Abdominal aortic aneurysm in women : risk factor profile and aneurysm wall

Abdominal aortic aneurysm (AAA) in women is rare; the prevalence is approximately 0.5% in elderly women, to compare with 2-4% in aging men. The few women that suffer from AAA are older and have a higher rupture risk. A preventive effect of estrogen on AAA formation in animal models implies that the lower prevalence of AAA in women can depend on a protective effect of female sex hormones. The knowledge is scarce of how the aneurysm wall of women differs from that of men.

Altogether, it is likely that biological gender differences could influence the risk of AAA development, growth rate and rupture risk. This thesis, based on five papers, focuses on risk factors for AAA in women and gender differences in the aneurysm wall.

In the first paper, a case-control study, the reproductive history in women with AAA and a control group of women with peripheral artery disease was investigated. 280 women were invited to answer a questionnaire about their reproductive history and general health. The response rate was 70% and the results showed a lower mean menopausal age in women with larger AAA compared with women with smaller AAA and women with peripheral artery disease.

The second paper, a case-control study, investigated previously reported, potential biomarkers for AAA. These had never been analysed in women with AAA and thus it was uncertain if they would apply to a female cohort. Men and women were in many aspects similar in biomarker profile, with the exception of matrix metalloproteinase 9 (MMP9). The levels of MMP9 were higher in women compared with men, with equally large AAA.

In the third paper elastin content and elastolytic proteins in the aneurysm wall of men and women were analysed. 37 patients were included. The results suggest a more pronounced elastolysis and a lower elastin content in women compared with men.

In the fourth paper collagen and its cross-linking were studied in 28 patients with AAA. The results showed no difference in the relative collagen content between men and women but a different collagen cross-linking in women compared with that in men. The findings might have implications for the biomechanical properties of the aneurysm wall in women, yet further analyses are required to clarify the mechanisms.

The fifth paper was a study of the degree of apoptosis and inflammation, in relation to smooth muscle cells in the aneurysm wall of men and women. 40 patients with AAA were included. The findings suggest a more pronounced apoptosis in the aneurysm wall of women compared with men, which might be related to a greater infiltration of inflammatory cells.

In conclusion, women with larger AAA have an altered reproductive history with a lower mean menopausal age, suggesting hormonal changes to be of importance for AAA development in women. The observed gender differences in the aortic wall described in this thesis, contribute to the presently poorly understood biological and morphological processes that trigger aneurysm development, progression and rupture.

List of scientific papers

I. Reproductive history in women with abdominal aortic aneurysms. Villard C, Swedenborg J, Eriksson P, Hultgren R. J Vasc Surg. 2011 Aug;54(2):341-5.
https://doi.org/10.1016/j.jvs.2010.12.069

II. Biomarkers for abdominal aortic aneurysms with a gender perspective. Villard C, Wågsäter D, Swedenborg J, Eriksson P, Hultgren R. Gend Med. 2012 Aug;9(4):259-266.
https://doi.org/10.1016/j.genm.2012.05.002

III. Differences in elastin and elastolytic enzymes between men and women with abdominal aortic aneurysm. Villard C, Eriksson P, Swedenborg J, Hultgren R. [Accepted]
https://doi.org/10.12945/j.aorta.2014.14-017

IV. Collagen cross-linking in men and women with abdominal aortic aneurysm. Villard C, Eriksson P, Hanemaaijer R, Lindeman J H, Swedenborg J, Hultgren R. [Manuscript]

V. More apoptosis in women with abdominal aortic aneurysm compared with men. Villard C, Eriksson P, Jorns C, Swedenborg J, Hultgren R, Roy J. [Manuscript]