Blood-brain barrier integrity decreases with higher blood pressure, a 7T DCE-MRI study

Background Blood-brain barrier (BBB) integrity is presumed to be impaired in hypertension, resulting from cerebral endothelial dysfunction. Hypertension antedates various cerebrovascular diseases, such as cerebral small vessel disease (cSVD), and is a risk factor for developing neurodegenerative diseases for which BBB disruption is a preceding pathophysiological process. In this study, we investigated the relation between hypertension, current blood pressure and BBB leakage in human subjects. Methods BBB leakage was determined in twenty-two patients with hypertension and nineteen normotensive controls, age- and sex-matched (median age[range]:65[45-80] years,19 males), using a sparsely time-sampled contrast-enhanced 7 Tesla MRI protocol. Structural cSVD markers were visually rated. Multivariable regression analyses, adjusted for age, sex, cardiovascular risk factors and cSVD markers, were performed to determine the relation between hypertension status, systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), drug treatment, and BBB leakage. Results Both hypertensive and normotensive participants showed mild scores of cSVD. BBB leakage did not differ between hypertensive and normotensive participants, however was significantly higher for SBP, DBP and MAP in the cortex, and DBP and MAP in the grey matter. Effectively treated patients showed less BBB leakage than those with current hypertension. Conclusion BBB integrity in the total and cortical grey matter decreases with increasing blood pressure, but is not related to hypertension status. These findings show that BBB disruption already occurs with increasing blood pressure, before the presence of overt cerebral tissue damage. Additionally, our results suggest that effective antihypertensive medication has a protective effect on the BBB. Registered at: ; Unique identifier: NL7537 ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ### Funding Statement This study was partly funded by the EU?s Horizon 2020 project ?CRUCIAL?, Grant agreement number 848109, and ?Stichting De Weijerhorst Foundation?. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Medical Ethical Committee of Maastricht University Medical Center I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes * BBB : blood-brain barrier cSVD : cerebral small vessel disease DBP : diastolic blood pressure DCE-MRI : dynamic contrast enhanced magnetic resonance imaging GM : grey matter MAP : mean arterial pressure PVS : perivascular spaces ROI : region of interest SBP : systolic blood pressure TE : echo time TR : repetition time VIF : vascular input function WM : white matter WMH : white matter hyperintensities