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Serum Chelatable Redox-Active Iron Is an Independent Predictor of Mortality After Myocardial Infarction in Individuals With Diabetes

  1. Mahmoud Sulieman, MD1,
  2. Rabea Asleh, MSC2,
  3. Zvi I. Cabantchik, MD, PHD3,
  4. William Breuer, PHD3,
  5. Doron Aronson, MD1,
  6. Abeer Suleiman, BSC2,
  7. Rachel Miller-Lotan, PHD2,
  8. Haim Hammerman, MD1 and
  9. Andrew P. Levy, MD, PHD2
  1. 1Department of Cardiology, Rambam Medical Center, Haifa, Israel
  2. 2Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
  3. 3Department of Biological Chemistry, Institute of Life Sciences, Hebrew University, Jerusalem, Israel
  1. Address correspondence and reprint requests to Andrew P. Levy, MD, PhD, FACC, Technion Faculty of Medicine, Haifa, Israel 31096. E-mail: alevy{at}tx.technion.ac.il

As a result of its strong oxidative activity, iron (1) has been hypothesized to be of importance in morbidity and mortality from atherosclerotic cardiovascular disease (CVD) (2). Numerous studies (3) have failed to show a relationship between total body iron and CVD. However, total iron may not be reflective of the risk of oxidative damage mediated by iron. A linkage between iron and CVD is more likely to be found in the amount of iron available for participating in oxidative reactions (4). Labile serum iron or labile plasma iron (LPI) represents iron bound to serum albumin, citrate, and other undefined, negatively charged ligands (5). Iron bound as LPI is associated with reactive oxygen species formation and increased oxidative stress (6).

LPI is elevated in only a small fraction of ambulatory diabetic individuals (<3%) and has not been seen in individuals without diabetes. However, LPI may become increased when large fluxes in iron occur, as in acute myocardial infarction (AMI) (7,8). We have therefore proposed that LPI is increased in the setting of AMI and that it is associated with mortality. We tested this hypothesis prospectively in individuals presenting with AMI.

RESEARCH DESIGN AND METHODS

All patients presenting to the coronary care unit with AMI from July 2001 to July 2003 were eligible for the study (n = 1,156). The investigational review committee on human research approved …

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