Ischemia-Modified Albumin Improves the Usefulness of Standard Cardiac Biomarkers for the Diagnosis of Myocardial Ischemia in the Emergency Department Setting

Saif Anwaruddin, MD; James L. Januzzi Jr, MD; Aaron L. Baggish, MD; Lee Lewandrowski, PhD, MPH; Kent B. Lewandrowski, MD

Disclosures

Am J Clin Pathol. 2005;123(1):140-145. 

In This Article

Abstract and Introduction

We studied the role of ischemia-modified albumin (IMA) with standard biomarkers (myoglobin, creatine kinase-MB [CK-MB], troponin I [TnI]) in assessment of 200 patients with suspected myocardial ischemia admitted to the emergency department. Every case was reviewed by a cardiologist. A clinical diagnosis of ischemia was assigned and correlated with biomarker test results. Of the patients, 25 (13.0%) had myocardial ischemia. Receiver operating characteristic curves demonstrated IMA as highly sensitive but somewhat poorly specific for the presence of ischemia (area under curve, 0.63; P = .01). With a cut point of 90 U/mL, the Albumin Cobalt Binding Test had 80% sensitivity and 31% specificity for diagnosing ischemia and a negative predictive value of 92%. IMA was positive in 4 of 5 patients with electrocardiographic (ECG) evidence of ischemia and 16 of 20 patients with coronary ischemia but negative ECG. Among the same patients, the myoglobin–CK-MB–TnI triad had a sensitivity of 57%. The combination of IMA–myoglobin–CK-MB–TnI increased the sensitivity for detecting ischemia to 97%, with a negative predictive value of 92%. IMA is highly sensitive and has a high negative predictive value, which might improve the usefulness of standard biomarkers of myocardial ischemia.

Establishing a diagnosis of acute coronary syndrome in the clinical setting remains a challenging task. The advent of testing for cardiac biomarkers, such as myoglobin, creatine kinase (CK-MB), and the troponins has facilitated this process. Unfortunately, although these blood markers are extremely sensitive for the identification of patients with myocardial necrosis, their ability to identify patients with acute coronary ischemia remains limited because the spectrum of acute coronary syndromes also includes stable and unstable angina, both of which describe transient ischemic events without associated myocardial necrosis. In addition, myocardial necrosis is time-dependent, such that these highly sensitive and specific markers might give negative results on admission but give positive results hours later. As such, the usefulness of the standard biomarkers of myocardial necrosis for the confident exclusion of the diagnosis of myocardial ischemia at the time of admission remains limited. Thus, markers able to identify patients with myocardial ischemia without infarction might serve an important role in the clinical setting.

A candidate marker for the detection of myocardial ischemia is ischemia-modified albumin (IMA). During myocardial ischemia, several changes occur in the amino-terminus of albumin, which result in a significant change in the ability of albumin to bind transition metals, notably, cobalt.[1] Therefore, if reliable, an assay measuring IMA might represent a promising marker for the identification of patients with myocardial ischemia, which, together with standard markers of myocyte necrosis, might be a superior screening method for patient evaluation to rule out acute myocardial ischemia. Accordingly, we studied the role of IMA together with myoglobin, CK-MB, and troponin I (TnI) for this use among patients admitted to an emergency department (ED) with symptoms suggestive of acute myocardial ischemia.

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