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1 Department of Biochemistry and Biophysics;
2 Department of Pathology, Integrated Pathology Residency Program; and
3 Department of Medicine, Integrated Medicine Residency Program, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96822.
4 Department of Pathology, Kaiser Foundation Hospital, Honolulu, HI 96819.
aAddress correspondence to this author at: Department of Biochemistry and Biophysics, John A. Burns School of Medicine, University of Hawaii at Manoa, 1960 East-West Rd., Honolulu, HI 96822. Fax 808-956-9498; e-mail bhagavan{at}hawaii.edu.
Background: Clinical diagnoses were correlated with results of a Co(II)–albumin binding assay in 167 patients treated at an emergency department of a health maintenance organization.
Methods: Patients were evaluated as being nonischemic or potentially ischemic through standard coronary disease indicators [creatine kinase (CK), CK-MB, cardiac troponin I, and electrocardiographic findings] and were tested by a Co(II)–albumin binding assay. Samples were tested anonymously, and the study was double-blinded. The sensitivity and specificity of this assay for the detection of ischemia were evaluated by ROC curve analysis. Known Co(II) binding sites on albumin were analyzed by N-terminal amino acid sequencing.
Results: The mean absorbance units (ABSU) ± 2 SD for non-myocardial ischemic and myocardial ischemic individuals measured at 470 nm were 0.43 ± 0.10 and 0.63 ± 0.25, respectively (P <0.0001). The area under the ROC curve was 0.95 [95% confidence interval (CI), 0.92–0.99], and at a cutoff value of 0.50 ABSU, sensitivity and specificity were 88% (78–94%) and 94% (86–98%), respectively, suggesting a high distinction between the two groups. When we compared non-acute myocardial infarction (AMI) and AMI ischemic individuals, the area under the ROC curve was 0.66 (95% CI, 0.53–0.79) and was considered a poor discriminator between these two groups. N-Terminal amino acid sequencing data for purified albumin showed normal amino acid residues for six of seven high-ABSU (
0.70) individuals and one nonischemic individual tested. However, only one individual with a high ABSU (0.80) had two missing amino acid residues (DA) from the N-terminal region. Clinical diagnosis for this patient did not reveal an ischemic event.
Conclusions: The Co(II)–albumin binding test may serve as a useful diagnostic tool in emergency facilities for the assessment of myocardial ischemia. High and low ABSU were associated with myocardial ischemic individuals and non-myocardial ischemic individuals, respectively. However, the Co(II)–albumin binding was a poor discriminator between ischemic individuals with and without MI.
The following articles in journals at HighWire Press have cited this article:
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  S. S. Talwalkar, M. Bon-Homme, J. J. Miller, and R. J. Elin Ischemia Modified Albumin, a Marker of Acute Ischemic Events: A Pilot Study Ann. Clin. Lab. Sci., January 1, 2008; 38(2): 132 - 137. [Abstract] [Full Text] [PDF]
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 NACB WRITING GROUP MEMBERS, D. A. Morrow, C. P. Cannon, R. L. Jesse, L. K. Newby, J. Ravkilde, A. B. Storrow, A. H.B. Wu, and R. H. Christenson National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes Circulation, April 3, 2007; 115(13): e356 - e375. [Full Text] [PDF]
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 NACB WRITING GROUP MEMBERS, D. A. Morrow, C. P. Cannon, R. L. Jesse, L. K. Newby, J. Ravkilde, A. B. Storrow, A. H.B. Wu, R. H. Christenson, NACB COMMITTEE MEMBERS, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes Clin. Chem., April 1, 2007; 53(4): 552 - 574. [Full Text] [PDF]
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 E. Sbarouni, P. Georgiadou, D. Panagiotakos, E. G. Livanis, G. N. Theodorakis, and D. Th. Kremastinos Ischaemia modified albumin in radiofrequency catheter ablation Europace, February 1, 2007; 9(2): 127 - 129. [Abstract] [Full Text] [PDF]
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 E. Sbarouni, P. Georgiadou, G. N. Theodorakis, and D. Th. Kremastinos Ischemia-Modified Albumin in Relation to Exercise Stress Testing J. Am. Coll. Cardiol., December 19, 2006; 48(12): 2482 - 2484. [Abstract] [Full Text] [PDF]
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 L Keating, J R Benger, R Beetham, S Bateman, S Veysey, J Kendall, and R Pullinger The PRIMA Study: presentation ischaemia-modified albumin in the emergency department. Emerg. Med. J., October 1, 2006; 23(10): 764 - 768. [Abstract] [Full Text] [PDF]
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M Can, S Demirtas, O Polat, and A Yildiz Evaluation of effects of ischaemia on the albumin cobalt binding (ACB) assay in patients exposed to trauma. Emerg. Med. J., July 1, 2006; 23(7): 537 - 539. [Abstract] [Full Text] [PDF]
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 N. Middleton, R. Shave, K. George, G. Whyte, J. Forster, D. Oxborough, D. Gaze, and P. Collinson Novel application of flow propagation velocity and ischaemia-modified albumin in analysis of postexercise cardiac function in man Exp Physiol, May 1, 2006; 91(3): 511 - 519. [Abstract] [Full Text] [PDF]
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P O Collinson, D C Gaze, K Bainbridge, F Morris, B Morris, A Price, and S Goodacre Utility of admission cardiac troponin and "Ischemia Modified Albumin" measurements for rapid evaluation and rule out of suspected acute myocardial infarction in the emergency department. Emerg. Med. J., April 1, 2006; 23(4): 256 - 261. [Abstract] [Full Text] [PDF]
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 M. Thielmann, P. Massoudy, A. Schmermund, M. Neuhauser, G. Marggraf, M. Kamler, U. Herold, I. Aleksic, K. Mann, M. Haude, et al. Diagnostic discrimination between graft-related and non-graft-related perioperative myocardial infarction with cardiac troponin I after coronary artery bypass surgery Eur. Heart J., November 2, 2005; 26(22): 2440 - 2447. [Abstract] [Full Text] [PDF]
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A. M. Mitchell, M. D. Brown, I. B.A. Menown, and J. A. Kline Novel Protein Markers of Acute Coronary Syndrome Complications in Low-Risk Outpatients: A Systematic Review of Potential Use in the Emergency Department Clin. Chem., November 1, 2005; 51(11): 2005 - 2012. [Abstract] [Full Text] [PDF]
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P. M. van der Zee, H. J. Verberne, J. P. van Straalen, G. T.B. Sanders, B. L.F. Van Eck-Smit, R. J. de Winter, and J. C. Fischer Ischemia-Modified Albumin Measurements in Symptom-Limited Exercise Myocardial Perfusion Scintigraphy Reflect Serum Albumin Concentrations but Not Myocardial Ischemia Clin. Chem., September 1, 2005; 51(9): 1744 - 1746. [Full Text] [PDF]
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F. S. Apple, A. H.B. Wu, J. Mair, J. Ravkilde, M. Panteghini, J. Tate, F. Pagani, R. H. Christenson, M. Mockel, O. Danne, et al. Future Biomarkers for Detection of Ischemia and Risk Stratification in Acute Coronary Syndrome Clin. Chem., May 1, 2005; 51(5): 810 - 824. [Abstract] [Full Text] [PDF]
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J. M. Abadie, C. L. Blassingame, and D. D. Bankson Albumin Cobalt Binding Assay to Rule Out Acute Coronary Syndrome Ann. Clin. Lab. Sci., January 1, 2005; 35(1): 66 - 72. [Abstract] [Full Text] [PDF]
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M. Panteghini Role and importance of biochemical markers in clinical cardiology Eur. Heart J., July 2, 2004; 25(14): 1187 - 1196. [Abstract] [Full Text] [PDF]
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 M. Kemp, J. Donovan, H. Higham, and J. Hooper Biochemical markers of myocardial injury Br. J. Anaesth., July 1, 2004; 93(1): 63 - 73. [Abstract] [Full Text] [PDF]
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E. Zapico-Muniz, M. Santalo-Bel, J. Merce-Muntanola, J. A. Montiel, A. Martinez-Rubio, and J. Ordonez-Llanos Ischemia-Modified Albumin during Skeletal Muscle Ischemia Clin. Chem., June 1, 2004; 50(6): 1063 - 1065. [Full Text] [PDF]
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M K Sinha, D Roy, D C Gaze, P O Collinson, and J-C Kaski Role of "Ischemia Modified Albumin", a new biochemical marker of myocardial ischaemia, in the early diagnosis of acute coronary syndromes Emerg. Med. J., January 1, 2004; 21(1): 29 - 34. [Abstract] [Full Text] [PDF]
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D. A. Morrow, J. A. de Lemos, M. S. Sabatine, and E. M. Antman The Search for a Biomarker of Cardiac Ischemia Clin. Chem., April 1, 2003; 49(4): 537 - 539. [Full Text] [PDF]
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