Endothelial dysfunction and arterial stiffness in coronary artery disease

Endothelial dysfunction (ED) is well documented in both resistance vessels and conduit arteries of coronary artery disease (CAD) patients and has been shown to be a predictor of future cardiovascular events in these patients. The mechanism of ED in CAD appears to be multi-factorial with possible mechanisms including: (1) decreased expression or synthesis of endothelial nitric oxide synthase, and (2) inactivation of nitric oxide (NO) by reactive oxygen species. Exercise-training has been shown to improve endothelial function in CAD but the mechanisms have yet to be elucidated. The objective of this study was to investigate the effects of 12 weeks of standard cardiac rehabilitation on endothelial function, arterial stiffness, oxidative stress and antioxidant defenses, and inflammation in CAD. Twenty CAD patients, 10 exercise trained (ET), 10 control (C), participated in the study. Exercise-training resulted in a significant improvement (p < 0.05) in brachial artery flow-mediated dilation (FMD) (7.2% at baseline v. 11.2% at 12 weeks) and a significant reduction (p < 0.05) in indices of arterial stiffness (augmentation index (AIx) (29.9% at baseline v. 26.2% at 12 weeks) and delay of the reflected wave (Δt) (136.2 ms at baseline v. 144.4 ms at 12 weeks) in the ET group with no change in the C group. Exercise-training also significantly increased (p < 0.05) plasma nitrate/nitrite (NOx) levels in the ET group (28.6 μmol/L at baseline v. 34.7 μmol/L at 12 weeks). Total plasma 8-isoprostane-F_2α , a marker of oxidative stress, was significantly reduced (490.5 pg/ml at baseline v. 406.7 pg/ml at 12 weeks, p < 0.05) and plasma superoxide dismutase activity was significantly increased in the ET group (1.49 U/ml at baseline v. 1.64 U/ml at 12 weeks, p < 0.05). Finally, C-reactive protein, a marker of inflammation, was significantly reduced (0.276 mg/dl at baseline v. 0.180 mg/dl at 12 weeks, p < 0.05) in the ET group following exercise-training. Twelve weeks of cardiac rehabilitation improved endothelial function and arterial stiffness possibly through increased nitric oxide production and reductions in oxidative stress and inflammation. These results suggest that exercise-training may reduce the risk of future cardiovascular events through improvements in endothelial function and arterial stiffness and reductions in oxidative stress and inflammation.