Abstract 3700: Mitochondrial Dysfunction Induced by Higher Dose Statin Usage Contributes to Endothelial Dysfunction in Patients with Coronary Artery Disease
Introduction: Despite the use of statin therapy, a significant proportion of patients (pts) with coronary artery disease (CAD) still develop cardiovascular events. It has been postulated that mitochondrial dysfunction (MD) induced by statin therapy may limit its beneficial effects by augmenting oxidative stress.
Methods: We studied the effect of MD on endothelial function in 78 pts (age 68±11 years, 80% men) with stable CAD on long-term statin therapy (>1 year). Brachial artery flow-mediated dilation (FMD) was assessed by high-resolution ultrasound and blood levels of lactate, pyruvate and fasting glucose and lipid profiles were measured.
Results: 21/78 (27%) pts had MD (defined by blood lactate/pyruvate ratio>=20). There were no significant differences in age, sex, prevalence of smoking, hypertension, total cholesterol, LDL and HDL between pts with or without MD (all P>0.05). However, pts with MD were more likely to receive high dose statin (33 vs 11%, P=0.017, defined by simvastatin equivalent dose >=40 mg), and had lower FMD (2.4±2.8 vs 4.0±2.5%, P=0.015, Fig 1⇓) than those without MD. Multivariate logistic regression showed that high dose statin usage remained an independent predictor of MD (OR: 3.7, CI: 1.0 –13.3, P=0.047). After adjustment for potential confounders, the presence of MD significantly predicted an absolute 2.3% decrease in FMD (P<0.01).
Conclusion: A significant proportion (27%) of CAD pts treated with statin developed MD, which was more likely to occur in those treated with high dose statin. MD was a negative independent predictor of impaired FMD. These suggest that MD related to higher dose statin usage may contribute to endothelial dysfunction in CAD pts.