Causes of Elevated Creatine Kinase Isoenzymes
Elevated creatine kinase (CK) isoenzymes can result from multiple pathological conditions affecting cardiac, skeletal muscle, and brain tissues, with specific isoenzyme patterns helping to distinguish between different etiologies.
Creatine Kinase Isoenzymes Overview
- CK is an intracellular enzyme found abundantly in skeletal muscle, myocardium, and brain tissue 1
- Three main isoenzymes exist: CK-MM (skeletal muscle), CK-MB (primarily myocardium), and CK-BB (brain) 2
- CK catalyzes the reversible reaction of phosphocreatine to create ATP, playing a critical role in cellular energy production 3
Cardiac Causes of Elevated CK Isoenzymes
Myocardial Injury/Infarction
- Acute myocardial infarction causes significant elevation of CK-MB, which is considered the most important biochemical marker when troponin assays are unavailable 4
- Other cardiac conditions causing CK-MB elevation include:
Interpretation Considerations
- CK-MB is typically measured by mass immunoassays, with elevation defined as measurement above the 99th percentile URL 4
- Sex-specific values should be employed for accurate interpretation 4
- CK-MB has a shorter half-life than troponin, making it useful for diagnosing reinfarction 4
Skeletal Muscle Causes of Elevated CK Isoenzymes
Exercise and Physical Activity
- Strenuous exercise commonly increases CK levels, especially with eccentric contractions 4
- Marathon runners can have CK-MB levels comparable to those seen in acute myocardial infarction patients, arising from skeletal muscle through exertional rhabdomyolysis 5
Muscle Disorders
- Rhabdomyolysis with cardiac involvement 4
- Muscular dystrophies, particularly Duchenne's muscular dystrophy, can elevate CK-MB due to regenerative skeletal muscle fibers 6
- Pompe disease (glycogen storage disease type II) typically presents with elevated CK levels, especially in infantile-onset patients 4
- Other glycogen storage diseases (types IIIa, IV, V, and VII) 4
Trauma and Injury
- Skeletal muscle trauma can cause nonspecific CK elevation 4
- Mechanical stress on muscle results in membrane damage, allowing CK to enter the bloodstream 4
Neurological Causes of Elevated CK Isoenzymes
- Severe acute neurological diseases (e.g., stroke, subarachnoid hemorrhage) 4
- Neurogenic disorders can cause CK elevation 1
Other Causes of Elevated CK Isoenzymes
- Renal failure 4
- Sepsis and critical illness 4
- Severe pulmonary embolism or pulmonary hypertension 4
- Infiltrative diseases (e.g., amyloidosis, sarcoidosis) 4
- Heart failure 4
- Coronary endothelial dysfunction without significant coronary artery disease 4
Clinical Interpretation Considerations
- CK-MB elevation is most helpful clinically when total CK is nonspecifically elevated 6
- Preinfarctional beta-blockade may result in lower CK-MB levels during myocardial infarction 7
- Three-vessel coronary disease is associated with higher peak CK-MB/CK values during acute myocardial infarction compared to 1-2 vessel disease 7
- When assessing for myocardial infarction, a rising and/or falling pattern of CK-MB is needed to distinguish acute from chronic elevations 4
- Lymphatic clearance affects CK kinetics, with activities that influence lymph flow potentially changing measured CK levels 4
Common Pitfalls in CK Isoenzyme Interpretation
- Normal CK-MB levels don't exclude myocardial injury, especially in late presentations 4
- Elevated CK-MB in trained athletes may be misinterpreted as cardiac injury when it actually originates from skeletal muscle 5
- Measuring only enzyme activity rather than mass can underestimate actual muscle damage 4
- Pre-analytic and analytic problems can induce elevated or reduced values of cardiac markers 4
- Some myopathies may present with normal or only marginally raised CK despite significant pathology 1