C1-INH-HAE Patients Show No Signs of Abnormal Blood Vessel Function, Study Reports

Despite being more prone to developing heart disease, patients with hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) show normal blood vessel function, a study reveals.

The study, “Flow mediated vasodilation assay indicates no endothelial dysfunction in hereditary angioedema patients with C1-inhibitor deficiency,” was published in Annals of Allergy, Asthma & Immunology.

C1-INH-HAE is a rare genetic disorder characterized by sudden and recurrent episodes of swelling and fluid accumulation (edema) in the face, tongue, hands, feet, gastrointestinal (GI) tract, genitalia, or upper airways.

The disease can be caused by lower levels of the C1 inhibitor protein — in the case of C1-INH-HAE type 1 — or to a dysfunctional C1 inhibitor whose levels remain normal or elevated — in the case of C1-INH-HAE type 2.

In C1-INH-HAE, edemas form due to high levels of circulating bradykinin — a substance that causes increased blood vessel leakiness and dilation.

In addition, Danocrine (danazol) — a modified testosterone derivative used to prevent angioedema attacks — can also affect blood vessel function in C1-INH-HAE patients because it promotes the formation and accumulation of fatty deposits within blood vessel walls (atherosclerosis).

In this study, investigators aimed to determine whether C1-INH-HAE patients showed signs of abnormal blood vessel function, compared with healthy individuals.

The study enrolled 33 C1-INH-HAE patients — 13 treated with Danocrine for at least five years and 20 nontreated — and 30 age- and sex-matched healthy individuals used as controls. Participants underwent flow mediated dilation at the brachial artery (the largest blood vessel of the upper arm) to analyze blood vessel function.

There were no significant differences in blood vessel function — measured by the rapid increase in blood flow at the brachial artery following sphygmomanometric cuff release (reactive hyperemia, or RH) — between C1-INH-HAE patients and controls.

Even though Danocrine-treated C1-INH-HAE patients had higher risks of developing cardiovascular disease due to their higher body mass index scores and LDL/HDL cholesterol ratio, their RH values were identical to those from nontreated patients.

“Our results suggest that [blood vessel] function is preserved in danazol treated C1-INH-HAE patients in spite of their proatherogenic [promoting the formation of atherosclerotic plaques] lipid profile. C1-INH-HAE patients’ elevated bradykinin level may well be in the background of our findings, however, further studies should clarify this assumption because of its possible therapeutic potential in atherosclerosis,” the researchers wrote.