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

From the Guidelines

Elevated creatine kinase (CK) levels can result from various conditions that cause muscle damage or increased muscle activity, including strenuous exercise, muscle trauma, rhabdomyolysis, medications such as statins, and medical conditions like muscular dystrophies and myocardial infarction. The most common causes of elevated CK levels include:

• Strenuous exercise
• Muscle trauma
• Rhabdomyolysis (severe muscle breakdown)
• Medications such as statins (like atorvastatin, simvastatin), certain antibiotics, and antipsychotics
• Medical conditions including muscular dystrophies, polymyositis, dermatomyositis, and myocardial infarction (heart attack) Other causes of elevated CK levels include:
• Seizures
• Electrolyte abnormalities
• Hypothyroidism
• Certain infections
• Alcohol abuse and illicit drug use, particularly cocaine and amphetamines When evaluating elevated CK, it's essential to consider recent physical activity, medication history, and symptoms of muscle pain or weakness, as noted in studies such as 1 and 1. CK is an enzyme primarily found in muscle cells that leaks into the bloodstream when muscle damage occurs, which explains why such diverse conditions can cause its elevation. The degree of elevation often correlates with the extent of muscle damage, with mild elevations (under 1,000 U/L) commonly seen after exercise while severe elevations (over 10,000 U/L) suggest significant muscle injury requiring prompt medical attention, as discussed in 1. It's also important to note that the interpretation of CK levels can be complex, and other factors such as ethnicity, body composition, and exercising with different individual intensities can lead to highly individual kinetics and time points of peak CK levels, as mentioned in 1. Therefore, a thorough evaluation of the patient's medical history, physical activity, and symptoms is necessary to determine the cause of elevated CK levels and provide appropriate treatment.

From the FDA Drug Label

Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred The risk of myopathy is increased by high levels of statin activity in plasma. Predisposing factors for myopathy include advanced age (≥65 years),female gender, uncontrolled hypothyroidism, and renal impairment. IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment;

The causes of elevated creatine kinase (CK) levels include:

• Myopathy: muscle pain, tenderness, or weakness associated with elevated CK
• Rhabdomyolysis: a severe form of myopathy with muscle breakdown and release of myoglobin into the blood
• Immune-mediated necrotizing myopathy (IMNM): an autoimmune myopathy characterized by proximal muscle weakness and elevated serum CK
• Advanced age (≥65 years)
• Female gender
• Uncontrolled hypothyroidism
• Renal impairment
• High levels of statin activity in plasma
• Concomitant use with certain other drugs 2
• Higher atorvastatin calcium dosage 2
• Concomitant intake of large quantities, more than 1.2 liters daily, of grapefruit juice 2
• Drug interactions due to inhibition of cytochrome P450 enzyme 3A4 (CYP3A4) and/or transporters 2

From the Research

Causes of Elevated Creatine Kinase (CK) Levels

Elevated CK levels can be caused by various factors, including:

• Muscle damage or injury, which can occur due to intense physical exercise 3
• Myopathy, a condition characterized by muscle weakness and wasting, which can be caused by statin therapy 4, 5, 6
• Immune-mediated necrotizing myopathy (IMNM), a rare condition caused by autoantibodies against HMG-CoA reductase, often associated with statin use 5, 6
• Hypothyroid myopathy, a condition characterized by muscle weakness and elevated CK levels, caused by hypothyroidism 7
• Muscular dystrophy, a group of genetic disorders characterized by progressive muscle weakness and wasting 3
• Myositis, inflammation of the muscles, which can cause elevated CK levels 5
• Statin-induced necrotising autoimmune myopathy (SINAM), a rare complication of statin therapy, characterized by significant proximal muscle weakness and raised CK levels 6

Other Factors that Can Affect CK Levels

Other factors that can affect CK levels include:

• Ethnicity, age, and gender, which can influence enzyme tissue activity and subsequent CK serum levels 3
• Physical activity, which can cause muscle damage and elevate CK levels 3
• Certain medications, such as statins, which can cause myopathy and elevate CK levels 4, 5, 6