What can cause 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 intense exercise, muscle trauma, medications like statins, alcohol abuse, and certain medical conditions, as supported by recent studies 1. The causes of elevated CK levels can be categorized into several groups, including:

• Intense exercise, particularly eccentric exercises or unaccustomed workouts, which can temporarily raise CK levels as muscle fibers break down 1
• Muscle injuries from accidents, falls, or surgeries, which release CK into the bloodstream 1
• Medications such as statins, colchicine, and some antipsychotics, which can cause muscle damage as a side effect 1
• Medical conditions including muscular dystrophies, inflammatory myopathies, rhabdomyolysis, seizures, heart attacks, and certain infections, which may also elevate CK 1
• Prolonged immobilization, electrolyte imbalances, and genetic disorders affecting muscle metabolism, which can contribute to elevated CK levels as well 1 CK elevation occurs because this enzyme, normally contained within muscle cells, leaks into the bloodstream when muscle cell membranes are damaged. The degree of elevation often correlates with the extent of muscle damage, with mild elevations (2-5 times normal) being less concerning than severe elevations (>10 times normal), which may indicate significant muscle breakdown requiring prompt medical attention 1. It is essential to consider the clinical context and other diagnostic markers, such as myoglobin and plasma creatinine, to accurately interpret CK levels and guide management decisions 1. In patients with severe limb trauma, elevated CK levels can be a sign of rhabdomyolysis and compartment syndrome, and prompt therapeutic intervention is crucial to reduce morbidity and mortality 1. Overall, a comprehensive understanding of the causes and clinical implications of elevated CK levels is necessary for optimal patient care.

From the FDA Drug Label

Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevations of creatine phosphokinase levels. The use of fibrates alone, including fenofibrate tablets, may occasionally be associated with myopathy. Treatment with drugs of the fibrate class has been associated on rare occasions with rhabdomyolysis, usually in patients with impaired renal function

Elevated Creatine Kinase (CK) levels can be caused by:

• Myopathy associated with statin use, including atorvastatin calcium
• Rhabdomyolysis, a rare but serious condition that can occur with statin use, including atorvastatin calcium
• Fibrate use, including fenofibrate tablets, which may occasionally be associated with myopathy and rhabdomyolysis, usually in patients with impaired renal function 2 3

From the Research

Causes of Elevated Creatine Kinase (CK) Levels

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

• Muscle damage or injury, such as skeletal muscle damage or rhabdomyolysis 4, 5, 6
• Myocardial infarction, as both serum CK activity and CKMB mass concentration may be elevated in patients with myocardial infarction 4
• Macroenzymes, such as macroCKemia, which can cause decreased clearance of CK and lead to elevated CK levels 7
• Use of intramuscular injections and physical restraints, which can result in muscle injury and elevated CK levels 5
• Trauma, inflammation, drug-induced toxicity, genetic disorders, metabolic, endocrine, or rheumatic diseases, which can lead to cell degeneration and leakage of CK and other cellular components 6
• Asymptomatic or pauci-symptomatic creatine kinase elevations (hyperCKemia), which can be caused by various underlying conditions and requires a rational clinical approach to reveal identifiable causes 8

Conditions Associated with Elevated CK Levels

Elevated CK levels have been associated with various conditions, including:

• Neuroleptic Malignant Syndrome (NMS), although raised CK levels are not specific to NMS and can be found in patients without NMS 5
• Rhabdomyolysis, which is defined as CK elevation combined with organ damage and requires immediate diagnostic and therapeutic intervention 6