Aerobic Exercise and Resistant Hypertension

Effects of Two Types of Aerobic Training on Ambulatory Blood Pressure in Hypertensives: a Systems Biology Approach

This study will examine the effects of 4 months of aerobic interval training versus continuous aerobic training on ambulatory blood pressure (ABP) and novel plasma protein biomarkers in patients with resistant hypertension. A randomized controlled trial will be performed including two exercise groups and a control group: a) moderate-intensity interval training (MIIT); b) moderate-intensity continuous training (MICT); c) usual care. MIIT could represent a superior training modality that exceeds the benefits of MICT in patients with resistant hypertension.

Study Overview

• Status: Active, not recruiting
• Conditions: Resistant Hypertension
• Intervention / Treatment: Other: Moderate-intensity interval training (MIIT); Other: Moderate-intensity continuous training (MICT)

Detailed Description

Hypertension is associated with an increased risk of cardiovascular morbidity and mortality, and its high prevalence remains a worldwide concern. Ambulatory blood pressure monitoring (ABPM) is recognized in the diagnosis and management of hypertension, and can control blood pressure better than clinic assessment. Different studies have examined the effects of aerobic training on ABP in patients with hypertension, but the effects of moderate-intensity interval training (MIIT) and moderate-intensity continuous training (MICT) on ABP and novel plasma protein biomarkers that could potentially serve to identify cardiovascular risk, have not yet been examined in patients with resistant hypertension.To fill this gap, our aims are to determine the effects of MIIT and MICT for 4 months on ABP (primary endpoint), and on proteomic biomarkers (secondary endpoints) in patients with resistant hypertension. A total of 72 participants will be randomly divided into three groups: the first group (n=24) will perform MIIT, the second group (n=24) will perform MICT, and the third control group (n=24) will maintain usual care for 4 months. All will receive usual care for 4 months, with the structured physical exercise as the only relevant change in the intervention groups.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid
    • Madrid, Madrid, Spain, 28670
      • Universidad Europea Madrid (UEM)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with resistant hypertension (RH) (i.e., systolic BP/diastolic BP >130/80 mmHg according to the American College of Cardiology/American Heart Association) despite the concurrent use of three or more antihypertensive drugs - commonly including a diuretic, a long-acting calcium channel blocker, and a blocker of the renin-angiotensin system. RH also includes patients whose BP achieves target values on ≥ 4 antihypertensive. medications (i.e., 'controlled' RH).
• Adherence to prescribed medications.
• Willing to be randomized to one of the 3 groups.
• Informed consent.

Exclusion Criteria:

• Exclusion criteria will include exercising more than 30 minutes on 3 days or more weekly.
• Severe ischemic heart disease, major psychiatric disorder and other health contraindications that may interfere in the evaluations or interventions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate-intensity interval training (MIIT); 24 participants with resistant hypertension will perform moderate-intensity interval training.	Other: Moderate-intensity interval training (MIIT); MIIT group: participants will perform 3 sessions per week for 4 months. Each session will involve a ∼3 min warm-up (joint mobility exercises and walking at ∼2.2 METs), a ∼40-50 min main period (∼6-7 reps of 4 min at ∼4.2 METs, with 3 min of active recovery at ∼2.2 METs between each interval), and a ∼3-min cool-down (joint mobility exercises and walking at ∼2.2 METs). We will select the same aerobic dose of training (i.e., kcal/kg of body weight per week) to match total energy expenditure in both exercise groups.
Experimental: Moderate-intensity continuous training (MICT); 24 participants with resistant hypertension will perform moderate-intensity continuous training.	Other: Moderate-intensity continuous training (MICT); MICT group: participants will perform 3 sessions per week for 4 months. Each session will involve a ∼3 min warm-up (joint mobility exercises and walking at ∼2.2 METs), a ∼40-50 min main period at ∼3.2 METs, and a ∼3-min cool-down (joint mobility exercises and walking at ∼2.2 METs).
No Intervention: Usual care; 24 participants with resistant hypertension will maintain usual care for 4 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 24-hour ambulatory blood pressure	Ambulatory SBP and DBP will be recorded with a validated oscillometric device over 24 hours.	Baseline to immediate post-treatment (4 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma proteome	Olink's Proximity Extension Assay (PEA) technology, using the inflammation panel, will be used to evaluate changes in the plasma proteome.	Baseline to immediate post-treatment (4 months)
Changes in albuminuria	Albuminuria will be determined from the albumin/creatinine ratio in urine.	Baseline to immediate post-treatment (4 months)
Changes in glomerular filtration rate	The estimated glomerular filtration rate (eGFR) will be determined from serum creatinine levels using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.	Baseline to immediate post-treatment (4 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body composition	Dual-energy X-ray absorptiometry (DXA) scans will performed to measure body composition (fat mass and lean mass).	Baseline to immediate post-treatment (4 months)
Change in lipid profiles	Blood analysis will be performed to evaluate HDL-C, LDL-C, total cholesterol, and triglyceride levels.	Baseline to immediate post-treatment (4 months).
Change in aerobic capacity	VO2 will be measured breath-by-breath using a gas exchange analysis system.	Baseline to immediate post-treatment (4 months).
Change in echocardiography-determined left ventricular ejection fraction	The percentage of blood volume ejected from the left ventricle with each systolic contraction [(left ventricular end-diastolic volume - left-ventricular end-systolic volume)/ left ventricular end-diastolic volume] × 100.	Baseline to immediate post-treatment (4 months).
Change in echocardiography-determined relative wall thickness (RWT)	The RWT will be calculated using the following formula: RWT = (Interventricular septum + left ventricular posterior wall thickness)/Left ventricular end-diastolic diameter).	Baseline to immediate post-treatment (4 months)
Change in echocardiography-determined left ventricular global longitudinal strain (LV-GLS)	Two-dimensional speckle tracking echocardiography will be used to determine LV-GLS The Auto Strain function will be used for out-of-cart strain assessment on saved records. GLS values will be obtained by analyzing multi-camera perspectives, including two-, three- and four-camera views.	Baseline to immediate post-treatment (4 months)
Change in echocardiography-determined left ventricular end-diastolic diameter (LVEDD)	LVEDD will be measured using two-dimensional guided M-mode imaging following recommendations from the American Society of Echocardiography.	Baseline to immediate post-treatment (4 months)
Change in echocardiography-determined left ventricular (LV) mass	LV dimensions will be expressed relative to body surface area (in m x^2).	Baseline to immediate post-treatment (4 months)
Change in echocardiography-determined left ventricular end- diastolic volume (LVEDV)	We will use the following equation to measure LVEDV: LVEDV (mL) = [7.0/(2.4 + Left ventricular end-diastolic diameter)] × Left ventricular end-diastolic diameter x^3.	Baseline to immediate post-treatment (4 months)
Change in echocardiography-determined interventricular septal wall thickness (IVS)	IVS will be measured using two-dimensional guided M-mode imaging following recommendations from the American Society of Echocardiography.	Baseline to immediate post-treatment (4 months)
Change in echocardiography-determined left ventricular posterior wall thickness (LVPW) (diastole)	LVPW will be measured using two-dimensional guided M-mode imaging following recommendations from the American Society of Echocardiography.	Baseline to immediate post-treatment (4 months)
Change in carotid intima-media thickness (IMT)	The IMT will be measured in a long axis view in each distal common carotid artery, at least 5 mm proximal to the bifurcation, as the mean distance between the luminal-intimal and the medial-adventitial interfaces over a 10-mm length in the far wall.	Baseline to immediate post-treatment (4 months)
Change in femoral intima-media thickness (IMT)	The IMT will be measured in a long axis view in each distal common carotid artery, at least 5 mm proximal to the bifurcation, as the mean distance between the luminal-intimal and the medial-adventitial interfaces over a 10-mm length in the far wall.	Baseline to immediate post-treatment (4 months)
Change in carotid plaque maximal thickness	A plaque will be defined as the presence of a focal wall thickening ≥50% greater than the surrounding vessel wall, a focal region with an IMT measurement ≥1.5 mm, or a ≥0.5 cm protrusion into the lumen exceeding the IMT.	Baseline to immediate post-treatment (4 months)
Change in femoral plaque maximal thickness	A plaque will be defined as the presence of a focal wall thickening ≥50% greater than the surrounding vessel wall, a focal region with an IMT measurement ≥1.5 mm, or a ≥0.5 cm protrusion into the lumen exceeding the IMT.	Baseline to immediate post-treatment (4 months)

Collaborators and Investigators

• Sponsor: Universidad Europea de Madrid
• Investigators: Principal Investigator: Luis Ruilope, PhD, UEM

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2022
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 15, 2025

Study Registration Dates

• First Submitted: September 21, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: blood pressure; physical exercise; resistant hypertension; proteomics
• Additional Relevant MeSH Terms: Behavior; Motor Activity
• Other Study ID Numbers: UEM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No