Aging is a major risk factor for cardiovascular disease (CVD), contributing to progressive macrovascular and microvascular dysfunction. Macrovascular impairments, such as arterial stiffening and endothelial dysfunction, reduce nitric oxide (NO) bioavailability, leading to hypertension and impaired blood flow regulation. Microvascular dysfunction exacerbates cardiovascular decline by compromising capillary perfusion and tissue oxygenation, increasing susceptibility to ischemic events. Preserving vascular function is essential for maintaining cardiovascular health in aging populations. Low-intensity aerobic exercise (LIAE) improves cardiovascular health and mobility, particularly in populations unable to perform high-intensity exercise. However, LIAE alone often fails to induce significant vascular adaptations, such as improved arterial compliance or endothelial function, highlighting the need for optimized interventions. Blood Flow Restriction (BFR) enhances vascular adaptations during low-intensity exercise by inducing localized hypoxia, stimulating endothelial function and arterial remodeling. While BFR may transiently increase blood pressure and arterial stiffness, its vascular benefits resemble those of high-intensity exercise at lower workloads. However, research on BFR's acute vascular effects during aerobic exercise in older adults remains limited. Current studies have focused on perceptual and hemodynamic responses to LIAE+BFR but lack direct assessments of macrovascular (e.g., flow-mediated slowing) and microvascular function. Older adults may exhibit distinct vascular responses, yet data are scarce. This study examines acute vascular responses to LIAE+BFR and high-intensity interval exercise (HIIE) in young and older adults. Hypothesis: 1. BFR combined with LIAE will elicit greater acute microvascular and macrovascular responses in older adults than in younger adults. 2. These responses will be comparable to HIIE without BFR, suggesting BFR enhances LIAE's efficacy to high-intensity levels. 3. Any transient vascular dysfunction (e.g., increased arterial stiffness) will normalize within 30 minutes post-exercise, supporting safety in aging populations.
In this parallel-group crossover randomized trial, young and older adult participants will be randomly assigned to two experimental conditions: LIAE+BFR and HIIE. These two conditions were specifically chosen because they are known to induce similar haemodynamic responses. Each participant will visit the laboratory on three separate occasions, with at least one week between visits allowing recovery and minimizing potential carryover effects. On Visit 1, participants will be familiarized with the exercise and testing protocols, undergo body composition measurements, and have baseline macrovascular and microvascular function evaluated twice, 30 minutes apart, in a resting condition (control). On Visits 2 and 3, participants will perform the experimental conditions in a simple randomized order, with allocation concealed until arrival at the laboratory. The simple randomization scheme sequence will be generated by Dr. XM using a web-based randomization tool (http://www.randomizer.org/) and placed in sequentially numbered, opaque, sealed envelopes to ensure allocation concealment and minimize bias. Researchers conducting field assessments will remain blinded to group allocation until the day of the first visit. Each session will begin with 15 minutes of supine rest on a cushioned examination table, followed by baseline assessments of brachial (bSBP) and central blood pressure (cSBP), heart rate (HR), microvascular function using finger photoplethysmography (Vicorder, 80 beats medical, Berlin, Germany)., macrovascular function using FMS, and central PWV (cPWV). After baseline assessments, participants will engage in one of the randomized aerobic exercise conditions, lasting approximately 30 minutes. The workload will be equalized considering intensity and stimulus time (intensity x duration) and the protocol is directly inspired by a previous study. In the LIAE+BFR condition, participants will walk on a treadmill (Technogym Excite Run, Technogym SpA, Cesena, Italy) for 20 minutes, using a 5 cm × 75 cm pneumatic cuff (Occlusion Cuff Pro®, Occlusion Cuff LLC, 2024) inflated to 1.3 times the individual's ankle SBP (Suga et al., 2012) The intensity will be set between 30-39% of heart rate reserve (HRR), a widely used method for prescribing aerobic exercise intensity (Liguori et al., 2021). In the HIIE condition, participants will perform a 20-minute treadmill-based high-intensity interval training, alternating between 60-seconds high-intensity intervals at 60-89% HRR and 60-second active recovery intervals at 40-50% HRR. Treadmill speed will be adjusted dynamically to maintain target intensities, while the incline remains at 1%. HR, the Modified Borg Rate of Perceived Exertion (RPE) scale, and the Rating of perceived discomfort will be continuously monitored throughout both exercise sessions to ensure adherence to the prescribed intensity levels. Immediately after exercise, participants will return to the examination table for a 30-minute recovery period, during which brachial blood pressure, heart rate, and micro- and macrovascular function will be reassessed at 5- and 30-minutes post-exercise and compared to resting values. These post-exercise time points aim to characterize the biphasic response of macro- and microvascular function. All participants will report to the laboratory between 8:00 AM and 12:00 PM, with room temperature controlled between 20-22°C. Participants will be instructed to avoid caffeine and alcohol for 24 hours, fully void before the session, and refrain from vigorous physical activity for 24 hours before each session, including the familiarization session. All evaluations will be conducted by four trained physiotherapy students per participant (4:1), each with over 30 hours of training in the evaluation and exercise protocols. Throughout all sessions, a certified professional in basic life support (BLS) and automated external defibrillator (AED) use will be present at the clinic.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
52
In the LIAE+BFR condition, participants will walk on a treadmill for 20 minutes at 30-40% of heart rate reserve (HRR), with a pneumatic cuff inflated to 1.3 times the individual's ankle systolic blood pressure, using a 5cm wide x 75cm long commercial cuff around each upper thigh. Treadmill speed will be adjusted dynamically to maintain target intensities, while the incline remains at 1%. Heart Rate, the Modified Borg Rate of Perceived Exertion scale, and the Rating of perceived discomfort will be continuously monitored throughout both exercise sessions to ensure adherence to the prescribed intensity levels.
In the HIIE condition, participants will perform a 20 minutes treadmill-based HIAE, alternating between 60-seconds high-intensity intervals at 60-89% HRR and 60-second active recovery intervals at 40-50% HRR. Treadmill speed will be adjusted dynamically to maintain target intensities, while the incline remains at 1%. Heart Rate, the Modified Borg Rate of Perceived Exertion scale, and the Rating of perceived discomfort will be continuously monitored throughout both exercise sessions to ensure adherence to the prescribed intensity levels.
Egas Moniz School of Health and Science
Almada, Portugal
Change in macrovascular function
We will use the slowing of the pulse wave velocity (PWV) recorded between the upper arm and the wrist as an index of macrovascular function. PWV is inversely related to arterial distensibility; a widening of the brachial artery cross-section will cause a drop in post-occlusive PWV. Macrovascular function will be evaluated using EndoFMS (Vicorder, Berlin, Germany), and the response parameters are PWVmin and PWV% change from pre-occlusion values. The percentage change from initial PWV is called FMS. The default cuff placement is a 10 cm brachial cuff on the upper arm and a 7 cm wrist cuff on the selected limb. The test is performed with the patient lying horizontally, the right arm extended at a 60-degree angle, and the hand rotated palm up. After the patient relaxes, the test starts with a target occlusion pressure 30 mmHg above systolic pressure. Brachial PWV is measured between the wrist and upper arm over 10 minutes, with a 5-minute occlusion period.
Time frame: At rest and re-evaluated 5- and 30-minutes into recovery following the experimental conditions
Change in central arterial stiffness
To measure arterial stiffness, we will assess carotid-femoral pulse wave velocity (cPWV) using a Vicorder module (Berlin, Germany). Participants will be in a reclined position, with a minimum of 10 minutes of rest. A 100 mm blood pressure cuff will encircle the upper thigh, and a 30 mm partial cuff will be applied around the neck at the level of the carotid arteries, above the thyroid prominence. The direct path length will be measured from the suprasternal angle to the middle of the femoral blood pressure cuff by the same operator. Both cuffs will be simultaneously inflated to 60 mm Hg to capture femoral and carotid waveforms. Continuous recordings will be obtained beat-to-beat for at least 3 minutes. Automated software will determine the wave\'s foot using an intersecting tangent algorithm. The time delay between the foot of the carotid and femoral waveforms will provide the average TT every 3.5 seconds.
Time frame: At rest and re-evaluated 5- and 30-minutes into recovery following the exercise condition
Change in blood pressure
The brachial artery pulse waveform obtained oscillometrically, will be analyzed using the Pulse Wave Analysis (PWA) function of the Vicorder® device (Berlin, Germany), and the aortic waveform calculated using a transfer function. This enables calculation of arterial system parameters, including cSBP, augmentation pressure (AugPress), augmentation index (AugInd), central peripheral pressure (cPP), cardiac output, and total peripheral resistance. Initial waves will be omitted, and good-quality consecutive pulse waves will be analyzed.
Time frame: At rest and re-evaluated after each set and 5- and 30-minutes into recovery following the exercise condition
Change in microvascular function
Microvascular function will be assessed using EndoCheckPAR (Vicorder, Berlin, Germany). Participants will be in a supine position with their arms comfortably positioned. Changes in the peripheral arterial dilation ratio (PAR) signal to reactive hyperemia (RH) will be measured at the fingertip with photoplethysmographs and an inflating device controlled by a computer algorithm. The RH procedure consists of a 30-second calibration, a 5-minute baseline recording, followed by 5 minutes of blood flow occlusion of the test arm using an upper arm blood pressure cuff inflated to 30 mmHg above the patient's systolic brachial pressure. After cuff deflation, the PAR tracing will be recorded for another 3 minutes. The software automatically normalizes this ratio to the concurrent signal from the contralateral, non-occluded forearm to correct for confounding variables. This ratio is then multiplied with a baseline correction factor to obtain Measured Peak, Max Reference Peak, and Max PAR.
Time frame: At rest and re-evaluated 5- and 30-minutes into recovery following the exercise condition
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