What is the clinical significance of elevated serum myeloperoxidase (MPO) levels?

Clinical Significance of Elevated Serum Myeloperoxidase Levels

Elevated serum myeloperoxidase (MPO) levels are most significantly associated with increased cardiovascular risk, serving as an independent predictor of adverse cardiovascular events and mortality, particularly in patients with coronary artery disease and acute coronary syndromes. 1

Cardiovascular Implications

Mechanism of Action

MPO is a heme peroxidase primarily expressed in neutrophils and monocytes that plays a key role in:

• Generating reactive oxidant species that contribute to oxidative stress
• Promoting endothelial dysfunction through reduced nitric oxide availability
• Creating dysfunctional lipoproteins with increased atherogenic potential
• Contributing to atherosclerotic plaque instability 2

Prognostic Value in Different Cardiovascular Conditions

1. Acute Coronary Syndromes:

   • In patients with acute coronary syndromes, MPO serum levels predict subsequent cardiovascular events 1
   • Elevated MPO (>322 pmol/L) is associated with a 1.78-fold increased risk of major adverse cardiovascular events (MACE) 3
   • MPO serves as an independent predictor of in-hospital cardiovascular events in non-ST-segment elevation myocardial infarction (NSTEMI) patients 4

2. Stable Coronary Artery Disease:

   • Provides independent prognostic value for long-term incident cardiovascular events in stable, medically managed patients 3
   • Remains significant even after adjusting for traditional cardiac risk factors, creatinine clearance, BNP, and high-sensitivity CRP 3

3. Risk Stratification:

   • When combined with other inflammatory markers like high-sensitivity CRP, MPO improves risk stratification 3
   • Particularly valuable in high-risk populations (age >65 years, elevated NT-proBNP) 4

Role in Inflammatory and Renal Conditions

ANCA-Associated Vasculitis

MPO is a major autoantigen in ANCA-associated vasculitis, with MPO-ANCA being one of the primary serological markers used for diagnosis 1:

• Testing for MPO-ANCA is recommended in patients with suspected ANCA-associated vasculitis 1
• High-quality antigen-specific immunoassays for MPO-ANCA are the preferred screening method 1
• MPO-ANCA positivity supports diagnosis and helps guide treatment decisions, especially in rapidly deteriorating patients 1

Chronic Kidney Disease

In chronic kidney disease (CKD), elevated MPO levels reflect:

• Increased oxidative stress in uremia 1
• Potential contribution to cardiovascular complications in CKD patients 1
• Formation of 3-chlortyrosine (a specific marker of MPO-catalyzed oxidation) has been demonstrated in hemodialysis patients 1

Clinical Applications

As a Biomarker

• Risk Assessment: MPO provides independent prognostic information beyond traditional risk factors and other inflammatory markers 3, 4
• Monitoring Disease Activity: Limited value in monitoring disease activity in conditions like eosinophilic granulomatosis with polyangiitis (EGPA) 1
• Diagnostic Support: Aids in diagnosis of ANCA-associated vasculitis when combined with clinical presentation 1

Potential Therapeutic Implications

• MPO inhibition represents a potential therapeutic target for cardiovascular protection 5
• Clinical value of MPO therapeutic inhibition remains to be fully established in human trials 2

Important Considerations and Limitations

• MPO levels should be interpreted in the context of other clinical and laboratory findings
• Elevated MPO may reflect general inflammatory states rather than specific disease processes
• The correlation between MPO levels and disease activity varies across different conditions
• In some conditions like stable angina, MPO may have less prognostic value than other inflammatory markers like CRP 6

MPO serves as an important bridge linking inflammation and oxidative stress with cardiovascular disease, providing valuable prognostic information that can help identify high-risk patients who may benefit from more aggressive management strategies.