Troponin vs CKMB in ACS

Abstract & Commentary

By Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.

This article originally appeared in the March 2006 issue of Clinical Cardiology Alert. It was peer reviewed by Rakesh Mishra, MD, FACC.

Synopsis: Among patients with NSTE ACS, an elevated troponin level identifies patients at increased acute risk regardless of CK-MB status, but an isolated CK-MB+ status has limited prognostic value.

Source: Newby LK, et al. Frequency and Clinical Implications of Discordant Creatine Kinase-MB and Troponin Measurements in Acute Coronary Syndromes. J Am Coll Cardiol. 2006;47:312-318.

Cardiac biomarker testing is part of the standard approach to evaluating patients with suspected acute coronary syndromes (ACS). Although troponin has become the diagnostic standard for myocardial infarction (MI), CKMB is often tested as well. Thus, Newby and colleagues evaluated the use of dual marker testing in patients with non-ST elevation ACS in the CRUSADE quality improvement initiative database. The end point chosen was in-hospital mortality. They specifically focused on the significance of discordant results of troponin and CKMB, which occurred in 28% of the 29,357 patients who had both measured. Most patients had concordant cardiac marker values; 12% were CKMB negative and troponin (Tn) negative and 60% were CKMB+/Tn+. CKMB+/ Tn- occurred in 10%; CKMB-/ Tn+ occurred in 18%. Hospital mortality was highest in the concordant positive (CKMB+/Tn+) patients at 5.9% and lowest in the concordant negative patients at 2.7%. Hospital mortality in the discordant patients was 3.0% in the CKMB+/Tn- patients and 4.5% in the CKMB-/Tn+ patients. Baseline characteristics showed that Tn+ patients were older, had more evidence of vascular disease, and more often had heart failure. After adjustment for baseline characteristic differences, troponin was more strongly associated with mortality than CKMB (chi square 23 for troponin and 8 for CKMB). Hospital therapy was similar for all cardiac marker groupings. Newby et al concluded that in patients with non-ST elevation ACS, an elevated troponin is associated with an increased risk of death regardless of the CKMB value, but an elevated CKMB alone is of little prognostic value.

Commentary

The major conclusion of this study is that an elevated troponin value defines the highest risk patients among non-ST elevation ACS patients who are admitted. However, all the patients in this database were treated similarly, despite their troponin values. For example, those who were CKMB- and Tn- were most likely to have an early cardiac catheterization approach as compared to either group with discordant results. Newby et al argue that cardiac biomarker results should be used to direct the most aggressive therapy to the highest risk patients, those who were troponin positive. They believe CKMB adds little to the troponin results, yet most centers do both in ACS patients. Should CKMB be eliminated? Perhaps it should in the triage of ACS patients, but it may be useful later to estimate infarct size in selected patients.

Why are we not responding more aggressively to an elevated troponin? Perhaps because of troponin desensitization. We are used to seeing elevated troponins in many hospitalized patients. We are annoyed by consultation requests to see terminally ill non-cardiac patients with slight troponin elevations. Thus, in ACS patients where an elevated troponin is of value, we may not react appropriately anymore. Also, troponin assays have been a moving target; troponin T, then I; changes in cutoff values; test inaccuracies. In this study, they used each center's test and values; there was no core laboratory. So, Newby et al note that as more centers convert to the latest troponin I system there could be changes in this ongoing database. Finally, it was pointed out that these results may not apply to lower risk patients who are not hospitalized, but held in chest pain observation units.