CORRESPONDENCE: LETTER TO THE EDITOR
Ischemia-Modified Albumin: The Importance of Oxidative Stress
Debashis Roy, MRCP, MD* and
Juan Carlos Kaski, MD, DSc, FACC
* Cardiovascular Biology Research Centre, Division of Cardiac and Vascular Sciences, St. George’s Hospital Medical School, University of London, London, United Kingdom (Email: droy{at}sghms.ac.uk).
We read with interest the recent study by Sbarouni et al. (1) which adds to the growing body of evidence regarding ischemia-modified albumin (IMA). Interestingly, in their study, the IMA levels dropped significantly at peak exercise in both patients with positive and negative exercise stress-test responses, suggesting that the observed changes in IMA levels may not reflect myocardial ischemia. In addition to Sbarouni et al. (1), other investigators have previously shown reduced IMA levels immediately after exercise in different clinical conditions: for example, exercise-induced skeletal muscle ischemia in patients with peripheral vascular disease (2) and induced forearm ischemia in normal volunteers (3). The possible explanations for the observed IMA changes after exertion include an increase in albumin levels due to hemoconcentration and the resultant decrease in the nonbound portion of cobalt. It has also been suggested that this immediate decrease in IMA concentration may be attributable to interference with the IMA measurement by lactate produced during skeletal muscle work or ischemia. These findings are important for 2 main reasons: 1) they may cast doubt as to whether IMA changes are truly representative of cardiac ischemia in patients with chest pain, and 2) they raise issues as to the nature of the true stimulus for an increase in IMA concentrations in patients with chest pain.
There is little doubt, if any, that IMA levels increase during myocardial ischemia triggered by a primary reduction of blood flow, as seen in patients during percutaneous coronary intervention (PCI). Several studies have shown a good correlation among objective markers of myocardial ischemia, such as lactate levels (4) isoprostane concentrations (5) and IMA levels, in this setting. We have therefore suggested that increased IMA levels may result from increased oxidative stress whether caused by ischemia reperfusion injury or other mechanisms linked to primary reductions of coronary blood flow (5) or muscle damage (6). Indeed, results from in vitro work from our group support this hypothesis and suggest that the generation of reactive oxygen species can at least transiently modify the N-terminal region of albumin to yield increased levels of IMA (7). It is conceivable that the greater the magnitude of reactive oxygen species formation the higher the elevation of IMA levels. The production of reactive oxygen species during balloon occlusion and reperfusion in patients undergoing PCI (8) and in the acute coronary syndrome setting (9)—where intracoronary thrombosis causes serious reductions in coronary blood flow—may result in the chemical modification of albumin that leads to IMA production. Increased oxidative stress production in these circumstances, together with the lack of antagonistic influences to IMA measurements that appear to occur during skeletal muscle exercise (1–3), can explain the consistent finding of increased IMA levels. Increased oxygen free-radical production, however, is commonly found in a wide variety of medical conditions other than myocardial ischemia, and this may at least partly explain both IMA’s baseline variability and relatively low specificity (9).
Further studies are required to understand the mechanisms leading to increased IMA levels in different clinical conditions of myocardial ischemia and nonischemic conditions. Moreover, future research should be specifically targeted toward identifying the exact nature of albumin modification and the reasons for the intriguing findings in relation to exercise, as reported by Sbarouni et al. (1). Only when these vital mechanisms are elucidated, should clinical studies be carried out to explore the true potential role of this marker in clinical practice.
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- Sbarouni E, Georgiadou P, Theodorakis GN, Kremastinos DT. Ischemia-modified albumin in relation to exercise stress testing J Am Coll Cardiol 2006;48:2482-2484.[Abstract/Free Full Text]
- Roy D, Quiles J, Sharma R, et al. Ischemia modified albumin levels in patients with peripheral vascular disease and exercise induced skeletal muscle ischaemia Clin Chem 2004;50:1656-1660.[Abstract/Free Full Text]
- Zapico-Muniz E, Santalo-Bel M, Merce-Muntanola J, Montiel JA, Martinez-Rubio A, Ordonez-Llanos J. Ischemia-modified albumin during skeletal muscle ischemia Clin Chem 2004;50:1063-1065.[Free Full Text]
- Sinha MK, Vasquez JM, Calvino R, Gaze DC, Collinson PO, Kaski JC. Effects of balloon occlusion during percutaneous coronary intervention on circulating ischemia modified albumin and transmyocardial lactate extraction Heart 2006;92:1852-1853.[Free Full Text]
- Sinha MK, Gaze DC, Tippins JR, et al. Ischemia modified albumin is a sensitive marker of myocardial ischemia after percutaneous coronary intervention Circulation 2003;107:2403-2405.[Abstract/Free Full Text]
- Roy D, Quiles J, Sinha M, et al. Effect of direct current cardioversion on ischemia modified albumin levels in patients with atrial fibrillation Am J Cardiol 2004;94:234-236.[CrossRef][ISI][Medline]
- Roy D, Quiles J, Gaze D, et al. Role of reactive oxygen species in the formation of the novel diagnostic marker ischemia modified albumin Heart 2006;92:113-114.[Free Full Text]
- Iuliano L, Pratico D, Greco C, et al. Angioplasty increases coronary sinus F2-isoprostane formation: evidence for in vivo oxidative stress during PTCA J Am Coll Cardial 2001;37:76-80.[Abstract/Free Full Text]
- Sinha MK, Roy D, Gaze DC, Collinson PO, Kaski JC. Role of "ischemia modified albumin," a new biochemical marker of myocardial ischaemia, in the early diagnosis of acute coronary syndromes Emerg Med J 2004;21:29-34.[Abstract/Free Full Text]
Related Article
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Reply
- Eftihia Sbarouni, Panagiota Georgiadou, George N. Theodorakis, and Dimitrios Th. Kremastinos
J. Am. Coll. Cardiol. 2007 49: 2376-2377.
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