CLINICAL TRIAL article
Front. Physiol.
Sec. Autonomic Neuroscience
Cardiac and vascular autonomic control in patients with hereditary angioedema
Provisionally accepted
Beatrice De Maria1*
Luca Ranucci2
Clara Gino1
Aida Zulueta3
Monica Parati1Azzurra Cesoni Marcelli2Lorenza Chiara Zingale2Riccardo Sideri2
Laura Adelaide Dalla Vecchia4
Francesca Perego2- 1Istituti Clinici Scientifici Maugeri IRCCS, Bioengineering Laboratory, Milan, Italy
- 2Istituti Clinici Scientifici Maugeri IRCCS, Department of Internal Medicine and Rehabilitation, Milan, Italy
- 3Istituti Clinici Scientifici Maugeri IRCCS, LaBioN, Milan, Italy
- 4Istituti Clinici Scientifici Maugeri IRCCS, Department of Cardiology, Milan, Italy
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Regulation of vascular permeability in Hereditary Angioedema due to C1 inhibitor deficiency (HAE-C1INH) is key to understanding the disease, but the role of the autonomic nervous system (ANS) in this mechanism remains unclear. Purpose: To compare cardiovascular autonomic response to head-up tilt test (HUTT) in HAE-C1INH patients and matched healthy controls (HC). Methods: HAE-C1INH patients were evaluated during a one-week symptom-free period. Electrocardiogram (ECG) and beat-to-beat non-invasive arterial blood pressure (BP) were recorded in supine position (REST) and during 70° tilt (TILT). Heart rate and systolic BP (SBP) variability indices were derived. Variance (σ²SBP) and low-frequency power (LFSBP) of SBP variability were used as markers of sympathetic vascular control. Results: Twenty-five HAE-C1INH patients (13 males, 44 [28.8-57.5] years) and 25 HC (13 males, 44 [30.8-54.3] years) were enrolled and divided into <45 and ≥45 age groups. Eighteen patients were on long-term prophylaxis (LTP). In the younger group, LFSBP increased from REST to TILT in both groups, with no differences. In older subjects, HAE-C1INH patients showed higher σ²SBP (21.2 [9.3-59.2] vs 7.5 [1.9-14.6] mmHg2) and a greater LFSBP increase (9.4 [4.6-22.4] vs 0.9 [0.2-7.6] mmHg2) than HC during TILT, suggesting sympathetic hyperactivation. No significant group differences in cardiac autonomic control were observed during REST or TILT, regardless of age. Findings in the LTP subgroup mirrored those of the full cohort. Conclusion: Older HAE-C1INH patients display altered vascular autonomic regulation, with an exaggerated sympathetic response during orthostatic stress. Further studies are needed to assess the role of LTP in these alterations.
Keywords: hereditary angioedema, rare disease, Long-term prophylaxis, Heart rate variability, systolic arterialpressure variability, Autonomic Nervous System, Secondary Prevention
Received: 22 Aug 2025; Accepted: 14 Nov 2025.
Copyright: © 2025 De Maria, Ranucci, Gino, Zulueta, Parati, Cesoni Marcelli, Zingale, Sideri, Dalla Vecchia and Perego. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Beatrice De Maria, beatrice.demaria@icsmaugeri.it
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.