Statin induced myopathy: Difference between revisions
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* Age more than 80<ref name="pmid19217515">{{cite journal| author=Venero CV, Thompson PD| title=Managing statin myopathy. | journal=Endocrinol Metab Clin North Am | year= 2009 | volume= 38 | issue= 1 | pages= 121-36 | pmid=19217515 | doi=10.1016/j.ecl.2008.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19217515 }} </ref> | * Age more than 80<ref name="pmid19217515">{{cite journal| author=Venero CV, Thompson PD| title=Managing statin myopathy. | journal=Endocrinol Metab Clin North Am | year= 2009 | volume= 38 | issue= 1 | pages= 121-36 | pmid=19217515 | doi=10.1016/j.ecl.2008.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19217515 }} </ref> | ||
* Genetics (single nucleotide polymorphism of the gene SLCO1B1)<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837 }} </ref>*High dose of statin<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837 }} </ref> | * Genetics (single nucleotide polymorphism of the gene SLCO1B1)<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837 }} </ref>*High dose of statin<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837 }} </ref> | ||
* Concurrent use of hepatic cytochrome P450 inhibitors | * Concurrent use of hepatic [[cytochrome P450 inhibitors]] | ||
* Concurrent use of fibrates | * Concurrent use of [[fibrates]] | ||
* Cerivastatin use | * Cerivastatin use especially in combination with [[gemfibrosil]]<ref name="pmid11758079">{{cite journal| author=Hamilton-Craig I| title=Statin-associated myopathy. | journal=Med J Aust | year= 2001 | volume= 175 | issue= 9| pages= 486-9 | pmid=11758079 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11758079 }} </ref>* Major trauma<ref name="pmid11758079">{{cite journal| author=Hamilton-Craig I| title=Statin-associated myopathy. | journal=Med J Aust | year= 2001 | volume= 175 | issue= 9 | pages= 486-9 | pmid=11758079 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11758079 }} </ref> | ||
* Major trauma<ref name="pmid11758079">{{cite journal| author=Hamilton-Craig I| title=Statin-associated myopathy. | journal=Med J Aust | year= 2001 | volume= 175 | issue= 9 | pages= 486-9 | pmid=11758079 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11758079 }} </ref> | |||
*Polypharmacy<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837 }} </ref> | *Polypharmacy<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837 }} </ref> | ||
* Small body size<ref name="pmid19217515">{{cite journal| author=Venero CV, Thompson PD| title=Managing statin myopathy. | journal=Endocrinol Metab Clin North Am | year= 2009 | volume= 38 | issue= 1 | pages= 121-36 | pmid=19217515 | doi=10.1016/j.ecl.2008.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19217515 }} </ref> | * Small body size<ref name="pmid19217515">{{cite journal| author=Venero CV, Thompson PD| title=Managing statin myopathy. | journal=Endocrinol Metab Clin North Am | year= 2009 | volume= 38 | issue= 1 | pages= 121-36 | pmid=19217515 | doi=10.1016/j.ecl.2008.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19217515 }} </ref> | ||
* Surgery<ref name="pmid11758079">{{cite journal| author=Hamilton-Craig I| title=Statin-associated myopathy. | journal=Med J Aust | year= 2001 | volume= 175 | issue= 9 | pages= 486-9 | pmid=11758079 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11758079 }} </ref> | * [[Surgery]]<ref name="pmid11758079">{{cite journal| author=Hamilton-Craig I| title=Statin-associated myopathy. | journal=Med J Aust | year= 2001 | volume= 175 | issue= 9 | pages= 486-9 | pmid=11758079 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11758079 }} </ref> | ||
* Systemic disease | * Systemic disease | ||
**Liver disease | **[[Liver]] disease | ||
**Kidney disease | **[[Kidney]] disease | ||
**Diabetes | **[[Diabetes]] | ||
**Hypothyroidism<ref name="pmid19217515">{{cite journal| author=Venero CV, Thompson PD| title=Managing statin myopathy. | journal=Endocrinol Metab Clin North Am | year= 2009 | volume= 38 | issue= 1 | pages= 121-36 | pmid=19217515 | doi=10.1016/j.ecl.2008.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19217515 }} </ref> | **[[Hypothyroidism]]<ref name="pmid19217515">{{cite journal| author=Venero CV, Thompson PD| title=Managing statin myopathy. | journal=Endocrinol Metab Clin North Am | year= 2009 | volume= 38 | issue= 1 | pages= 121-36 | pmid=19217515 | doi=10.1016/j.ecl.2008.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19217515 }} </ref> | ||
==Pathophysiology== | ==Pathophysiology== | ||
Revision as of 19:47, 28 November 2012
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby
Overview
Definition
Statin induced myopathy is a spectrum of muscular problems caused by the intake of statin. Myopathy by definition is the abnormal function of the muscle. The spectrum of statin induced myopathy includes:
Myalgia
- Myalgia is defined as one or combination of muscle weakness, tenderness or pain.
- Patients usually complain of cramping feeling in the muscles.
- Creatine kinase may be normal or minimally elevated.
Asymptomatic increase in creatine kinase
Myositis
- Myositis is the inflammation of the muscle characterised by muscular complaints in the setting of elevated creatine kinase up to ten folds.
Rhabdomyositis
- Rhabdomyositis is the acute degeneration of the skeletal muscle.
- It is a potentially lethal condition due to its associated nephrotoxicity caused by myoglobinuria and myoglobinemia.
- Creatine kinase is elevated in rhabdomyosistis similarly to myositis.
- The complications of rhabdomyositis are acute tubular necrosis, hypocalcemia, hyperkalemia, metabolic acidosis, hyperuricemia, DIC and cardiomyopathy.[1]
Other Statin Induced Myopathies
- Elevated creatine kinase after statin withdrawal[2]
- Autoimmune myopathy requiring immunosuppressive therapy[3]
Prevalence
The prevalence of statin induced myopathy, described as a spectrum of clinical conditions ranging from myalgia to myositis and rhabdomyolysis, is almost 10-15%[4]
Risk Factors
- Age more than 80[5]
- Genetics (single nucleotide polymorphism of the gene SLCO1B1)[4]*High dose of statin[4]
- Concurrent use of hepatic cytochrome P450 inhibitors
- Concurrent use of fibrates
- Cerivastatin use especially in combination with gemfibrosil[6]* Major trauma[6]
- Polypharmacy[4]
- Small body size[5]
- Surgery[6]
- Systemic disease
- Liver disease
- Kidney disease
- Diabetes
- Hypothyroidism[5]
Pathophysiology
Statin induced myopathies has a complex poorly understood multifactorial pathophysiology. It is postulated that statin causes myopathy through the following changes:
- Changes in cholesterol content and alteration of the membrane fluidity of skeletal muscle cells which disrupts their normal function
- Changes in skeletal muscle cells membrane electrical properties
- Changes in Na+/K+ pump density resulting in decreased production of ATP
- Changes in the excitation-contraction coupling
- Changes in the cell surface receptor transduction cascades
- Decreased synthesis of ubiquinone (Q10), a component of the mitochondrial electron transport chain, leading to decreased ATP production and decreased free radical scavenging
- Increased intracellular calcium causing apoptosis of the skeletal muscle cells[1]
- Decreased mevalonate metabolism products, particularly isoprenoids, leading to a chain of events that culminate in apoptosis of skeletal muscle cells[7]
- Shown below is an image depicting the mechanism of statin induced myopathy through increasing the intracellular calcium concentration.
Treatment
References
- ↑ 1.0 1.1 Baker, S.K. & Tarnopolsky, M.A. (2001). Statin myopathies: pathophysiologic and clinical perspectives. Clin. Invest. Med., 24(5): 258-272.
- ↑ Thompson PD, Clarkson P, Karas RH (2003). "Statin-associated myopathy". JAMA. 289 (13): 1681–90. doi:10.1001/jama.289.13.1681. PMID 12672737.
- ↑ Radcliffe KA, Campbell WW (2008). "Statin myopathy". Curr Neurol Neurosci Rep. 8 (1): 66–72. PMID 18367041.
- ↑ 4.0 4.1 4.2 4.3 Harper CR, Jacobson TA (2010). "Evidence-based management of statin myopathy". Curr Atheroscler Rep. 12 (5): 322–30. doi:10.1007/s11883-010-0120-9. PMID 20628837.
- ↑ 5.0 5.1 5.2 Venero CV, Thompson PD (2009). "Managing statin myopathy". Endocrinol Metab Clin North Am. 38 (1): 121–36. doi:10.1016/j.ecl.2008.11.002. PMID 19217515.
- ↑ 6.0 6.1 6.2 Hamilton-Craig I (2001). "Statin-associated myopathy". Med J Aust. 175 (9): 486–9. PMID 11758079.
- ↑ Dirks AJ, Jones KM (2006). "Statin-induced apoptosis and skeletal myopathy". Am J Physiol Cell Physiol. 291 (6): C1208–12. doi:10.1152/ajpcell.00226.2006. PMID 16885396.