Journal Article

Functional physiological, psychological, and biochemical reactivity to socially evaluated cold pressor test in hereditary angioedema patients (FRoSEn)

Dalla Vecchia, Laura Adelaide, Perego, Francesca, Zingale, Lorenza Chiara, Gorini, Alessandra, Gino, Clara, Ranucci, Luca, De Maria, Beatrice, Cesoni Marcelli, Azzurra, Zulueta, Aida

2026

Overview

Stressful physical or psychological events can trigger acute swelling attacks in patients with Hereditary Angioedema due to C1 Inhibitor deficiency (HAE-C1INH), although the stress-disease relationship remains unclear. The Socially Evaluated Cold Pressor Test (SECPT) reliably induces acute stress under controlled conditions. This study aimed to compare perceived stress, inflammatory markers, and cardiovascular responses to SECPT between HAE-C1INH patients and healthy controls (HC). Twenty HAE-C1INH patients (9 males, 44 ± 14 years) and age and sex matched HC underwent a 3-minute SECPT. Participants completed questionnaires assessing anxiety and depression (HADS), pain catastrophizing (PCS), and subjective stress (0-100 scale) before and after SECPT. Heart rate (HR) and arterial pressure (AP) were recorded. Blood samples for inflammatory cytokines (IL-6, IL-1ß, TNF-α) were collected at baseline, and 10 and 40 minutes after SECPT. Compared to HC, patients showed higher baseline HADS-A (7.3 ± 4.5 vs 4.7 ± 2.7), overall PCS (19.7 ± 12.6 vs 12.9 ± 8.7), and perceived stress during SECPT (60.6 ± 34.3 vs 34.6 ± 23.8). IL-6 levels were higher at baseline and 10 minutes post-test (2.63 ± 1.21 vs 1.84 ± 0.87; 2.78 ± 1.20 vs 1.91 ± 0.79 pg/ml), as were TNF-α levels across all phases (4.19 ± 1.38 vs 3.26 ± 1.55; 4.09 ± 1.39 vs 3.40 ± 1.48; 4.09 ± 1.28 vs 3.20 ± 1.57) while IL-1 ß remained unchanged. HR and AP variations were similar between groups. HAE-C1INH patients exhibited heightened perceived stress response to SECPT, and elevated baseline inflammation, despite comparable cardiovascular reactivity. These findings highlight a complex psychophysiological-inflammatory interplay in acute stress responses, suggesting the need to integrate psychological and biological frameworks in understanding HAE-C1INH triggers. NCT06414252.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adult / Angioedema / Angioedemas, Hereditary - blood / Angioedemas, Hereditary - physiopathology / Angioedemas, Hereditary - psychology / Anxiety / Anxiety - psychology / Biomarkers / Biomarkers - blood / Blood pressure / Cardiovascular system / Catheters / Chronic illnesses / Clinical trials / Cold Temperature / Complement component C1 / Controlled conditions / Cytokines - blood / Disease / Electrocardiography / Female / Heart Rate / hereditary angioedema / Humans / Inflammation / Interleukin 6 / Male / Middle Aged / Original Research / Pain / Perceptions / Physiology / rare disease / secondary prevention / Signal processing / Stress / Stress response / Stress, Psychological - psychology / Time series / Tumor necrosis factor-α