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/m(2) 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.