In which clinical scenarios can elevated Creatine Kinase (CK) levels be seen?

Clinical Scenarios with Elevated Creatine Kinase (CK)

Cardiac Causes

Elevated CK-MB occurs most importantly in acute myocardial infarction, though cardiac troponins have now replaced it as the preferred biomarker due to superior cardiac specificity. 1

• Acute myocardial infarction causes significant CK-MB elevation, with levels peaking 24 hours after symptom onset and remaining elevated for up to 48 hours 1, 2
• Myocarditis, cardiac contusion, and cardiotoxic agents (such as anthracyclines) cause CK-MB elevation through direct myocardial injury 1, 3
• Cardiac surgery, ablation, pacing, or defibrillator shocks elevate CK-MB through procedural trauma—post-PCI MI is diagnosed when CK-MB rises ≥10× upper limit of normal within 48 hours with normal baseline 3, 4
• Stress (Takotsubo) cardiomyopathy and severe aortic valve disease can cause supply-demand mismatch leading to myocardial injury and CK elevation 1
• Cardiopulmonary resuscitation elevates both total CK and CK-MB through physical injury from chest compressions and electrical injury from defibrillation, with positive correlations between enzyme levels and both number of compressions (p<0.001) and joules administered (p<0.001) 5

Skeletal Muscle Injury and Exercise

Strenuous exercise, particularly eccentric contractions like downhill running or marathon racing, commonly elevates total CK with levels peaking 24 hours post-exercise and gradually returning to baseline with rest. 3, 6

• Marathon runners show substantially elevated CK-MB activities (91±30 U/L at 24 hours), often higher than post-MI levels (46±38 U/L), though the percentage of CK-MB remains similar (7.0% vs 7.2%) 7
• Weight-bearing exercises and prolonged ultradistance running cause the highest post-exercise serum CK activities through sarcomeric damage 6
• CK clearance is significantly prolonged following marathon races (T½ CK: 49 hours; T½ CK-MB: 29 hours) compared to post-MI (T½ CK: 27 hours; T½ CK-MB: 12 hours), suggesting skeletal muscle as the CK-MB source 7
• Individual variability exists—some athletes are "high responders" with chronically elevated CK levels, while others are "low responders" with persistently low values despite similar training 3, 6
• Acute skeletal muscle trauma elevates both total CK and CK-MB isoform ratios (MB2/MB1), making early MI diagnosis challenging within the first 12 hours 2

Neuromuscular and Genetic Disorders

Muscular dystrophies, particularly Duchenne/Becker carriers and limb-girdle muscular dystrophies, must be considered in patients with persistent hyperCKemia regardless of symptom presentation. 3, 8

• Duchenne/Becker muscular dystrophy carriers—even asymptomatic girls without family history—can present with persistently elevated CK, with 85.7% of symptomatic and 57.1% of asymptomatic girls having muscular dystrophy in one series 8
• Glycogen storage diseases (such as Pompe disease) and sarcoglycanopathies (LGMDR4) cause CK elevation through progressive muscle fiber breakdown 3, 8
• Inflammatory myopathies including dermatomyositis and polymyositis elevate CK alongside other muscle enzymes (aldolase, AST, ALT, LDH) 3, 9
• Persistently increased CK levels in apparently healthy individuals may represent pre-clinical stages of muscle disease, though most cases of isolated hyperCKemia do not imply disease 6

Medication-Induced and Metabolic Causes

• Statin-associated myopathy causes CK elevation, with discontinuation recommended when CK >10× ULN with muscle symptoms to prevent progression to rhabdomyolysis 3, 9
• Rhabdomyolysis (CK typically >10× ULN) occurs from severe muscle breakdown with risk of acute kidney injury, requiring immediate hospitalization and aggressive hydration 3, 9
• Immune checkpoint inhibitor-related myositis can cause rapidly progressive CK elevation (≥3× ULN), requiring immediate therapy discontinuation and corticosteroid initiation 9

Non-Ischemic Cardiac and Systemic Conditions

• Severe tachyarrhythmias or bradyarrhythmias cause supply-demand mismatch leading to myocardial injury and troponin/CK elevation 1
• Aortic dissection, severe pulmonary embolism, and sepsis can elevate cardiac biomarkers through various mechanisms of myocardial stress 1
• Renal failure causes chronic troponin elevation (though typically stable, not rising/falling), while CK elevation may reflect uremic myopathy 1, 9
• Severe acute neurological diseases (stroke, subarachnoid hemorrhage) and seizures can elevate CK through muscle activity or neurogenic mechanisms 1, 2

Critical Interpretation Pitfalls

A rising and/or falling pattern of CK-MB distinguishes acute injury from chronic elevation, though this pattern may be absent in late presentations near the peak or on the declining portion of the time-concentration curve. 1

• CK-MB lacks cardiac specificity compared to troponins, as it is present in skeletal muscle and falsely elevated in numerous non-cardiac conditions 1, 4
• Elevated CK-MB in trained athletes should not be automatically attributed to exercise without excluding pathological causes, particularly when values remain elevated after 72 hours of rest 6, 7
• Pre-analytic and analytic problems can induce falsely elevated or reduced cardiac marker values, requiring careful interpretation in clinical context 1, 3