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Statin-Associated Myopathy with Normal Creatine Kinase Levels
- Paul S. Phillips, MD; and
- Richard H. Haas, MD
- Scripps Mercy Hospital; San Diego, CA 92103 (Phillips) University of California, San Diego; La Jolla, CA 92093-0935 (Haas)
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IN RESPONSE:
Dr. Hyman asks whether other biochemical markers might identify patients with statin-induced myopathy. Levels of aldolase and myoglobin, which would be released by disrupted myocyte membranes, have been normal whenever we have tested them in our patients. We are currently testing other indicators of the metabolic defect associated with this muscle toxicity (1).
Drs. Torgovnick and Arsura inquire about the relation of this toxicity to exercise. Postexercise creatine kinase level is more sensitive than resting creatine kinase level in assessing muscle toxicity. The latter is related to membrane disruption but has not met with much success in assessing statin toxicity (2, 3). We required that all study patients maintain a consistent exercise and dietary regimen during the 5-month evaluation. Although all of the creatine kinase evaluations were performed after exercise, they were not performed late enough (6 to 12 hours later) to make this a sensitive test. We believe that the preoccupation with muscle membrane abnormalities and elevation of creatine kinase levels as indicators of toxicity has delayed the detection of the metabolic toxicity we described. Other afflictions with similar pathologic characteristics—mitochondrial myopathies, for example—cause significant abnormalities in muscle function without disrupting membranes sufficiently to elevate creatine kinase levels. We suspect that further evaluation of metabolic defects in patients with statin myotoxicity will prove more fruitful than repeated attempts to evaluate this abnormality from the perspective of muscle membrane toxicities or rhabdomyolysis.
The comments of Dr. Toma and Ms. Loignon and Dr. Teichholz regarding the possible relationships of carnitine and coenzyme Q10 to statin myotoxicity are correct. While we found no depression in either serum or muscle carnitine levels in our patients, measurement of coenzyme Q10 may be more productive. Muscle coenzyme Q10 levels correlated with toxicity in one of the three patients in our study who underwent muscle biopsy, both while myopathic and again when toxicity had resolved. We have a report in preparation that discusses measurement of coenzyme Q10 level in a series of 50 muscle biopsy specimens from patients under evaluation for statin myotoxicity. The results of that study should provide further impetus for future trials assessing coenzyme Q10 and carnitine.
Statins are the best therapy available to reduce cardiovascular end points in patients with atherosclerotic risks. The optimal use of these agents requires a thorough understanding of their toxicities as well as of their efficacy. We agree that we know too little about the mechanism and pathophysiology of statin myotoxicity and that further clinical evaluations and biochemical description are essential.
Richard H. Haas, MD
University of California, San Diego; La Jolla, CA 92093-0935
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
