Association between blood pressure, blood pressure variability and the risk of post-stroke dementia

Lead Investigator: Nina Hilkens, Radboudumc Nijmegen
Title of Proposed Research: Association between blood pressure, blood pressure variability and the risk of post-stroke dementia
Vivli Data Request: 4918
Funding Source: None.
Potential Conflicts of Interest: None.

Summary of the Proposed Research:

Patients who have suffered a transient ischemic attack (TIA) or ischaemic stroke are at increased risk of developing post-stroke dementia. The incidence of post stroke dementia is approximately 30% after five years, which is four to six times higher as compared to the general population.

Known risk factors for post-stroke dementia include patient characteristics such as increasing age and low education level, as well as stroke characteristics, including stroke severity and recurrent stroke. Apart from these non-modifiable risk factors, vascular risk factors (e.g. diabetes, hypertension) have also been associated with an increased risk of both vascular dementia and Alzheimer’s disease. Effectively targeting vascular risk factors could potentially reduce risk of post-stroke dementia.

Thus far, trials that investigated the efficacy of blood pressure lowering on the risk of post-stroke dementia and cognitive decline have shown conflicting results. One trial found a statistically significant reduction in risk of cognitive decline and dementia with perindopril as compared with placebo,[9] while two other trials found no effect of treatment with telmisartan versus placebo, or a lower blood pressure target as compared with a higher target in patients with a recent TIA or ischaemic stroke. Some observational studies in the general population suggest that low blood pressure may even cause harm especially among older individuals, possibly due to cerebral hypoperfusion.

Next to blood pressure levels, visit-to-visit variability in blood pressure might also impact on cognitive function. Blood pressure variability has been identified as an independent risk factor for cerebrovascular disease, and is known to result in an increased burden of white matter lesions.

Better understanding of the association between blood pressure, blood pressure variability and post-stroke dementia may help to define optimal blood pressure targets and may inform future trials on blood pressure and cognitive impairment following stroke. In the present study, we aim to investigate the association between blood pressure, blood pressure variability and the risk of post-stroke dementia. Furthermore, we will investigate whether a potential association between blood pressure and dementia is mediated by age, stroke subtype and type of anti-hypertensive treatment.

Statistical Analysis Plan:

We will calculate incidence rates of post-stroke dementia per blood pressure category. Next, we will perform univariable and multivariable Cox regression analysis. In the first multivariable model we will adjust for age and sex, in the second model we will additionally adjust for education level, obesity, cholesterol, smoking, diabetes, previous stroke, event severity, dysphasia and pre-morbid dependency. Furthermore, the association between blood pressure and dementia will be visualized by plotting the adjusted hazard ratios from the Cox regression model with a restricted cubic spline transformation of systolic and diastolic blood pressure. To assess whether an association between blood pressure variability and dementia is influenced by overall changes in blood pressure, we will additionally adjust for the slope in blood pressure over all visits. We will study effect modification by adding interaction terms for age, stroke subtype and anti-hypertensive drug class. The proportional hazard assumption will be assessed by studying log-log plots. We plan to perform the analyses using R statistical software.

Requested Studies:

PRoFESS – Prevention Regimen For Effectively Avoiding Second Strokes: A Double-blind, Active and Placebo Controlled Study of Aggrenox vs. Clopidogrel, With and Without Micardis
Sponsor: Boehringer Ingelheim
Study ID: NCT00153062
Sponsor ID: 9.159

Public Disclosure:

Hilkens, Nina A.; Klijn, Catharina J.M.; Richard, Edo Blood pressure, blood pressure variability and the risk of poststroke dementia, Journal of Hypertension: March 11, 2021 – Volume Publish Ahead of Print – Issue – doi: 10.1097/HJH.0000000000002841