Myeloperoxidase (MPO)

Optimal Result: 0 - 469 pmol/L.

Low CVD Risk: <470

Moderate Risk: 470 - 539

High Risk: >539

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MPO is a white blood cell-derived inflammatory enzyme that measures disease activity from the luminal aspect of the arterial wall.

Briefly, when the artery wall is damaged, or inflamed, MPO is released by invading macrophages where it accumulates.

MPO mediates the vascular inflammation that propagates plaque formation and activates protease cascades that are linked to plaque vulnerability. White blood cell activation in the bloodstream, in response to luminal injury of the artery wall including fissures, erosions or a degrading collagen cap, leads to MPO release in the bloodstream. This combination of detrimental effects demonstrates that MPO is actively involved in the progression of atherosclerosis. 

References:

Khan AA, Alsahli MA, Rahmani AH. Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspectives. Med Sci (Basel). 2018;6(2):33. Published 2018 Apr 18. [L]

Tavora F et al. Monocytes and neutrophils expressing myeloper¬oxidase occur in fibrous caps and thrombi in unstable coronary plaques. BMC Cardiovascular Disord. 2009; 9: 27-33. [L]

Hazen SL and Heinecke JW. 3-chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima. J Clin Invest. 1997; 99: 2075-2081. [L]

Fu X et al. Hypochlorous acid oxygenates the cysteine switch domain of pro-matrilysin (MMP-7). A mechanism for matrix metalloproteinase activation and atherosclerotic plaque rupture by myeloperoxidase. J Biol Chem. 2001; 276: 41279-41287. [L]

Meuwese MC 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; 50: 159-165. [L]

Karakas M et al. Myeloperoxidase is associated with incident coro¬nary heart disease independently of traditional risk factors: Results from the MONICA/KORA Augsburg study. J Intern Med. 2012; 271: 43-50. [L]

Baldus S et al. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation. 2003; 108: 1440-1145. [L]

Cavusoglu E 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; 99: 1364-1368. [L]

Heslop CL et al. Myeloperoxidase and C-reactive protein have combined utility for long-term prediction of cardiovascular mortality after coronary angiography. J Am Coll Cardiol. 2010; 55: 1102-1109. [L]

Buhlin K et al. Periodontitis is associated with angiographically verified coronary artery disease. J Clin Periodontol. 2011; 38: 1107-1014. [L]

Toyama K et al. Rosuvastatin combined with regular exercise preserves coenzyme Q10 levels associated with a significant increase in high-density lipoprotein cholesterol in patients with coronary artery disease. Atherosclerosis. 2011; 217: 158-164. [L]

Maradit-Kremers H et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: A population-based cohort study. Arthritis Rheu [L]

What does it mean if your Myeloperoxidase (MPO) result is too high?

- Elevated MPO levels predict the risk of heart disease in subgroups otherwise associated with low risk

- Elevated MPO levels independently predict the risk of future cardiovascular events in patients presenting with an acute coronary syndrome

- Individuals with elevated MPO levels are more than 2x as likely to experience cardiovascular mortality

- MPO enhances cardiovascular risk prediction when used independently or alongside standard biomarker testing such as hsCRP8

- MPO levels are not likely to be elevated due to chronic infections or rheumatologic disorders due to the fact that free MPO in the blood is a specific marker of vascular inflammation and vulnerable plaque/erosions/fissures.

Treatment Considerations:

These treatment considerations are for educational purposes only. Specific treatment plans should be provided and reviewed by the treating practitioner.

Assess LDL-C levels.

If not at goal, consider lipid-lowering therapy, ideally with a statin-based regimen if not contraindicated.

Assess risk for pre-diabetes/diabetes.

If abnormal fasting glucose or oral glucose tolerance test, consider PPAR agonists, metformin or DPP-IV inhibitor if not contraindicated. 

Assess the presence of coronary artery disease (CAD) with imaging techniques such as carotid intima media thickness testing (CIMT) or coronary artery calcium scoring.

- Consider aspirin therapy if not contraindicated.

- Consider clopidogrel if history of CAD (i.e., myocardial infarction or revascularization) and/or a history of cerebrovascular disease (i.e., TIA or stroke).

Assess dental health (periodontal disease).

Refer to dentist to identify gum disease. NOTE: Poor dental health may cause significant inflammation and is associated with the presence of atherosclerosis.

Assess HDL-C levels.

If not at goal, consider niacin or fenofibrate therapy.

Assess CoQ10 levels.

Recent evidence suggests that low ApoA1 and/or HDL-C levels are associated with low CoQ10 levels10.

Assess smoking habits.

NOTE: Smoking cessation is essential as individuals who smoke are at increased risk of heart disease and blood clots.

Assess blood pressure.

If not at goal, consider initiating, or titrating, anti-hypertensive therapy. NOTE: An elevated blood pressure may contribute to endothelial dysfunction and coronary disease formation.

Assess lifestyle habits.

Consider diet/exercise/weight reduction efforts if appropriate.

Assess the presence of inflammatory conditions such as Crohn’s disease, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

NOTE: Chronic inflammatory diseases may exhibit elevated MPO values due to increased vascular disease associated with these conditions. For example, RA is associated with a 5x increased risk for myocardial infarction.

Assess the presence of vasculitis.

NOTE: MPO values may be elevated in individuals with vasculitis as it is characterized by increased vascular inflammation.

Assess the presence of bone marrow dyscrasias.

NOTE: MPO values may be elevated in individuals with chronic lymphocytic leukemia or other leukemias, that cause increased white blood cell destruction.

Assess level of exercise.

NOTE: MPO values may be elevated in marathon runners and extreme athletes and may identify those with increased oxidative stress and basal levels of inflammation.

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If asymptomatic, with all of the above factors ruled out, an elevated MPO value may in fact be the patient’s baseline. MPO levels should be monitored every 3-6 months.

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