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Aerobic exercise increases brain vessel lumen size and blood flow in young adults with elevated blood pressure. Secondary analysis of the TEPHRA randomized clinical trial

Lapidaire W 1 , Forkert ND 2 , Williamson W 3 , Huckstep O 4 , Tan CM 5 , Alsharqi M 6 Show all authors , Mohamed A 7 , Kitt J 8 , Burchert H 9 , Mouches P 10 , Dawes H 11 , Foster C 12 , Okell TW 13 , Lewandowski AJ 14 , Leeson P 15

Affiliations 

  • 1 Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address: winok.lapidaire@cardiov.ox.ac.uk
  • 2 Department of Radiology and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada. Electronic address: nils.forkert@ucalgary.ca
  • 3 Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; School of Medicine, Trinity College Dublin, Dublin, Ireland. Electronic address: wilby.williamson@vhi.ie
  • 4 Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Life Sciences Research Center, Department of Biology, United States Air Force Academy, United States. Electronic address: Odaro.huckstep@afacademy.af.edu
  • 5 Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: cheryl-mj.tan@ludwig.ox.ac.uk
  • 6 Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Department of Cardiac Technology, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. Electronic address: maryam.alsharqi@cardiov.ox.ac.uk
  • 7 Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Department of Diagnostic Imaging and Radiotherapy, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Malaysia. Electronic address: afifahmohamed@ukm.edu.my
  • 8 Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address: jamie.kitt@cardiov.ox.ac.uk
  • 9 Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland. Electronic address: holger.burchert@cardiov.ox.ac.uk
  • 10 Department of Radiology and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
  • 11 NIHR Exeter BRC, Medical School, University of Exeter, Exeter, United Kingdom. Electronic address: H.Dawes@exeter.ac.uk
  • 12 Bristol Medical School, University of Bristol, Bristol, United Kingdom. Electronic address: charlie.foster@bristol.ac.uk
  • 13 Wellcome Centre for Integrative Neuroimaging (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom. Electronic address: thomas.okell@ndcn.ox.ac.uk
  • 14 Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address: adam.lewandowski@cardiov.ox.ac.uk
  • 15 Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address: paul.leeson@cardiov.ox.ac.uk
Neuroimage Clin, 2023;37:103337.
PMID: 36709637 DOI: 10.1016/j.nicl.2023.103337

Abstract

IMPORTANCE: Cerebrovascular changes are already evident in young adults with hypertension and exercise is recommended to reduce cardiovascular risk. To what extent exercise benefits the cerebrovasculature at an early stage of the disease remains unclear.

OBJECTIVE: To investigate whether structured aerobic exercise increases brain vessel lumen diameter or cerebral blood flow (CBF) and whether lumen diameter is associated with CBF.

DESIGN: Open, parallel, two-arm superiority randomized controlled (1:1) trial in the TEPHRA study on an intention-to-treat basis. The MRI sub-study was an optional part of the protocol. The outcome assessors remained blinded until the data lock.

SETTING: Single-centre trial in Oxford, UK.

PARTICIPANTS: Participants were physically inactive (<150 min/week moderate to vigorous physical activity), 18 to 35 years old, 24-hour ambulatory blood pressure 115/75 mmHg-159/99 mmHg, body mass index below 35 kg/m2 and never been on prescribed hypertension medications. Out of 203 randomized participants, 135 participated in the MRI sub-study. Randomisation was stratified for sex, age (<24, 24-29, 30-35 years) and gestational age at birth (<32, 32-37, >37 weeks).

INTERVENTION: Study participants were randomised to a 16 week aerobic exercise intervention targeting 3×60 min sessions per week at 60 to 80 % peak heart rate.

MAIN OUTCOMES AND MEASURES: cerebral blood flow (CBF) maps from ASL MRI scans, internal carotid artery (ICA), middle cerebral artery (MCA) M1 and M2 segments, anterior cerebral artery (ACA), basilar artery (BA), and posterior cerebral artery (PCA) diameters extracted from TOF MRI scans.

RESULTS: Of the 135 randomized participants (median age 28 years, 58 % women) who had high quality baseline MRI data available, 93 participants also had high quality follow-up data available. The exercise group showed an increase in ICA (0.1 cm, 95 % CI 0.01 to 0.18, p =.03) and MCA M1 (0.05 cm, 95 % CI 0.01 to 0.10, p =.03) vessel diameter compared to the control group. Differences in the MCA M2 (0.03 cm, 95 % CI 0.0 to 0.06, p =.08), ACA (0.04 cm, 95 % CI 0.0 to 0.08, p =.06), BA (0.02 cm, 95 % CI -0.04 to 0.09, p =.48), and PCA (0.03 cm, 95 % CI -0.01 to 0.06, p =.17) diameters or CBF were not statistically significant. The increase in ICA vessel diameter in the exercise group was associated with local increases in CBF.

CONCLUSIONS AND RELEVANCE: Aerobic exercise induces positive cerebrovascular remodelling in young people with early hypertension, independent of blood pressure. The long-term benefit of these changes requires further study.

TRIAL REGISTRATION: Clinicaltrials.gov NCT02723552, 30 March 2016.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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