Is myeloperoxidase a risk marker for cardiovascular disease?

Myeloperoxidase as a Risk Marker for Cardiovascular Disease

Myeloperoxidase (MPO) is an emerging inflammatory marker that shows promise as a risk marker for cardiovascular disease, particularly for acute coronary syndromes, but it is not yet recommended for routine clinical use in cardiovascular risk assessment. While evidence suggests MPO may contribute to atherosclerosis pathogenesis and plaque vulnerability, standardization of sampling and laboratory procedures is needed before clinical implementation.

Biological Role and Mechanism

MPO is a leukocyte-derived enzyme primarily expressed in neutrophils and monocytes that:

• Functions as a bridge linking inflammation and oxidative stress with cardiovascular disease 1
• Generates reactive oxidant species that can damage vascular tissues 2
• Contributes to atherogenesis through several mechanisms:
  • Oxidation of LDL and HDL, leading to cholesterol accumulation in arterial walls 3
  • Reduction of nitric oxide bioavailability, resulting in endothelial dysfunction 3
  • Destabilization of atherosclerotic plaques 3, 1

Evidence for MPO as a Cardiovascular Risk Marker

Strengths

• MPO is present and catalytically active within atherosclerotic lesions 2
• Elevated MPO levels are associated with:
  • Acute coronary syndromes 4
  • Poor prognosis including increased risk for overall and CVD-related mortality 1
  • Independent prediction of major adverse cardiac events during hospitalization in ACS patients 4

Limitations

• Not included in established cardiovascular risk assessment guidelines 5
• Comparison of studies is hampered by differences in:
  • Assay methods
  • Sampling materials
  • Preanalytical and analytical procedures 3
• Lacks standardization needed for routine clinical use 3

Current Guideline Recommendations

Current guidelines from major cardiovascular societies do not include MPO among recommended inflammatory markers for cardiovascular risk assessment:

• The American Heart Association (AHA) and Centers for Disease Control and Prevention (CDC) have extensively evaluated inflammatory markers for cardiovascular risk assessment, focusing primarily on high-sensitivity C-reactive protein (hsCRP), fibrinogen, and white blood cell count 5
• The 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults discusses inflammatory markers but does not mention MPO 5

Comparison with Established Inflammatory Markers

When considering inflammatory markers for cardiovascular risk assessment:

• hsCRP is the most extensively studied inflammatory marker with:

  • Standardized assays available 5
  • Established association with cardiovascular events 5
  • Demonstrated ability to reclassify risk beyond traditional risk factors in some studies 5

• MPO shows different patterns than CRP:

  • MPO levels are significantly higher in acute coronary syndrome patients compared to stable angina patients 4
  • In one study, MPO was an independent predictor of in-hospital events for ACS patients, while CRP was associated with hospital mortality 4
  • CRP was predictive of future events in stable angina patients, while MPO was not 4

Clinical Application Considerations

For clinicians considering inflammatory markers for cardiovascular risk assessment:

• Focus on established markers like hsCRP that have:

  • Standardized assays
  • Extensive validation
  • Inclusion in clinical guidelines

• Consider that inflammatory markers generally:

  • Add modest incremental value to traditional risk factors 5
  • May be most useful in patients at intermediate risk 5
  • Are not specific to cardiovascular disease and can be elevated due to other inflammatory conditions 5

• Be aware that MPO may have future clinical utility, particularly in:

  • Acute coronary syndromes
  • Risk stratification for plaque vulnerability
  • Complementing other biomarkers

Conclusion

While MPO shows promise as a cardiovascular risk marker with mechanistic links to atherosclerosis, it requires further standardization and validation before routine clinical use. Currently, established inflammatory markers like hsCRP have more robust evidence and standardized assays for cardiovascular risk assessment.