Prevention and Management of Hypertriglyceridemia-Induced Acute Pancreatitis During Pregnancy: A Systematic Review.

Severe gestational hypertriglyceridemia can lead to acute pancreatitis, with maternal mortality rate of approximately 20%. The recent National Lipid Association part 2 expert panel recommendations provide guidance on monitoring pregnant women at high risk for hyperlipidemia. We suggest that high-risk women have triglyceride levels checked once every trimester. Fasting triglycerides >250 mg/dL should prompt monthly triglyceride levels, screening for gestational diabetes, and implementing a strict low-carbohydrate, low-fat diet, exercise. Fasting triglycerides >500 mg/dL, despite a strict dietary and lifestyle modifications, should prompt treatment with omega-3-fatty acids and continue a fat-restricted diet (<20 g total fat/d or <15% total calories) under the guidance of a registered dietician. The use of fibrates should be considered as a second-line therapy due to their unclear risk versus benefit and potential teratogenic effects. Plasmapheresis should be considered early in asymptomatic pregnant women with fasting triglyceride levels >1000 mg/dL or in pregnant women with clinical signs and symptoms of pancreatitis and triglyceride levels >500 mg/dL despite maximal lifestyle changes and pharmacologic therapy.

Coenzyme Q10 as Treatment for Statin-Associated Muscle Symptoms-A Good Idea, but .

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are extremely well tolerated but are associated with a range of mild-to-moderate statin-associated muscle symptoms (SAMS). Estimates of SAMS incidence vary from <1% in industry-funded clinical trials to 10-25% in nonindustry-funded clinical trials and ∼60% in some observational studies. SAMS are important because they result in dose reduction or discontinuation of these life-saving medications, accompanied by higher healthcare costs and cardiac events. The mechanisms that produce SAMS are not clearly defined. Statins block the production of farnesyl pyrophosphate, an intermediate in the mevalonate pathway, which is responsible for the production of coenzyme Q10 (CoQ10). This knowledge has prompted the hypothesis that reductions in plasma CoQ10 concentrations contribute to SAMS. Consequently, CoQ10 is popular as a form of adjuvant therapy for the treatment of SAMS. However, the data evaluating the efficacy of CoQ10 supplementation has been equivocal, with some, but not all, studies suggesting that CoQ10 supplementation mitigates muscular complaints. This review discusses the rationale for using CoQ10 in SAMS, the results of CoQ10 clinical trials, the suggested management of SAMS, and the lessons learned about CoQ10 treatment of this problem.

Creatine supplementation does not alter the creatine kinase response to eccentric exercise in healthy adults on atorvastatin.

BACKGROUND: Serum creatine kinase (CK) levels are higher after eccentric, muscle-damaging exercise in statin-treated patients. This could contribute to the increased statin-associated muscle symptoms reported in physically active individuals. OBJECTIVE: We tested the hypothesis in this pilot study that creatine (Cr) monohydrate supplementation would reduce the CK response to eccentric exercise in patients using statins to determine if Cr supplementation could be a strategy to mitigate statin-associated muscle symptoms in physically active individuals. METHODS: Healthy, nonsmoking men (n = 5) and women (n = 14) were randomized to Cr monohydrate = atorvastatin 80 mg + 10 g Cr monohydrate (n = 10, age = 60 ± 7 years) or to placebo (PL) = atorvastatin 80 mg + PL (n = 9, age = 52 ± 6 years). After 4 weeks of treatment, subjects performed 45 minutes of eccentric exercise (downhill walking at a -15% grade). Serum CK levels, muscle soreness (visual analog scale after two squats), and muscle pain severity and interference (using the brief pain inventory) were measured before and after 4 weeks of treatment, and then for 4 consecutive days after downhill walking. Vitamin D, or serum 25(OH)D, was also measured at baseline. RESULTS: The PL group was younger (P = .01) but not otherwise different in blood lipids, vitamin D, CK, muscle visual analog scale, and pain scores before (all P > .21) or after (all P > .12) treatment. CK increased in all subjects after downhill walking (P < .01), but neither the relative peak change (expressed as group mean difference with 95% confidence intervals: 43.52% [-196.41, 283.45]) nor the absolute peak change (67.38 U/L [-121.55, 256.31]) relative to baseline was different between groups (P = .46 and .71, respectively). A similar lack of treatment effect was observed for muscle soreness (11.03 mm [-9.49, 31.55]), pain severity (0.77 pts [-0.95, 2.50]), and pain interference (1.02 pts [-1.25, 3.29]) with P-values for group comparisons = 0.27, 0.36, and 0.35, respectively. However, subjects with "insufficient" Vitamin D < 30 ng/mL (n = 10) had an ∼2-fold greater CK increase with eccentric exercise (nominal P-value = .04) than subjects with higher vitamin D levels. CONCLUSION: Cr monohydrate did not reduce CK increases after exercise in statin-treated subjects. We did observe that low vitamin D levels are associated with a greater CK response to eccentric exercise in statin-treated subjects.

The effect of high-dose atorvastatin on neural activity and cognitive function.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has not been used to assess the effects of statins on the brain. We assessed the effect of statins on cognition using standard neuropsychological assessments and brain neural activation with fMRI on two tasks. METHODS: Healthy statin-naïve men and women (48±15 years) were randomized to 80 mg/day atorvastatin (n=66; 27 men) or placebo (n=84; 48 men) for 6 months. Participants completed cognitive testing while on study drug and 2 months after treatment cessation using alternative test and task versions. RESULTS: There were few changes in standard neuropsychological tests with drug treatment (all P>.56). Total and delayed recall from the Hopkins Verbal Learning Test-Revised increased in both groups (P<.05). The Stroop Color-Word score increased (P<.01) and the 18-Point Clock Test decreased in the placebo group (P=.02) after drug cessation. There were, however, small but significant group-time interactions for each fMRI task: participants on placebo had greater activation in the right putamen/dorsal striatum during the maintenance phase of the Sternberg task while on placebo but the effect was reversed after drug washout (P<.001). Participants on atorvastatin had greater activation in the bilateral precuneus during the encoding phase of the Figural Memory task while on-drug but the effect was reversed after drug washout (P<.001). CONCLUSION: Six months of high dose atorvastatin therapy is not associated with measurable changes in neuropsychological test scores, but did evoke transient differences in brain activation patterns. Larger, longer-term clinical trials are necessary to confirm these findings and evaluate their clinical implications.

Chelation therapy in the treatment of cardiovascular diseases.

OBJECTIVE: We examined the effect of chelation therapy on cardiovascular diseases (CVDs). BACKGROUND: EDTA is a chelating agent that binds to metals including calcium and facilitates their excretion. Chelation with EDTA is recommended by some practitioners to treat CVD with the hypothesis that reducing calcium reduces atherosclerotic calcification of arteries. However, chelation therapy has not been approved by the Food and Drug Administration, and its effectiveness is unclear. METHODS: We searched PubMed for English language articles addressing the effect of chelation therapy on CVD events. Articles pertinent to the topic were reviewed in detail. RESULTS: We identified 128 articles addressing the therapeutic value of chelation therapy on CVD; 38 were reviewed in detail including 20 case series and 7 randomized controlled trials. Sixteen case series and 3 randomized controlled trials showed benefit with chelation. The Trial to Assess Chelation Therapy included 1708 post-myocardial infarction patients and demonstrated benefit with chelation therapy, but the Trial to Assess Chelation Therapy investigators concluded that their results did not support the routine use of chelation therapy for post-myocardial infarction patients. CONCLUSIONS: The effectiveness of chelation therapy in reducing recurrent CVD events is unclear, but possible, and warrants additional, carefully designed clinical trials.

High-Dose versus Low-Dose Vitamin D Supplementation and Arterial Stiffness among Individuals with Prehypertension and Vitamin D Deficiency.

INTRODUCTION: Vitamin D deficiency is associated with the onset and progression of hypertension and cardiovascular disease (CVD). However, mechanisms underlying vitamin D deficiency-mediated increased risk of CVD remain unknown. We sought to examine the differential effect of high-dose versus low-dose vitamin D supplementation on markers of arterial stiffness among ~40 vitamin D deficient adults with prehypertension. METHODS: Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D3 for 6 months. 24 hr ambulatory blood pressure (BP), carotid-femoral pulse wave velocity, and pulse wave analyses were obtained at baseline and after 6 months of vitamin D supplementation. RESULTS: There were no changes in resting BP or pulse wave velocity over 6 mo regardless of vitamin D dose (all p > 0.202). High-dose vitamin D decreased augmentation index and pressure by 12.3 ± 5.3% (p = 0.047) and 4.0 ± 1.5 mmHg (p = 0.02), respectively. However, these decreases in arterial stiffness were not associated with increases in serum 25-hydroxyvitamin D over 6 mo (p = 0.425). CONCLUSION: High-dose vitamin D supplementation appears to lower surrogate measures of arterial stiffness but not indices of central pulse wave velocity. Clinical Trial Registration. This trial is registered with www.clinicaltrials.gov (Unique Identifier: NCT01240512).

Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management.

Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7-29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential.

A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy.

BACKGROUND: Coenzyme Q10 (CoQ10) supplementation is the most popular therapy for statin myalgia among both physicians and patients despite limited and conflicting evidence of its efficacy. OBJECTIVE: This study examined the effect of coenzyme Q10 (CoQ10) supplementation on simvastatin-associated muscle pain, muscle strength and aerobic performance in patients with confirmed statin myalgia. METHODS: Statin myalgia was confirmed in 120 patients with prior symptoms of statin myalgia using an 8-week randomized, double-blind crossover trial of simvastatin 20 mg/d and placebo. Forty-one subjects developed muscle pain with simvastatin but not with placebo and were randomized to simvastatin 20 mg/d combined with CoQ10 (600 mg/d ubiquinol) or placebo for 8 weeks. Muscle pain (Brief Pain Inventory [BPI]), time to pain onset, arm and leg muscle strength, and maximal oxygen uptake (VO2max) were measured before and after each treatment. RESULTS: Serum CoQ10 increased from 1.3 ± 0.4 to 5.2 ± 2.3 mcg/mL with simvastatin and CoQ10, but did not increase with simvastatin and placebo (1.3 ± 0.3 to 0.8 ± 0.2) (p < 0.05). BPI pain severity and interference scores increased with simvastatin therapy (both p < 0.01), irrespective of CoQ10 assignment (p = 0.53 and 0.56). There were no changes in muscle strength or VO2max with simvastatin with or without CoQ10 (all p > 0.10). Marginally more subjects reported pain with CoQ10 (14 of 20 vs 7 of 18; p = 0.05). There was no difference in time to pain onset in the CoQ10 (3.0 ± 2.0 weeks) vs. placebo (2.4 ± 2.1 wks) groups (p = 0.55). A similar lack of CoQ10 effect was observed in 24 subjects who were then crossed over to the alternative treatment. CONCLUSIONS: Only 36% of patients complaining of statin myalgia develop symptoms during a randomized, double-blind crossover of statin vs placebo. CoQ10 supplementation does not reduce muscle pain in patients with statin myalgia. Trial RegistrationNCT01140308; www.clinicaltrials.gov.

Physical activity is associated with positive responses during carotid sinus massage and head-up tilt-table test in patients with unexplained syncope.

AIMS: Physical exercise is known to alter the physiological response to orthostatic stress. This study compared reported physical activity levels in patients with unexplained syncope who did or did not demonstrate positive responses to carotid sinus massage and head-up tilt-table testing. METHODS: We reviewed the records of 1,336 patients with unexplained syncope who underwent carotid sinus massage and head-up tilt-table testing. Patients with positive responses (cases) were compared with patients with negative responses (controls). Multivariable regression analysis was used to identify independent predictors of positive responses to carotid sinus massage and head-up tilt-table testing. RESULTS: Seventy patients had a positive response to carotid sinus massage and 564 patients had a positive response to head-up tilt-table testing. Physical activity was an independent positive predictor of a positive response to both carotid sinus massage {adjusted odds ratio (AOR) 1.86, 95% CI (1.14-3.05); p = 0.01} and head-up tilt-table testing {AOR 1.31, 95% CI (1.04-1.65); P = 0.02} even after adjustment for multiple other factors including age, gender, and other medical conditions. CONCLUSION: Physical activity is associated with greater likelihood of positive responses during carotid sinus massage and head-up tilt-table testing.

Increases in creatine kinase with atorvastatin treatment are not associated with decreases in muscular performance.

BACKGROUND: The present study examined if increases in creatine kinase (CK) levels during high-dose atorvastatin treatment are associated with changes in skeletal muscle function and symptoms. METHODS: The Effect of Statins on Muscle Performance study (STOMP) investigated the effects of atorvastatin 80 mg daily for 6 months on muscle performance, exercise capacity, and the incidence of statin-associated muscle complaints in healthy adults. RESULTS: CK levels increased with atorvastatin (n = 202) from 132.3 ± 120.9 U/L (mean ± SD) at baseline to 159.7 ± 170.4 and 153.1 ± 139.4 U/L at 3 and 6 months, respectively (P ≤ 0.002 for both). Changes in CK with atorvastatin treatment were not associated with changes in muscle function or the incidence of myalgia. More subjects on atorvastatin (n = 24) compared to placebo (n = 12 of 217) doubled their CK level at 6 months (P = 0.02). No differences in muscle function or physical activity were observed between atorvastatin-treated subjects who did or did not double their CK. CONCLUSIONS: Results of the present investigation extend the findings of STOMP by demonstrating that greater increases in CK levels with high-dose atorvastatin treatment did not deleteriously impact skeletal muscle function or predict skeletal muscle complaints. This study was registered at ClinicalTrials.gov (NCT00609063).

A randomized trial of coenzyme Q10 in patients with statin myopathy: rationale and study design.

BACKGROUND: Statins are the most commonly prescribed and effective medications for reducing low-density lipoprotein levels. Some patients experience myopathic symptoms during statin treatment. The etiology is not known, but depletion of mevalonate pathway metabolites, including coenzyme Q10 (CoQ10), has been suggested. Despite a lack of conclusive evidence supporting its utility, CoQ10 supplementation has been recommended to patients who experience myalgic symptoms. OBJECTIVE: The Co-Enzyme Q10 in Statin Myopathy study is designed to examine the effect of CoQ10 supplementation on the extent and intensity of muscle pain during treatment with simvastatin. METHODS: We will recruit patients with a documented history of myalgia during statin treatment. The presence of statin-related myalgia will be confirmed in a crossover run-in trial during which the presence and absence of symptoms will be documented during statin and placebo treatment, respectively. Individuals experience myalgic symptoms while taking statins but not placebo will be randomized to receive simvastatin 20 mg daily plus either 600 mg daily of CoQ10 or placebo. Muscle pain intensity will be documented during weekly phone calls via use of the Brief Pain Inventory, Short Form. Treatment will continue for 8 weeks or until muscle symptoms are reported continuously for 1 week or become intolerable, and then subjects will crossover to the alternative treatment (CoQ10 or placebo). RESULTS: This study is an ongoing clinical trial. CONCLUSIONS: This study will determine the utility of CoQ10 for reducing pain intensity in myalgic patients and will provide guidance for clinicians treating patients with hypercholesterolemia who are intolerant to statins.

25(OH) vitamin D is associated with greater muscle strength in healthy men and women.

PURPOSE: The purpose of the study was to examine the relation between serum 25-hydroxy vitamin D (25(OH)D) levels and muscle strength in 419 healthy men and women over a broad age range (20-76 yr). METHODS: Isometric and isokinetic strength of the arms and legs was measured using computerized dynamometry, and its relation to vitamin D was tested in multivariate models controlling for age, gender, resting HR, systolic blood pressure, diastolic blood pressure, body mass index, maximal oxygen uptake (VO(2max)), physical activity counts, and season of vitamin D measurement. RESULTS: Vitamin D was significantly associated with arm and leg muscle strength when controlling for age and gender. When controlling for other covariates listed previously, vitamin D remained directly related to both isometric and isokinetic arm strength but only to isometric leg strength. CONCLUSION: These data suggest that there may be a differential effect of vitamin D on upper and lower body strength. The mechanism for this difference remains unclear but could be related to differences in androgenic effects or to differences in vitamin D receptor expression. Our study supports a direct relation between vitamin D and muscle strength and suggests that vitamin D supplementation be evaluated to determine whether it is an effective therapy to preserve muscle strength in adults.

Effect of statins on skeletal muscle function.

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, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.8±141.1 U/L (P<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 versus 10; P=0.05). Myalgic subjects on atorvastatin or placebo had 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 creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in creatine kinase should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00609063.

Atorvastatin increases exercise leg blood flow in healthy adults.

OBJECTIVES: We sought to examine the effect of atorvastatin therapy on exercise leg blood flow in healthy middle-aged and older-men and women. BACKGROUND: The vasodilatory response to exercise decreases in humans with aging and disease and this reduction may contribute to reduced exercise capacity. METHODS: We used a double-blind, randomly assigned, placebo-controlled protocol to assess the effect of atorvastatin treatment on exercising leg hemodynamics. We measured femoral artery blood flow (FBF) using Doppler ultrasound and calculated femoral vascular conductance (FVC) from brachial mean arterial pressure (MAP) before and during single knee-extensor exercise in healthy adults (ages 40-71) before (PRE) and after (POST) 6 months of 80 mg atorvastatin (A: 14 men, 16 women) or placebo (P: 14 men, 22 women) treatment. FBF and FVC were normalized to exercise power output and estimated quadriceps muscle mass. RESULTS: Atorvastatin reduced LDL cholesterol by approximately 50%, but not in the placebo group (p < 0.01). Atorvastatin also increased exercise FBF from 44.2 ± 19.0 to 51.4 ± 22.0 mL/min/W/kg muscle whereas FBF in the placebo group was unchanged (40.1 ± 16.0 vs. 39.5 ± 16.1) (p < 0.01). FVC also increased with atorvastatin from 0.5 ± 0.2 to 0.6 ± 0.2 mL/min/mmHg/W/kg muscle, but not in the placebo subjects (P: 0.4 ± 0.2 vs. 0.4 ± 0.2) (p < 0.01). CONCLUSIONS: High-dose atorvastatin augments exercising leg hyperemia. Statins may mitigate reductions in the exercise vasodilatory response in humans that are associated with aging and disease.

The relationship of vitamin D deficiency to statin myopathy.

OBJECTIVE: Our goal was to examine the interaction between vitamin D and statins and the possible role of vitamin D deficiency in statin myopathy. BACKGROUND: The vitamin D receptor is present in skeletal muscle and vitamin D deficiency can cause myopathy. Statins (3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors) are generally well tolerated, but have been associated with a spectrum of skeletal muscle complaints, ranging from myalgia and asymptomatic mild elevations of creatine kinase (CK) to rhabdomyolysis. There has been recent interest in the possible interaction between statin myopathy and vitamin D deficiency. We performed a systematic medical literature review to examine this possible relationship. METHODS: We identified English language articles relating statins, vitamin D and statin myopathy via a PubMed search through July 2010. Articles pertinent to the topic were reviewed in detail. RESULTS/CONCLUSIONS: Our review suggests that some but not all statins increase 25(OH) D levels. Two cross sectional studies have associated vitamin D deficiency with statin-associated myalgias, and suggested that that increasing vitamin D levels can reverse the myalgia. Nevertheless, given the quality and paucity of studies examining this possibility, additional studies are needed to examine the potential role of vitamin D deficiency in statin myopathy. It is presently premature to recommend vitamin D supplementation as treatment for statin associated muscle complaints in the absence of low vitamin D levels although such supplementation could be tried in patients with deficient or reduced vitamin D levels.

Lipid-lowering efficacy of red yeast rice in a population intolerant to statins.

Chinese red yeast rice is a dietary supplement containing monacolins, unsaturated fatty acids, and phytosterols capable of lowering low-density lipoprotein (LDL) cholesterol. Few studies have reported on its use in clinical practice or in statin-intolerant patients. We reviewed approximately 1,400 clinical charts and identified 25 patients treated with red yeast rice for > or =4 weeks. The patients were included if they had pre- and post-treatment lipid levels without simultaneous changes in other lipid-lowering medications. These patients had experienced myalgias (68%), gastrointestinal intolerance (16%), and/or elevated alanine aminotransferase levels (8%) with previous use of other lipid-lowering agents. The total cholesterol decreased 15% (-37 +/- 26 mg/dl, p <0.001) and LDL cholesterol decreased 21% (-35 +/- 25 mg/dl, p <0.001) during 74 +/- 39 days of treatment. Most (92%) patients tolerated the treatment, and many (56%) achieved their LDL cholesterol goal. In patients unable to tolerate daily statin use, the total cholesterol level decreased 13% (-33 +/- 10 mg/dl, p <0.001) and LDL cholesterol decreased 19% (-31 +/- 4 mg/dl, p <0.001). In conclusion, red yeast rice modestly decreased total and LDL cholesterol, was well-tolerated, and was an acceptable alternative in patients intolerant of other lipid-lowering medications.

Tolerability of red yeast rice (2,400 mg twice daily) versus pravastatin (20 mg twice daily) in patients with previous statin intolerance.

Currently, no consensus has been reached regarding the management of hyperlipidemia in patients who develop statin-associated myalgia (SAM). Many statin-intolerant patients use alternative lipid-lowering therapies, including red yeast rice. The present trial evaluated the tolerability of red yeast rice versus pravastatin in patients unable to tolerate other statins because of myalgia. The study was conducted in a community-based setting in Philadelphia, Pennsylvania. A total of 43 adults with dyslipidemia and a history of statin discontinuation because of myalgia were randomly assigned to red yeast rice 2,400 mg twice daily or pravastatin 20 mg twice daily for 12 weeks. All subjects were concomitantly enrolled in a 12-week therapeutic lifestyle change program. The primary outcomes included the incidence of treatment discontinuation because of myalgia and a daily pain severity score. The secondary outcomes were muscle strength and plasma lipids. The incidence of withdrawal from medication owing to myalgia was 5% (1 of 21) in the red yeast rice group and 9% (2 of 22) in the pravastatin group (p = 0.99). The mean pain severity did not differ significantly between the 2 groups. No difference was found in muscle strength between the 2 groups at week 4 (p = 0.61), week 8 (p = 0.81), or week 12 (p = 0.82). The low-density lipoprotein cholesterol level decreased 30% in the red yeast rice group and 27% in the pravastatin group. In conclusion, red yeast rice was tolerated as well as pravastatin and achieved a comparable reduction of low-density lipoprotein cholesterol in a population previously intolerant to statins.

Efficacy of rosuvastatin (5 mg and 10 mg) twice a week in patients intolerant to daily statins.

The aim of this study was to evaluate the efficacy of rosuvastatin twice weekly in 40 patients intolerant to daily statins. Rosuvastatin twice weekly alone or added to other lipid-lowering medications decreased total cholesterol by 19%, low-density lipoprotein cholesterol by 26%, and triglycerides by 14% (p<0.01 for all). High-density lipoprotein cholesterol did not change. Eight of the 40 patients (20%) discontinued twice-weekly rosuvastatin treatment because of muscle-related symptoms, during an average of 8 weeks of treatment. In conclusion, rosuvastatin twice weekly reduced total cholesterol, low-density lipoprotein cholesterol, and triglycerides and was well tolerated, but determining long-term tolerability requires more prolonged treatment.

The creatine kinase response to eccentric exercise with atorvastatin 10 mg or 80 mg.

INTRODUCTION: Hydroxy-methyl-glutaryl co-enzyme A (HMG-CoA) reductase inhibitors or statins are well tolerated by most patients, but can produce a variety of skeletal muscle problems including myalgia, creatine kinase (CK) elevations and clinically important rhabdomyolysis. We have previously demonstrated that the CK response to downhill walking is greater in statin compared to placebo treated subjects. This study examined the CK response to downhill walking in subjects treated with low and high dose of atorvastatin. METHODS: 79 subjects with LDL cholesterol>100mg/dL were randomly assigned to atorvastatin 10mg (N=42) or 80 mg (N=37) for 5 weeks. Subjects performed a downhill walking exercise during the fifth week of treatment. Leg muscle soreness, plasma CK and CK-MB levels were measured daily for 4 days following the exercise. RESULTS: CK, CK-MB and muscle soreness increased above pre-exercise levels in all subjects after the exercise. There were no differences in the CK, CK-MB or soreness response between the high and low dose treatment groups at any time point. CONCLUSION: The downhill walking model of muscle injury does not distinguish between high and low dose atorvastatin therapy either because this test is insensitive to differences among statin doses or because there is no difference in muscle injury between these two drug doses with this statin. Clinicians should be aware, however, that exercise can increase CK levels with even low dose statin therapy.

The role of coenzyme Q10 in statin-associated myopathy: a systematic review.

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are currently the most effective medications for reducing low-density lipoprotein cholesterol concentrations. Although generally safe, they have been associated with a variety of myopathic complaints. Statins block production of farnesyl pyrophosphate, an intermediate in the synthesis of ubiquinone or coenzyme Q10 (CoQ10). This fact, plus the role of CoQ10 in mitochondrial energy production, has prompted the hypothesis that statin-induced CoQ10 deficiency is involved in the pathogenesis of statin myopathy. We identified English language articles relating statin treatment and CoQ10 levels via a PubMed search through August 2006. Abstracts were reviewed and articles addressing the relationship between statin treatment and CoQ10 levels were examined in detail. Statin treatment reduces circulating levels of CoQ10. The effect of statin therapy on intramuscular levels of CoQ10 is not clear, and data on intramuscular CoQ10 levels in symptomatic patients with statin-associated myopathy are scarce. Mitochondrial function may be impaired by statin therapy, and this effect may be exacerbated by exercise. Supplementation can raise the circulating levels of CoQ10, but data on the effect of CoQ10 supplementation on myopathic symptoms are scarce and contradictory. We conclude that there is insufficient evidence to prove the etiologic role of CoQ10 deficiency in statin-associated myopathy and that large, well-designed clinical trials are required to address this issue. The routine use of CoQ10 cannot be recommended in statin-treated patients. Nevertheless, there are no known risks to this supplement and there is some anecdotal and preliminary trial evidence of its effectiveness. Consequently, CoQ10 can be tested in patients requiring statin treatment, who develop statin myalgia, and who cannot be satisfactorily treated with other agents. Some patients may respond, if only via a placebo effect.