TY - JOUR
T1 - Association of Intensive vs Standard Blood Pressure Control With Cerebral Blood Flow Secondary Analysis of the SPRINT MIND Randomized Clinical Trial
AU - Dolui, Sudipto
AU - Detre, John A.
AU - Gaussoin, Sarah A.
AU - Herrick, Jennifer S.
AU - Wang, Danny J.J.
AU - Tamura, Manjula Kurella
AU - Cho, Monique E.
AU - Haley, William E.
AU - Launer, Lenore J.
AU - Punzi, Henry A.
AU - Rastogi, Anjay
AU - Still, Carolyn H.
AU - Weiner, Daniel E.
AU - Wright, Jackson T.
AU - Williamson, Jeff D.
AU - Wright, Clinton B.
AU - Bryan, R. Nick
AU - Bress, Adam P.
AU - Pajewski, Nicholas M.
AU - Nasrallah, Ilya M.
N1 - Funding Information:
UL1RR025755 (Ohio State University); UL1RR024134 and UL1TR000003 (University of Pennsylvania); UL1RR025771 (Boston University); UL1TR000093 (Stanford University); UL1RR025752, UL1TR000073, and UL1TR001064 (Tufts University); UL1TR000050 (University of Illinois); UL1TR000005 (University of Pittsburgh); 9U54TR000017-06 (University of Texas Southwestern Medical Center); UL1TR000105-05 (University of Utah); UL1 TR000445 (Vanderbilt University); UL1TR000075 (George Washington University); UL1 TR000002 (University of California, Davis); UL1 TR000064 (University of Florida); and UL1TR000433 (University of Michigan); and by National Institute of General Medical Sciences, Centers of Biomedical Research Excellence award NIGMS P30GM103337 (awarded to Tulane University). The work presented here was also supported by grants 1RF1AG054409 and R01 AG055606 and funding from the Alzheimer’s Association. Dr Dolui was supported by the NIH (grant R01 NS111115 and R03 AG063213). Dr Bress was supported by the National Institute on Aging of the National Institutes of Health (grant R01AG065805).
Funding Information:
Intervention Trial (SPRINT) was funded by the National Institutes of Health (NIH; including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke; grants HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and interagency agreement A-HL-13-002-001). SPRINT was also supported in part with resources and use of facilities through the US Department of Veterans Affairs. Azilsartan and chlorthalidone (combined with azilsartan) were provided by Takeda Pharmaceuticals International Inc. Computing resources were supported through 1S10OD023495-01 and additional support was provided through the following National Center for Advancing Translational Sciences clinical and translational science awards: UL1TR000439 (awarded to Case Western Reserve University);
Funding Information:
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.
Funding Information:
The Systolic Blood Pressure Intervention Trial (SPRINT) was funded by the National Institutes of Health (NIH; including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke; grants HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and interagency agreement A-HL-13-002-001). SPRINT was also supported in part with resources and use of facilities through the US Department of Veterans Affairs. Azilsartan and chlorthalidone (combined with azilsartan) were provided by Takeda Pharmaceuticals International Inc. Computing resources were supported through 1S10OD023495-01 and additional support was provided through the following National Center for Advancing Translational Sciences clinical and translational science awards: UL1TR000439 (awarded to Case Western Reserve University); UL1RR025755 (Ohio State University); UL1RR024134 and UL1TR000003 (University of Pennsylvania); UL1RR025771 (Boston University); UL1TR000093 (Stanford University); UL1RR025752, UL1TR000073, and UL1TR001064 (Tufts University); UL1TR000050 (University of Illinois); UL1TR000005 (University of Pittsburgh); 9U54TR000017-06 (University of Texas Southwestern Medical Center); UL1TR000105-05 (University of Utah); UL1 TR000445 (Vanderbilt University); UL1TR000075 (George Washington University); UL1 TR000002 (University of California, Davis); UL1 TR000064 (University of Florida); and UL1TR000433 (University of Michigan); and by National Institute of General Medical Sciences, Centers of Biomedical Research Excellence award NIGMS P30GM103337 (awarded to Tulane University). The work presented here was also supported by grants 1RF1AG054409 and R01 AG055606 and funding from the Alzheimer's Association. Dr Dolui was supported by the NIH (grant R01 NS111115 and R03 AG063213). Dr Bress was supported by the National Institute on Aging of the National Institutes of Health (grant R01AG065805).
Publisher Copyright:
© 2022 American Medical Association. All rights reserved
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
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U2 - 10.1001/jamaneurol.2022.0074
DO - 10.1001/jamaneurol.2022.0074
M3 - Review article
C2 - 35254390
AN - SCOPUS:85125924307
VL - 79
SP - 380
EP - 389
JO - JAMA Neurology
JF - JAMA Neurology
SN - 2168-6149
IS - 4
ER -