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. 2025 Oct 15.
doi: 10.1161/HYPERTENSIONAHA.125.25290. Online ahead of print.

Higher Blood-Brain Barrier Permeability in Middle-Aged Adults With Hypertension

Esther Janssen  1   2 , Joost J A de Jong  3 , Esmee Verburgt  1   2 , Annemieke Ter Telgte  4   5 , Danielle T N A van den Berg  6 , José P Marques  2 , Marnix C Maas  7 , Frederick J A Meijer  7 , Anil Tuladhar  1   2 , Niels P Riksen  8 , Jaap Deinum  8 , Walter H Backes  3   9   10 , Frank-Erik de Leeuw  1   2
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Higher Blood-Brain Barrier Permeability in Middle-Aged Adults With Hypertension

Esther Janssen et al. Hypertension. .

Abstract

Background: Hypertension is a major risk factor for cerebral small vessel disease (SVD), but the underlying mechanisms remain incompletely understood. Blood-brain barrier (BBB) leakage is hypothesized to be involved in SVD pathogenesis, but this was mainly demonstrated in older patients with established SVD on magnetic resonance imaging. We investigated BBB leakage in young patients with hypertension, at risk for SVD, compared with controls.

Methods: BBB leakage of gadolinium contrast agent was measured with 3T magnetic resonance imaging in 59 patients with hypertension (mean age, 35.8±9.7 years; 54% female; mean blood pressure, 146/92 mm Hg) and 21 healthy controls (mean age, 29.9±4.8 years; 52% female; mean blood pressure, 120/75 mm Hg). Dynamic contrast-enhanced magnetic resonance imaging was used to measure BBB leakage (leakage rate, Ki [min-1] and blood plasma volume fraction [Vp]). Linear regression adjusted for age and sex was used to compare BBB leakage between patients and controls. We additionally adjusted for the amended SVD score and white matter hyperintensity volume. We also compared patients with primary aldosteronism to those with hypertension due to other causes.

Results: Patients with hypertension had 17% higher BBB leakage (Ki) in the white matter (P=0.049) and 15% in the gray matter (P=0.070) compared with controls, independent of SVD burden. No differences were found in Vp or between patients with primary aldosteronism and other causes.

Conclusions: Young patients with hypertension show BBB disruption independent of magnetic resonance imaging-detectable SVD. This suggests a possible role of BBB dysfunction in SVD pathogenesis. Restoration of BBB integrity may be a relevant target for interventions in SVD, but longitudinal and intervention studies are needed to confirm causality.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06175663.

Keywords: adults; blood-brain barrier; cerebral small vessel diseases; hypertension; magnetic resonance imaging.

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