Myeloperoxidase, Subclinical Atherosclerosis, and Cardiovascular Disease Events

Division of Cardiology, University of California, Irvine, California, USA.
JACC. Cardiovascular imaging (Impact Factor: 7.19). 09/2009; 2(9):1093-9. DOI: 10.1016/j.jcmg.2009.05.012
Source: PubMed


We evaluated whether myeloperoxidase (MPO) predicts future cardiovascular disease (CVD) events in asymptomatic adults and whether subclinical atherosclerosis may affect this relation.
Myeloperoxidase is a leukocyte-derived enzyme-generating reactive oxidant species that has been shown to predict risk of CVD in selected populations.
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 (> or = 100). Cox regression, adjusted for age, sex, and other risk factors, examined the relation of CAC and/or MPO with incident CVD events.
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 > or = 100 and MPO below the median and 14.0% (adjusted HR: 19.5, p < 0.0001) in those with CAC scores of > or = 100 and MPO at or above the median.
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.

Download full-text


Available from: Heidi Gransar, Jan 15, 2015
  • Source
    • "Another study included 1,302 asymptomatic adults (mean age 59 years, 47% women) without known CVD who were followed for 3.8 years. After measuring MPO and coronary artery calcium, by computed tomography, the study suggested that persons with both increased levels of both MPO and CAC are at an increased risk of CVD events [189]. However, the concentration of MPO depends on the assay method, sampling material, and preanalytical and analytical procedures. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Atherosclerotic cardiovascular disease is the leading cause of death in many developed countries. It is characterized by complex endocrine, paracrine and juxtacrine interactions between immune and vascular cells, as well as several tissues and organs. Oxidative stress and inflammation have an important role in the promotion of atherosclerotic cardiovascular disease. Considering the complicated mechanisms and signals involved in atherosclerosis, research is focused on blood-based biomarkers, gene-based markers, metabolomics and other potentially interesting approaches for biomarker discovery. These biomarkers can be introduced as routine diagnostic tests if they prove to be cost-effective and to predict future cardiovascular events. Given the overlap of circulating inflammatory and oxidative stress biomarkers in atherosclerosis and rheumatic diseases, we aim to overview their potential to screen cardiovascular risk and also to predict the evolution of associated rheumatic diseases.
    Current pharmaceutical design 04/2013; 20(4). DOI:10.2174/138161282004140213145806 · 3.45 Impact Factor
  • Source
    • "This effect of leucocytes on vascular function may be physiological under states of acute infection and sepsis, in which the secreted MPO provides a sink for the excess synthesis of NO provided but may be detrimental under conditions of chronic vascular disease such as atherosclerosis, in which diffuse MPO sequestration into the vessel lumen may lead to oxidation of endothelium-derived NO thereby pathologically increasing vascular tone. Thus the current studies reinforces observational studies in humans with MPO deficiency indeed being characterized by a reduced occurrence of cardiovascular disease,31 whereas increased levels of MPO were indicative of cardiovascular disease in asymptomatic individuals.32,33 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Observational studies have suggested a mechanistic link between the leucocyte-derived enzyme myeloperoxidase (MPO) and vasomotor function. Here, we tested whether MPO is systemically affecting vascular tone in humans. A total of 12 135 patients were screened for leucocyte peroxidase activity. We identified 15 individuals with low MPO expression and activity (MPO(low)), who were matched with 30 participants exhibiting normal MPO protein content and activity (control). Nicotine-dependent activation of leucocytes caused attenuation of endothelial nitric oxide (NO) bioavailability in the control group (P < 0.01), but not in MPO(low) individuals (P = 0.12); here the MPO burden of leucocytes correlated with the degree of vasomotor dysfunction (P = 0.008). To directly test the vasoactive properties of free circulating MPO, the enzyme was injected into the left atrium of anaesthetized, open-chest pigs. Myeloperoxidase plasma levels peaked within minutes and rapidly declined thereafter, reflecting vascular binding of MPO. Blood flow in the left anterior descending artery and the internal mammary artery (IMA) as well as myocardial perfusion decreased following MPO injection when compared with albumin-treated animals (P < 0.001). Isolated IMA-rings from animals subjected to MPO revealed markedly diminished relaxation in response to acetylcholine (P < 0.01) and nitroglycerine as opposed to controls (P < 0.001). Myeloperoxidase elicits profound effects on vascular tone of conductance and resistance vessels in vivo. These findings not only call for revisiting the biological functions of leucocytes as systemic and mobile effectors of vascular tone, but also identify MPO as a critical systemic regulator of vasomotion in humans and thus a potential therapeutic target.
    European Heart Journal 06/2011; 33(13):1625-34. DOI:10.1093/eurheartj/ehr193 · 15.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Myeloperoxidase (MPO), a member of the peroxidase family, emerged as a major player in the initiation and propagation of atherosclerotic cardiovascular disease (CVD). Evidence for its role in atherosclerosis include that MPO: a) induces endothelial dysfunction, b) modifies physiologically functional high density lipoprotein (HDL) into “dysfunctional HDL”, c) converts low density lipoprotein (LDL) into more atherogenic modified LDL form, and d) induces endothelial cell death and tissue factor expression involved in plaque vulnerability. Elevated levels of blood MPO are associated with CVD, predict incident risks for myocardial infarction and cardiac death in subjects with acute coronary syndrome, and predict future risk of coronary artery disease (CAD) in healthy individuals. In this article, we review current understandings on the role of MPO in pathophysiological processes involved in atherosclerosis and CVD.
    Current Cardiovascular Risk Reports 04/2013; 7(2). DOI:10.1007/s12170-013-0291-3
Show more