Mohaupt MG, Karas RH, Babiychuk EB, et al. Association between statin-associated myopathy and skeletal muscle damage. CMAJ 2009 Jul 7;181:E11-E18.
http://www.cmaj.ca/cgi/content/abstract/181/1-2/E11
http://www.cmaj.ca/cgi/content/full/181/1-2/E11
http://www.cmaj.ca/cgi/reprint/181/1-2/E11.pdf
key info:
Structural muscle damage may be present in patients with statin-associated myopathy even if the levels of serum creatine phosphokinase are normal. Increased expression of ryanodine receptor 3 may indicate muscle damage in some of these patients.
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CMAJ • July 7, 2009; 181 (1-2). doi:10.1503/cmaj.081785.
© 2009 Canadian Medical Association or its licensors
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
Research
Association between statin-associated myopathy and skeletal muscle damage
Markus G. Mohaupt, MD, Richard H. Karas, MD PhD, Eduard B. Babiychuk, PhD, Verónica Sanchez-Freire, Katia Monastyrskaya, PhD, Lakshmanan Iyer, PhD, Hans Hoppeler, MD, Fabio Breil and Annette Draeger, MD
From the Department of Nephrology and Hypertension (Mohaupt), Inselspital, University of Bern, Bern, Switzerland; the Molecular Cardiology Research Institute and Division of Cardiology (Karas, Iyer), Tufts-New England Medical Center, Boston, USA; and the Institute of Anatomy (Babiychuk, Sanchez-Freire, Monastyrskaya, Hoppeler, Breil, Draeger), University of Bern, Bern, Switzerland
Correspondence to: Dr. Annette Draeger, Institute of Anatomy, University of Bern, Baltzerstr. 2, 3012 Bern Switzerland; fax 41 3163 13807;
Background: Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown.
Methods: We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury.
Results: Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10x the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3).
Interpretation: Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak.
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