What is the significance of an elevated serum myeloperoxidase level?

Significance of Elevated Serum Myeloperoxidase

Elevated serum myeloperoxidase (MPO) is a significant biomarker of inflammation, oxidative stress, and cardiovascular risk that independently predicts future cardiovascular events and mortality in both apparently healthy individuals and patients with established cardiovascular disease.

What is Myeloperoxidase?

Myeloperoxidase is a leukocyte-derived enzyme primarily released from neutrophils and monocytes during inflammatory processes. It has several key characteristics:

• Produces reactive oxidant species that contribute to tissue damage, inflammation, and immune processes within atherosclerotic lesions 1
• Generates highly reactive species that can modify lipoproteins, reduce nitric oxide availability, and promote endothelial dysfunction 2
• Serves as a bridge linking inflammation and oxidative stress with cardiovascular disease 2

Clinical Significance of Elevated MPO

Cardiovascular Risk Prediction

Elevated MPO levels have strong prognostic implications:

• Independently predicts future risk of coronary artery disease (CAD) in apparently healthy individuals 3
• Plasma MPO concentrations >322 pmol/L are associated with a 1.78-fold increased risk of developing major adverse cardiovascular events (MACE) over a 3-year period, even after adjusting for traditional cardiac risk factors 4
• Provides prognostic value independent of other established biomarkers including high-sensitivity C-reactive protein (hsCRP) and B-type natriuretic peptide 4
• Significantly predicts mortality in patients with acute coronary syndrome (odds ratio 2.03) 5

Specific Clinical Contexts

MPO elevation is particularly relevant in:

1. Acute Coronary Syndromes:

   • Systematically increases with advancement of coronary artery disease 6
   • Significantly higher in patients with unstable coronary disease and myocardial infarction compared to stable angina 6
   • May have higher diagnostic sensitivity than traditional cardiac markers like troponin I, CK-MB, CRP, and fibrinogen 6

2. Stable Coronary Artery Disease:

   • Provides independent prognostic value for prediction of long-term incident cardiovascular events in stable, medically managed patients 4
   • Can help identify high-risk patients who might benefit from more aggressive preventive strategies

3. Chronic Kidney Disease:

   • Elevated MPO is associated with cardiovascular morbidity and mortality in dialysis patients 1
   • A functional genetic variant of MPO in position -463 (G→A) is associated with lower MPO expression and lower prevalence of cardiovascular disease in hemodialysis patients 1

Clinical Application and Limitations

Despite its prognostic value, current guidelines note some limitations:

• The ACC/AHA guidelines acknowledge that MPO is being studied but state that it has not been adequately validated to be recommended for routine clinical application in unstable angina/non-ST elevation myocardial infarction 1
• MPO should be considered alongside other inflammatory markers rather than in isolation

Interpretation in Different Populations

The prognostic value of MPO may vary based on patient characteristics:

• Female gender and smoking status strongly influence the prognostic value of MPO for mortality and recurrent myocardial infarction 5
• MPO can predict increased risk of future CAD even among patients with optimal lipid profiles (LDL <130 mg/dl or HDL >50 mg/dl) 3
• MPO can provide additional risk stratification even in patients with low CRP levels (<2.0 mg/l) 3

Conclusion

While not yet universally recommended for routine clinical application, elevated serum myeloperoxidase represents a valuable biomarker that reflects underlying inflammatory and oxidative processes contributing to cardiovascular pathology. Its ability to independently predict adverse cardiovascular outcomes makes it a promising tool for risk stratification, particularly in patients where traditional risk factors may not fully capture their cardiovascular risk profile.