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Journal of Postgraduate Medicine, Vol. 56, No. 3, July-September, 2010, pp. 226-228 View Point Clinically effective CK-MB reporting: How to do it? Vivekanandan S, Swaminathan R1 Department of Clinical Biochemistry, Global Hospitals & Health City, Chennai, India, Correspondence Address: Dr. S Vivekanandan, Department of Clinical Biochemistry, Global Hospitals & Health City, Chennai, India, sachidanandamv@yahoo.co.uk Date of Submission: 26-Feb-2009 Code Number: jp10068 PMID: 20739777 DOI: 10.4103/0022-3859.68646 Abstract The clinical utility of measuring the Muscle Brain (MB) isoenzyme of creatine kinase (CK) in the diagnosis of myocardial injury is well established. CK/CK-MB measurement in combination or CK-MB alone is widely used and reporting the results of CK-MB in absolute unit is the common current practice. CK-MB is widely measured by "Immunoinhibition" in India, which gives falsely elevated CK-MB results in the following circumstances: Central nervous system damage, childbirth, macro CK-immunoglobulin complex, in patients with carcinoma of various organs, such as prostate carcinoma and other adenocarcinomas. But, reporting %CK-MB rather than the absolute CK-MB results assists in detection of macroCK (or CK variants), associated proliferative and autoimmune pathologies and their prognosis.Keywords: Creatine kinase, %CK-MB, immunoinhibition, macroCK Introduction The clinical utility of measuring the muscle brain (MB) isoenzyme of creatine kinase (CK; EC 2.7.3.2) in the diagnosis of myocardial injury is well established. [1],[2],[3] Although cardiac troponins have been recommended to be the new laboratory standard for AMI diagnosis, CK and CK-MB measurements are useful in detecting myocardial infarction, particularly in places/circumstances where cardiac troponins (cTn) are not available/affordable/useful. [4] In many hospitals/laboratories in India, CK/CK-MB measurement in combination or CK-MB alone is widely used but it is the usual practice to report the results of CK-MB in absolute unit. The aim of this letter is to suggest that reporting CK-MB as a relative index (%CK-MB) is clinically superior and yields additional clinically useful information not only as a cardiac marker but also in revealing other systemic pathologies, rather than reporting absolute levels. CK and its Isoenzyme Distribution CK is found in skeletal muscle, heart and the brain. It is formed of two subunits, M and B. From a combination of these subunits, three isoenzymes are possible - MM, BB and MB. MM is the predominant isoenzyme in the skeletal and the cardiac muscle. BB is mainly found in the brain. [5] MB isoenzyme is predominantly found in the heart muscle, consisting of about 15% of the total CK in this tissue. It is also present in the skeletal muscle, accounting for <1% of the total CK. [5] Sometimes, CK in circulation can be found as a large molecular weight variant, which is called macro-CK (also called variant CK). There are two types of macro-CK - type 1 is complexed with immunoglobulin G (IgG) and is chiefly associated with autoimmune diseases and type 2 is an oligomer of mitochondrial CK. [5],[6] CK-MB Measurement Method CK-MB is widely measured by "Immunoinhibition" in India. In this, the sample is incubated with an antibody against the "M" subunit and the residual CK activity is measured and multiplied by 2 to give the value for CK-MB activity. [7] Activity remaining after "M" inhibition is the result of the "B" subunit of MB and BB activity, although CK-BB is not normally detectable. [7],[8] Causes of Falsely High CK-MB Activity The immunoinhibition method may give falsely elevated CK-MB results in the following circumstances: 1. If CK-BB is present in serum then a falsely elevated CK-MB result will follow. A very good example is that healthy infants and children have CK-BB values above-normal to that found in healthy adults and they have high CK-MB results. [9],[10] 2. Raised absolute CK and CK-MB results [along with traditional cardiac markers (AST, LDH)] observed in subjects following prolonged or strenuous exercise (such as marathon running). But, the relative index (%CKMB) remains normal, confirming that the rise in this isoenzyme originated from the skeletal muscle rather than from the cardiac muscle. [11],[12] 3. Falsely high CK-MB values by this method are observed in patients with macro CK: (e.g. patients with gastrointestinal disorders (with macro CK type 1), patients with neoplasms (may have macro CK type 2), CK-BB and dermatomyositis. [6] Each of these conditions may result in apparent elevations in the % CK-MB (more than 25%) activities and, if present in patients suspected of having an AMI, might cause clinical ambiguities. [6] Among the atypical CK isoenzymes, CK-BB is a clearly defined and well-described entity. [6],[13],[14] The prevalence of macro-CK is about 1-6% in the western hospital population, [15] predominantly in women, and usually in the higher age groups (>60 years). [14] The most common cause of CK-BB elevations are central nervous system damage [16] and childbirth, and the macro-CK-immunoglobulin complex is particularly elevated in patients with carcinoma of various organs, such as prostate carcinoma and other adenocarcinomas. [6] 4. The skeletal muscle mostly contains CK-MM, but carries about 1% of CK-MB. A very high level of plasma CK activity due to skeletal muscle damage will show quite high absolute levels of CK-MB, but the relative index, i.e. %CK-MB, will still be <1% (more commonly seen during prolonged/strenuous exercise). [12] An additional caveat of this assay is interference by "CK"-like activity (similar to creatinine-like substances interfering in Jaffe reaction) not inhibited by M antiserum and adenylate kinase (EC 2.7.4.3). [17] Prognostic Value of CK Variants The presence of these variant CK isoenzymes has prognostic value, because macro CK type 1 is usually present in patients who develop cardiovascular or autoimmune processes, whereas macro-CK type 2 is most commonly found in patients with malignant proliferation. The prognostic utility of variant CK can be achieved only when %CK-MB is reported and if it is more than 25% and Not by CK-MB absolute result. [18] This proliferation-prognostic utility is achievable only by %CKMB and neither by absolute CK-MB nor by any other cardiac marker such as cardiac Troponins. Why %CK-MB is Better? The single %CK-MB (relative index) is more specific than the single CK-MB absolute result for detecting AMI specificity (96.1 vs. 93.2), acute coronary syndrome (specificity, 96.3 vs. 93.3) and serious cardiac events (96.3 vs. 93.3). The %CK-MB has a higher positive predictive value for all three outcomes. Thus, CK-MB >25% suggests the need to use other reliable cardiac markers such as cTn to rule in/out cardiac pathology and also warrants to focus on other pathologies, as given above, for optimal clinical effectiveness. If used with the full knowledge of its limitation, single CK/CK-MB measurement by immunoinhibition and reporting as %CK-MB alone can reliably detect and prognosticate macro-CK. The current CK-MB kits (both local and international) neither mention this limitation nor offer any solution for this limitation. Hence, the reason, reporting %CK-MB, is clinically superior and yields additional clinically useful information. References
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