Hereditary angioedema: Assessing the hypothesis for underlying autonomic dysfunction

Maddalena A. Wu, Francesco Casella, Francesca Perego, Chiara Suffritti, Nada Afifi Afifi, Eleonora Tobaldini, Andrea Zanichelli, Chiara Cogliati, Nicola Montano, Marco Cicardi

Research output: Contribution to journalArticlepeer-review


Background: Attacks of Hereditary Angioedema due to C1-inhibitor deficiency (C1-INH-HAE)are often triggered by stressful events/hormonal changes. Objective: Our study evaluates the relationship between autonomic nervous system (ANS) and contact/complement system activation. Methods: Twenty-three HAE patients (6 males, mean age 47.5±11.4 years) during remission and 24 healthy controls (8 males, mean age 45.3±10.6 years) were studied. ECG, beat-by-beat blood pressure, respiratory activity were continuously recorded during rest (10’) and 75-degrees-head-up tilt (10’). C1-INH, C4, cleaved high molecular weight kininogen (cHK) were assessed; in 16 patients and 11 controls plasma catecholamines were also evaluated. Spectral analysis of heart rate variability allowed extraction of low-(LF) and high-(HF) frequency components, markers of sympathetic and vagal modulation respectively. Results: HAE patients showed higher mean systolic arterial pressure (SAP) than controls during both rest and tilt. Tilt induced a significant increase in SAP and its variability only in controls. Although sympathetic modulation (LFnu) increased significantly with tilt in both groups, LF/ HF ratio, index of sympathovagal balance, increased significantly only in controls. At rest HAE patients showed higher noradrenaline values (301.4±132.9 pg/ml vs 210.5 ±89.6pg/ml, p = 0.05). Moreover, in patients tilt was associated with a significant increase in cHK, marker of contact system activation (49.5 ± 7.5% after T vs 47.1 ± 7.8% at R, p = 0.01). Conclusions: Our data are consistent with altered ANS modulation in HAE patients, i.e. increased sympathetic activation at rest and blunted response to orthostatic challenge. Tilt test-induced increased HK cleavage suggests a link between stress and bradykinin production.

Original languageEnglish
Article numbere0187110
JournalPLoS One
Issue number11
Publication statusPublished - Nov 1 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


Dive into the research topics of 'Hereditary angioedema: Assessing the hypothesis for underlying autonomic dysfunction'. Together they form a unique fingerprint.

Cite this