title: Mitochondrial dysfunction induced by statin contributes to endothelial dysfunction in patients with coronary artery disease.
abstract: 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.
authors.affiliation: Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Rm 1928, Block K, Pokfulam, Hong Kong.
authors.forename: Yuk-Ling
authors.initials: YL
authors.lastname: Dai
authors.forename: Ting-Hin
authors.initials: TH
authors.lastname: Luk
authors.forename: Chung-Wah
authors.initials: CW
authors.lastname: Siu
authors.forename: Kai-Hang
authors.initials: KH
authors.lastname: Yiu
authors.forename: Hiu-Ting
authors.initials: HT
authors.lastname: Chan
authors.forename: Stephen W L
authors.initials: SW
authors.lastname: Lee
authors.forename: Sheung-Wai
authors.initials: SW
authors.lastname: Li
authors.forename: Sidney
authors.initials: S
authors.lastname: Tam
authors.forename: Bonnie
authors.initials: B
authors.lastname: Fong
authors.forename: Chu-Pak
authors.initials: CP
authors.lastname: Lau
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000139:chemically induced* / Q000378:metabolism; D019289:Pyruvic Acid / Q000097:blood; D012039:Regional Blood Flow / Q000187:drug effects; D019821:Simvastatin / Q000009:adverse effects*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019344:Lactic Acid; D019289:Pyruvic Acid; D019821:Simvastatin