Intensive Systolic Blood Pressure Treatment Remodels Brain Perivascular Spaces: A Secondary Analysis of SPRINT

BACKGROUND: Brain perivascular spaces (PVS) are part of the glymphatic system and facilitate clearance of metabolic byproducts. Since enlarged PVS are associated with vascular health, we tested whether intensive systolic blood pressure (SBP) treatment affects PVS structure. METHODS: This is a secondary analysis of the Systolic PRessure INTervention (SPRINT) Trial MRI Substudy: a randomized trial of intensive SBP treatment to goal < 120 mm Hg vs. < 140 mm Hg. Participants had increased cardiovascular risk, pre-treatment SBP 130-180, and no clinical stroke, dementia, or diabetes. Brain MRIs acquired at baseline and follow-up were used to automatically segment PVS in the supratentorial white matter and basal ganglia using a Frangi filtering method. PVS volumes were quantified as a fraction of the total tissue volume. The effects of SBP treatment group and major antihypertensive classes on PVS volume fraction were separately tested using linear mixed-effects models while covarying for MRI site, age, sex, black race, baseline SBP, history of cardiovascular disease (CVD), chronic kidney disease, and white matter hyperintensities (WMH). RESULTS: For 610 participants with sufficient quality MRI at baseline (mean age 67±8, 40% female, 32% black), greater PVS volume fraction was associated with older age, male sex, non-Black race, concurrent CVD, WMH, and brain atrophy. For 381 participants with MRI at baseline and at follow-up (median = 3.9 years), intensive treatment was associated with decreased PVS volume fraction relative to standard treatment (interaction coefficient: −0.029 [−0.055 to −0.0029] p=0.029). Reduced PVS volume fraction was also associated with exposure to calcium channel blockers (CCB) and diuretics. CONCLUSIONS: Intensive SBP lowering partially reverses PVS enlargement. The effects of CCB use suggests that improved vascular compliance may be partly responsible. Improved vascular health may facilitate glymphatic clearance. CLINCALTRIALS.GOV: NCT01206062