Effects of Exercise Training on Endothelial Function, Inflammation, Arterial Stiffness and Autonomic Function in CAD

Effects of Exercise Training on Endothelial Function, Inflammation, Arterial Stiffness and Autonomic Function in CAD

Effects of Exercise Training on Endothelial Function, Inflammation, Arterial Stiffness and Autonomic Function in Coronary Artery Disease Patients

Centro Hospitalar de Vila Nova de Gaia/Espinho, Research Center in Physical Activity, Health and Leisure, Portugal

The main purposes of this study is to analyze, in a randomized controlled trial, the effects of an exercise-based cardiac rehabilitation program (i) on biomarkers of endothelial function, (ii) on biomarkers of inflammation, (iii) on autonomic function, and (iv) on arterial stiffness in coronary artery disease patients (CAD). Additionally, the investigators aim to analyze the (v) contribution of age and the changes in traditional risk factors to the modification of the endothelial dysfunction and inflammation, and (vi) the contribution of the changes in inflammatory and endothelial function biomarkers to the modification of autonomic function and arterial stiffness. The investigators hypothesize that exercise training will improve the autonomic function, arterial stiffness and mitigate the endothelial dysfunction and inflammation in CAD patients even in the absence of significant changes in traditional risk factors. Thus, the investigators expect with the present study to promote, develop and expand the knowledge in this field by assessing the impact of exercise on a pool of markers that provide a wide picture of the pathophysiological processes underlying CAD.

Myocardial infarction, Autonomic function, Arterial Stiffness, Endothelial function, Inflammation, Rehabilitation program, Exercise

The intervention consists of usual medical care (i.e., medicine prescription and counseling of lifestyle modifications) and an supervised outpatient aerobic exercise training, which will be performed 3 days per week for 8 weeks. Each exercise session include 10 min of warm up, 35 min of aerobic exercise (i.e., cycloergometer or treadmill) and 10 min of cool down. The exercise intensity will be calculated as 65- 75% of maximal heart rate achieved in the treadmill exercise testing. Individualized exercise prescription will be periodically adjusted. A perceived exertion scale will be used as an adjunctive intensity modulator. In addition, each patient will be encouraged to daily exercise outside the formal exercise program.

Autonomic function will be assessed by resting heart rate variability, heart rate recovery after maximal exercise and circulating levels of norepinephrine and epinephrine.

Arterial Stiffness will be assessed by carotid-femoral pulse wave velocity and the aortic augmentation index.

Using commercially available assay kits (R&D Systems, Minneapolis, MN, USA), the serum levels of sICAM-1 and sVCAM-1 will be measured in serum by an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions and read at 450 nm using a microplate reader (Labsystems iEMS MF controlled by Ascent software v. 2.4, Dynex Labsystems).

Maximal or symptom-limited treadmill exercise testing will be conducted using the modified Bruce protocol.

Using commercially available assay kits (R&D Systems, Minneapolis, MN, USA), the serum levels of CRP, IL-10 and IL-6 will be measured in serum by an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions and read at 450 nm using a microplate reader (Labsystems iEMS MF controlled by Ascent software v. 2.4, Dynex Labsystems).

Height and weight measurements will be assessed using a standard wall-mounted stadiometer and portable digital beam scale (SECA, 708), respectively. Body mass index will be calculated from the ratio of weight (kg) to squared height (m2). Percentage of fat mass will be estimated by bioelectrical impedance analysis (BC-532, Tanita, Tokyo, Japan).

Resting systolic and diastolic blood pressure will be measured using a digital automatic blood pressure monitor (Omron Pressmate BP10, Omron Healthcare Co., Ltd, Kyoto, Japan).

Dietary intake will be assessed using a 4-day food diary as representative of the usual intake. Patients will be asked to provide detailed information concerning the food and beverages intake for four days (Sunday and 3-week days).

Physical activity will be objectively measured for 7 consecutive days using the ActiGraph accelerometer (model GT1M, Florida, USA).

Fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol, triglycerides, and HbA1c will be measured by enzymatic methods (912 automatic analyzer, Roche Diagnostic, Basel, Switzerland). Low-density lipoprotein cholesterol will be calculated using the Friedewald equation, except if triglycerides > 400 mg/dL.

Inclusion Criteria: acute myocardial infarction Exclusion Criteria: ventricular tachyarrhythmia uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg) significant valvular disease unstable angina pectoris reduced left ventricular function (ejection fraction < 45%) abnormal hemodynamic response myocardial ischemia and/or severe ventricular arrhythmias during baseline exercise testing uncontrolled metabolic disease (e.g. uncontrolled diabetes or thyroid disease) presence of pulmonary and renal co-morbidities peripheral artery disease and/or orthopedic limitations

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