Mitochondrial Dysfunction Induced by Statin Contributes to Endothelial Dysfunction in Patients with Coronary Artery Disease

• Published in: Cardiovascular toxicology 2010-06, Vol.10 (2), p.130-138
• Main Authors: Dai, Yuk-Ling, Luk, Ting-Hin, Siu, Chung-Wah, Yiu, Kai-Hang, Chan, Hiu-Ting, Lee, Stephen W. L, Li, Sheung-Wai, Tam, Sidney, Fong, Bonnie, Lau, Chu-Pak, Tse, Hung-Fat
• Format: Article
• Language: English
• Subjects: Age; Aged; Apolipoproteins; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Blood levels; Brachial Artery - drug effects; Brachial Artery - physiology; Cardiac patients; Cardiology; Cardiovascular agents; Cardiovascular disease; Care and treatment; Cholesterol; Coronary Artery Disease - drug therapy; Coronary Artery Disease - physiopathology; Coronary heart disease; Coronary vessels; Diabetes; Dose-Response Relationship, Drug; Drug dosages; Endothelial dysfunction; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Fasting; Female; Glucose; Heart diseases; Hospitals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Lactates; Lactic acid; Lactic Acid - blood; Lipids; Lipoproteins; Male; Mitochondria; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Mitochondrial Diseases - chemically induced; Mitochondrial Diseases - metabolism; Mitochondrial dysfunction; Multivariate analysis; Pharmacology/Toxicology; Pyruvic acid; Pyruvic Acid - blood; Regional Blood Flow - drug effects; Simvastatin - adverse effects; Statin; Statins; Ultrasonography; Vasodilation - drug effects; Vasodilation - physiology; Vein & artery diseases
• ISSN: 1530-7905; 1559-0259
• 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., ≥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.