Effects of Exercise Training on Endothelial Function, Inflammation, Arterial Stiffness and Autonomic Function in CAD - Full Text View

Purpose

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.

Condition	Intervention
Coronary Artery Disease	Other: Exercise-based cardiac rehabilitation program

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Effects of Exercise Training on Endothelial Function, Inflammation, Arterial Stiffness and Autonomic Function in Coronary Artery Disease Patients

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease Exercise and Physical Fitness Rehabilitation

U.S. FDA Resources

Further study details as provided by Universidade do Porto:

Primary Outcome Measures:

Autonomic Function [ Time Frame: Change from Baseline in Autonomic Function at 8 weeks of Cardiac Rehabilitation Program ] [ Designated as safety issue: No ]
Autonomic function will be assessed by resting heart rate variability, heart rate recovery after maximal exercise and circulating levels of norepinephrine and epinephrine.

Secondary Outcome Measures:

Arterial Stiffness [ Time Frame: Change from Baseline in Arterial Stiffness at 8 weeks of Cardiac Rehabilitation Program ] [ Designated as safety issue: No ]
Arterial Stiffness will be assessed by carotid-femoral pulse wave velocity and the aortic augmentation index.
Endothelial Function [ Time Frame: Change from Baseline in Endothelial Function at 8 weeks of Cardiac Rehabilitation Program ] [ Designated as safety issue: No ]
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).
Cardiorespiratory Fitness [ Time Frame: Change from Baseline in Cardiorespiratory Fitness at 8 weeks of Cardiac Rehabilitation Program ] [ Designated as safety issue: No ]
Maximal or symptom-limited treadmill exercise testing will be conducted using the modified Bruce protocol.
Inflammatory Biomarkers [ Time Frame: Change from Baseline in Inflammatory Biomarkers at 8 weeks of Cardiac Rehabilitation Program ] [ Designated as safety issue: No ]
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).
Anthropometrics [ Time Frame: Change from Baseline in Anthropometrics at 8 weeks of Cardiac Rehabilitation Program ] [ Designated as safety issue: No ]
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).
Blood Pressure [ Time Frame: Change from Baseline in Blood Pressure at 8 weeks of Cardiac Rehabilitation Program ] [ Designated as safety issue: No ]
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 [ Time Frame: Change from Baseline in Dietary Intake at 8 weeks of Cardiac Rehabilitation Program ] [ Designated as safety issue: No ]
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).
Daily Physical Activity [ Time Frame: Change from Baseline in Daily Physical Activity at 8 weeks of Cardiac Rehabilitation Program ] [ Designated as safety issue: No ]
Physical activity will be objectively measured for 7 consecutive days using the ActiGraph accelerometer (model GT1M, Florida, USA).
Biochemical Parameters [ Time Frame: Change from Baseline in Biochemical Parameters at 8 weeks of Cardiac Rehabilitation Program ] [ Designated as safety issue: No ]
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.

Enrollment:	100
Study Start Date:	May 2011
Study Completion Date:	November 2012
Primary Completion Date:	November 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Experimental group Patients undergoing the exercise-based cardiac rehabilitation program (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. Other Name: Cardiac rehabilitation program
No Intervention: Control group Usual medical care

Arms

Assigned Interventions

Experimental: Experimental group

Patients undergoing the exercise-based cardiac rehabilitation program (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.

Other Name: Cardiac rehabilitation program

No Intervention: Control group

Usual medical care

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01432639

Locations

Portugal
Centro Hospitalar de Vila Nova de Gaia/Espinho
Vila Nova de Gaia, Portugal, 4434-502

Sponsors and Collaborators

Universidade do Porto

Centro Hospitalar de Vila Nova de Gaia/Espinho

Research Center in Physical Activity, Health and Leisure, Portugal

Investigators

Study Chair:	Jose Oliveira, PhD	Research Center in Physical Activity, Health and Leisure, Portugal
Study Director:	Fernando Ribeiro, PhD	Research Center in Physical Activity, Health and Leisure, Portugal
Principal Investigator:	Nórton L Oliveira, MSc	Research Center in Physical Activity, Health and Leisure, Portugal
Principal Investigator:	Madalena Teixeira, MD	Centro Hospitalar de Vila Nova de Gaia/Espinho

More Information

Publications:

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. Epub 2009 Nov 6. Review.

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.

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.

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.

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.

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.

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.

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.

Responsible Party:	Jose Manuel Fernandes Oliveira, Professor, Universidade do Porto
ClinicalTrials.gov Identifier:	NCT01432639 History of Changes
Other Study ID Numbers:	PTDC/DES/113753/2009
Study First Received:	September 7, 2011
Last Updated:	November 29, 2012
Health Authority:	Portugal: Health Ethic Committee

Keywords provided by Universidade do Porto:

Myocardial infarction
Autonomic function
Arterial Stiffness
Endothelial function

Inflammation
Rehabilitation program
Exercise

Additional relevant MeSH terms:

Arteritis
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Inflammation
Vascular Diseases

Cardiovascular Diseases
Vasculitis
Heart Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on May 16, 2013