Warning signs

Xchange newsletter - Spring 2008

Myeloperoxidase (MPO) is an inflammatory marker that may be elevated in patients with heart failure and cardiac dysfunction. With a rise in MPO appearing earlier than with other traditional cardiac biomarkers (such as troponin), MPOoffers new possibilities for early identification of cardiac events. Release of MPO can even precede myocardial injury and hence identify at-risk patients. Here we examine its clinical use in more detail.

Introducing MPO

MPO is a haemoprotein stored in leucocytes that functions in host-defence mechanisms against a broad range of microorganisms. Activation of leucocytes results in the secretion of MPO which catalyses the hydrogen peroxide-mediated peroxidation of halide ions. These products promote oxidative damage at sites of inflammation.

MPO has been shown to accumulate in atherosclerotic plaques (the fatty build ups in the lining of an artery). The oxidative products generated have been attributed to promoting destabilisation of the plaque and its subsequent rupture in atherosclerosis and coronary artery disease.

Clinical utility in chest pain

For patients presenting with chest pain, MPO analysis together with troponin enables early cardiac disease detection even before necrosis (irreversible damage) occurs (see table).

Whereas troponin takes 3-6 hours to rise to measurable circulating levels after myocardial injury, MPO levels have been shown to be significantly elevated (even within two hours of the onset of symptoms) in patients who were initially negative for troponin¹.

MPO serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers². MPO assessment may also be useful in triage in the emergency department.

Clinical utility in heart failure

In a study of patients with chronic heart failure³, higher plasma levels of MPO were associated with an increased likelihood of more advanced heart failure. Moreover, elevated plasma MPO levels within a heart failure subject seem to be predictive of increased adverse clinical outcomes. This is of great prognostic value to the clinician.

Clinical utility in risk assessment

Elevated MPO levels can also be used to predict future risk of coronary artery disease (CAD) in apparently healthy individuals. In a case-control study⁴, MPO was measured in baseline samples of 1,138 apparently healthy men and women who developed CAD during an 8-year follow-up. Control subjects (n=2,237) remained free of CAD. The MPO levels were significantly higher in case subjects than control subjects and correlated with C-reactive protein and white blood cell count. This study suggests that inflammatory activation precedes the onset of overt CAD by many years.

Conclusion

Recent studies have added to the body of evidence supporting the use of MPO as an early marker of cardiac disease. Used together with traditional biomarkers, MPO offers a valuable new tool for the clinician for assessing patients with chest pain or at risk of a cardiac event.

1. Brennan et al, Prognostic Value of Myeloperoxidase in Patients With Chest Pain. NEJM, 2003; 349: 17
2. Baldus et al, Myeloperoxidase Serum Levels Predict Risk in Patients With Acute Coronary Syndromes. Circulation, 2003; 108: 1440-1445
3. Tang et al, Prognostic Value and Echocardiogram Determinants of Plasma Myeloperoxidase Levels in Chronic Heart Failure. JACC, 2007; 24
4. Meuwese et al, Serum Myeloperoxidase Levels Are Associated With the Future Risk of Coronary Artery Disease in Apparently Healthy Individuals. JACC, 2007; 50:159-65