This is a novel protein for which the measurement has been approved by the FDA for measurement of cardiac ischemia. The premise behind this test lies in the decreased ability of the N-terminal region of human albumin to bind cobalt in he presence of myocardial ischemia. Combined with other cardiac markers such as troponin, this test represents an important diagnostic advance in the detection of an early heart attack.
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A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia-a preliminary report.
Bar-Or D, Lau E, Winkler JV.
Department of Trauma Research, Swedish Medical Center, Englewood, Colorado 80110, USA
J Emerg Med 2000 Nov;19(4):311-5 Abstract quote
We initially observed a phenomenon of reduced in vitro binding of exogenous cobalt [Co(II)] to the N-terminus of human serum albumin (HSA) in emergency chest pain patients with early onset unstable angina and myocardial infarction.
We then developed a colorimetric assay to measure cobalt-HSA binding and record the results in absorbance units (ABSU). In a preliminary clinical study of 139 emergency patients with acute chest pain, 99 patients with evidence of myocardial ischemia (Group 1) had elevated assay levels (mean ABSU +/- SD; 0.519 +/- 0.086) compared to 40 patients (Group 2) with no evidence of ischemia (0.316 +/- 0.092) (p < 0.00001). In Group 1, 95 of 99 (96.0%) patients had levels higher than a decision threshold of 0.400 ABSU and in Group 2, 37 of 40 (92.5%) samples had higher cobalt binding capacity (ABSU </= 0.400). Further studies are warranted to determine if an assay measuring altered cobalt-HSA binding is a clinically useful diagnostic test to rule out myocardial ischemia.
CLINICAL UTILITY CHARACTERIZATION CARDIAC ISCHEMIA Ischemia-Modified Albumin Improves the Usefulness of Standard Cardiac Biomarkers for the Diagnosis of Myocardial Ischemia in the Emergency Department Setting
Saif Anwaruddin, MD, etal.
Am J Clin Pathol 2005;123:140-145 Abstract quote
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.
Ischemia modified albumin is a sensitive marker of myocardial ischemia after percutaneous coronary intervention.
Sinha MK, Gaze DC, Tippins JR, Collinson PO, Kaski JC.
Coronary Artery Disease Research Unit, St George's Hospital, London, UK.
Circulation. 2003 May 20;107(19):2403-5. Abstract quote
BACKGROUND: Ischemia modified albumin (IMA; Ischemia Technologies, Inc) blood levels rise in patients who develop ischemia during percutaneous coronary intervention (PCI). It is not known whether IMA elevations correlate with increases in other markers of oxidative stress, ie, 8-iso prostaglandin F2-A (iP).
METHODS AND RESULTS: We compared IMA versus iP plasma levels in 19 patients (mean age 62.8+/-11.9 years) undergoing PCI and 11 patients (mean age 64+/-13.6 years) undergoing diagnostic angiography (controls). In the PCI patients, blood samples for IMA and iP were taken from the guide catheter before PCI and after balloon inflations, and from the femoral sheath 30 minutes after PCI. IMA was measured by the albumin cobalt binding (ACB) test and plasma iP by enzyme immunoassay. During PCI, all 19 patients had chest pain and 18 had transient ischemic ST segment changes. IMA was elevated from baseline in 18 of the 19 patients after PCI. Median IMA levels were higher after PCI (101.4 U/mL, 95%CI 82 to 116) compared with baseline (72.8 U/mL, CI 55 to 93; P<0.0001). Levels remained elevated at 30 minutes (87.9 U/mL, CI 78 to 99; P<0.0001) and returned to baseline at 12 hours (70.3 U/mL, CI 65 to 87; P=0.65). iP levels were raised after PCI in 9 of the 19 patients. However, median iP levels were not significantly different immediately (P=0.6) or 30 minutes after PCI (P=0.1). In the control group, IMA and iP levels remained unchanged before and after angiography (P=0.2 and 0.16, respectively).
CONCLUSIONS: IMA is a more consistent marker of ischemia than iP in patients who develop chest pain and ST segment changes during PCI.
Evaluation of human serum albumin cobalt binding assay for the assessment of myocardial ischemia and myocardial infarction.
Bhagavan NV, Lai EM, Rios PA, Yang J, Ortega-Lopez AM, Shinoda H, Honda SA, Rios CN, Sugiyama CE, Ha CE.
Department of Biochemistry and Biophysics, John A. Burns School of Medicine, University of Hawaii, Honolulu 96822, USA.
Clin Chem 2003 Apr;49(4):581-5 Abstract quote
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 (> or =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.
Analysis of the Albumin Cobalt Binding (ACB) test as an adjunct to cardiac troponin I for the early detection of acute myocardial infarction.
Wu AH, Morris DL, Fletcher DR, Apple FS, Christenson RH, Painter PC.
Department of Pathology and Laboratory Medicine, Hartford Hospital, Hartford, CT 06102, USA.
Cardiovasc Toxicol 2001;1(2):147-51 Abstract quote
Human albumin has the ability to bind cobalt at the N-terminus. The exposure of circulating albumin to ischemic tissue alters the ability of albumin to bind cobalt, probably through a mechanism involving free-radical production. The Albumin Cobalt Binding (ACB) test measures the alteration in albumin metal binding, and elevation of the ACB test is thought to be an early indicator of myocardial ischemia.
In a previous multicenter study of chest pain patients presenting to the emergency department (ED), this test demonstrated high negative predictive value and sensitivity in the sample collected at presentation for predicting cardiac troponin I (cTnI)-negative or cTnI-positive results 6-24 h later. Since the completion of that report, the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) have redefined the criteria for the diagnosis of acute myocardial infarction (AMI). The data from the multicenter ACB study were re-examined using the new diagnostic criteria for AMI to determine if combining the ACB test with troponin improved the sensitivity of either assay used alone for early diagnosis of AMI.
Assay values were compared to either the final discharge diagnosis made at each site or to a diagnosis of AMI using the strict application of the ESC/ACC guidelines. Using the criterion of physician's discharge diagnosis and using blood collected at ED presentation, the cTnI test alone had a sensitivity of 23.9%, and the ACB test alone had a sensitivity of 39.1%, but the sensitivity significantly increased to 55.9% (p < 0.001 over cTnI alone) when both tests were used in combination. The sensitivity of the combination of ACB and cTnI tests at the 1- to 6-h time-point was 86.7% and at the >6- to 12-h time-point was 93.5%, but they were not significantly improved over the cTnI test alone. In conclusion, using the new ESC/ACC criteria, the combination also resulted in a statistically significant higher diagnostic sensitivity on blood collected at presentation.
These data indicate a possible role of the ACB test in the early triage of patients with chest pain.
Characteristics of an Albumin Cobalt Binding Test for assessment of acute coronary syndrome patients: a multicenter study.
Christenson RH, Duh SH, Sanhai WR, Wu AH, Holtman V, Painter P, Branham E, Apple FS, Murakami M, Morris DL.
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Clin Chem 2001 Mar;47(3):464-70 Abstract quote
BACKGROUND: The ability of the N-terminal region of human albumin to bind cobalt is diminished by myocardial ischemia. The characteristics of an assay based on albumin cobalt binding were assessed in suspected acute coronary syndrome patients and in a control reference population. The ability of the Albumin Cobalt Binding (ACB) Test measurement at presentation to predict troponin-positive or -negative results 6-24 h later was also examined.
METHODS: We enrolled 256 acute coronary syndrome patients at four medical centers. Blood specimens were collected at presentation and then 6-24 h later. The dichotomous decision limit and performance characteristics of the ACB Test for predicting troponin-positive or -negative status 6 h-24 h later were determined using ROC curve analysis. Results for 32 patients could not be used because the time of onset of ischemia appeared to have been >3 h before presentation or was uncertain. The reference interval was determined by parametric analysis to estimate the upper 95th percentile of a reference population (n = 109) of ostensibly healthy individuals.
RESULTS: Increased cTnI was found in 35 of 224 patients. The ROC curve area for the ACB Test was 0.78 [95% confidence interval (CI), 0.70-0.86]. At the optimum decision point of 75 units/mL, the sensitivity and specificity of the ACB Test were 83% (95% CI, 66-93%) and 69% (95% CI, 62-76%). The negative predictive value was 96% (95% CI, 91-98%), and the positive predictive value was 33% (95% CI, 24-44%). The within-run CV of the ACB Test was 7.3%. Results for the reference population were normally distributed; the one-sided parametric 95th percentile was 80.2 units/mL.
CONCLUSIONS: This exploratory study suggests that the ACB Test has high negative predictive value and sensitivity in the presentation sample for predicting troponin-negative or -positive results 6-24 h later.
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