What is the difference between Creatine Kinase (CK) and Creatine Kinase-MB (CKMB)?

Differences Between Creatine Kinase (CK) and Creatine Kinase-MB (CKMB)

Creatine Kinase-MB (CKMB) is a cardiac-specific isoenzyme of Creatine Kinase (CK), with CKMB being more specific but less sensitive than cardiac troponins for detecting myocardial injury, while total CK is a non-specific marker found in both cardiac and skeletal muscle. 1

Basic Characteristics and Structure

• CK is a cytosolic carrier protein for high-energy phosphates found in various tissues including striated muscle, smooth muscle, and brain 1, 2
• CK exists in three cytoplasmic isoenzyme forms: CK-MM (predominantly in skeletal muscle), CK-MB (predominantly in cardiac muscle), and CK-BB (predominantly in brain tissue) 2
• CK-MB is a specific isoenzyme that has historically been the standard marker for myocardial infarction diagnosis before troponins became available 1

Tissue Distribution and Specificity

• CK-MB is found primarily in cardiac muscle, with concentrations averaging 202 ng/U in myocardium compared to only 0.9-44 ng/U in skeletal muscles 3
• Total CK is found in high concentrations in both cardiac and skeletal muscle, making it less specific for cardiac injury 1
• Low levels of CK-MB can be found in the blood of healthy persons, and elevated levels can occur with damage to skeletal muscle, limiting its absolute cardiac specificity 1
• CK-MB typically constitutes about 16% of total CK release in myocardial infarction without skeletal muscle injury 4

Clinical Utility and Diagnostic Value

• CK-MB is more specific for myocardial injury than total CK but less specific and sensitive than cardiac troponins 1
• The CK-MB index (ratio of CK-MB mass to total CK activity) helps differentiate between cardiac and skeletal muscle injury - values >5.0 are diagnostic of myocardial infarction while values <3.0 virtually exclude this diagnosis 5
• CK-MB has a shorter half-life than troponin, making it useful for detecting early reinfarction (recurrent MI) when troponin levels are still elevated from the initial event 1
• CK-MB is also valuable in diagnosing periprocedural myocardial infarction following interventions, as its diagnostic and prognostic value has been extensively validated in these situations 1

Time Course and Release Kinetics

• Both CK and CK-MB can be detected in blood 4-6 hours after myocardial injury, with peak levels occurring at 18-24 hours 1
• CK-MB has a faster release rate from damaged myocardium compared to total CK 4
• CK-MB returns to normal within 36-48 hours, while troponins may remain elevated for 5-14 days 1
• This shorter half-life of CK-MB compared to troponin allows for detection of reinfarction that might be missed if only troponin is measured 1

Current Role in Clinical Practice

• Cardiac troponins have largely replaced CK-MB as the preferred biomarker for diagnosing myocardial infarction due to their superior sensitivity and specificity 1
• CK-MB remains useful in specific clinical scenarios:
  • Diagnosis of reinfarction (due to its shorter half-life) 1
  • Evaluation of periprocedural myocardial injury during cardiac interventions 1
  • Timing of myocardial injury when the exact onset is unclear 1

Measurement Considerations

• CK-MB should be measured by mass immunoassays rather than older methods for optimal accuracy 1
• The CK-MB/total CK ratio (CK-MB index) with a cutoff value of 80 ng/U is recommended for differentiating myocardial necrosis from skeletal muscle injury 3
• Point-of-care testing systems are available for both markers but require stringent quality control 1

Common Pitfalls and Caveats

• Elevated total CK without elevated CK-MB suggests skeletal muscle injury rather than cardiac injury 1
• Elevated CK-MB can occur in severe skeletal muscle damage even without cardiac involvement, particularly in conditions like rhabdomyolysis 5
• Patients with three-vessel coronary disease may have higher CK-MB/CK ratios during myocardial infarction than those with 1-2 vessel disease 6
• Pre-infarction beta-blocker therapy may result in lower relative CK-MB levels during myocardial infarction 6
• Older non-specific markers like alanine transaminase, aspartate transaminase, and lactate dehydrogenase should be avoided for cardiac evaluation in contemporary practice 1