Abstract
The measurement of ischaemia-modified albumin (IMA) has been proposed as a rule out test for myocardial ischaemia in patients presenting with chest pain, in conjunction with troponin and ECG testing. 1 IMA has a reduced capacity for binding cobalt and this property forms the basis of its measurement. 2 In the Inverness Medical assay, the albumin cobalt binding (ACB) test, IMA is measured by the detection of unbound cobalt after incubation with patient's serum. Ourselves 3 and others 4 have previously raised concerns about the effect of differing albumin concentrations on the binding of cobalt and hence on the assay result. We were the first authors to devise a formula to correct measured IMA concentration taking into account total albumin concentration. 3 Although the commercial ACB assay has recently been withdrawn, a significant number of studies on IMA have made use of ‘in-house’ cobalt-binding assays based on the original publication. 2
We read with interest a recent article in this journal whereby IMA concentrations were reported to be raised in patients immediately following percutaneous coronary intervention (PCI) but not after correction for albumin concentration. 5 It was found that albumin concentration (median, g/L) fell significantly (P < 0.05) during the procedure from 38 to 33 g/L. The reduced cobalt binding of lower albumin concentrations post PCI resulted in a greater quantity of unbound cobalt being detected in the assay procedure.
Since it has now been shown that raised IMA concentrations in the setting of PCI, considered an in vivo model of transient myocardial ischaemia, reflect total albumin concentration, the question needs to be posed, what is the ‘cobalt binding to albumin’ assay actually measuring? It has been suggested that during myocardial ischaemia, an increased release of free fatty acids, subsequently binding to albumin, may reduce the ability of albumin to bind cobalt. 6 In the ACB test, is it valid that the assay result obtained is attributed entirely to the reduced binding of cobalt to IMA? We feel that, before reporting results, it is essential that measured ‘IMA’ concentrations are corrected for the amount of albumin present. To date, this has not been the case in the majority of studies reporting IMA results.
Indeed, to go further, is there a possibility that the ACB assay is merely representing the binding of cobalt by albumin in serum? The fact that the characterisation of IMA has remained elusive for so long must raise doubts about its existence. During our evaluation of the ACB assay, we found that measured IMA concentrations were consistently higher in diluted patient samples; as much as 37% higher in a 1:1 (saline) dilution. However, after correction for the sample albumin concentration, the results were more or less identical (unpublished findings) lending support to the possibility that the assay is primarily measuring the binding of cobalt to serum albumin. Is it conceivable that the original finding of reduced cobalt binding in serum post myocardial ischaemia reflected principally a lowering of total albumin concentration in this condition?
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