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Effect of Standard vs Intensive blood pressure control on cerebral blood flowin small vessel disease the preserve randomized clinical trial

Lookup NU author(s): Iain Croall, Professor John O'Brien, Professor Andrew BlamireORCiD, Professor Gary Ford



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2018 American Medical Association. All rights reserved. IMPORTANCE Blood pressure (BP) lowering is considered neuroprotective in patients with cerebral small vessel disease; however, more intensive regimens may increase cerebral hypoperfusion. This study examined the effect of standard vs intensive BP treatment on cerebral perfusion in patients with severe small vessel disease. OBJECTIVE To investigate whether standard vs intensive BP lowering over 3 months causes decreased cerebral perfusion in small vessel disease. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial took place at 2 English university medical centers. Patientswere randomized via a central online system (in a 1:1 ratio). Seventy patients with hypertension and withmagnetic resonance imaging-confirmed symptomatic lacunar infarct and confluent white matter hyperintensitieswere recruited between February 29, 2012, and October 21, 2015, and randomized (36 in the standard group and 34 in the intensive group). Analyzable datawere available in 62 patients, 33 in the standard group and 29 in the intensive group, for intent-To-Treat analysis. This experiment examines the 3-month follow-up period. INTERVENTIONS Patients were randomized to standard (systolic, 130-140mmHg) or intensive (systolic, <125mmHg) BP targets, to be achieved through medication changes. MAIN OUTCOMES AND MEASURES Cerebral perfusionwas measured using arterial spin labeling; the primary end point was change in global perfusion between baseline and 3 months, compared between treatment groups by analysis of variance. Linear regression compared change in perfusion against change in BP.Magnetic resonance imaging scan analysis was masked to treatment group. RESULTS Among 62 analyzable patients, the mean age was 69.3 years, and 60%(n = 37) were male. The mean (SD) systolic BP decreased by 8 (12)mmHg in the standard group and by 27 (17)mmHg in the intensive group (P < .001), with mean (SD) achieved pressures of 141 (13) and 126 (10)mmHg, respectively. Change in global perfusion did not differ between treatment groups: The mean (SD) change was -0.5 (9.4) mL/min/100 g in the standard group vs 0.7 (8.6) mL/min/100 g in the intensive group (partial η2, 0.004; 95%CI, -3.551 to 5.818; P = .63). No differences were observed when the analysis examined gray or white matter only or was confined to those achieving target BP. The number of adverse events did not differ between treatment groups, with a mean (SD) of 0.21 (0.65) for the standard group and 0.32 (0.75) for the intensive group (P = .44). CONCLUSIONS AND RELEVANCE Intensive BP lowering did not reduce cerebral perfusion in severe small vessel disease.

Publication metadata

Author(s): Croall ID, Tozer DJ, Moynihan B, Khan U, O'Brien JT, Morris RG, Cambridge VC, Barrick TR, Blamire AM, Ford GA, Markus HS

Publication type: Article

Publication status: Published

Journal: JAMA Neurology

Year: 2018

Volume: 75

Issue: 6

Pages: 720-727

Print publication date: 01/06/2018

Online publication date: 05/03/2018

Acceptance date: 08/12/2017

Date deposited: 02/07/2018

ISSN (print): 2168-6149

ISSN (electronic): 2168-6157

Publisher: American Medical Association


DOI: 10.1001/jamaneurol.2017.5153


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Funder referenceFunder name
TSA BHF 2010/01The Stroke Association