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

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01432639
• Other study ID #: PTDC/DES/113753/2009
• Status: Completed
• Phase: N/A
• First received: September 7, 2011
• Last updated: June 5, 2013
• Start date: May 2011
• Est. completion date: November 2012

Study information

• Verified date: June 2013
• Source: Universidade do Porto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Portugal: Health Ethic Committee
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arteritis
• Coronary Artery Disease
• Coronary Disease
• Inflammation
• Myocardial Ischemia

Intervention

Other:
• Exercise-based cardiac rehabilitation program
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.

Locations

Country	Name	City	State
Portugal	Centro Hospitalar de Vila Nova de Gaia/Espinho	Vila Nova de Gaia

Sponsors (3)

Lead Sponsor	Collaborator
Universidade do Porto	Centro Hospitalar de Vila Nova de Gaia/Espinho, Research Center in Physical Activity, Health and Leisure, Portugal

Country where clinical trial is conducted

Portugal, 

References & Publications (8)

Chesterton LJ, Sigrist MK, Bennett T, Taal MW, McIntyre CW. Reduced baroreflex sensitivity is associated with increased vascular calcification and arterial stiffness. Nephrol Dial Transplant. 2005 Jun;20(6):1140-7. Epub 2005 Apr 12. — View Citation

Edwards DG, Schofield RS, Magyari PM, Nichols WW, Braith RW. Effect of exercise training on central aortic pressure wave reflection in coronary artery disease. Am J Hypertens. 2004 Jun;17(6):540-3. — View Citation

Graham LN, Smith PA, Stoker JB, Mackintosh AF, Mary DA. Time course of sympathetic neural hyperactivity after uncomplicated acute myocardial infarction. Circulation. 2002 Aug 13;106(7):793-7. — View Citation

Laing ST, Gluckman TJ, Weinberg KM, Lahiri MK, Ng J, Goldberger JJ. Autonomic effects of exercise-based cardiac rehabilitation. J Cardiopulm Rehabil Prev. 2011 Mar-Apr;31(2):87-91. doi: 10.1097/HCR.0b013e3181f1fda0. — View Citation

Psychari SN, Apostolou TS, Iliodromitis EK, Kourakos P, Liakos G, Kremastinos DT. Inverse relation of C-reactive protein levels to heart rate variability in patients after acute myocardial infarction. Hellenic J Cardiol. 2007 Mar-Apr;48(2):64-71. — View Citation

Ribeiro F, Alves AJ, Duarte JA, Oliveira J. Is exercise training an effective therapy targeting endothelial dysfunction and vascular wall inflammation? Int J Cardiol. 2010 Jun 11;141(3):214-21. doi: 10.1016/j.ijcard.2009.09.548. Epub 2009 Nov 6. Review. — View Citation

Sandercock GR, Grocott-Mason R, Brodie DA. Changes in short-term measures of heart rate variability after eight weeks of cardiac rehabilitation. Clin Auton Res. 2007 Feb;17(1):39-45. Epub 2007 Feb 6. — View Citation

Weber T, Auer J, O'rourke MF, Kvas E, Lassnig E, Lamm G, Stark N, Rammer M, Eber B. Increased arterial wave reflections predict severe cardiovascular events in patients undergoing percutaneous coronary interventions. Eur Heart J. 2005 Dec;26(24):2657-63. Epub 2005 Sep 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Autonomic Function	Autonomic function will be assessed by resting heart rate variability, heart rate recovery after maximal exercise and circulating levels of norepinephrine and epinephrine.	Change from Baseline in Autonomic Function at 8 weeks of Cardiac Rehabilitation Program	No
Secondary	Arterial Stiffness	Arterial Stiffness will be assessed by carotid-femoral pulse wave velocity and the aortic augmentation index.	Change from Baseline in Arterial Stiffness at 8 weeks of Cardiac Rehabilitation Program	No
Secondary	Endothelial Function	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).	Change from Baseline in Endothelial Function at 8 weeks of Cardiac Rehabilitation Program	No
Secondary	Cardiorespiratory Fitness	Maximal or symptom-limited treadmill exercise testing will be conducted using the modified Bruce protocol.	Change from Baseline in Cardiorespiratory Fitness at 8 weeks of Cardiac Rehabilitation Program	No
Secondary	Inflammatory Biomarkers	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).	Change from Baseline in Inflammatory Biomarkers at 8 weeks of Cardiac Rehabilitation Program	No
Secondary	Anthropometrics	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).	Change from Baseline in Anthropometrics at 8 weeks of Cardiac Rehabilitation Program	No
Secondary	Blood Pressure	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).	Change from Baseline in Blood Pressure at 8 weeks of Cardiac Rehabilitation Program	No
Secondary	Dietary Intake	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).	Change from Baseline in Dietary Intake at 8 weeks of Cardiac Rehabilitation Program	No
Secondary	Daily Physical Activity	Physical activity will be objectively measured for 7 consecutive days using the ActiGraph accelerometer (model GT1M, Florida, USA).	Change from Baseline in Daily Physical Activity at 8 weeks of Cardiac Rehabilitation Program	No
Secondary	Biochemical Parameters	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.	Change from Baseline in Biochemical Parameters at 8 weeks of Cardiac Rehabilitation Program	No