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High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial.
Clin Pharmacol Ther. 2005 Jul; 78(1):60-8.CP

Abstract

BACKGROUND

Myopathy, probably caused by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition in skeletal muscle, rarely occurs in patients taking statins. This study was designed to assess the effect of high-dose statin treatment on cholesterol and ubiquinone metabolism and mitochondrial function in human skeletal muscle.

METHODS

Forty-eight patients with hypercholesterolemia (33 men and 15 women) were randomly assigned to receive 80 mg/d of simvastatin (n = 16), 40 mg/d of atorvastatin (n = 16), or placebo (n = 16) for 8 weeks. Plasma samples and muscle biopsy specimens were obtained at baseline and at the end of the follow-up.

RESULTS

The ratio of plasma lathosterol to cholesterol, a marker of endogenous cholesterol synthesis, decreased significantly by 66% in both statin groups. Muscle campesterol concentrations increased from 21.1 +/- 7.1 nmol/g to 41.2 +/- 27.0 nmol/g in the simvastatin group and from 22.6 +/- 8.6 nmol/g to 40.0 +/- 18.7 nmol/g in the atorvastatin group (P = .005, repeated-measurements ANOVA). The muscle ubiquinone concentration was reduced significantly from 39.7 +/- 13.6 nmol/g to 26.4 +/- 7.9 nmol/g (P = .031, repeated-measurements ANOVA) in the simvastatin group, but no reduction was observed in the atorvastatin or placebo group. Respiratory chain enzyme activities were assessed in 6 patients taking simvastatin with markedly reduced muscle ubiquinone and in matched subjects selected from the atorvastatin (n = 6) and placebo (n = 6) groups. Respiratory chain enzyme and citrate synthase activities were reduced in the patients taking simvastatin.

CONCLUSIONS

High-dose statin treatment leads to changes in the skeletal muscle sterol metabolism. Furthermore, aggressive statin treatment may affect mitochondrial volume.

Authors+Show Affiliations

Department of Internal Medicine, University Hospital of Tampere, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16003294

Citation

Päivä, Hannu, et al. "High-dose Statins and Skeletal Muscle Metabolism in Humans: a Randomized, Controlled Trial." Clinical Pharmacology and Therapeutics, vol. 78, no. 1, 2005, pp. 60-8.
Päivä H, Thelen KM, Van Coster R, et al. High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. Clin Pharmacol Ther. 2005;78(1):60-8.
Päivä, H., Thelen, K. M., Van Coster, R., Smet, J., De Paepe, B., Mattila, K. M., Laakso, J., Lehtimäki, T., von Bergmann, K., Lütjohann, D., & Laaksonen, R. (2005). High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. Clinical Pharmacology and Therapeutics, 78(1), 60-8.
Päivä H, et al. High-dose Statins and Skeletal Muscle Metabolism in Humans: a Randomized, Controlled Trial. Clin Pharmacol Ther. 2005;78(1):60-8. PubMed PMID: 16003294.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. AU - Päivä,Hannu, AU - Thelen,Karin M, AU - Van Coster,Rudy, AU - Smet,Joél, AU - De Paepe,Boel, AU - Mattila,Kari M, AU - Laakso,Juha, AU - Lehtimäki,Terho, AU - von Bergmann,Klaus, AU - Lütjohann,Dieter, AU - Laaksonen,Reijo, PY - 2005/7/9/pubmed PY - 2005/8/19/medline PY - 2005/7/9/entrez SP - 60 EP - 8 JF - Clinical pharmacology and therapeutics JO - Clin Pharmacol Ther VL - 78 IS - 1 N2 - BACKGROUND: Myopathy, probably caused by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition in skeletal muscle, rarely occurs in patients taking statins. This study was designed to assess the effect of high-dose statin treatment on cholesterol and ubiquinone metabolism and mitochondrial function in human skeletal muscle. METHODS: Forty-eight patients with hypercholesterolemia (33 men and 15 women) were randomly assigned to receive 80 mg/d of simvastatin (n = 16), 40 mg/d of atorvastatin (n = 16), or placebo (n = 16) for 8 weeks. Plasma samples and muscle biopsy specimens were obtained at baseline and at the end of the follow-up. RESULTS: The ratio of plasma lathosterol to cholesterol, a marker of endogenous cholesterol synthesis, decreased significantly by 66% in both statin groups. Muscle campesterol concentrations increased from 21.1 +/- 7.1 nmol/g to 41.2 +/- 27.0 nmol/g in the simvastatin group and from 22.6 +/- 8.6 nmol/g to 40.0 +/- 18.7 nmol/g in the atorvastatin group (P = .005, repeated-measurements ANOVA). The muscle ubiquinone concentration was reduced significantly from 39.7 +/- 13.6 nmol/g to 26.4 +/- 7.9 nmol/g (P = .031, repeated-measurements ANOVA) in the simvastatin group, but no reduction was observed in the atorvastatin or placebo group. Respiratory chain enzyme activities were assessed in 6 patients taking simvastatin with markedly reduced muscle ubiquinone and in matched subjects selected from the atorvastatin (n = 6) and placebo (n = 6) groups. Respiratory chain enzyme and citrate synthase activities were reduced in the patients taking simvastatin. CONCLUSIONS: High-dose statin treatment leads to changes in the skeletal muscle sterol metabolism. Furthermore, aggressive statin treatment may affect mitochondrial volume. SN - 0009-9236 UR - https://www.unboundmedicine.com/medline/citation/16003294/High_dose_statins_and_skeletal_muscle_metabolism_in_humans:_a_randomized_controlled_trial_ L2 - https://doi.org/10.1016/j.clpt.2005.03.006 DB - PRIME DP - Unbound Medicine ER -