Prognostic value of plasma myeloperoxidase concentration in patients with stable coronary artery disease

doi:10.1016/j.ahj.2007.10.017

American Heart Journal

Volume 155, Issue 2, February 2008, Pages 356-360

https://doi.org/10.1016/j.ahj.2007.10.017 Get rights and content

Background

There are no studies yet on the usefulness of myeloperoxidase (MPO) as a prognostic tool in patients with stable coronary artery disease (CAD).

Methods

The study included 382 patients with clinical and angiographic confirmation of stable CAD. Blood samples for MPO measurement were taken before angiography. Myeloperoxidase was determined using an enzyme immunoassay. The primary end point of the study was all-cause mortality.

Results

Patients were categorized into 2 groups: the high-MPO group included patients in the third tertile of MPO levels (>75.0 μg/L; 127 patients), and the low-MPO group included patients in the first (<52.6 μg/L) and second tertiles (52.6-75.0 μg/L) of MPO levels (255 patients). The median follow-up was 3.5 [3.3-4.8] years. There were 35 deaths (9.2%) during the follow-up. The MPO concentration was 60.1 [47.0; 83.8] μg/L in survivors and 72.7 [54.8; 105.1] μg/L in nonsurvivors (P = .06). There were 17 deaths in the high-MPO level and 18 deaths in the low-MPO group: Kaplan-Meier estimates of mortality were 18.3% and 10.5% with an odds ratio of 1.96 (95% confidence interval [1.02-3.76], P = .04). The Cox proportional hazards model adjusting for correlates of mortality showed that plasma MPO was not an independent correlate of mortality (hazard ratio 1.06, 95% confidence interval [0.71-1.59], P = .77 for 1 SD increase in the log variable).

Conclusion

Although elevated plasma MPO concentration is associated with a more advanced cardiovascular risk profile, plasma MPO does not predict mortality independent of other cardiovascular risk factors in patients with stable CAD.

Section snippets

Patients

The study included 382 patients with stable CAD undergoing coronary angiography at the Deutsches Herzzentrum, Munich, Germany. Patients were recruited in a prospective cohort study to investigate the prognostic value of biochemical markers in patients with angiographically proven CAD. The diagnosis of stable CAD was based on the presence of chest pain that did not change its pattern during the preceding 2 months. We did not include patients who presented with ACS, diagnosed on the basis of

Results

Myeloperoxidase values did not follow a normal distribution. Patients were categorized into 2 groups based on the tertile values of MPO levels. The high-MPO group included patients in the third tertile of MPO levels (>75.0 μg/L; 127 patients). The low-MPO group levels included patients in the first (<52.6 μg/L) and second tertiles (52.6 to <75.0 μg/L) of MPO levels (255 patients).

Discussion

In this study, we assessed the prognostic value of plasma MPO concentration in patients with stable CAD. We used a cohort of well-characterized patients with stable CAD, in whom the presence of disease was identified by using coronary angiography. The main findings of the study can be summarized as follows: (1) elevated MPO plasma concentration is associated with an increased risk of death in patients with stable CAD, and (2) elevated MPO concentration does not predict the increased risk of

References (27)

T.J. Mocatta et al.
Plasma concentrations of myeloperoxidase predict mortality after myocardial infarction
J Am Coll Cardiol
(2007)
D. Lau et al.
Myeloperoxidase and its contributory role in inflammatory vascular disease
Pharmacol Ther
(2006)
E. Malle et al.
Myeloperoxidase-mediated oxidation of high-density lipoproteins: fingerprints of newly recognized potential proatherogenic lipoproteins
Arch Biochem Biophys
(2006)
R. Zhang et al.
Myeloperoxidase functions as a major enzymatic catalyst for initiation of lipid peroxidation at sites of inflammation
J Biol Chem
(2002)
S. Baldus et al.
Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion
Free Radic Biol Med
(2004)
W.W.H. Tang et al.
Prognostic value and echocardiographic determinants of plasma myeloperoxidase levels in chronic heart failure
J Am Coll Cardiol
(2007)
M.C. Meuwese et al.
Serum myeloperoxidase levels are associated with the future risk of coronary artery disease in apparently healthy individuals: the EPIC-Norfolk prospective population study
J Am Coll Cardiol
(2007)
A. Dibra et al.
Association between C-reactive protein levels and subsequent cardiac events among patients with stable angina treated with coronary artery stenting
Am J Med
(2003)
S. Sugiyama et al.
Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes
Am J Pathol
(2001)
E. Cavusoglu et al.
Usefulness of baseline plasma myeloperoxidase levels as an independent predictor of myocardial infarction at two years in patients presenting with acute coronary syndrome
Am J Cardiol
(2007)

M.H. Shishehbor et al.

Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy

JAMA

(2003)

A. Daugherty et al.

Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions

J Clin Invest

(1994)

A. Buffon et al.

Widespread coronary inflammation in unstable angina

N Engl J Med

(2002)

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Target-induced site-specific cleavage of phosphorothioate-modified hairpin DNA for amplified and label-free sensitive electrochemical myeloperoxidase assay
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Abnormal myeloperoxidase (MPO) expression is associated with inflammation and neurodegenerative diseases. By using a new phosphorothioate (PT)-modified DNA hairpin probe, we fabricate a label-free and highly sensitive electrochemical sensor for monitoring MPO via integration of DNAzyme-assisted cleavage recycling with DNA polymerization reaction catalyzed by terminal deoxynucleotidyl transferase (TdT). The target MPO mediates the specific cleavage of PT-modified hairpin probes with assistance of hydrogen peroxide and chloride ion to initiate DNAzyme-based cyclic cleavage of substrate hairpin probes for the release of numerous trigger strands. Subsequent hybridizations of the trigger strands with the thiolated-hairpin probes on the electrode surface expose the 3′-OH termini of hairpin probes for triggering TdT–catalyzed in situ DNA polymerization formation of long ssDNAs containing multiple G-quadruplex repeats. Hemin is confined on the electrode surface via the formation of G-quadruplex/hemin complexes to produce highly enhanced current signals for the determination of MPO in a sensitive and label-free way. The proposed sensor exhibits a linear range of 0.1–100 ng mL⁻¹ and achieves a low detection limit of 0.046 ng mL⁻¹ for MPO. Such sensor also shows high selectivity against other interferents and shows the capability to detect MPO in diluted human serum samples.
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Myeloperoxidase (MPO) is a prominent mammalian heme peroxidase and a fundamental component of the innate immune response against microbial pathogens. In recent times, MPO has received considerable attention as a key oxidative enzyme capable of impairing the bioactivity of nitric oxide (NO) and promoting endothelial dysfunction; a clinically relevant event that manifests throughout the development of inflammatory cardiovascular disease. Increasing evidence indicates that during cardiovascular disease, MPO is released intravascularly by activated leukocytes resulting in its transport and sequestration within the vascular endothelium. At this site, MPO catalyzes various oxidative reactions that are capable of promoting vascular inflammation and impairing NO bioactivity and endothelial function. In particular, MPO catalyzes the production of the potent oxidant hypochlorous acid (HOCl) and the catalytic consumption of NO via the enzyme's NO oxidase activity. An emerging paradigm is the ability of MPO to also influence endothelial function via non-catalytic, cytokine-like activities. In this review article we discuss the implications of our increasing knowledge of the versatility of MPO's actions as a mediator of cardiovascular disease and endothelial dysfunction for the development of new pharmacological agents capable of effectively combating MPO's pathogenic activities. More specifically, we will (i) discuss the various transport mechanisms by which MPO accumulates into the endothelium of inflamed or diseased arteries, (ii) detail the clinical and basic scientific evidence identifying MPO as a significant cause of endothelial dysfunction and cardiovascular disease, (iii) provide an up-to-date coverage on the different oxidative mechanisms by which MPO can impair endothelial function during cardiovascular disease including an evaluation of the contributions of MPO-catalyzed HOCl production and NO oxidation, and (iv) outline the novel non-enzymatic mechanisms of MPO and their potential contribution to endothelial dysfunction. Finally, we deliver a detailed appraisal of the different pharmacological strategies available for targeting the catalytic and non-catalytic modes-of-action of MPO in order to protect against endothelial dysfunction in cardiovascular disease.
Myeloperoxidase – A bridge linking inflammation and oxidative stress with cardiovascular disease
2019, Clinica Chimica Acta
Citation Excerpt :
MPO (>125.6 μg/L vs. ≤125.6) was not associated with the risk of mortality or composite adverse events. Stefanescu et al. [98] failed to show an independent association between MPO and mortality in 382 patients with angiographic CAD over a median follow-up of 3.5 years. Although the association was significant in unadjusted analysis, it was attenuated after adjustment for cardiovascular risk factors.
Myeloperoxidase (MPO) is a member of the superfamily of heme peroxidases that is mainly expressed in neutrophils and monocytes. MPO-derived reactive species play a key role in neutrophil antimicrobial activity and human defense against various pathogens primarily by participating in phagocytosis. Elevated MPO levels in circulation are associated with inflammation and increased oxidative stress. Multiple lines of evidence suggest an association between MPO and cardiovascular disease (CVD) including coronary artery disease, congestive heart failure, arterial hypertension, pulmonary arterial hypertension, peripheral arterial disease, myocardial ischemia/reperfusion-related injury, stroke, cardiac arrhythmia and venous thrombosis. Elevated MPO levels are associated with a poor prognosis including increased risk for overall and CVD-related mortality. Elevated MPO may signify an increased risk for CVD for at least 2 reasons. First, low-grade inflammation and increased oxidative stress coexist with many metabolic abnormalities and comorbidities and consequently an elevated MPO level may represent an increased cardiometabolic risk in general. Second, MPO produces a large number of highly reactive species which can attack, destroy or modify the function of every known cellular component. The most common MPO actions relevant to CVD are generation of dysfunctional lipoproteins with an increased atherogenicity potential, reduced NO availability, endothelial dysfunction, impaired vasoreactivity and atherosclerotic plaque instability. These actions strongly suggest that MPO is directly involved in the pathophysiology of CVD. In this regard MPO may be seen as a mediator or an instrument through which inflammation promotes CVD at molecular and cellular level. Clinical value of MPO therapeutic inhibition remains to be tested.
Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population: Observations from the Dallas Heart Study
2017, Atherosclerosis
Citation Excerpt :
In contrast, the associations between MPO and ASCVD in those without ACS have been inconsistent. While several case-control studies linked higher MPO levels to presence of CAD or increased risk of incident CAD [11,20], one cohort study found that plasma MPO did not predict mortality independent of other cardiovascular risk factors in patients with stable CAD [22]. Similarly, in a cross-sectional study of patients undergoing elective coronary angiography, there were no significant differences in MPO concentrations for those with proven stable CAD compared to those without [19].
Myeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline.
Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years.
Adjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12–2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27–2.85).
Increased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period.
Cardiovascular Biomarker Assessment Across Glycemic Status
2015, Glucose Intake and Utilization in Pre-Diabetes and Diabetes: Implications for Cardiovascular Disease
The current state of cardiovascular biomarkers to aid the risk stratification and cardiovascular disease management of patients with diabetes mellitus is inadequate. Despite its role in assessing microvascular diseases, decades of research on the utility of glycated hemoglobin as a guide for assessing macrovascular risk has not achieved the expected results. In this chapter, we review current research on five clinically available serum biomarkers: C-reactive protein, myeloperoxidase, cardiac troponin, B-type natriuretic peptide, and albuminuria. We will briefly summarize the biomarkers’ prognostic ability for adverse outcomes, utility in marker-guided therapeutics, and capacity to provide additional cardiovascular risk information for diabetes patients. Finally, we discuss the benefits of utilizing multiple biomarkers to further aid risk assessment in patients across glycemic status.
Association of myeloperoxidase with total and cardiovascular mortality in individuals undergoing coronary angiography - The LURIC study
2014, International Journal of Cardiology
Citation Excerpt :
In one study with a follow-up of 3 years (1895 patients with stable CAD), MPO concentrations were associated with a 1.71-fold risk for major adverse coronary events [30]. Another group [31] failed to reveal an association of MPO levels with mortality in 382 patients with stable CAD. Heslop and coworkers [32] were the first to report an association of MPO levels with cardiovascular mortality (885 coronary angiography patients) with adjusted HRs slightly higher (2.06 vs. 1.48) than observed in the present study.
The phagocytic enzyme myeloperoxidase (MPO) acts as a front-line defender against microorganisms. However, increased MPO levels have been found to be associated with complex and calcified atherosclerotic lesions and incident cardiovascular disease. Therefore, this study aimed to investigate a predictive role of MPO, a biomarker of inflammation and oxidative stress, for total and cardiovascular mortality in patients referred to coronary angiography.
MPO plasma concentrations along with eight MPO polymorphisms were determined in 3036 participants of the Ludwigshafen Risk and Cardiovascular Health study (median follow-up 7.75 years). MPO concentrations were positively associated with age, diabetes, smoking, markers of systemic inflammation (interleukin-6, fibrinogen, C-reactive protein, serum amyloid A) and vascular damage (vascular cellular adhesion molecule-1 and intercellular adhesion molecule-1) but negatively associated with HDL-cholesterol and apolipoprotein A-I. After adjustment for cardiovascular risk factors MPO concentrations in the highest versus the lowest quartile were associated with a 1.34-fold risk (95% CI: 1.09–1.67) for total mortality. In the adjusted model the hazard ratio for cardiovascular mortality in the highest MPO quartile was 1.42 (95% CI: 1.07–1.88). Five MPO polymorphisms were positively associated with MPO concentrations but not with mortality. Using Mendelian randomization, we did not obtain evidence for a causal association of MPO with either total or cardiovascular mortality.
MPO concentrations but not genetic variants at the MPO locus are independently associated with risk for total and cardiovascular mortality in coronary artery disease patients.

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Clinical InvestigationCoronary Artery DiseasePrognostic value of plasma myeloperoxidase concentration in patients with stable coronary artery disease

Background

Methods

Results

Conclusion

Section snippets

Patients

Results

Discussion

J Am Coll Cardiol

Pharmacol Ther

Arch Biochem Biophys

J Biol Chem

Free Radic Biol Med

J Am Coll Cardiol

J Am Coll Cardiol

Am J Med

Am J Pathol

Am J Cardiol

Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy

JAMA

Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions

J Clin Invest

Widespread coronary inflammation in unstable angina

N Engl J Med

Clinical Investigation
Coronary Artery Disease
Prognostic value of plasma myeloperoxidase concentration in patients with stable coronary artery disease