Flow-mediated vasodilation assay indicates no endothelial dysfunction in hereditary angioedema patients with C1-inhibitor deficiency.

Abstract

BACKGROUND:

Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is a rare, potentially life-threatening disorder characterized by recurrent edematous attacks. The edema formation is the consequence of interaction of bradykinin and various vasoactive peptides with endothelium. Besides these agents, danazol, a modified testosterone derivative used in these patients to prevent edematous attacks, can also affect the function of the endothelium, because it shifts the blood lipid profile to a pro-atherogenic phenotype.

OBJECTIVE:

To assess the endothelial function in C1-INH-HAE patients and in healthy matched controls.

METHODS:

To evaluate the endothelial function, we used the flow-mediated dilation method measured in the region of the brachial artery in 33 C1-INH-HAE patients and in 30 healthy matched controls. Laboratory measurements of standard biochemical parameters were performed on computerized laboratory analyzers.

RESULTS:

No difference was found in endothelial function (reactive hyperemia, RH) between patients (median, 9.0; 25%-75% percentile, 6.3-12.9) and controls (median, 7.37; 25%-75% percentile, 4.52-9.93). Although we found elevated cardiovascular risk (high body mass index and low-density lipoprotein/high-density lipoprotein ratio) in danazol-treated C1-INH-HAE patients, RH values did not differ between danazol-treated and nontreated patients. Furthermore, risk factors correlated with the endothelial function only in healthy controls and patients not treated with danazol.

CONCLUSION:

In summary, our results did not indicate any signs of endothelial dysfunction in C1-INH-HAE patients. Moreover, the normal endothelial function in danazol-treated patients with pro-atherogenic lipid profile suggests that elevated bradykinin level or other factor(s) involved in the pathogenesis of edematous attacks may have a protective role against endothelial dysfunction and atherosclerosis.

• Authors: Zsuzsa Nebenführer, Erika Szabó, Erika Kajdácsi, Kinga Viktória Kőhalmi, István Karádi, András Zsáry, Henriette Farkas, László Cervenak
• Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol) Vol. 122 Issue 1 Pg. 86-92 (01 2019) ISSN: 1534-4436 [Electronic] United States
• PMID: 30312677 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier Inc.

Chemical References

• Complement C1 Inhibitor Protein
• Estrogen Antagonists
• Lipoproteins, HDL
• Lipoproteins, LDL
• Danazol
• Bradykinin

Topics

• Adult
• Atherosclerosis (diagnosis)
• Bradykinin (blood)
• Case-Control Studies
• Complement C1 Inhibitor Protein (genetics)
• Danazol (adverse effects, therapeutic use)
• Disease Progression
• Endothelial Cells (metabolism)
• Endothelium, Vascular (cytology, physiology)
• Estrogen Antagonists (adverse effects, therapeutic use)
• Female
• Hereditary Angioedema Types I and II (diagnosis, drug therapy, pathology)
• Humans
• Lipoproteins, HDL (blood)
• Lipoproteins, LDL (blood)
• Male
• Surveys and Questionnaires
• Vasodilation
• Young Adult