Association between statin-associated myopathy and skeletal muscle damage
Open accessAbstract
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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No clear correlation between plasma creatine kinase and statin-induced myopathy has been demonstrated, indicating that plasma creatine kinase is not a sensitive marker for statin-induced myopathy.
“no clear correlation between plasma CK and statin‐induced myopathy has yet been demonstrated, indicating that plasma CK would not be regarded as a sensitive marker for statin‐induced myopathy.37, 38”
From Effects of Coenzyme Q10 on Statin‐Induced Myopathy: An Updated Meta‐Analysis of Randomized Controlled Trials (2018) · cites this paper as [38]
Muscle biopsy studies in a limited number of patients with SAMS and normal CK levels suggested a role for abnormal mitochondrial function.
“Muscle biopsy studies in a limited number of patients with SAMS and normal CK levels suggested a role for abnormal mitochondrial function.80,81”
One study showed muscle injury in 25 of 44 patients with myopathy and in one patient taking statin without myopathy.
“One study showed muscle injury in 25 of 44 patients with myopathy and in one patient taking statin without myopathy,81”
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- Authors
- Mohaupt, M. G., Karas, R. H., Babiychuk, E. B., Sanchez-Freire, V., Monastyrskaya, K., Iyer, L., Hoppeler, H., Breil, F., & Draeger, A.
- Affiliations
- University of Bern (CH)
- Venue
- Canadian Medical Association Journal
- Publisher
- CMA Joule Inc.
- Published
- 2009-07-06
- Volume
- 181
- Issue
- 1-2
- Pages
- E11-E18
- ISSN
- 0820-3946 (ISSN-L)
- 1488-2329
- PMC
- PMC2704421
- OpenAlex
- W2148546401
- Cited by
- 166
- References
- 27
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 3 · 2022: 8 · 2021: 5 · 2020: 2 · 2019: 15 · 2018: 9 · 2017: 8 · 2016: 13 · 2015: 9 · 2014: 19 · 2013: 15 · 2012: 12
- FWCI
- 18.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Canadian Medical Association Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (121980, 320000, 3100A0_121980/1, 111778, 405340-104679/1, NRP 53, 104679, 3100A0)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Surgery › Muscle and Compartmental Disorders
- Keywords
- statin-induced myopathy, statins, skeletal muscle injury, muscle biopsy, creatine kinase, myalgia, muscle weakness, vastus lateralis
- MeSH terms
- Adult, Aged, Aged, 80 and over, Biopsy, Creatine Kinase, Female, Follow-Up Studies, Humans, Hypercholesterolemia, Immunohistochemistry, Male, Microscopy, Electron, Microscopy, Fluorescence, Middle Aged, Muscular Diseases, Myofibrils, Prognosis, RNA, Gene Expression, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Ryanodine Receptor Calcium Release Channel, Reverse Transcriptase Polymerase Chain Reaction, Quadriceps Muscle, Young Adult
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