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| Year : 2010 | Volume
: 56
| Issue : 3 | Page : 226-228 |
Clinically effective CK-MB reporting: How to do it?
S Vivekanandan1, R Swaminathan2
1 Department of Clinical Biochemistry, Global Hospitals & Health City, Chennai, India
2 Department of Chemical Pathology, Guy's & St. Thomas Hospitals NHS Trust, London SE1 7EH, United Kingdom
| Date of Submission | 26-Feb-2009 |
| Date of Decision | 22-Nov-2009 |
| Date of Acceptance | 23-May-2010 |
| Date of Web Publication | 23-Aug-2010 |
Correspondence Address:
S Vivekanandan
Department of Clinical Biochemistry, Global Hospitals & Health City, Chennai
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0022-3859.68646
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
How to cite this article:
Vivekanandan S, Swaminathan R. Clinically effective CK-MB reporting: How to do it?. J Postgrad Med 2010;56:226-8 |
| :: 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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