Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia

Institute of Anatomy, Department of Cell Biology, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland.
The Journal of Pathology (Impact Factor: 7.43). 09/2006; 210(1):94-102. DOI: 10.1002/path.2018
Source: PubMed


Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable.

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Available from: Katia Monastyrskaya
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    • "Comprehensive interaction of these processes may contribute to development of diabetes by statin and may become more significant in elderly persons with age-dependent loss of β-cells. Also, statin-induced cholesterol lowering per se contributes to myocyte damage of skeletal muscle fiber in a majority of patients, despite their being asymptomatic, which may cause skeletal muscle insulin resistance [41]. Furthermore aging-related skeletal muscle wasting may accelerate statin-induced peripheral insulin resistance [29,42]. "
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    ABSTRACT: Statins are widely prescribed cholesterol-lowering agents, which have been demonstrated to significantly reduce cardiovascular morbidity and mortality. However, recent trials have reported that statins cause worsening of hyperglycemia and increase the risk of new-onset diabetes. The association between the diabetogenic effect of statins with intensive dose and accompanying major risk factors for diabetes has been demonstrated. However, statins do not appear to have a class effect on insulin sensitivity in non-diabetic patients. Numerous mechanisms have been suggested to explain how statins cause β-cell insulin secretory dysfunction and peripheral insulin resistance leading to incident diabetes. According to findings from an aggregate of large clinical trials, the benefits of statin treatment appear to outweigh the risk of new-onset diabetes. Therefore, it would be inappropriate to discontinue the use of statins for prevention of cardiovascular events because of its potential risk for development of incident diabetes. This review addresses the currently available evidence related to statin use and new-onset diabetes from a clinical perspective.
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    • "Adverse muscle reactions are one of the most common reasons for non-compliance with statin therapy [3] [4], and they can have a significant impact on quality of life [5]. The myotoxicity of statins can be mild such as asymptomatic hyperCKaemia [6], and increasing in severity through a spectrum of myalgia without hyperCKaemia, proximal weakness with hyperCKaemia, necrotizing autoimmune myositis (NAM), to severe and at times fatal rhabdomyolysis. "
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    ABSTRACT: The 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors (statins) are among the most common medications prescribed worldwide, but their efficacy and toxicity vary between individuals. One of the major factors contributing to intolerance and non-compliance are the muscle side-effects, which range from mild myalgia through to severe life-threatening rhabdomyolysis. One way to address this is pharmacogenomic screening, which aims to individualize therapy to maximize efficacy whilst avoiding toxicity. Genes encoding proteins involved in the metabolism of statins as well as genes known to cause inherited muscle disorders have been investigated. To-date only polymorphisms in the SLCO1B1 gene, which encodes the protein responsible for hepatic uptake of statins, and the COQ2 gene, important in the synthesis of coenzyme Q10, have been validated as being strongly associated with statin-induced myopathy. The aim of this review is to summarize studies investigating genetic factors predisposing to statin myopathy and myalgia, as the first step towards pharmacogenomic screening to identify at risk individuals.
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    • "However, the level of myoglobin reached with this interaction was far below to cause any renal toxicity. The most prominent cellular damage in myocytes can be seen in the form of disruption of T-tubular system and rupture of sub-sarcoplasma.[8721] The interruption of sarcoplasmic reticulum calcium cycling pathway at mitochondrial level can have varied consequences ranging from apoptosis oxidation injury which interrupt the growth and development of muscular tissue causing muscular toxicity and damage.[21] "
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    ABSTRACT: Statins are being extensively used in cardiac patient throughout the globe. Succinylcholine has been the mainstay of profound relaxation during induction and intubation of anesthesia for almost six decades now. The interactive properties of these drugs have been of major concern during routine anesthesiology practice in the last few years. However, no major research trial, prospective studies or meta-analysis are available, which can truly allay the fears of possible potential negative synergistic interactions between these two commonly used drugs. Whatever the evidence is available is hardly enough to support a positive outcome and the results have been drawn from observations of only few small studies. As a result, a continuous need among anesthesiologist fraternity is felt to arrive at a suitable inference, which can predict definite consequences of this synergistic interaction. The present article reviews some of the important observations of few handful studies which were carried out to observe any potential adverse interactions between succinylcholine and statins.
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