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

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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., ≥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.

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Acknowledgments

This study was supported by the CRCG Small Project Funding of University of Hong Kong (Project No. 200907176063) and Sun Chieh Yeh Heart Foundation.

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Authors and Affiliations

  1. Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Rm 1928, Block K, Pokfulam, Hong Kong

    Yuk-Ling Dai, Ting-Hin Luk, Chung-Wah Siu, Kai-Hang Yiu, Hiu-Ting Chan, Stephen W. L. Lee, Chu-Pak Lau & Hung-Fat Tse

  2. Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong

    Chung-Wah Siu & Hung-Fat Tse

  3. Department of Medicine, Tung Wah Hospital, Hong Kong, Hong Kong

    Sheung-Wai Li

  4. Department of Clinical Biochemistry Unit, Queen Mary Hospital, Hong Kong, Hong Kong SAR, China

    Sidney Tam & Bonnie Fong

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  1. Yuk-Ling Dai
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Dai, YL., Luk, TH., Siu, CW. et al. Mitochondrial Dysfunction Induced by Statin Contributes to Endothelial Dysfunction in Patients with Coronary Artery Disease. Cardiovasc Toxicol 10, 130–138 (2010). https://doi.org/10.1007/s12012-010-9071-1

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