Association of Lower Habitual Physical Activity Level With Mitochondrial and Endothelial Dysfunction in Patients With Stable Coronary Artery Disease

Abstract

BACKGROUND: Exercise training improves endothelial function in patients with coronary artery disease (CAD) through unclear mechanisms. We hypothesized that mitochondrial dysfunction related to a lower habitual physical activity level (PAL) is associated with endothelial dysfunction. METHODS AND RESULTS: We assessed habitual PAL by a validated International Physical Activity Questionnaire, brachial flow-mediated dilation (FMD) and serum lactate, pyruvate, fasting glucose and lipid profiles in 105 CAD patients (age 68±10; 87% men). As defined by the lactate/pyruvate ratio (LP ratio) ≥75(th) percentile of the age-and sex-matched controls (ie, ≥18), mitochondrial dysfunction was observed in 33/105 (31%) patients. With decreasing PAL tertiles, there were significant linear trends of lower FMD (P=0.004) and higher LP ratio (P=0.009). Multivariate logistic regression found that the lowest compared with the highest PAL tertile (adjusted odds ratio=3.78, P=0.02) had more patients with high LP ratio. After adjustment for cardiovascular risk factors and medications, the lowest compared to the highest PAL tertile had significantly lower FMD (absolute decrease 1.25%, P=0.03); and high LP ratio was associated with impaired FMD (absolute reduction 1.09%, P=0.03). CONCLUSIONS: In CAD patients, a lower level of habitual PAL is associated with impaired FMD and increased prevalence of mitochondrial dysfunction as defined by high LP ratio. Moreover, high LP ratio predicts a lower FMD, suggesting that the occurrence of mitochondrial dysfunction with lower habitual PAL is associated with endothelial dysfunction in CAD patients.