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 journalArticle

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Abstract

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
Volume12
Issue number11
DOIs
Publication statusPublished - Nov 1 2017

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Hereditary Angioedemas
Chemical activation
Modulation
Neurology
autonomic nervous system
Autonomic Nervous System
High Molecular Weight Kininogens
Blood Pressure
Pressure control
Blood pressure
Arterial Pressure
Bradykinin
Electrocardiography
Spectrum analysis
Catecholamines
cystatins
bradykinin
Norepinephrine
Complement Activation
remission

ASJC Scopus subject areas

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

Cite this

Wu, M. A., Casella, F., Perego, F., Suffritti, C., Afifi Afifi, N., Tobaldini, E., ... Cicardi, M. (2017). Hereditary angioedema: Assessing the hypothesis for underlying autonomic dysfunction. PLoS One, 12(11), [e0187110]. https://doi.org/10.1371/journal.pone.0187110

Hereditary angioedema : Assessing the hypothesis for underlying autonomic dysfunction. / Wu, Maddalena A.; Casella, Francesco; Perego, Francesca; Suffritti, Chiara; Afifi Afifi, Nada; Tobaldini, Eleonora; Zanichelli, Andrea; Cogliati, Chiara; Montano, Nicola; Cicardi, Marco.

In: PLoS One, Vol. 12, No. 11, e0187110, 01.11.2017.

Research output: Contribution to journalArticle

Wu, MA, Casella, F, Perego, F, Suffritti, C, Afifi Afifi, N, Tobaldini, E, Zanichelli, A, Cogliati, C, Montano, N & Cicardi, M 2017, 'Hereditary angioedema: Assessing the hypothesis for underlying autonomic dysfunction', PLoS One, vol. 12, no. 11, e0187110. https://doi.org/10.1371/journal.pone.0187110
Wu, Maddalena A. ; Casella, Francesco ; Perego, Francesca ; Suffritti, Chiara ; Afifi Afifi, Nada ; Tobaldini, Eleonora ; Zanichelli, Andrea ; Cogliati, Chiara ; Montano, Nicola ; Cicardi, Marco. / Hereditary angioedema : Assessing the hypothesis for underlying autonomic dysfunction. In: PLoS One. 2017 ; Vol. 12, No. 11.
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abstract = "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.",
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AU - Afifi Afifi, Nada

AU - Tobaldini, Eleonora

AU - Zanichelli, Andrea

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AB - 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.

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