Toggle Main Menu Toggle Search

Open Access padlockePrints

Association of Blood Pressure Lowering Intensity With White Matter Network Integrity in Patients With Cerebral Small Vessel Disease

Lookup NU author(s): Professor John O'Brien, Professor Andrew BlamireORCiD



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


Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.BACKGROUND AND OBJECTIVES: Diffusion tensor imaging (DTI) networks integrate damage from a variety of pathologic processes in cerebral small vessel disease (SVD) and may be a sensitive marker to detect treatment effects. We determined whether brain network analysis could detect treatment effects in the PRESERVE trial data set, in which intensive vs standard blood pressure (BP) lowering was compared. The primary end point of DTI had not shown treatment differences. METHODS: Participants with lacunar stroke were randomized to standard (systolic 130-140 mm Hg) or intensive (systolic ≤ 125 mm Hg) BP lowering and followed for 2 years with MRI at baseline and at 2 years. Graph theory-based metrics were derived from DTI data to produce a measure of network integrity weighted global efficiency and compared with individual MRI markers of DTI, brain volume, and white matter hyperintensities. RESULTS: Data were available in 82 subjects: standard n = 40 (mean age 66.3 ± 1.5 years) and intensive n = 42 (mean age 69.6 ± 1.0 years). The mean (SD) systolic BP was reduced by 13(14) and 23(23) mm Hg in the standard and intensive groups, respectively (p < 0.001 between groups). Significant differences in diffusion network metrics were found, with improved network integrity (weighted global efficiency, p = 0.002) seen with intensive BP lowering. In contrast, there were no significant differences in individual MRI markers including DTI histogram metrics, brain volume, or white matter hyperintensities. DISCUSSION: Brain network analysis may be a sensitive surrogate marker in trials in SVD. This work suggests that measures of brain network efficiency may be more sensitive to the effects of BP control treatment than conventional DTI metrics. TRIAL REGISTRATION INFORMATION: The trial is registered with the ISRCTN Registry (ISRCTN37694103; and the NIHR Clinical Research Network (CRN 10962; CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that intensive BP lowering in patients with SVD results in improved brain network function when assessed by DTI-based brain network metrics.

Publication metadata

Author(s): Pflanz CP, Egle MS, O'Brien JT, Morris RG, Barrick TR, Blamire AM, Ford GA, Tozer D, Markus HS

Publication type: Article

Publication status: Published

Journal: Neurology

Year: 2022

Volume: 99

Issue: 17

Pages: e1945-e1953

Print publication date: 25/10/2022

Online publication date: 17/08/2022

Acceptance date: 13/06/2022

Date deposited: 07/11/2022

ISSN (print): 0028-3878

ISSN (electronic): 1526-632X

Publisher: Wolters Kluwer Health


DOI: 10.1212/WNL.0000000000201018

PubMed id: 35977831


Altmetrics provided by Altmetric


Funder referenceFunder name
Additional support was provided by the NIHR-funded Newcastle Biomedical Research Centre
Cambridge University Hospitals NIHR Comprehensive Biomedical Research Centre (BRC-1215-20014)
British Heart Foundation and the Stroke Association program grant (TSA BHF 2010/01)
Sheffield Hospitals NIHR-funded Clinical Research Facility
TSA BHF 2010/01The Stroke Association