High Intensity Aerobic Interval Training With Mediterranean Diet Recommendations in Post-Myocardial Infarct Patients

Study Overview
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Brief Summary
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Acute myocardial infarction (MI) continues remains to be a major cause of death and disability worldwide. Exercise therapy has long been used for rehabilitation purposes and the benefit of regular physical exercise is also well established. The intensity of aerobic exercise training is a key issue in cardiac rehabilitation programmes.Endurance aerobic training is typically performed as continuous training at moderate to-high exercise intensity in steady-state conditions of aerobic energetic yield. However, interval training (i.e., repeated bouts of short-duration, high to severe- or severe to extreme-intensity exercise, separated by brief periods of lower-intensity) has been proposed to be more effective than continuous exercise for improving exercise capacity. Adding to that, health-related adaptations to low-volume and high intensity interval training have been presented. On the other hand, the Mediterranean Diet has been widely reported to be a model of healthy eating for its contribution to a favourable health status and a better quality of life, reducing in overall mortality from cardiovascular diseases. Considering all the above mentioned in MI population, the principal objective for the INTERFARCT study will be to assess the effects of different programs of high intensity aerobic interval training and Mediterranean Diet recommendations in the clinical condition, cardio-respiratory fitness, biomarkers, ventricular function and perception of quality of life after myocardial infarction. Methods/Design: One hundred and fifty people after suffering acute MI will perform different assessments to evaluate clinical history, physical, biochemical and nutritional condition, and quality of life before and after 16-week of follow-up. All participants will receive Mediterranean diet recommendations and will be randomly assigned to attention control group (diet and physical activity recommendations) or exercise groups (diet recommendations plus high-intensity aerobic interval exercise). Participants assigned to an exercise group will train 2 days/week under supervision (day 1-treadmill and day 2-bike protocol). There will be two aerobic exercise groups: 1) high-intensity interval training and high-volume (HV-HIIT) group, and 2) high-intensity interval training and low-volume (LV-HIIT) group.

Detailed Description
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The management of acute myocardial infarction (MI) continues to undergo major changes, because it remains to be a major cause of death and disability worldwide. Myocardial infarction may be the first manifestation of coronary artery disease or it may occur, repeatedly, in patients with established disease. The term myocardial infarction may have major psychological and legal implications for the individual and society. It is an indicator of one of the leading health problems in the world and it is an outcome measure in clinical trials. Coronary heart disease is a chronic condition and patients are at high risk for new events and premature death. Several evidence-based interventions can improve prognosis. Lifestyle changes should be explained and proposed to the patients before discharge, including cessation of smoking, blood pressure control, and advice regarding diet and weight control, and the encouragement of physical activity. Exercise therapy has long been used for rehabilitation purposes and the benefit of regular physical exercise is also well established. 1 The intensity of aerobic exercise training is a key issue in cardiac rehabilitation programmes. Exercise intensity is directly linked to both the amount of improvement in exercise capacity and the risk of adverse events during exercise, and intensity ranges for aerobic training prescription and design are included in several guidelines and publications regarding secondary prevention and cardiac rehabilitation. Aerobic fitness is recognized as a robust indicator of cardiovascular health and a well-established predictor of total and cardiovascular mortality in subjects with and without coronary heart disease. Direct measurements of peak oxygen uptake (VO2peak) and ventilatory thresholds are considered the gold standard references for the evaluation of aerobic metabolism function and, consequently, for aerobic exercise intensity assessment and design. The increase of VO2peak after a period of exercise training depends of the components of frequency, intensity, time or volume, and type or modality (FITT principle), which constitute the key to achieve a safe exercise training effect. Endurance aerobic training is typically performed as continuous training at moderate to-high exercise intensity in steady-state conditions of aerobic energetic yield. However, interval training (i.e., repeated bouts of short-duration, high to severe- or severe to extreme-intensity exercise, separated by brief periods of lower-intensity) has been proposed to be more effective than continuous exercise for improving exercise capacity. Adding to that, health-related adaptations to low-volume and high intensity interval training have been presented. This type of training is characterized by sessions that involve a relatively small total amount of exercise at high-intensity (i.e., ≤10 min). To our knowledge, there are no studies that compare HIIT with different volume exercise in patients who have suffered MI. On the other hand, the relevance of overall high-quality food patterns, rather than focus on single nutrients and foods, has emerged as a powerful paradigm to address the diet and to assess their potential cardiovascular disease preventive effects. The Mediterranean Diet, representing the dietary pattern usually consumed among the populations bordering the Mediterranean sea, has been widely reported to be a model of healthy eating for its contribution to a favourable health status and a better quality of life, reducing in overall mortality from cardiovascular diseases. Considering all the above mentioned in MI population: 1) the combination of the Mediterranean Diet with exercise seems critical in greater reduction of mortality from cardiovascular disease and improved cardiovascular biomarkers, 2) no previous studies have compared the effects of a combined dietary recommendations specific to people after MI with exercise training at high intensity interval training and different volumes (i.e., high- and low-volume).INTERFARCT study is designed to investigate what effect different 16-week aerobic INTERval exercise programs with Mediterranean Diet recommendations will have in people after suffering an acute myocardial inFARCTion. PRIMARY OBJECTIVE: To assess the effects of different programs of high intensity aerobic interval training and Mediterranean Diet recommendations in the clinical condition, cardio-respiratory fitness, biomarkers, ventricular function and perception of quality of life after myocardial infarction. SECONDARY OBJECTIVES To analyze the differences in the studied variables between the two high intensity aerobic interval training programs (high volumen vs low volume) with Mediterranean Diet recommendations to observe the effect of exercise volume. To analyze whether a treatment with only recommendations (exercise and diet) is effective in the secondary prevention of cardiovascular disease comparing to supervised exercise.

Official Title
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Effects of Combined High Intensity Aerobic Interval Training Program and Mediterranean Diet Recommendations in Post-Myocardial Infarct Patients: INTERFARCT Controlled Trial

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Other: HIGH VOLUME (HV) Supervised exercise
* Other: Mediterranean Diet Recommendations
* Other: Physical Activity Recommendations
* Other: LOW VOLUME (LW) Supervised exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Two months to 10 years from the cardiovascular event. Left ventricular ejection fraction > 30% Ability to undertake regular physical activity (walking and biking) Exclusion Criteria: Moderate to severe heart valvular disease. Atrial fibrilation. Uncontrolled atrial or ventricular arrhythmias. Exercise induced myocardial ischaemia. Pericardial disease. Uncontrolled hypertension. Insulin dependent diabetes mellitus. Moderate to severe chronic lung disease (Vital capacity and/or forced expiratory volume during the first second <80% to that expected for the age). Severe kidney disease (renal creatinine clearance <30 mL/min, calculated by Cockcroft-Gault formula). Anaemia (haemoglobin <12 g/dL). Life expectancy less than one year.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Attention Control Group (AC)<br>Moderate to high- intensity physical activity and Mediterranean Diet recommendations | Other: Mediterranean Diet Recommendations<br>* Participants will be interviewed regarding their usual eating habits. They will receive practical information about which are the Mediterranean Diet (DMed) foods according to the model proposed in the PREDIMED trial. Medical doctors or nurses will give this information. Before starting the program of intervention, participants will assist to an informative talk in which benefits for the health of the DMed will be exposed and general information about food composition, frequencies of consumption, etc. will be explained. Nutritional management: Diet reviews and body mass control will be performed every two weeks to assess the body composition and adherence to treatment. In the event of poor compliance strategies will be addressed for its correction.<br>Other: Physical Activity Recommendations<br>* Participants will be advised to perform, without supervision, moderate to high-intensity dynamic aerobic exercise (walking, jogging, cycling or swimming) 3-5 days per week, following an adequate warm-up of 5-15 min, at moderate to high intensity (below the ischemic threshold) for a period of 20 to 40 min (not including warm-up and cool-down) followed by a cool-down period of 5-10min. Participants will receive information related to heart rate values regarding moderate and high exercise intensity domains for the self monitoring of exercise intensity.<br>|
| Experimental: HV-HIIT<br>Supervised high volume and high intensity interval training exercise group with Mediterranean Diet recommendations. High-intensity [heart rate (HR) values up to second ventilatory threshold (VT2) to peak intensity] interval training and high-volume increasing gradually from 20 to 40 min and alternating high and moderate [HR values between first ventilatory threshold (VT1) and VT2] intensities at different protocols. | Other: HIGH VOLUME (HV) Supervised exercise<br>* Supervised exercise two nonconsecutive days per week (day 1-on the treadmill, day 2-on the bike) for 16 weeks. High-intensity interval training (HIIT) protocol on the treadmill: 5-min warm-up at a moderate-intensity, before walking 2 intervals of 4 min at high-intensity interspersed with intervals of 3 min of walking at moderate-intensity. 1-4 min cool-down at moderate-intensity. HIIT protocol on the bike: 5 to 10-min warm-up at moderate intensity. After that, 4 repetitions (1rep = 30 s high-intensity followed by 60 s moderate-intensity) and gradually increased to 16 repetitions in HV-HIIT week by week. 5-10 min cool-down at moderate-intensity<br>Other: Mediterranean Diet Recommendations<br>* Participants will be interviewed regarding their usual eating habits. They will receive practical information about which are the Mediterranean Diet (DMed) foods according to the model proposed in the PREDIMED trial. Medical doctors or nurses will give this information. Before starting the program of intervention, participants will assist to an informative talk in which benefits for the health of the DMed will be exposed and general information about food composition, frequencies of consumption, etc. will be explained. Nutritional management: Diet reviews and body mass control will be performed every two weeks to assess the body composition and adherence to treatment. In the event of poor compliance strategies will be addressed for its correction.<br>|
| Experimental: LV-HIIT<br>Supervised low volume and high intensity interval training exercise group with Mediterranean Diet recommendations. High-intensity (HR values up to VT2 to peak intensity) interval training and low-volume (20 min) alternating high and moderate (HR values between VT1 and VT2) intensities at different protocols. | Other: Mediterranean Diet Recommendations<br>* Participants will be interviewed regarding their usual eating habits. They will receive practical information about which are the Mediterranean Diet (DMed) foods according to the model proposed in the PREDIMED trial. Medical doctors or nurses will give this information. Before starting the program of intervention, participants will assist to an informative talk in which benefits for the health of the DMed will be exposed and general information about food composition, frequencies of consumption, etc. will be explained. Nutritional management: Diet reviews and body mass control will be performed every two weeks to assess the body composition and adherence to treatment. In the event of poor compliance strategies will be addressed for its correction.<br>Other: LOW VOLUME (LW) Supervised exercise<br>* Supervised exercise two nonconsecutive days per week (one day on the treadmill, and the second one on the bike) for 16 weeks. HIIT protocol on the treadmill: 5-min warm-up at a moderate-intensity, before walking 2 intervals of 4 min at high-intensity interspersed with intervals of 3 min of walking at moderate-intensity. The training session will end with a 1-4 min cool-down period at moderate-intensity. Total exercise time of 20min HIIT protocol on the bike: 10-min warm-up at moderate intensity. After that, participants will cycle for 4 repetitions (1rep = 30 s high-intensity followed by 60 s moderate-intensity) and gradually increased to 8 repetitions in LV-HIIT week by week. The training session will end with a 5-10 min cool-down period at moderate-intensity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Direct Cardio-respiratory fitness | Direct cardio-respiratory fitness will be evaluated through objectives variables such as peak oxygen uptake and ventilatory thresholds with a cardio pulmonary exercise test. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Function | Left ventricular function will focus on the assessment of cardiovascular hemodynamics by cardiac ultrasound, global cardiac mechanics in systole and diastole, and the relationship between the cardiac structure and regional myocardial function. | 16 weeks | 
| Biochemical measures: lipid metabolism | Medical doctors will ask for a biochemical analysis including all the below variables to analyze the lipid metabolism of participant: Lipid metabolism: total cholesterol (mg/dL), low-density lipoprotein cholesterol (mg/dL), high-density lipoprotein cholesterol (mg/dL), Triglycerides (mg/dL). | 16 weeks | 
| Biochemical measures: general metabolism | Medical doctors will ask for a general biochemical analysis including all the below variables to analyze a general participant's profile related to: General metabolism: urea (mg/dL), creatinine (mg/dL), glomerular filtrate (mL/min), basal glucose (mg/dL), HbA1c (%), insulin, homoeostasis model assessment index (HOMA), uric acid (mg/dL), ionogram, alanine aminotransferase (U/L), aspartate aminotransferase (U/L), blood count. | 16 weeks | 
| Biochemical measures: myocardial stress and damage | Medical doctors will ask for a general biochemical analysis including all the below variables to analyze a general participant's profile: Myocardial damage: troponin T (ng/dL), total and creatine phosphokinase cardiac specific isoenzyme (MB) (U/mL). Myocardial stress: brain natriuretic peptide (pg/mL). Neuro-hormonal state: renin, aldosterone (ng/dL). Systemic inflammation: protein C reactive (PCRus) (mg/dL), Interleukin 6 (IL-6) (pg/mL), Tumor necrosis factor-alpha (TNF-alpha) (pg/mL). Procoagulant state: D-dimer (ng/mL), fibrinogen (mg/dL). Oxidative stress: ox-LDL (units/mL). | 16 weeks | 
| Quality of Life | Participants' health-related quality of life will be determined using the 36-item Short Form Medical Outcome Questionnaire (SF-36). | 16 weeks | 
| Vascular endothelial function | Determination of carotid artery-intima-media thickness through carotid ultrasonography. | 16 weeks | 
| Dietary Assessment: dietary recall | Dietary intake and habits will be assessed by subjective assessments using open-ended surveys such as dietary recalls or records | 16 weeks | 
| Dietary Assessment: food frequency questionnaire | Dietary intake and habits will be assessed by subjective assessments using closed-ended surveys including food frequency questionnaires | 16 weeks | 
| Dietary Assessment:Mediterranean Diet Adherence Screener questionnaire | Dietary intake and habits will be assessed by subjective assessments using Mediterranean Diet Adherence Screener questionnaire. | 16 weeks | 
| Height | Height (cm) | 16 weeks | 
| Body mass | body mass (kg) | 16 weeks | 
| Waist and hip ratio | Measurements:waist and hip perimeters (cm). | 16 weeks | 
| Indirect cardiorespiratory fitness | Indirect cardiorespiratory fitness will be assessed through a fiel test called Modified Shuttle Walk Test | 16-weeks | 
| Assessment of state of depression and anxiety | Self-assessment scale instrument for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic: Hospital Anxiety & Depression Scale | 16 weeks | 
| Body composition | Bioelectrical impedance analysis (BIA) is a commonly used method for estimating body composition, and in particular body fat, fat free body fat and water. All of them as a percentage of the total body mass | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardio-respiratory fitness, high intensity exercise training