Interpretation of creatine kinase and aldolase for statin-induced myopathy: Reliance on serial testing based on biological variation

Background: Statins are widely used drugs to reduce LDL cholesterol and risk for cardiovascular disease. Varying degrees of myopathies occur with statin use, ranging from mild myalgic symptoms alone to documented muscle damage and rhabdomyolysis. The activity of creatine kinase (CK) above a population-based reference range has been used to differentiate myalgias from documented myositic injury due to statins. However, because normal ranges for CK depend on gender, exercise, and ethnicity and are necessarily broad, it is possible for a patient to have myositic injury with a result that is within the reference range. Therefore, serial testing relative to baseline levels may be more effective in detecting mild increases in CK. Methods: To properly interpret results of serial testing, we determined the biologic variation of CK and aldolase, another enzyme released from muscle, from biweekly blood collections for 8 weeks from 17 healthy subjects. Results: Using log transformation, we calculated a reference change value of about + 140% and - 60% for both CK and aldolase. Conclusions: The use of calculated RCV could help to improve the detection of those statin side effects promoting variation in CK values, which must be determined in clinical studies. The clinical significance of detecting more cases of statin-induced myopathy must also be examined. (C) 2008 Elsevier B.V. All rights reserved.