Myeloperoxidase, Subclinical Atherosclerosis, and Cardiovascular Disease Events
Nathan D. Wong, PhD*,
Heidi Gransar, MS ,
Jagat Narula, MD, PhD*,
Leslee Shaw, PhD ,
Johanna H. Moon, MPH,
Romalisa Miranda-Peats, MPH,
Alan Rozanski, MD ,
Sean W. Hayes, MD,
Louise E.J. Thomson, MB, ChB,||,
John D. Friedman, MD,||,
Daniel S. Berman, MD,||,*
* Division of Cardiology, University of California, Irvine, California
Department of Imaging, Division of Nuclear Medicine, and Department of Medicine, Division of Cardiology, and the CSMC Burns & Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, California
Emory University School of Medicine, Atlanta, Georgia
Department of Cardiology, St. Luke's Roosevelt Hospital Center, New York, New York
|| Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, California
* Reprint requests and correspondence: Dr. Daniel S. Berman, Department of Imaging, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room 1258, Los Angeles, California 90048 (Email: bermand{at}cshs.org).
Objectives: We evaluated whether myeloperoxidase (MPO) predicts future cardiovascular disease (CVD) events in asymptomatic adults and whether subclinical atherosclerosis may affect this relation.
Background: Myeloperoxidase is a leukocyte-derived enzyme-generating reactive oxidant species that has been shown to predict risk of CVD in selected populations.
Methods: We studied 1,302 asymptomatic adults (mean age 59 years, 47% women) without known CVD who were followed for 3.8 years. We measured MPO by the use of immunoassay. Coronary artery calcium (CAC), a measure of subclinical atherosclerosis, was measured by computed tomography with the Agatston score categorized as none/minimal (0 to 9), mild (10 to 99), and moderate/significant ( 100). Cox regression, adjusted for age, sex, and other risk factors, examined the relation of CAC and/or MPO with incident CVD events.
Results: Persons with MPO levels at or above compared with below the median (257 pM) were more likely (p < 0.05 to p < 0.001) to be women, have a higher body mass index, greater low-density lipoprotein cholesterol, greater systolic and diastolic blood pressure, and lower high-density lipoprotein cholesterol. Mean MPO levels increased according to CAC categories (p trend = 0.02). Incident CVD events were more likely in those at or above versus below the median MPO level (4.6% vs. 2.3%, p = 0.02), even after adjustment for age, sex, CAC, and risk factors (hazard ratio [HR]: 1.9, 95% confidence interval: 1.0 to 3.6, p = 0.04). Combining CAC and MPO categories, CVD incidence ranged from 0.6% in those with a CAC score of 0 to 9 to 7.1% (adjusted HR: 9.2, p < 0.001) in those with CAC scores of 100 and MPO below the median and 14.0% (adjusted HR: 19.5, p < 0.0001) in those with CAC scores of 100 and MPO at or above the median.
Conclusions: Our study suggests persons with both increased levels of both MPO and CAC are at an increased risk of CVD events. Imaging of subclinical atherosclerosis combined with assessment of biomarkers of plaque vulnerability may help improve CVD risk stratification.
Key Words: computed tomography • biomarkers • risk factors • prevention • cardiovascular disease
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Abbreviations and Acronyms
| | AUC = area under the curve | | CAC = coronary artery calcium | | CI = confidence interval | | CVD = cardiovascular disease | | HDL-C = high-density lipoprotein cholesterol | | HR = hazard ratio | | LDL-C = low-density lipoprotein cholesterol | | MI = myocardial infarction | | MPO = myeloperoxidase |
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