Association of Intensive vs Standard Blood Pressure Control With Cerebral Blood Flow: Secondary Analysis of the SPRINT MIND Randomized Clinical Trial

Abstract

Importance: Antihypertensive treatments benefit cerebrovascular health and cognitive function in patients with hypertension, but it is uncertain whether an intensive blood pressure target leads to potentially harmful cerebral hypoperfusion.

Objective: To investigate the association of intensive systolic blood pressure (SBP) control vs standard control with whole-brain cerebral blood flow (CBF).

Design, setting, and participants: This substudy of the Systolic Blood Pressure Intervention Trial (SPRINT) randomized clinical trial compared the efficacy of 2 different blood pressure-lowering strategies with longitudinal brain magnetic resonance imaging (MRI) including arterial spin labeled perfusion imaging to quantify CBF. A total of 1267 adults 50 years or older with hypertension and increased cardiovascular risk but free of diabetes or dementia were screened for the SPRINT substudy from 6 sites in the US. Randomization began in November 2010 with final follow-up MRI in July 2016. Analyses were performed from September 2020 through December 2021.

Interventions: Study participants with baseline CBF measures were randomized to an intensive SBP target less than 120 mm Hg or standard SBP target less than 140 mm Hg.

Main outcomes and measures: The primary outcome was change in whole-brain CBF from baseline. Secondary outcomes were change in gray matter, white matter, and periventricular white matter CBF.

Results: Among 547 participants with CBF measured at baseline, the mean (SD) age was 67.5 (8.1) years and 219 (40.0%) were women; 315 completed follow-up MRI at a median (IQR) of 4.0 (3.7-4.1) years after randomization. Mean whole-brain CBF increased from 38.90 to 40.36 (difference, 1.46 [95% CI, 0.08-2.83]) mL/100 g/min in the intensive treatment group, with no mean increase in the standard treatment group (37.96 to 37.12; difference, -0.84 [95% CI, -2.30 to 0.61] mL/100 g/min; between-group difference, 2.30 [95% CI, 0.30-4.30; P = .02]). Gray, white, and periventricular white matter CBF showed similar changes. The association of intensive vs standard treatment with CBF was generally similar across subgroups defined by age, sex, race, chronic kidney disease, SBP, orthostatic hypotension, and frailty, with the exception of an indication of larger mean increases in CBF associated with intensive treatment among participants with a history of cardiovascular disease (interaction P = .05).

Conclusions and relevance: Intensive vs standard antihypertensive treatment was associated with increased, rather than decreased, cerebral perfusion, most notably in participants with a history of cardiovascular disease.

Trial registration: ClinicalTrials.gov Identifier: NCT01206062.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Detre reported a patent 5,402,785 (measuring perfusion using magnetic resonance imaging) with royalties paid from Carnegie Mellon University; this patent expired in 2012 before the data described in this manuscript were available. Dr Gaussoin reported grants from National Institutes of Health (NIH) to support Systolic Blood Pressure Intervention Trial (SPRINT) during the conduct of the study. Dr Tamura reported personal fees from American Federation for Aging Research Advisory Committee outside the submitted work. Dr Punzi reported grants from NIH during the conduct of the study. Dr Rastogi reported serving on the speaker’s bureau of Amgen, Aurinia Pharmaceuticals, AstraZeneca, Baxter, Bayer, Fresenius Medical Care, Genzyme/Sanofi; Janssen Pharmaceuticals, Natera, and Vifor Pharma; serving on the advisory board of Aurinia Pharmaceuticals, AstraZeneca, Akebia Therapeutics, Ardelyx, Chiesi, Chinook Therapeutics, Genzyme/Sanofi, GlaxoSmithKline, Fresenius Medical Care, Otsuka Pharmaceutical, and Tricida; and research support from Bayer, AstraZeneca, Alnylam Pharmaceuticals, Gilead Sciences, Idorsia, Kadmon, GlaxoSmithKline, NIH, Novo Nordisk, Omeros, and Palladio during the conduct of the study. Dr Weiner reported grants from NIH via a subcontract with the University of Utah during the conduct of the study. Dr Williamson reported grants from NIH during the conduct of the study and grants from Biogen outside the submitted work. Dr C. Wright reported grants from Wake Forest (subcontract) during the conduct of the study. Dr Bryan reported grants from the NIH during the conduct of the study; equity from Galileo, Inc outside the submitted work; and a patent for UPenn licensed to Galileo, Inc. Dr Bress reported grants from NIH during the conduct of the study and grants from Amarin and Amgen outside the submitted work. Dr Pajewski reported grants from National Heart, Lung, and Blood Institute; National Institute on Aging; and Alzheimer's Association during the conduct of the study. Dr Nasrallah reported personal fees from Biogen outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Eligibility, Randomization, and Follow-up for Participants in the Magnetic Resonance Imaging (MRI) Substudy

The total randomization number indicates the number of participants in the Systolic Blood Pressure Intervention Trial (SPRINT) magnetic resonance imaging substudy who were located in proximity to a study MRI scanner. ASL indicates arterial spin labeling.

Figure 2.. Baseline and Longitudinal Associations Between Whole-Brain Cerebral Blood Flow (CBF), Total Brain Volume, and Cerebral White Matter Lesions (WML)

Rho denotes partial rank correlation coefficient adjusting for age, sex, and magnetic resonance imaging facility. Lines denote estimated least-squares regression line with corresponding 95% CI. WML volumes presented using inverse hyperbolic sine transformation, f(x) = log(x + [x2 + 1]0.5). ICV indicates intracranial volume.

Figure 3.. Longitudinal Change in Whole-Brain Cerebral Blood Flow (CBF) by Age and Treatment Group

Bold colored lines represent age-specific change in whole-brain CBF estimated from a treatment group–specific linear mixed model, with associated 95% CIs. Gray lines represent individual participant trajectories.