Myeloperoxidase: Continuing the Search for the Holy Grail of Cardiac Markers
Abstract & Commentary
Source: Brennan ML, et al. Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med 2003;349: 1595-1604.
The holy grail of all emergency department (ED) cardiac markers would have a very high sensitivity (you don’t want to miss any cases), would be abnormal very early in the course of the disease process, and would not only be diagnostic of the current problem but be prognostic of future morbidity and mortality associated with an abnormal marker. OK it also would be cheap and easy to perform without highly specialized equipment, but you can’t have everything.
Fractionated creatine phosphokinase (CK), myoglobin, and the troponins have demonstrated clear benefit in the diagnosis and risk stratification of patients presenting to the ED with potential acute coronary syndromes (ACS). A noted limitation of these cardiac markers is their lack of early sensitivity in acute myocardial infarction (MI), which does not rise to 80% until approximately eight hours from the onset of chest pain in the acute MI patient, and ultimately reaches 100% at approximately 12 hours. The objective of this study from the Cleveland Clinic was to determine if myeloperoxidase, an enzyme released by activated leukocytes and found to be present at elevated levels in ruptured coronary plaques, could be a useful cardiac marker for patients presenting to the ED with chest pain.
The authors provide the background that myeloperioxidase levels have been found to be elevated in patients with angiographically documented coronary artery disease, and particularly within culprit lesions prone to rupture. As part of their chest pain (CP) protocol, 604 sequential patients presenting with chest pain to an ED had CK, troponin, and myeloperoxidase levels assayed. Patients were followed to determine final diagnosis (i.e., acute MI, unstable angina, suspected coronary syndrome, or non-cardiac etiologies) and then followed an additional six months to determine subsequent events (i.e., death, MI, or need for cardiac intervention). The results reported by the authors show that the mean time from CP onset to presentation was four hours and the final diagnoses were MI in 23%, unstable angina pectoris in 17%, suspected coronary syndrome in 37%, and noncardiac CP in 21%.
Initial plasma myeloperoxidase levels independently predicted risk of MI and ACS during the acute presentation and also predicted the risk of major adverse cardiac events within 30 days and six months. Notably, the myeloperoxidase levels seemed to identify patients at risk for future (within six months) cardiac events even in the absence of myocardial necrosis (i.e., CK and troponin were negative).
Commentary by Andrew D. Perron, MD, FACEP
When was the last time you brought your children to a toy store? They invariably see something they like, promise you that it will be their favorite toy forever, and that they’ll give all their old toys to charity. I usually give in, only to find the same item a week later buried in a toy chest with an old Rubik’s cube, a pet rock, and a Cabbage Patch doll. So is myeloperoxidase the real deal or the latest mood ring ("sees all/tells all") in biological markers of cardiac disease? I don’t know yet.
This is potentially an important paper if the findings can be reproduced elsewhere. This test, if the results are accurate, has all the hallmarks of a useful diagnostic adjunct: 1) It provides independent information about risk, both in the short- and long term; 2) it is associated with a significant increase in risk for adverse events (relative risk = 2-3 times baseline); and 3) it has a receiver-operating-characteristic (ROC) curve with a moderately high sensitivity throughout the range of specificity. My main concern regarding the applicability of this data to my ED population relates to the study patient characteristics. As noted above, the final diagnosis was acute MI in 23%, and unstable angina/suspected coronary syndrome in 55%! All non-cardiac causes of chest pain accounted for only 21% of patients. This is consistent with neither my clinical experience nor with published data regarding ED chest pain etiologies, where AMI accounts for fewer than 15% of cases, and cardiac etiologies in general for 30-40%.1 If this is a selected population (as it seems to be), I am unsure what the characteristics and applicability of the test will be in a population where the incidence of acute MI/ACS is considerable lower. I eagerly await the results of such a study, and will make my decision regarding myeloperoxidase at that time.
Dr. Perron, Associate Residency Director, Department of Emergency Medicine, Maine Medical Center,Portland, ME, is on the Editorial Board of Emergency Medicine Alert.
Reference
1. Lee T H, et al. Evaluation of the patient with acute chest pain. N Engl J Med 2000;342:1187-1195.
The holy grail of emergency department cardiac markers would have a very high sensitivity (you dont want to miss any cases), would be abnormal very early in the course of the disease process, and would not only be diagnostic of the current problem but be prognostic of future morbidity and mortality associated with an abnormal marker. OK it also would be cheap and easy to perform without highly specialized equipment, but you cant have everything.
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