Mitochondrial dysfunction induced by statin contributes to endothelial dysfunction in patients with coronary artery disease

Cardiovasc Toxicol. 2010 Jun;10(2):130-8. doi: 10.1007/s12012-010-9071-1.


Despite the use of statin therapy, a significant proportion of patients with coronary artery disease (CAD) still develop cardiovascular events. We hypothesized that development of mitochondrial dysfunction (MD) after statin therapy might be linked to endothelial dysfunction and thus limiting its beneficial effects. We studied the effect of MD on endothelial function in 119 patients with CAD on long-term statins (>1 year). Brachial artery flow-mediated dilation (FMD) was assessed by high-resolution ultrasonography and blood levels of lactate, pyruvate, fasting glucose, and lipids were measured. MD (defined by a lactate/pyruvate ratio >75th percentile of the age- and sex-matched normal controls, i.e., > or = 18) was observed in 43/119(36%) patients. There were no significant differences in age, gender, and clinical characteristics between patients with or without MD (all P > 0.05). Patients with MD received higher dose of statin (23.5 +/- 19.3 vs. 17.1 +/- 10.5 mg simvastatin-equivalent dose, P = 0.05) and had lower FMD (2.69 +/- 2.94 vs. 4.33 +/- 2.80%, P = 0.003) than those without MD. Multivariate analysis showed that statin dosage was independently associated with MD (OR:1.03, P = 0.03), and MD significantly predicted an absolute 1.36% decrease in FMD (P = 0.01). In conclusion, a significant proportion of patients with CAD on statin developed MD, which was associated with high-dose statin and with impaired FMD, suggesting that increased statin dosage may induce MD and contribute to endothelial dysfunction in patients with CAD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Brachial Artery / drug effects
  • Brachial Artery / physiology
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / physiopathology
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Lactic Acid / blood
  • Male
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • Mitochondrial Diseases / chemically induced*
  • Mitochondrial Diseases / metabolism
  • Pyruvic Acid / blood
  • Regional Blood Flow / drug effects
  • Simvastatin / adverse effects*
  • Vasodilation / drug effects
  • Vasodilation / physiology


  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lactic Acid
  • Pyruvic Acid
  • Simvastatin