What are the causes of elevated creatine kinase (CK) cardiac marker levels?

Causes of Elevated CK Cardiac Marker

Elevated creatine kinase (CK) cardiac marker levels can be caused by both cardiac and non-cardiac conditions, with skeletal muscle injury being the most common non-cardiac cause due to CK's poor specificity for cardiac injury. 1

Cardiac Causes

1. Acute Coronary Syndromes

• Myocardial infarction (MI)
• Unstable angina progressing to NSTEMI
• Myocardial damage due to prolonged ischemia

2. Other Cardiac Conditions

• Myocarditis
• Severe congestive heart failure
• Cardiac procedures (PCI, CABG)
• Cardiac contusion (trauma)

Non-Cardiac Causes

1. Skeletal Muscle Injury (Most Common)

• Strenuous exercise, especially eccentric contractions 1
• Trauma or crush injuries
• Intramuscular injections
• Falls and resulting hematomas 2
• Rhabdomyolysis

2. Drug-Induced Elevations

• Statins
• Fibrates
• Cocaine and methamphetamine use 1
  • After cocaine use, increased motor activity, skeletal muscle injury, and rhabdomyolysis can cause CK and even CK-MB elevation in the absence of MI

3. Medical Conditions

• Neuromuscular disorders (though rare, accounting for only about 2% of CK elevations in medical departments) 2
• Malignancies (reported in 11% of cases with elevated CK) 2
• Renal failure
• Hypothyroidism
• Seizures

4. Other Factors

• Surgical procedures
• Chronic high-intensity physical training 3
• Age, gender, race, and muscle mass can influence baseline CK levels 3

Specificity Issues with CK

CK has poor specificity for cardiac injury due to its high concentration in skeletal muscle 1. This is why:

1. Total CK is no longer recommended for diagnosing MI 1
2. CK-MB offers improved specificity but still has limitations:
   • CK-MB constitutes 1-3% of the CK in skeletal muscle 1
   • Present in minor quantities in intestine, diaphragm, uterus, and prostate 1
   • Specificity may be impaired with major injury to these organs 1

Improving Diagnostic Accuracy

To improve diagnostic accuracy when evaluating elevated CK:

1. Use cardiac troponins instead of CK when available - they are more specific and reliable markers of myocardial necrosis 1

2. Calculate the CK-MB index (ratio of CK-MB to total CK):

   • Index >5.0: Diagnostic of myocardial infarction
   • Index <3.0: Virtually excludes myocardial infarction
   • Index >3.0 in a single test: Makes rhabdomyolysis improbable and strongly indicates MI 4

3. Perform serial measurements to document characteristic rise and fall patterns 1

4. Consider timing - CK levels typically begin to rise 5-6 hours after onset of chest pain in MI, peak at 24 hours, and return to normal within 24-36 hours 1, 5

Clinical Perspective

In a medical department study, the prevalence of CK elevation was found to be 11.2% of patients, with acute MI accounting for only 32% of these cases. In 61% of cases, at least two potential causes for CK elevation were identified, highlighting its non-specific nature 2.

When evaluating elevated CK, always consider the clinical context, use more specific markers like troponin when available, and remember that a single CK measurement has limited sensitivity (38%) and specificity (80%) for diagnosing MI 6.