Arterial Stiffening is Associated with Exercise Intolerance and Hyperventilatory Response in Patients with Coronary Artery Disease

Exercise intolerance is a common feature of patients with coronary artery disease (CAD). Arterial stiffness is increased in CAD patients; however, the association between arterial stiffness and exercise capacity of CAD patients has not been fully clarified. In this study, we investigated the association between arterial stiffness and the exercise capacity of 62 CAD patients (67 ± 7 yo, 49 men). The patients underwent symptom-limited cardiopulmonary exercise testing and measurement of pulse wave velocity (PWV). The patients were divided into the high-PWV group (n = 31) and the low-PWV group (n = 31), according to the median PWV (1622 cm/sec). In exercise testing, the peak VO 2 was lower in the high-PWV group than in the low-PWV group. VE/VCO 2 slope was higher and the time to ST depression was shorter in the high-PWV group than in the low-PWV group. Multivariate analysis results showed that PWV significantly correlated with peak VO 2 as well as sex. PWV also significantly correlated with time to ST depression and VE/VCO 2 slope. In conclusion, patients with high PWV had lower exercise capacity than patients with low PWV. A low myocardial ischemia threshold, as well as an enhancement of the ventilatory response to exercise, was also found in patients with high PWV

Beta-Blockers and Oxidative Stress in Patients with Heart Failure

Oxidative stress has been implicated in the pathogenesis of heart failure. Reactive oxygen species (ROS) are produced in the failing myocardium, and ROS cause hypertrophy, apoptosis/cell death and intracellular Ca2+ overload in cardiac myocytes. ROS also cause damage to lipid cell membranes in the process of lipid peroxidation. In this process, several aldehydes, including 4-hydroxy-2-nonenal (HNE), are generated and the amount of HNE is increased in the human failing myocardium. HNE exacerbates the formation of ROS, especially H2O2 and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca2+ overload. Treatment with beta-blockers such as metoprolol, carvedilol and bisoprolol reduces the levels of oxidative stress, together with amelioration of heart failure. This reduction could be caused by several possible mechanisms. First, the beta-blocking effect is important, because catecholamines such as isoproterenol and norepinephrine induce oxidative stress in the myocardium. Second, anti-ischemic effects and negative chronotropic effects are also important. Furthermore, direct antioxidative effects of carvedilol contribute to the reduction of oxidative stress. Carvedilol inhibited HNE-induced intracellular Ca2+ overload. Beta-blocker therapy is a useful antioxidative therapy in patients with heart failure