STUDIO DEL PROFILO CARDIO-VASCOLARE IN PAZIENTI CON ANGIOEDEMA DA CARENZA DI C1 INIBITORE: RELAZIONI TRA IL SISTEMA NERVOSO AUTONOMO E LA VASO-REATTIVITA¿

Backround: Hereditary angioedema (HAE) is a rare autosomal disease resulting from a inherited deficiency or dysfunction of the C1 inhibitor. It is characterized by acute attacks of angioedema that involve skin, upper airway and gastrointestinal tract. Psychological stress is a well recognized trigger for angioedema attacks mediated by bradykinin, a peptide released from cleavage of high molecular weight kininogen (HK) by plasma callicrein. Study aim: In this study we investigated the interaction of sympathetic nervous system and contact system to better understand the relationship between psychological stress and angioedema attacks. Methods: 16 patients with hereditary angioedema during remission and 12 healthy volunteers were studied. ECG and beat-to-beat blood pressure were recorded during rest and 75° head-up tilt. Plasma catecholamines, C1 inhibitor, C4 and cleaved high molecular weight kininogen were assessed. Cardiovascular signals were analyzed by means of spectral analysis of heart rate variability, allowing to extract low and high-frequency components, indexes of respectively sympathetic and vagal modulation. Results: During rest significant differences in systolic blood pressure and noradrenaline levels in HAE patients compared with healthy volunteers were observed. During tilt a significant reduction in low-frequency modulation increase was observed in HAE patients. No change was observed in C1 inhibitor and C4 between rest and tilt in both groups; tilt was associated with a significant increase in cleaved HK as compared to rest in HAE patients and healthy volunteers. Discussion: In HAE patients higher systolic blood pressure and noradrenaline values suggest an increased sympathetic activation in rest. They showed a normal autonomic cardiovascular modulation in rest while a reduction in sympathetic activation was observed during tilt. The increase in the cleavage of HK upon sympathetic activation suggests a link between stress and bradykinin generation.