Elsevier

Atherosclerosis

Volume 219, Issue 2, December 2011, Pages 833-838
Atherosclerosis

Race-specific associations of myeloperoxidase with atherosclerosis in a population-based sample: The Dallas Heart Study

https://doi.org/10.1016/j.atherosclerosis.2011.08.029Get rights and content

Abstract

Objective

Myeloperoxidase (MPO) is a leukocyte-derived enzyme that appears to be directly involved in atherosclerosis development. We evaluated the association of circulating MPO with coronary and aortic atherosclerosis in a large, multiethnic population.

Methods and results

Plasma levels of MPO were measured in 3294 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcification (CAC) was measured by EBCT, and abdominal aorta plaque prevalence (AP) and burden (APB), as well as abdominal aorta wall thickness (AWT) were determined by MRI. Associations between MPO and atherosclerosis phenotypes were assessed in multivariable analyses adjusting for traditional atherosclerosis risk factors. MPO levels in the 4th compared with 1st quartile independently associated with prevalent AP (OR 1.41, 95% CI 1.08–1.84), APB (beta coefficient 0.23, p = 0.02), and AWT (beta coefficient 0.04, p = 0.03), but not with prevalent CAC (OR 0.84, 95% CI 0.61–1.17). MPO remained associated with aortic atherosclerosis phenotypes but not coronary calcification after adjustment for other inflammatory biomarkers. A significant interaction was observed between race/ethnicity, MPO and AP (pinteraction = 0.038), such that MPO levels in the 4th vs 1st quartile associated with prevalent AP in African Americans, (OR 1.81, 95% CI 1.23–2.65) but not in White or Hispanic participants (OR 0.99, 95% CI 0.68–1.44).

Conclusion

Higher levels of MPO associated with aortic but not coronary atherosclerosis, with significant associations limited to African American participants. These findings suggest that MPO might be a novel risk factor contributing to racial disparities in peripheral vascular disease.

Introduction

Inflammation plays a critical role in the initiation and progression of atherosclerosis. Myeloperoxidase (MPO), a bactericidal enzyme present in neutrophils, monocytes and macrophages, also has pro-inflammatory functions that may contribute to vascular injury. In vitro, MPO contributes to peroxidation of low density lipoprotein (LDL) and high density lipoprotein (HDL) as well as consumption of nitric oxide which may contribute to endothelial damage [1], [2]. In vivo experimental evidence further supports a potential role of MPO in atherosclerosis development in both animal models [3], [4] and in human studies [5], [6]. MPO has also been investigated as a potential biomarker of coronary atherosclerosis and of the corresponding risk for adverse clinical outcomes. Several studies have reported associations between higher levels of MPO and a greater extent of coronary artery disease (CAD) [7], [8], [9], and increased risk of adverse cardiac events [10].

Fewer data are available regarding an association between MPO and peripheral vascular disease (PVD), which affects about 8 million Americans. Although risk factors for PVD overlap with those of CAD, smoking is particularly important as a PVD risk factor; moreover, PVD also disproportionately affects African Americans [11]. Although prior studies have identified several inflammatory biomarkers associated with atherosclerosis in the aorta and peripheral vascular beds [12], [13], [14], little is known about the association of MPO and PVD, and whether MPO may contribute to racial disparities in PVD outcomes. In the present study, we performed a comprehensive evaluation of the association between MPO and atherosclerosis in multiple different vascular beds in a large, multi-ethnic population.

Section snippets

Study population

The Dallas Heart Study (DHS) is a probability-based population sample of 6101 Dallas County residents [15]. African Americans and women were oversampled intentionally to achieve a final cohort of approximately 50% African Americans and 50% women. Following an initial in-home visit for collection of survey data, body mass index and measurement of blood pressure, participants between the ages of 30 and 65 were invited to participate in a second visit where they provided in-home fasting blood and

Associations of MPO with atherosclerosis risk factors and biomarkers

MPO levels followed a right-skewed distribution and were higher in African American (median 17.5 [13.9, 22.3] ng/mL) compared with non-African American participants (median 16.8 [12.9, 21.0] ng/mL; p < 0.0001) (Fig. 1). Increasing quartiles of MPO were associated with traditional risk factors such as current smoking, diabetes, low HDL, higher body mass index, but not with hypertension or hypercholesterolemia (Table 1). In addition, MPO did not differ by age or sex. MPO was significantly correlated

Discussion

In this large population-based study, higher MPO levels associated with African American race and with multiple traditional atherosclerosis risk factors. In the overall population, MPO was modestly associated with prevalent aortic plaque, aortic plaque burden and aortic wall thickness after adjusting for traditional risk factors, but not with coronary artery calcification. We found a significant interaction by race, such that MPO independently associated with aortic atherosclerosis in African

Conclusion

In a large and multi-ethnic population, MPO was independently associated with aortic atherosclerosis but not coronary atherosclerosis. These associations were restricted to African Americans, a finding that suggests differences in inflammation may in part explain ethnic disparities in peripheral vascular disease.

Acknowledgements

Dr. de Lemos has received grant support from Roche Diagnostics and Alere, and consulting income from Tethys Biomedical. Dr. McGuire has received consulting income from Tethys Biomedical.

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