Abstract 4164: Decreased Skeletal Muscle Mitochondrial DNA in Patients on High-Dose Simvastatin Therapy
Background: Statins are used widely to treat dyslipidemia. Statin-induced myopathy (SIM) is a well-recognized side effect that decreases quality of life and complicates patient management. A reliable and convenient method of diagnosing SIM is needed, as patient self-report and creatinine kinase levels are unreliable and light microscopy of skeletal muscle is inconvenient. Statins have been associated with mitochondrial toxicity, which may be related to mitochondrial DNA (mtDNA) levels; mtDNA levels could be a useful marker of SIM. We studied the effect of high-dose statin treatment on mtDNA levels in human skeletal muscle.
Method: Skeletal muscle mtDNA to nuclear DNA (nDNA) ratios were measured retrospectively in 86 biopsies obtained from an earlier randomized, double-blind, placebo-controlled trial. Forty-three hypercholesterolemic subjects aged 31 to 69 years were randomly assigned into 3 treatment groups and received placebo (n=14), atorvastatin 40mg/d (n=15), or simvastatin 80mg/d (n=14) for 8 weeks. Biopsy specimens were acquired at baseline and 8 weeks. mtDNA was quantified by extracting total DNA from muscle homogenates then quantifying a nuclear gene (ASPG) and a mitochondrial gene (CCOI) with real-time PCR. Results are expressed as the mtDNA/nDNA ratio. Differences within groups were assessed by the paired t-test and differences between groups by ANOVA with repeated measurements.
Results: mtDNA significantly decreased (47%; P=0.0020) in the simvastatin group. Non-significant decreases of 12% occurred in the atorvastatin (P=0.24) and placebo (P=0.20) groups. Average baseline ratios of the three groups did not differ significantly (F=0.655).
Conclusion: High-dose simvastatin therapy significantly decreased skeletal muscle mtDNA. mtDNA may be a useful marker of mitochondrial toxicity in statin users, but the clinical relevance of our findings needs to be further investigated.