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. 2025 Sep;39(9):626-633.
doi: 10.1038/s41371-025-01058-w. Epub 2025 Aug 2.

Cerebrovascular reactivity impairment in resistant hypertension

G Miceli  1   2 , M Velardo  3 , A Casuccio  3 , M Daidone  3   4 , M G Basso  3 , A Tuttolomondo  3   4
Affiliations

Cerebrovascular reactivity impairment in resistant hypertension

G Miceli et al. J Hum Hypertens. 2025 Sep.

Abstract

Resistant hypertension (RH) is defined as office systolic blood pressure (BP) that remains uncontrolled despite the concurrent use of three or more antihypertensive drug classes and may be associated with altered vasomotor responses to physiological stimuli. However, the effect of RH on cerebrovascular reactivity (CVR) remains poorly understood. Furthermore, the potential contribution of autonomic nervous system dysfunction to these alterations has not yet been fully clarified. Understanding these mechanisms may offer insights into the pathophysiology of resistant hypertension and could have important prognostic implications. This study aims to analyze CVR in a cohort of patients with RH, compared with patients with non-resistant hypertension (NRH), taking into account the differences in sympathovagal balance between the two groups. Forty consecutive hypertension patients, 20 with NRH and 20 with RH, underwent heart rate variability analysis and transcranial color-coded Doppler at rest and during a breath-holding maneuver to evaluate CVR. Hypertensive individuals presented a significant reduction of the Breath Holding Index (BHI) and time-domain parameters (SDNN and SDANN) in comparison to the control group (BHI control 1.32 ± 0.41 vs hypertensive 0.92 ± 0.65; p = 0.018; SDANN control 125.76 ± 24.96 vs hypertensive 87.65 ± 20.63; p < 0.0001). RH patients presented a significant reduction in BHI (NRH BHI 1.15 ± 0.65 vs RH BHI 0.70 ± 0.58; p = 0.027) and HRV parameters (SDANN in NRH 95.09 ± 22.12 vs RH 80.21 ± 16.36; p = 0.021). Our results show that RH is associated with impaired HRV and CRV. Autonomic dysfunction could be a concurrent cause of cerebral vasomotor reactivity impairment.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: All patients gave their informed consent to the study. The study protocol received approval from the Ethics Committee of the “Paolo Giaccone” University Hospital, and in accordance with the Helsinki Declaration. Consent to participate and publication: all patients expressed their informed consent to participate in the study and supplied their personal information for publication.

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