Lead Investigator: Nina Hilkens, Radboudumc Nijmegen
Title of Proposal Research: Blood pressure variability and progression of white matter hyperintensities after ischemic stroke
Vivli Data Request: 7493
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
After stroke, one in three patients will develop dementia in the next five years. The number of patients with dementia after stroke is predicted to increase in the years to come, due to the ageing population and improved survival after stroke. As there is no effective treatment for dementia, prevention is a top priority.
Previous studies have shown that large variation in blood pressure (from one visit to another, so called visit-to-visit variability) is associated with an increased risk of dementia. The exact mechanism underlying this association is unknown. A possible explanation is that high blood pressure variability results in faster progression of white matter lesions, which is damage to the white matter that connects different areas within the brain. The presence and severity of white matter lesions, which can be visualized with brain imaging, is a known risk factor for cognitive decline and dementia.
With this study we aim to investigate whether patients with large variations in their blood pressure show more progression of white matter lesions on brain imaging. If this association is confirmed, a next step would be to investigate whether reducing variability of blood pressure actually results in less progression of white matter lesions, and ultimately a lower risk of dementia. Blood pressure variability may be reduced with specific drugs that are currently used to treat high blood pressure.
In order to answer our research question, we will re-analyse data from 771 patients who had an ischemic stroke and underwent repeated blood pressure measurements as well as brain imaging shortly after their stroke and approximately two years later. We will investigate whether the amount of variation in blood pressure is associated with more progression of white matter lesions.
Statistical Analysis Plan:
We chose the PRoFESS trial for our analysis because of the large sample size, with 771 patients with ischemic stroke undergoing repeated blood pressure measurements and repeated MRI. Missing data will be excluded if missing in less than 5% of patients. Blood pressure variability (BPV) will be calculated for all patients (primary definition: coefficient of variation (standard deviation / mean blood pressure * 100)). We will calculate mean increase in periventricular white matter lesion (WML) score and subcortical WML volume per quintile of BPV. We will compare differences across quintiles with analysis of variance (ANOVA). Next, we will perform multivariable linear regression analysis to study the association between BPV and progression of WML. In the first model we will adjust for age and sex, in a second model we will additionally adjust for hypertension, diabetes, smoking, obesity, previous stroke and baseline WML load. We will perform subgroup analyses according to age (above or below 65 years), WML load at baseline (dichotomized at the median) and antihypertensive drug use (calcium channel blocker versus other), and include an interaction term in the multivariable model.
PRoFESS – Prevention Regimen For Effectively Avoiding Second Strokes: A Double-blind, Active and Placebo Controlled Study of Aggrenox vs. Clopidogrel, With and Without Micardis
Data Contributor: Boehringer Ingelheim
Study ID: NCT00153062
Sponsor ID: 9.159
Hilkens, N.A., de Leeuw, F.E., Klijn, C.J. and Richard, E., 2024. Blood pressure variability and white matter hyperintensities after ischemic stroke. Cerebral Circulation-Cognition and Behavior, p.100205. Doi: 10.1016/j.cccb.2024.100205