Clin Chem Lab Med 2011;49(2):177–184  2011 by Walter de Gruyter • Berlin • New York. DOI 10.1515/CCLM.2011.037 2011/405 Article in press - uncorrected proof Review Ischemia modified albumin changes – review and clinical implications Eftihia Sbarouni*, Panagiota Georgiadou and Vassilis Voudris 2nd Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece Abstract Ischemia modified albumin (IMA), as measured using the albumin cobalt binding test, is currently the most promising biomarker for early detection of ischemia before the onset of irreversible cardiac injury. This paper reviews the infor- mation available on IMA, including its pathophysiology, analysis, clinical applications and future perspectives. The data provided was identified by a search of MEDLINE using the terms IMA, biomarkers and ischemia. IMA may be use- ful to cover the complete diagnostic window of patients pre- senting with acute coronary syndromes (ACS) in the Emergency Department, along with the electrocardiogram and cardiac troponins. Preliminary data regarding the signif- icance of IMA in the prognosis of either ACS or following revascularization need further study. Keywords: biomarkers; ischemia; ischemia modified albumin. Introduction A number of cardiac biomarkers have been described for detecting the different stages of development of acute coro- nary syndromes (ACS) (1, 2). However, there are still no well-defined biochemical markers for identification of myo- cardial ischemia in advance or in the absence of myocardial necrosis. Such a marker of ischemia would offer the oppor- tunity to intervene early and prevent progression to infarc- tion. Clinical studies of ischemia markers are challenging (1, 2). Limitations include the selection of the appropriate study population, use of the optimal cut-off value, performance of the available diagnostic assays, lack of cardiac specificity and the absence of a reference ‘gold standard’ for myocardial *Corresponding author: Eftihia Sbarouni, 2nd Department of Cardiology, Onassis Cardiac Surgery Center, 356 Syngrou Avenue, 176 74 Athens, Greece Phone: q30 210 9493372, Fax: q30 210 9493373, E-mail: esbarouni@yahoo.gr Received July 12, 2010; accepted August 25, 2010; previously published online November 18, 2010 ischemia (1, 2). A low threshold for diagnosis of ACS is necessary because failure to recognize ACS carries consid- erable risk and may have unfavorable consequences. There is a need for a sensitive, inexpensive and early accessible marker of ischemia that would complement the established markers of myonecrosis. To date, the only clinical test approved by the Food and Drug Administration for ischemia is ischemia modified albu- min (IMA) (3). In this review, we discuss the physiology and pathophysiology of IMA, the analytical characteristics and its clinical applications as an emerging biomarker for cardiac ischemia. What is ischemia modified albumin? Decreased human serum albumin, which is the most abun- dant circulating protein in blood, is associated with an increased risk of mortality as well as an increased incidence of coronary heart disease (4). These relationships have been attributed primarily to the ability of albumin to bind various ligands. This acts as a buffering agent for toxic molecules of endogenous or exogenous origin within the circulation. The amino terminal end (N-terminal) of the albumin mole- cule, and especially the aspartyl-alanyl-histidyl-lysine sequence, appears to be the primary binding site for transi- tional metals, such as cobalt, copper and nickel (4, 5). In the early 1990s, it was first discovered that exposure to ischemic tissue alters the N-terminus of the albumin, decreasing its binding capacity for metals and resulting in the formation of IMA (5). Proposed mechanisms for the conversion of serum albumin to IMA include hypoxia, acidosis, superoxide-radi- cal injury, energy-dependent membrane disruption and expo- sure to free iron and copper (3, 6). Data supporting the hypothesis that IMA generation depends strongly on the high oxidative stress state in different ischemia-reperfusion mod- els affect not only myocardium, but other organs (6–12). However, these conditions may also be associated with increases in other markers of cardiac damage and dysfunc- tion (13). IMA does not appear to be highly tissue or a clinically specific marker of ischemia. Table 1 shows the pathologies and diseases associated with an increase in IMA (13–18). IMA is also increased in conditions that produce free radi- cals, such as liver cirrhosis, acute infections and advanced cancer (19). IMA does not appear to increase in immune Brought to you by | University of Iowa Libraries Authenticated Download Date | 5/24/15 8:16 AM