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Creatinine Kinase (CK) isoenzymes for Acute Coronary Syndrome (ACS); Lactate Dehydrogenase (LDH) isoenzymes for ACS MB: Optimal Testing Recommendations
Creatinine Kinase isoenzymes and Lactate Dehydrogenase isoenzymes are no longer recommended for acute coronary syndrome diagnosis or monitoring. Please use high sensitivity cardiac Troponin I or Troponin T assays.
Guidelines for Test Utilization
- What does the test tell me?
- When should I order this test?
- When should I NOT order this test?
- How should I interpret the result?
- Is the test result diagnostic/confirmatory of the condition? If not, is there a diagnostic/confirmatory test?
- Are there factors that can affect the lab result?
- Are there considerations for special populations?
- What other test(s) might be indicated?
What does the test tell me?
CK is an enzyme found in muscles. The level of total CK rises when there is muscle damage. CK isoenzyme test reports total CK concentration and the percentages of CK isoforms: BB (CK-1), MB (CK-2), and MM (CK-3), as well as the percentage of macro CK if present. CK isoenzyme test may help pinpoint where the muscle damage has taken place.
Tissue source of CK isoenzymes.
- CK-MM, skeletal muscle and heart
- CK-MB, found in the heart and the level increases when heart muscle is damaged
CK-BB, found mostly in the brain. It's also found in smooth muscles such as the intestine or uterus.
LDH isoenzymes are found in many tissues in the body, including the heart, red blood cells, liver, kidneys, brain, lungs, and skeletal muscles. The rise in LDH level and certain isoenzymes indicates damaged or diseased tissue.
LDH exists in 5 isoenzymes, each with a slightly different structure and is found in different concentrations in different tissues.
- LD1: Heart, red blood cells, kidney
- LD2: Heart, red blood cells, kidney (less than LD1)
- LD3: Lungs and other tissues
- LD4: White blood cells, lymph nodes, muscle, liver (less than LD5)
LD5: Liver, skeletal muscle
When should I order this test?
While historically used for this purpose, CK-isoenzymes are no longer useful for monitoring patients undergoing cardiac procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).
LDH isoenzymes are no longer utilized in assessing tissue damage and identifying the source of cellular injury in liver diseases, hemolytic anemia, megaloblastic anemia, and muscular dystrophy. [back to top]
When should I NOT order this test?
Do not order CK isoenzymes or LDH isoenzymes in the diagnosis or management of ACS. [back to top]
How should I interpret the result?
Increase in CK-MB has been reported in myocarditis, some instances of cardiomyopathy, extensive rhabdomyolysis, Duchenne muscular dystrophy, malignant hyperthermia, and other tissue damages. CK-MB generally does not show abrupt rise and fall in non-acute myocardial infarction (MI) settings, as opposed to acute MI.
CK-BB can be elevated in severe shock and/or hypothermia, infarction of bowel, brain injury, and stroke.
LD1:LD2 inversion (when there is greater increase in LD1 than LD2) is seen in acute MI as opposed to the normal ratio (<1.0) seen in hemolytic anemia and megaloblastic anemia (folate deficiency, pernicious anemia).
An increase in LD5 and particularly increase in LD5:LD4 ratio is seen in striated muscle lesions such as trauma and in liver diseases including hepatitis and cirrhosis.
If there are 2 diseases that have caused more than 1 LDH isoenzyme to rise, 1 disease could be masked by the other. [back to top]
Is the test result diagnostic/confirmatory of the condition?
No. CK isoenzymes or LDH isoenzymes are not sensitive or specific markers for the diagnosis of MI. Instead, high sensitivity cardiac Troponin testing is recommended for diagnosis and management of ACS. [back to top]
Are there factors that can affect the lab result?
Exercise, intramuscular injections, myxedema, grand mal seizures, prior trauma or surgery can lead to increased total CK but usually normal CK-MB.
Hemolysis contamination results in elevation of total LDH.
Strenuous exercise could lead to elevated LD1, LD2 and LD5.
Anesthetics, aspirin, and narcotics can elevate LDH. Ascorbic acid (vitamin C) can decrease LDH levels.
Bacterial pneumonia increases total LDH, while acute pulmonary edema may raise LD5.
Macroenzyme complexes occur with both CK and LDH.
Streptokinase therapy was found to produce an LD-streptokinase band at the origin in electrophoresis.
Are there considerations for special populations?
Marathon runners tend to have higher CK-MB than others. Elderly people with low muscle mass have lower CK-MB levels.
A variety of malignant tumors are characterized by an increase in total LDH as an isomorphic pattern or with greater increase in LD5.
LD1 increase is associated with testicular seminoma and non-seminomatous testicular tumors. The ovarian equivalent of seminoma, dysgerminoma, may also be associated with LD1 increase. [back to top]
What other test(s) might be indicated?
For liver disease or injury investigation, these tests are indicated: aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, and prothrombin time.
For aacute MI high sensitivity cardiac troponin I or T is the test of choice.
To differentiate hemolytic anemia, other tests of option include haptoglobin and plasma free hemoglobin. [back to top]
References
Kavsak PA, Macrae AR, Newman AM, Lustig V, Palomaki GE, Ko DT, Tu JV, Jaffe AS. Effects of contemporary troponin assay sensitivity on the utility of the early markers myoglobin and CKMB isoforms in evaluating patients with possible acute myocardial infarction. Clin Chem Acta. 2007;380(1-2):213-6.
Saenger AK, Jaffe AS. Requiem for a heavyweight: the demise of the creatine kinase-MB. Circulation. 2008;118(21):2200-6.
Volz KA, McGillicuddy DC, Horowitz GL, Sanchez LD. Creatine kinase-MB does not add additional benefit to a negative troponin in the evaluation of chest pain. Am. J. Emerg. Med. 2012; 30, 188–190.
Jialal I, Sokoll LJ. Clinical Utility of Lactate Dehydrogenase: A Historical Perspective. American Journal of Clinical Pathology, 2015; 143(2): 158–159.
Last reviewed: March 2026. The content for Optimal Testing: the Association for Diagnostics & Laboratory Medicine’s (ADLM) Guide to Lab Test Utilization has been developed and approved by the Academy of Diagnostics & Laboratory Medicine and ADLM’s Science and Practice Core Committee.
As the fields of laboratory medicine and diagnostic testing continue to grow at an incredible rate, the knowledge and expertise of clinical laboratory professionals is essential to ensure that patients receive the highest quality and most useful laboratory tests. ADLM’s Academy and Science and Practice Core Committee have developed a test utilization resource focusing on commonly misused tests in hospitals and clinics. Improper test utilization can result in poor patient outcomes and waste in the healthcare system. This important resource geared toward medical professionals recommends better tests and diagnostic practices. Always consult your laboratory director to make sure these recommendations are appropriate for your patient population.