Aerobic Exercise-induced Effect on Endothelial Function in Patients With Ischaemic Heart Disease

Effect of Different Aerobic Exercise Methods in Cardiac Rehabilitation on Endothelial Function in Patients With Ischaemic Heart Disease and Study of the Associated Physiological Mechanisms (ENDO-R)

Endothelial dysfunction is one of the aetiological factors in ischaemic heart disease (IHD). Aerobic exercise is effective in improving endothelial function, as measured by flow-mediated dilation (FMD), in patients with IHD. Within the aerobic exercise methods, there is evidence showing that high-intensity interval training (HIIT) increases FMD to a greater extent than moderate-intensity training (MIT) in these patients. Notably, in a recent review, our research group found that only studies performing long bouts of HIIT (long HIIT: higher than 1 min) found a greater effect on FMD, while no differences were found in those studies using short bouts of HIIT (short HIIT: ≤ 1 min) and MIT. However, no experimental studies comparing the effect of long HIIT, short HIIT, and MIT on endothelial function, as well as other predictors of mortality, such as cardiorespiratory fitness, brain-derived neurotrophic factor (BDNF) levels or parasympathetic branch activity, have been performed. Therefore, the main objective of this project will be to compare the effect of the three aerobic exercise methods on endothelial function, as measured by FMD, in patients with IHD. Complementarily, the effect of aerobic exercise, depending on the exercise method, on different mortality predictors will be compared. For this purpose, a multicentre randomised study will be carried out (2 hospitals in Elche and one in Alicante). Assessors will be blinded to the patients allocation. Participants will be aware about their allocation in the experimental groups due to the nature of the study. A total of 132 men and women with IHD (66 per sex), diagnosed between three and 12 months before the start of the intervention, aged between 45 and 75 years, and without limitations for the practice of exercise training, will be recruited. All patients will train 3 days a week for 12 weeks. Participants will be assessed before the intervention (i.e., pre), at 6 weeks of training (i.e., mid) and after the intervention (i.e., post). Physiological and psychological variables will be registered in the assessment periods. Training intensity will be individually prescribed based on the cardiopulmonary exercise test (CPET). Intensity exercise will be adapted after the first part of the intervention. Analysis of covariance will be used to compare the values of the three groups after the intervention for the continuous variables, including the pre-intervention value as a covariate, while a logistic regression model will be used for the categorical variables.

Inclusion Criteria:

• Men and women aged between 45 and 75 years.
• Diagnosed with acute myocardial infarction, unstable or stable angina.
• Treated with percutaneous coronary intervention, coronary artery bypass grafting, or conservative treatment.
• Event or intervention within 3 to 12 months prior to participation in the study.
• Fluency in speaking and reading Spanish.
• Residing in Elche or surrounding areas and able to attend evaluations and the exercise programme (not planning to be absent for more than one week during the programme).
• Functional Class I-II according to the New York Heart Association (NYHA) classification.
• No physical limitations for exercise.
• Stable optimal medical treatment.
• Physically inactive, defined as 1) not meeting the World Health Organization recommendations for both aerobic and strength exercise, and 2) not participating in a structured exercise programme at least 3 days per week for more than 3 months. Both conditions must be met for inclusion. Note: Casual walking is not considered grounds for exclusion.

Exclusion Criteria:

• Use of walking assistive devices.
• Treatment with chemotherapy for any type of cancer in the past 2 years.
• Hospitalisation in an intensive care unit in the past 6 months for reasons other than the ischaemic event.
• Acute myocardial infarction group IV Killip-Kimball.
• Obesity grade III (≥40.0 kg/m²).
• Medical contraindication for inclusion in an exercise programme.
• Diabetes with uncontrolled blood glucose levels.
• Poorly controlled hypertension: resting blood pressure > 180/110 mmHg.
• Chest pain with exertion or ST-segment changes suggestive of residual ischemia during ergometry. Residual ischemia.
• Severely reduced functional capacity on initial ergometry (<5 metabolic equivalent of task).
• Left ventricular ejection fraction less than 50%.
• Severe stenosis of the left main coronary artery (>50% significant disease).
• Severe aortic stenosis, left ventricular outflow tract obstruction (e.g., obstructive hypertrophic cardiomyopathy) or aortic dissection.
• Severe valvulopathy.
• Acute pulmonary embolism or deep vein thrombosis.
• Severe pulmonary hypertension.
• Acute heart failure.
• Acute endocarditis, myocarditis, or pericarditis.
• Acute or chronic renal insufficiency (estimated glomerular filtration rate <30 ml/min).
• Pulmonary fibrosis or interstitial disease (severe respiratory insufficiency or confirmed chronic obstructive pulmonary disease).
• Uncontrolled cardiac arrhythmias/hemodynamically unstable.
• Permanent or persistent/paroxysmal atrial fibrillation with episodes in the past 6 months.
• High-grade cardiac block.
• Presence of implantable devices: cardiac resynchronization therapy pacemaker, implantable cardioverter defibrillators, or pacemaker.
• Presence of ischaemic symptoms during the incremental exercise test performed before the intervention.
• Severe autonomic or peripheral neuropathy.
• Use of nitrates in pharmacological treatment.
• Any planned surgical or medical intervention during the study period.
• Plans to participate in or current participation in other studies that may interfere with this study.
• Current pregnancy or intention to become pregnant during the study period.