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

Официальное название

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)

Обзор

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.

Вмешательства

• Поведенческое Aerobic exercise (MIT)
  Patients allocated to the MIT group will train on a cycle ergometer three days a week for 12 weeks (36 sessions). They will cycle continuously between the first and second ventilatory thresholds. The duration of each exercise session will be set according to the estimated energy expenditure of the long HIIT and short HIIT groups for each training block (energy expenditure-adjusted exercise sessions). All sessions will be supervised, and patients will be asked to avoid additional exercise. They w
• Поведенческое Aerobic exercise (Short HIIT)
  Patients allocated to the Short HIIT group will train on a cycle ergometer three days a week for 12 weeks (36 sessions). They will perform from two to four 4-repetition sets of 1-min above the second ventilatory threshold. Patients will perform 1- and 3-min active recovery periods below the first ventilatory threshold between repetitions and sets, respectively. The total time spent at high intensity will range from eight to 16 min. All sessions will be supervised, and patients will be asked to a
• Поведенческое Aerobic exercise (Long HIIT)
  Patients allocated to the Long HIIT will train on a cycle ergometer three days a week for 12 weeks (36 sessions). They will perform from two to four 4-min high-intensity exercise bouts above the second ventilatory threshold separated by 4-min active recovery periods below the first ventilatory threshold. The total time spent at high intensity will range from eight to 16 min. All sessions will be supervised, and patients will be asked to avoid additional exercise training. They will be allowed to

Первичные конечные точки

• Change from baseline in endothelial function at 7 weeks [Срок оценки: 7 weeks]
• Change from baseline in endothelial function at 14 weeks [Срок оценки: 14 weeks]
• Change from baseline in endothelial-independent dilation at 7 weeks [Срок оценки: 7 weeks]
• Change from baseline in endothelial-independent dilation at 14 weeks [Срок оценки: 14 weeks]
• Change from baseline in peak cardiopulmonary parameters at 7 weeks [Срок оценки: 7 weeks]
• Change from baseline in peak cardiopulmonary parameters at 14 weeks [Срок оценки: 14 weeks]
• Change from baseline in aerobic efficiency at 7 weeks [Срок оценки: 7 weeks]
• Change from baseline in aerobic efficiency at 14 weeks [Срок оценки: 14 weeks]
• Change from baseline in resting serum BDNF concentration at 7 weeks [Срок оценки: 7 weeks]
• Change from baseline in resting serum BDNF concentration at 14 weeks [Срок оценки: 14 weeks]

Вторичные конечные точки (12)

• Change from baseline in pulmonary function at 7 and 14 weeks [Срок оценки: 7 and 14 weeks]
• Change from baseline in resting cardiopulmonary parameters at 7 and 14 weeks [Срок оценки: 7 and 14 weeks]
• Change from baseline in cardiopulmonary parameters at first and second ventilatory thresholds at 7 and 14 weeks [Срок оценки: 7 and 14 weeks]
• Change from baseline in cardiopulmonary variables measured during the recovery at 7 and 14 weeks. [Срок оценки: 7 and 14 weeks]
• Change from baseline in MacNew domains at 7 and 14 weeks [Срок оценки: 7 and 14 weeks]
• Change from baseline in body composition at 7 and 14 weeks [Срок оценки: 7 and 14 weeks]
• Change from baseline in resting heart rate variability (HRV) at 7 and 14 weeks [Срок оценки: 7 and 14 weeks]
• Change from baseline in echocardiographic variables at 7 and 14 weeks [Срок оценки: 7 and 14 weeks]
• Change from baseline in blood analysis variables at 14 weeks. [Срок оценки: 14 weeks]
• Change from baseline in ability to inhibit cognitive interference at 7 and 14 weeks [Срок оценки: 7 and 14 weeks]
• Change from baseline in verbal memory performance at 14 weeks [Срок оценки: 14 weeks]
• Change from baseline in visuospatial working memory performance at 14 weeks [Срок оценки: 14 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Испания · 2 центра

• Instituto de Investigación Sanitaria y Biomédica de Alicante — Alicante
• Centro de Investigación del deporte — Elche

Публикации

• Fuertes-Kenneally L, Blasco-Peris C, Casanova-Lizon A, Baladzhaeva S, Climent V, Sarabia JM, Manresa-Rocamora A. Effects of high-intensity interval training on vascular function in patients with cardiovascular disease: a systematic review and meta-analysis. Front Physiol. 2023 Jul 27;14:1196665. doi: 10.3389/fphys.2023.1196665. eCollection 2023. PMID 37576344

Идентификаторы

NCT: NCT06788275 · PI2023/154 · ISABIAL

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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