Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia

Abstract

Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable.

Fluvastatin-induced alterations of skeletal muscle function in hypercholesterolaemic rats

“…Sacher et al 2005). A structural weakness in the T-tubular system, as T-tubules are more vulnerable to cholesterol depletion than other parts of the sarcolemma or the sarcoplasmic reticulum, of statin-treated patients has been demonstrated (Draeger et al 2006). Furthermore, altered Ca 2+ spark activity has been reported following the acute treatment of muscle fibers by simvastatin (Sirvent et al 2005).…”

“…Even in patients without myopathic complaints, statin therapy induced ultrastructural skeletal muscle damage (Draeger et al 2006). …”

Statin Therapy as Primary Prevention in Exercising Adults: Best Evidence for Avoiding Myalgia

“…Despite this, there is clear evidence from a blinded biopsy study of slight but consistent damage to myocyte structural integrity in asymptomatic subjects taking statins. 28 CK elevation is more common among exercising people who are taking statins, 29 but an increase in the enzyme is not a consistent feature of symptomatic statin-induced myopathy.…”

Statin-related myotoxicity

“…13,46 Finally, not all patients with statin-related muscle disorders are symptomatic, and myotoxicity has been histologically documented in asymptomatic patients. 47 Symptoms may occur at any time while taking statins, but usually appear in the first 4---6 weeks. Symptoms may also appear or worsen when statin dose is increased, when an interacting drug is introduced, or when a statin that has caused symptoms is restarted.…”