Hereditary angioedema: Assessing the hypothesis for underlying autonomic dysfunction

• Published in: PloS one Vol. 12; no. 11; p. e0187110
• Main Authors: Wu, Maddalena A, Casella, Francesco, Perego, Francesca, Suffritti, Chiara, Afifi Afifi, Nada, Tobaldini, Eleonora, Zanichelli, Andrea, Cogliati, Chiara, Montano, Nicola, Cicardi, Marco
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.11.2017; Public Library of Science (PLoS)
• Subjects: Activation; Adult; Angioedema; Angioedemas, Hereditary - physiopathology; Angioneurotic edema; Autonomic nervous system; Autonomic Nervous System - physiopathology; Biology and Life Sciences; Blood Pressure; Bradykinin; Case-Control Studies; Catecholamines; Complement activation; Complement component C4; Dysautonomia; Edema; EKG; Electrocardiography; Female; Health aspects; Heart Rate; Humans; Inflammation; Kininogens; Male; Males; Medicine and Health Sciences; Middle Aged; Modulation; Molecular weight; Nervous system; Noradrenaline; Norepinephrine; Patients; Permeability; Physiology; Remission; Rest; Rodents; SAP protein; Social Sciences; Spectral analysis; Trauma; Vagus nerve; Variability
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0187110

Attacks of Hereditary Angioedema due to C1-inhibitor deficiency (C1-INH-HAE)are often triggered by stressful events/hormonal changes. Our study evaluates the relationship between autonomic nervous system (ANS) and contact/complement system activation. 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. 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). 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.