Background: Statins have well-known benefits in the prevention of cardiovascular disease, however, 7-29% of patients develop muscle side effects and up to 0.5% develop severe symptoms. Mitochondrial dysfunction has been associated with severe statin-induced myopathy (SM); however, there is a paucity of systematic studies in affected individuals.
Objectives: The goal of this study was to combine clinical and laboratory features with quantitative biochemical and histopathologic studies of skeletal muscle biopsies from SM cases to determine what proportion could be attributed to mitochondrial dysfunction and how many of these had primary respiratory chain defects.
Methods: A retrospective analysis was performed on patient records derived from 279 SM patients whose muscle biopsies were referred to our clinical diagnostic laboratory for analysis. Clinical, histopathologic and biochemical features were compared with two myopathic control groups unexposed to statins: individuals with idiopathic mitochondrial myopathy (MMP; n = 94) and with unknown metabolic myopathy (UMP; n = 86); normal controls were unavailable for this record review study.
Results: More SM patients had significantly elevated plasma CK than in the other two groups (p < 0.01). A subset of SM patients (67 of 279; 24%) had histopathologic and/or electron microscopic (EM) evidence for mitochondrial dysfunction in skeletal muscle; more cases were identified by EM than by histochemical analysis. Of 279 cases, 29 (10%) were confirmed to have respiratory chain defects by biochemical analysis; 4 of these had mitochondrial abnormalities by EM. An additional 20 cases had mitochondrial abnormalities by EM without a biochemical diagnosis.
Conclusions: Both primary and secondary mitochondrial dysfunction was found in subsets of SM patients. The fact that respiratory chain defects were not found in most cases with histopathologic mitochondrial abnormalities does not rule out primary mitochondrial disease in these cases, however, it is more likely that secondary effects on mitochondrial structure and function have occurred; molecular analysis may be helpful only in a small number of cases.
Keywords: Statin myopathy; electron microscopy; mitochondrial dysfunction; respiratory chain defect.