The Effect of Statins on Skeletal Muscle Function

Your doctor better know about this and inform you of what you may need to do.
http://circ.ahajournals.org/content/early/2012/11/26/CIRCULATIONAHA.112.136101.abstract?sid=9dbca7c2-cde4-447b-a4c9-9b6b3727da87

Abstract

Background—Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials and the effect of statins on muscle performance has not been carefully studied.

Methods and Results—The Effect of STatins On Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase (CK), exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo were administered for 6 months to 420 healthy, statin-naive subjects. No individual CK value exceeded 10 times normal, but average CK increased 20.8 ± 141.1 U/L (p less than 0.0001) with atorvastatin. There were no significant changes in several measures of muscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 vs 10; p = 0.05). Myalgic subjects on atorvastatin or placebo decreased muscle strength in 5 of 14 and 4 of 14 variables respectively (p = 0.69).

Conclusions—These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average CK suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in CK should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance.

Clinical Trial Registration Information—www.clinicaltrials.gov; Identifier: NCT00609063.

Chemical in many antibacterial soaps linked with impaired muscle function

This rather alarmist headline should provoke some thinking on our part and our medical staff. When I was still doing therapy there were antibacterial stations into every therapy station and  we were expected to use them prior to any therapy. Myself being one-handed I would only ineffectually do my good hand. But that does lead to the question, should  survivors even use this stuff on their affected hands/arms? Research needed, but ask your doctor first.
http://www.foxnews.com/health/2012/08/14/chemical-in-many-antibacterial-soaps-linked-with-impaired-muscle-function/
Only 6 paragraphs here, rest at the link.
Introduced in the 1970s, the compound triclosan has become an increasingly popular ingredient in many antibacterial soaps and other personal-care items, such as deodorants and mouthwashes.  However, as the chemical’s popularity continues to grow, a recent report has raised concerns about some frightening risks that triclosan could pose to public health.
A new study published in the Proceedings of the National Academy of Sciences has revealed that exposure to triclosan is linked with muscle function impairments in humans and mice, as well as slowing the swimming of fish.  By reducing contractions in both cardiac and skeletal muscles, the chemical has the potential to contribute to heart disease and heart failure.
The researchers from the University of California, Davis, and the University of Colorado decided to examine the possible effects of triclosan due to recent literature raising health concerns about the chemical, as well as substantial increases in its production.
“We consider [triclosan] a high volume chemical,” Dr. Isaac Pessah, professor and chair of the Department of Molecular Biosciences in the UC Davis School of Veterinary Medicine, as well as the study’s lead author, told FoxNews.com.  “Its production levels are quite high, and the levels in humans have been increasing since it was first used as an antibacterial agent in the early ‘70s.  So the body levels in humans – including plasma, urine and breast milk – have been steadily increasing.”
“The levels in the environment have been increasing as well, because it can’t all be trapped in the treatment plants,” Pessah added about triclosan’s prevalence.  “[Companies] try to prevent some chemicals getting out past the water treatment plants so they can dispose of them in a different way, but they can’t capture all of [triclosan] because there is so much of it.”
Primarily used in antibacterial hand soaps, triclosan can also be found in a number of bath and household products, including mouthwashes, toothpastes, deodorants, bedding, washcloths and towels, kitchen utensils and toys.

Read more: http://www.foxnews.com/health/2012/08/14/chemical-in-many-antibacterial-soaps-linked-with-impaired-muscle-function/#ixzz23fGn1IRd

Effects of Statins on Energy and Fatigue With Exertion: Results From a Randomized Controlled Trial

So ask your doctor.
 http://archinte.jamanetwork.com/article.aspx?doi=10.1001/archinternmed.2012.2171

No drug is without adverse effect potential, and fatigue and exertional intolerance are adverse effects reported by patients receiving statins.^{1 - 2} Little direct information is available regarding the typical or average impact of statins on energy or exertional fatigue.

Although many observational reports have cited fatigue and exertional fatigue with statin use, to our knowledge, no randomized trials have addressed this issue to date. Energy and exertional fatigue were measured as tertiary and/or exploratory outcomes in the University of California, San Diego (UCSD) Statin Study, which aimed to examine a range of noncardiac outcomes.³ We capitalized on these data to evaluate whether moderate-dose statins affected energy and exertional fatigue in a broadly sampled primary prevention population.

METHODS

Methods

A total of 1016 subjects (692 men 20 years or older and 324 nonprocreative women, with screening low-density lipoprotein cholesterol levels 115-190 mg/dL [to convert to millimoles per liter, multiply by 0.0259] and no cardiovascular disease or diabetes) were randomized equally to 20-mg simvastatin (lipophilic statin), 40-mg pravastatin (hydrophilic statin), or microcrystalline-cellulose placebo, to be taken at bedtime in identical blinding capsules for 6 months.

Methods

The off-site study pharmacist matched sequentially numbered bottles to sequential computer-generated randomization assignment stratified by sex (block size, 20; designed by statistician [H.L.W.]). Bottles were transferred to the study site and given to successive eligible subjects by staff blinded to the randomization schedule.⁴

Methods

The protocol was approved by the UCSD Human Subjects Protection Program. All subjects (seen exclusively at UCSD) gave written informed consent. The data and safety monitoring board provided independent study oversight.

Methods

Outcome

Single-item self-ratings of change from baseline in “energy” and “fatigue with exertion” were used, assessed on 6-month follow-up, and rated (5-point scale) from “much less”(−2) to “much more”(+2) vs baseline.

Outcome

Energy and fatigue with exertion were rated at baseline from 0 (none) to 10 (maximum possible). All subjects rated energy; the final 397 subjects (a randomized subset) rated baseline fatigue with exertion (omitted initially to limit subject burden, restored for the final 40% of subjects). Missing values of baseline and change score were imputed using the Stata “impute” command (StataCorp). “EnergyFatigEx” values were generated by summing ratings for the energy and fatigue with exertion measures, aligning signs with lower values worse (ie, recoding such that for both variables lower values signified worse status), for baseline and on-treatment, yielding a single outcome (on-treatment score range, −4 to +4).

Methods

Statistical Analysis

We assessed the correlation of EnergyFatigEx with actual exercise (baseline assessment: episodes per week of vigorous exercise >20minutes). The unpaired t test was used to examine the difference in mean on-treatment EnergyFatigEx in all subjects and women separately. Ordinal logistic regression with robust (“White”) standard errors⁵ adjusted for baseline values of the combined variable, addressing baseline disparities and regression to the mean (a source of power-eroding variance). The χ² test was used to examine whether statins shifted, relative to placebo, the proportion reporting changes of subjectively large magnitude (“much worse” or “much better” vs placebo on both outcomes; the same principle that guides sign tests). Analyses used Stata statistical software versions 8.0 and 11.0 (StataCorp). A 2-sided α level of .05 designated significance.

RESULTS

Results

For CONSORT (Consolidated Standards for Reporting of Trials) and study baseline characteristics, see eFigure and eTable. Energy and predictors of exertional fatigue were comparable at baseline; however, in the subsample with measured baseline exertional fatigue, pravastatin values differed from other arms and influenced imputed baseline values (Table). There was a significant relation between measured baseline EnergyFatigEx and actual exercise (r = 0.20; P < .001). The drop in low-density lipoprotein cholesterol level with 20-mg simvastatin (49 mg/dL) exceeded that with 40-mg pravastatin (40 mg/dL) (P < .001).

Results

Results of t tests of difference in mean on-treatment change in EnergyFatigEx were significant for combined statins vs placebo. Each statin contributed (effects separately significant for simvastatin) (Table). Women were disproportionately affected. The 0.4 mean difference observed for women receiving simvastatin vs placebo would arise if 4 in 10 treated women cited worsening in either energy or exertional fatigue; 2 in 10 characterized both as “worse” or either as “much worse”; 1 in 10 characterized both components as “much worse”; or combinations of these conditions, with the fractions of subjects for which each statement holds, summing to 1. Adjusted for baseline EnergyFatigEx (via ordinal logit), effects on EnergyFatigEx were significantly unfavorable for combined statins and each statin separately.

Results

The balance of those reporting maximal worsening vs maximal improvement (“much worse” vs baseline on each component vs “much better” on each) was adversely shifted for statins vs placebo (P = .002) and for each statin separately (simvastatin, P = .03; pravastatin, P = .01). These are based on small numbers, and findings are provisional.

COMMENT

Comment

To our knowledge, this is the first randomized evidence affirming unfavorable statin effects on energy and exertional fatigue. Effects were seen in a generally healthy sample given modest statin doses, and both simvastatin and pravastatin contributed to the significant adverse effect of statins on energy and fatigue with exertion. Particularly for women, these unfavorable effects were not uncommon. Findings support case reports citing adverse effects to these outcomes and are buttressed by literature rationale.^{1 ,6} These findings are important, given the central relevance of energy and functional status to well-being.

Comment

These effects, germane to quality of life, merit consideration when prescribing or contemplating use of statins, particularly in groups without expected net morbidity/mortality benefit, extending to “high-risk” primary prevention and women and elderly persons (including those with coronary artery disease).^{7 - 9} There was a significant relation between EnergyFatigEx and actual activity: reduced activity and exertional tolerance (irrespective of activity) in turn predict hard adverse outcomes. Effects may take time to manifest, as may benefits of statin use. Thus, long-term trials are important, if statin use is to be recommended in younger individuals. Meanwhile, physicians should be alert to patients' reports of exertional fatigue or diminished energy during statin use.

A news report on it.
http://www.msnbc.msn.com/id/47772793/ns/health/#.T9bdzsVPGxM

A blogger writing about it.
 http://www.medrants.com/archives/6864

Protective Reflexes Through Sensory Feedback in the Musculoskeletal System

This may explain some of the questions I had on why eStim was only used to contract muscles rather than using it to relax muscles. It only took 5 years to find this out when it should have been available for easy searching years ago. We as stroke survivors need to know this to understand how to direct our own recovery.
http://treatmentfacility.co/protective-reflexes-through-sensory-feedback-in-the-musculoskeletal-system/

Any movement of the musculoskeletal system involves both acceleration and deceleration phases. If acceleration is not precisely controlled, or if deceleration is delayed or not strong enough, the resulting over acceleration of the body part can cause rupture of the muscles, tendons, and even bones. Two types of peripheral nerve cells are involved in this coordination to protect a muscle against unnecessary injury: muscle spindles and tendon spindles. Muscle spindles prevent overstretching of the muscle fibers, and tendon spindles prevent over contraction. Tendinitis, a common injury in athletes, is usually the result of ignoring warnings from these two spindles.

Muscle Spindles

The muscle spindles are located throughout the muscle between regular skeletal muscle fibers. A muscle spindle consists of 4 to 20 small, specialized muscle fibers called intrafusal fibers (inside the spindles), and certain sensory and motor nerve endings are associated with these fibers. A sheath of connective tissues surrounds the muscle spindle and attaches to the endomysium of the extrafusal fibers. The intrafusal fibers are controlled by specialized spinal motor neurons: the γ-motor neurons. Regular muscle fibers are controlled by the larger α-motor neurons of the spinal cord.

The central region of an intrafusal fiber contains no or only a few actin and myosin filaments; therefore, it cannot contract but can only stretch. Because the muscle spindle is attached to the extrafusal fibers, any time those fibers are stretched, the central region of the muscle spindle is also stretched. In other words, when the muscle fibers stretch, so do the muscle spindles.

Sensory nerve endings wrapped around this central region of the muscle spindle transmit information to the spinal cord when this region is stretched, informing the central nervous system about the muscle length. In the spinal cord sensory neurons synapses with an α-motor neuron, which triggers reflexive muscle contraction in the extrafusal fibers to resist further stretching. γ-motor neurons excite the intrafusal fibers, prestretching them slightly. Although the central region of the intrafusal fibers cannot contract, the ends can. The γ-motor neurons cause a slight contraction of the ends of these fibers, which stretches the central region slightly. This prestretch makes the muscle spindle highly sensitive to even small degrees of stretch.

If the muscle stretches enough that there is a risk of rupture, the spindle responds by sending a signal to the muscle to contract. This keeps the muscle from being injured. In response to that stretch, the sensory neurons send action potentials to the spinal cord, which then activates the α-motor neurons of the motor unit in the same muscles to increase the force of contraction to overcome stretching.

After the information is sent to the spinal cord from the sensory neurons associated with muscle spindles, the same signals continue to travel up to higher parts of the central nervous system, supplying the brain with continuous feedback about the exact length of the muscle and the rate at which that length is changing. This information is essential for maintaining muscle tone and posture and for executing movements. The muscle spindle functions as a servo mechanism to provide continuous correction to motion. The brain is simultaneously aware of errors in the intended movement, and so it sends descending commands to correct the muscle contraction at the spinal cord level.

If the muscles are fatigued or injured, as with overtraining, the muscles become shortened to resist physical stretching, the coordination between intrafusal and extrafusal fibers disintegrates, and central commands cannot be executed. If the fatigued or injured muscles are forced to work, worse injury results.

Tendon Spindles

Unlike muscle spindles, the tendon spindles give an inhibiting signal, which prevents the muscle from contracting. Tendon spindles are encapsulated sensory receptors and located just proximal to where the tendon fibers attach to the muscle fibers. Usually, 5 to 25 muscle fibers are connected to each tendon spindle.

Whereas muscle spindles monitor the length of muscle fibers, tendon spindles are sensitive to tension in the muscle-tendon complex and serve as a strain gauge, a way of sensing changes in tension. The tendon spindles are so sensitive that they can respond to the contraction of even a single muscle fiber.

These inhibitory sensory receptors perform a protective function by reducing the potential for injury. When stimulated, tendon spindles inhibit the contracting (agonist) muscles and excite the antagonist muscles.

Coordination between agonist and antagonist muscles is crucial in maintaining normal mechanical balance in the joint, as well as in protecting the muscles from overstretching.

When muscles are fatigued or over trained, they become shorter and less flexible, with soreness or sensation of pain. If these symptoms are ignored and the muscles are forced to work, the stiff muscles will transfer the stress to the tendon, resulting in tendinitis. This indicates that in the treatment of tendinitis, both muscles and tendons should be treated simultaneously.

The above figure illustrates a situation in which reflexes protect the muscles and tendon from injury. If a person moves one arm backwards quickly toward its outermost position to do a powerful throwing action, and if the arm moves backwards too far or with too much speed, there is a risk of muscle or tendon rupture. Normally, the muscle spindles send a warning signal and the muscle contracts; the arm will then stops and turns back before it reaches the critical position. If the muscles are fatigued or injured, this movement will not be controlled precisely, and it is possible to tear or rupture the muscles or tendons.

When a muscle contracts, the tension in the tendons increases. The above picture depicts the direction of the forces sustained in the tendon. This shows how both conflicting forces contribute to tendinitis.

Other Protective Sensory Organs

Additional sensory organs around the joints and in the joint capsules transmit information used to adjust movements and protect the body from injury. The above figure shows three different sensory organs, each of them responsible for sending specific sensory information: Pacinian corpuscles are sensitive to pressure, Ruffini corpuscles are sensitive to position and speed, and the free nerve endings are sensitive to pain.

These sensory organs are distributed in capsules, in perimysium around muscle, and in periosteum around bones. A kick on the tibia can cause severe and immediate pain, but if there is no damage, the pain will disappear in as little as 10 seconds. If an injury such as contusion occurs, the pain-producing substances will be synthesized, and the pain will persist.

Association between statin-associated myopathy and skeletal muscle damage

Ask your doctor about statin side effects, From a review of the article came this:
Since the heart is a muscle there was a concern that there maybe some underlying damage being done to the heart. I asked the lead author, Dr. Annette Draeger, if it was possible that a certain amount of damage maybe occurring in the heart muscle even in patient not experiencing any symptoms? She replied that "That is a very good question. Cardiomyopathy is not a prominent feature in statin users.
http://www.cmaj.ca/content/181/1-2/E11.full?sid=16f82ed0-6ed0-43e0-8e5f-de9d7d9da4b6

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 (10× 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.

Statins are among the most widely prescribed medications worldwide. Although their overall safety profile is excellent, myalgia without functional muscle impairment commonly affects patients taking statins. The clinical manifestations of statin-associated myopathy include pain and muscle weakness. Observational studies have shown a myalgia rate of 10%–15% among patients taking statins. 1^,2 Fulminant and potentially fatal rhabdomyolysis may also occur. Myalgia is typically considered by patients and physicians to be a minor adverse effect. 3^–5 Current consensus guideline support continuation of the statin therapy as long as circulating levels of creatine phosphokinase are less than 1950 U/L (10× the upper limit of normal). 6

We sought to determine whether statin-associated myopathy is associated with underlying structural muscle damage. We investigated whether the extent of muscle damage is reflected by the level of circulating creatine phosphokinase. We also sought to identify alterations in the expression of genes expressed in myocytes, which could provide insight into the cause of statin-associated myopathy.

Methods

Patients

Samples of the vastus lateralis muscle were collected from 83 people in 5 groups. The first control group comprised 10 healthy male volunteers who had never taken statins and who had no complaints of muscle pain (biopsy samples from these patients were obtained for a previous study 7). The second control group included 10 patients who were age-matched to patients in the myopathy group. These patients were each receiving treatment for a condition not related to their muscles. These patients were recruited from a pool of patients in the Department of Nephrology and Hypertension, and they had no history of statin use or muscle complaints. Several patients in this group had hypercholesterolemia but had never taken statins. Biopsy samples were obtained from these patients before they began statin therapy as part of an ongoing longitudinal study.

The third group comprised 15 patients with clinically diagnosed statin-associated myopathy who had discontinued statin therapy (discontinued for a minimum of 3 [median 12] weeks before biopsy). These patients were referred to the Department of Nephrology and Hypertension for alternative treatment options for hypercholesterinemia because they refused to continue statin therapy. These patients reported persistent myalgia or muscle weakness, or both, in the absence of other reasons for muscle disease.

The fourth group included 29 patients who had a history of clinically diagnosed statin-associated myopathy and who were receiving statin therapy at the time of the biopsy. These patients were recruited from the pool of patients in the Department of Nephrology and Hypertension

The fifth group included 19 patients who had received statin therapy for hypercholesterolemia for 4–20 years and were taking statins at the time of the biopsy. These patients had no muscle complaints.

Patients were identified as having statin-associated myopathy by clinical criteria consistent with the recommendations of the Muscle Safety Expert Panel. 3 These patients had persistent complaints of myalgia, cramps or muscle weakness predominately in the trunk or proximal muscle groups. Some reported that their pain worsened with exertion while taking statins and in the absence of other reasons for myopathy. Some patients had elevated serum concentrations of creatine phosphokinase (585–975 U/L [3–5× the upper limit of normal]).

Patients with myopathy (with or without statin use) were referred to the Department of Nephrology and Hypertension by local hospitals or physicians for management of their muscle symptoms. The diagnosis of statin-associated myopathy and decisions about the continued use of statins were made by the clinical team caring for each patient. Patients taking statins without muscle complaints were recruited via advertisements in local newspapers.

The vastus lateralis muscle was biopsied at midthigh level by use of the technique of Bergström. 8 The samples were processed within 10 minutes after excision. Although the vastus lateralis muscle is rarely affected by myalgia, it serves as a reference muscle and is routinely biopsied when systemic muscle pathology is investigated.

This study was conducted with the approval of the ethics committee of the Canton of Bern Switzerland. All patients gave informed consent.

Tissue processing

An average of 3 tissue blocks (about 3 mm − 6 mm) per patient were fixed and processed for semi-thin sectioning and ultrastructural analysis by electron microscopy. All samples were fixed in 6.25% glutaraldehyde solution and embedded in epoxy resin. 9

Immunohistochemistry and ultracryomicrotomy

One or more cylinders of some tissue samples were fixed in 4% paraformaldehyde and processed for ultra-thin frozen sectioning. 10 We labelled the T tubules with a monoclonal antibody against annexin A6 and a secondary polyclonal antibody coupled to Cy3. 10 We viewed the T tubules using a ZEISS Axiophot 2 fluorescence microscope, and we captured photomicrographs using a digital CCD camera (Ultra-pix, Astrocam).

RNA isolation and gene expression

We isolated total RNA from muscle biopsy samples using the RNeasy Fibrous Tissue Kit (Qiagen), according to the manufacturer’s instructions. The samples were treated with DNase I (Qiagen) to avoid genomic DNA contamination. We measured the total RNA concentration by ultraviolet spectrophotometry at 260 nm (DU 530, Beckman Coulter). The purity of the RNA was determined by the ratio of the absorbance at 260 nm to the absorbance at 280 nm and confirmed by agarose gel electrophoresis. We synthesized cDNA using random hexamer primers and the High Capacity cDNA Reverse Transcription Kit (Applied Biosystems).

We analyzed the expression of the following 8 genes that code for proteins located in the T-tubule membrane and adjacent sarcoplasmic reticulum and that are involved in the regulation of intracellular calcium homeostasis: Inositol 1,4,5-triphosphate receptor, type 1 (ITPR1-Hs00181881_m1); inositol 1,4,5-triphosphate receptor, type 2 (ITPR2-Hs00181916_m1); inositol 1,4,5-triphosphate receptor, type 3 (ITPR3-Hs00609908_m1); ryanodine receptor 1 (RYR1-Hs00166991_m1); ryanodine receptor 3 (RYR3-Hs00168821_m1); sarco-endoplasmic reticulum transporting Ca²⁺ ATPase 1 (ATP2A1-Hs00188877_m1); sarco-endoplasmic reticulum transporting Ca²⁺ ATPase 2 (ATP2A2-Hs00544877_m1); and sarco-endoplasmic reticulum transporting Ca²⁺ ATPase 3 (ATP2A3-Hs00193090_m1).

We performed expression studies using validated TaqMan Gene Expression Assays with 18S rRNA as a reference gene. The reactions were performed using the 7900HT Fast Real-Time PCR System (Applied Biosystems). The default program was used (40 cycles, each consisting of 15 seconds at 95°C followed by 1 minute at 60°C). Data acquisition was performed according to the manufacturer’s instructions.

For analysis of the expression data, we carried out a relative quantity study. The expression values of the target genes were normalized to the concentration of 18S rRNA. We calculated gene expression values based on the comparative threshold cycle (Ct) method. The threshold cycle for each gene and 18S rRNA in each sample was determined and used to calculate Ct values. The Ct values were calculated by subtracting the Ct of the calibrator from the Ct value of each target (Ct = Ct_gene − Ct_{18S rRNA}). The relative quantities were calculated with the equation: relative quantity = 2^−Ct. To calculate the relative quantity, we designated as calibrators the average Ct values from the group without structural damage. All gene amplification reactions were performed in triplicate.

Tissue analysis

An observer (A.D.) skilled in light and electron microscopy evaluated the specimens. The observer was unaware of the patient groups. The number of muscle fibres with structural abnormalities in each section was determined. Significant injury was defined as 2% or more damaged fibres per biopsy sample. This arbitrary value reflected what we considered to be a clinically meaningful level of damage. Smaller amounts of damage may be found in patients with no symptoms of myopathy.

Statistical analysis

The data are expressed as mean and standard error of the mean (SEM). We compared the prevalence of muscle injury among the groups by the use of the Fisher exact test. We performed multiple group comparisons for categorical variables by nonparametric analysis of variance by ranks. For continuous variables, we performed analysis of variance followed by the Dunn Multiple Comparison Test. We evaluated the correlation between the circulating level of creatine phosphokinase and the extent of injury using the Pearson correlation coefficient. For mRNA expression analysis, normality was evaluated with the Kolmogorov–Smirnov test (α = 0.05), with the Lilliefors significance correction. Because the expression of the genes did not have a normal distribution, we performed a Mann–Whitney U test. The level of significance was set at p < 0.05.

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Results

Most of the patients with statin-associated myopathy were men with moderate hypercholesterolemia (Table 1). The average age was 56.5 years. Simvastatin and pravastatin were the most commonly reported statins used, and 25% of patients had taken more than 1 statin.