Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Article type: Research Article
Authors: Hou, Tieyinga; 1 | Li, Yilana; 1 | Chen, Weiweib | Heffner, Reid R.a | Vladutiu, Georgirene D.c; d; *
Affiliations: [a] Department of Pathology and Anatomical Sciences, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA | [b] Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA | [c] Departments of Pediatrics, Neurology, and Pathology and Anatomical Sciences, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA | [d] Kaleida Health Laboratories, Buffalo, NY, USA
Correspondence: [*] Correspondence to: Georgirene D. Vladutiu, PhD, Room A-767, 100 High Street, Buffalo, NY 14203, USA. Tel.: +1 716 859 7741; Fax: +1 716 859 7749; E-mail: gdv@buffalo.edu.
Note: [1] Co-first authors: These authors contributed equally to this paper.
Abstract: Background: Statins have well-known benefits in the prevention of cardiovascular disease, however, 7–29% of patients develop muscle side effects and up to 0.5% develop severe symptoms. Mitochondrial dysfunction has been associated with severe statin-induced myopathy (SM); however, there is a paucity of systematic studies in affected individuals. Objectives: The goal of this study was to combine clinical and laboratory features with quantitative biochemical and histopathologic studies of skeletal muscle biopsies from SM cases to determine what proportion could be attributed to mitochondrial dysfunction and how many of these had primary respiratory chain defects. Methods: A retrospective analysis was performed on patient records derived from 279 SM patients whose muscle biopsies were referred to our clinical diagnostic laboratory for analysis. Clinical, histopathologic and biochemical features were compared with two myopathic control groups unexposed to statins: individuals with idiopathic mitochondrial myopathy (MMP; n = 94) and with unknown metabolic myopathy (UMP; n = 86); normal controls were unavailable for this record review study. Results: More SM patients had significantly elevated plasma CK than in the other two groups (p < 0.01). A subset of SM patients (67 of 279; 24%) had histopathologic and/or electron microscopic (EM) evidence for mitochondrial dysfunction in skeletal muscle; more cases were identified by EM than by histochemical analysis. Of 279 cases, 29 (10%) were confirmed to have respiratory chain defects by biochemical analysis; 4 of these had mitochondrial abnormalities by EM. An additional 20 cases had mitochondrial abnormalities by EM without a biochemical diagnosis. Conclusions: Both primary and secondary mitochondrial dysfunction was found in subsets of SM patients. The fact that respiratory chain defects were not found in most cases with histopathologic mitochondrial abnormalities does not rule out primary mitochondrial disease in these cases, however, it is more likely that secondary effects on mitochondrial structure and function have occurred; molecular analysis may be helpful only in a small number of cases.
Keywords: Statin myopathy, respiratory chain defect, mitochondrial dysfunction, electron microscopy
DOI: 10.3233/JND-160184
Journal: Journal of Neuromuscular Diseases, vol. 4, no. 1, pp. 77-87, 2017
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
sales@iospress.com
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
info@iospress.nl
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office info@iospress.nl
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
china@iospress.cn
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
如果您在出版方面需要帮助或有任何建, 件至: editorial@iospress.nl