016/j.jacc.2007.03.033

Journal of the American College of Cardiology

Volume 50, Issue 2, 10 July 2007, Pages 159-165

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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) (ρ = 0.25; p < 0.001) and white blood cell count (ρ = 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

odds ratio

Cited by (0)

: Supported in part by Wyeth. Dr. Hazen is named as a co-inventor on pending patents filed by the Cleveland Clinic Foundation that relate to the use of myeloperoxidase as a biomarker for cardiovascular disease. The EPIC-Norfolk study is supported by program grants from the Medical Research Council UK and Cancer Research UK, with additional support from the European Union, Stroke Association, British Heart Foundation, and the Wellcome Trust. Chris Cannon, MD, acted as the Guest Editor for this article.