From the Guidelines
Myeloperoxidase (MPO) is significantly associated with cardiac disease, and elevated MPO levels are linked to an increased risk of coronary artery disease, heart failure, and adverse cardiac events. The clinical importance of MPO activation is further underscored by the fact that both elevated leukocyte and blood MPO levels are associated, in the general population, with signs of CAD 1. Furthermore, in patients with acute coronary syndromes, MPO serum levels predicted subsequent cardiovascular events 1 and identified patients at risk for cardiac events.
Key Findings
- Elevated MPO levels are associated with increased oxidative stress, which contributes to the development of atherosclerosis and cardiovascular disease 1.
- MPO-catalyzed oxidation leads to the formation of 3-chlorotyrosine, a specific marker of oxidative stress, which has been demonstrated to be increased in HD patients 1.
- Increased levels of advanced oxidation protein products (AOPP) in CKD patients have been demonstrated, and AOPP is an independent risk factor for CAD in the general population 1.
- Oxidative stress is related to impaired endothelial function in CKD patients, which is a key factor in the development of cardiovascular disease 1.
Clinical Implications
- MPO testing may be valuable in emergency settings to help evaluate chest pain patients, as MPO rises earlier than troponin in myocardial infarction.
- Measurement of MPO may provide additional prognostic information beyond traditional cardiac biomarkers, especially in patients with intermediate risk profiles.
- Elevated MPO levels should be considered a risk factor for cardiac disease, and patients with high MPO levels should be closely monitored and managed to reduce their risk of adverse cardiac events.
From the Research
Myeloperoxidase and Cardiac Disease Association
- Myeloperoxidase (MPO) is a member of the superfamily of heme peroxidases that is mainly expressed in neutrophils and monocytes, and elevated MPO levels in circulation are associated with inflammation and increased oxidative stress 2.
- 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 2.
- Elevated MPO levels are associated with a poor prognosis including increased risk for overall and CVD-related mortality, and may signify an increased risk for CVD due to low-grade inflammation and increased oxidative stress, as well as the production of highly reactive species that can attack and modify cellular components 2, 3.
Prognostic Value of Myeloperoxidase
- The prognostic value of MPO in patients with peripheral artery disease has been examined, and high MPO levels were found to be associated with poor outcomes, including increased risk of major adverse cardiac events (MACEs) and limb ischaemia 4.
- A meta-analysis of 13 studies with 9090 subjects found that high MPO levels significantly predicted mortality in patients with acute coronary syndrome, but were not significantly predictive of major adverse cardiac events and recurrent myocardial infarction 5.
- Elevated MPO levels have also been linked to coronary artery disease in patients without traditional risk factors such as diabetes, hypertension, obesity, and hyperlipidemia, although the relationship is not entirely clear 6.
Mechanisms of Myeloperoxidase in Cardiac Disease
- MPO-derived reactive species play a key role in neutrophil antimicrobial activity and human defense against various pathogens, but dysregulated MPO release can lead to tissue damage and contribute to the pathophysiology of CVD 2, 3.
- The mechanisms by which MPO exerts its detrimental effects in CVD are not fully understood, but may involve the generation of dysfunctional lipoproteins, reduced NO availability, endothelial dysfunction, and atherosclerotic plaque instability 2, 3.