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

Ann Allergy Asthma Immunol. 2019 Jan;122(1):86-92. doi: 10.1016/j.anai.2018.10.004. Epub 2018 Oct 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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