Statins, Muscle Disease and Mitochondria
Radha Ramachandran1,2, Anthony S Wierzbicki3
1Departments of Chemical Pathology/Metabolic Medicine, Guys and St Thomas' Hospitals NHS Foundation Trust, London SE1 7EH, UK. radha.ramachandran@gstt.nhs.uk.
Insights
Cardiovascular disease (CVD) is a major global health issue. This paper explores statin-associated muscle disease (SAMS), a common reason for stopping statin therapy, focusing on mitochondrial dysfunction as a potential cause.
Area of Science:
- Cardiology and Pharmacology
- Biochemistry and Molecular Biology
Background:
- Cardiovascular disease (CVD) causes millions of deaths annually, with dyslipidemia a key factor in atherosclerosis.
- Statins are primary treatments for dyslipidemia, offering significant benefits despite potential adverse events.
- Statin-associated muscle disease (SAMS) is the most frequent reason for statin discontinuation, with varying reported incidences.
Purpose of the Study:
- To review the current understanding of the pathophysiology and mechanisms behind statin-associated muscle disease (SAMS).
- To focus on etiological hypotheses related to mitochondrial dysfunction as the likely cause of SAMS.
Main Methods:
- Literature review of studies investigating statin-associated muscle disease (SAMS).
- Analysis of proposed etiological hypotheses, with a focus on mitochondrial dysfunction.
Main Results:
- Statin-associated muscle disease (SAMS) incidence ranges from 5% to 29%, with severe rhabdomyolysis being rare (approx. 1 in 10,000).
- Mitochondrial dysfunction is implicated as the most probable cause of SAMS.
- The precise mechanisms leading to statin-induced mitochondrial dysfunction remain under investigation.
Conclusions:
- Understanding the mechanisms of SAMS is crucial for optimizing statin therapy.
- Further research into statin-induced mitochondrial dysfunction is needed to elucidate SAMS pathophysiology.
- This review highlights key hypotheses regarding mitochondrial dysfunction in SAMS development.
Abstract:
Cardiovascular disease (CVD) accounts for >17 million deaths globally every year, and this figure is predicted to rise to >23 million by 2030. Numerous studies have explored the relationship between cholesterol and CVD and there is now consensus that dyslipidaemia is a causal factor in the pathogenesis of atherosclerosis. Statins have become the cornerstone of the management of dyslipidaemia. Statins have proved to have a very good safety profile. The risk of adverse events is small compared to the benefits. Nevertheless, the potential risk of an adverse event occurring must be considered when prescribing and monitoring statin therapy to individual patients. Statin-associated muscle disease (SAMS) is by far the most studied and the most common reason for discontinuation of therapy. The reported incidence varies greatly, ranging between 5% and 29%. Milder disease is common and the more serious form, rhabdomyolysis is far rarer with an incidence of approximately 1 in 10,000. The pathophysiology of, and mechanisms leading to SAMS, are yet to be fully understood. Literature points towards statin-induced mitochondrial dysfunction as the most likely cause of SAMS. However, the exact processes leading to mitochondrial dysfunction are not yet fully understood. This paper details some of the different aetiological hypotheses put forward, focussing particularly on those related to mitochondrial dysfunction.
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