Identifying Women at High Risk of 90 Day Death after Elective Open Abdominal Aortic Aneurysm Repair:A Multicentre Case Control Study

Objective: The aim of this study was to identify risk factors for 90 day death after elective open surgical repair (OSR) of abdominal aortic aneurysms (AAAs) in women.Methods: This was a multicentre case control study. The nationwide Dutch Surgical Aneurysm Audit registry (2013–2019) was solely used to identify women who underwent elective OSR as eligible patients. Data for this study were subsequently collected from the patients’ medical files. Women with AAA were included and those who died (cases) were compared with those who survived (controls) 90 days after surgery. Inflammatory, mycotic, or symptomatic or ruptured AAA were excluded. The association between pre- and peri-operative risk factors and death was assessed by logistic regression analysis in the whole sample and after matching cases to controls of the same age at the time of repair. Mesenteric artery patency was also assessed on pre-operative computed tomography and used in the analysis.Results: In total, 266 patients (30 cases and 236 controls) from 21 hospitals were included. Cases were older (median [interquartile range; IQR] 75 years [71, 78.3] vs. 71 years [66, 77]; p =.002) and more often had symptomatic peripheral arterial disease (PAD) (14/29 [48%] vs. 49/227 [22%]; p =.002). Intra-operative blood loss (median [IQR] 1.6 L [1.1, 3.0] vs. 1.2 L [0.7, 1.8]), acute myocardial infarction (AMI) (10/30 [33%] vs. 8/236 [3%]), renal failure (17/30 [57%] vs. 33/236 [14%]), and bowel ischaemia (BI) (17/29 [59%] vs. 12/236 [5%]) were more prevalent among cases. Older age (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.03–1.19) and PAD (OR 3.91, 95% CI 1.57–9.74) were associated with death. Multivariable analysis demonstrated that, after adjustment for age, AMI (OR 9.34, 95% CI 1.66–52.4) and BI (OR 35.6, 95% CI 3.41–370) were associated with death. Superior mesenteric artery stenosis of &gt;70% had a clinically relevant association with BI (OR 5.23, 95% CI 1.43–19.13; p =.012).Conclusion: Age, symptomatic PAD, AMI, and BI were risk factors for death after elective OSR in women. The association between a &gt;70% SMA stenosis and BI may call for action in selected cases.</p

A Novel Hypothesis: A Role for Follicle Stimulating Hormone in Abdominal Aortic Aneurysm Development in Postmenopausal Women

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta, which can potentially be fatal due to exsanguination following rupture. Although AAA is less prevalent in women, women with AAA have a more severe AAA progression compared to men as reflected by enhanced aneurysm growth rates and a higher rupture risk. Women are diagnosed with AAA at an older age than men, and in line with increased osteoporosis and cardiovascular events, the delayed AAA onset has been attributed to the reduction of the protective effect of oestrogens during the menopausal transition. However, new insights have shown that a high follicle stimulating hormone (FSH) level during menopause may also play a key role in those diseases. In this report we hypothesize that FSH may aggravate AAA development and progression in postmenopausal women via a direct and/or indirect role, promoting aorta pathology. Since FSH receptors (FSHR) are reported on many other cell types than granulosa cells in the ovaries, it is feasible that FSH stimulation of FSHR-bearing cells such as aortic endothelial cells or inflammatory cells, could promote AAA formation directly. Indirectly, AAA progression may be influenced by an FSH-mediated increase in osteoporosis, which is associated with aortic calcification. Also, an FSH-mediated decrease in cholesterol uptake by the liver and an increase in cholesterol biosynthesis will increase the cholesterol level in the circulation, and subsequently promote aortic atherosclerosis and inflammation. Lastly, FSH-induced adipogenesis may lead to obesity-mediated dysfunction of the microvasculature of the aorta and/or modulation of the periaortic adipose tissue. Thus the long term increased plasma FSH levels during the menopausal transition may contribute to enhanced AAA disease in menopausal women and could be a potential novel target for treatment to lower AAA-related events in women

A Novel Hypothesis: A Role for Follicle Stimulating Hormone in Abdominal Aortic Aneurysm Development in Postmenopausal Women

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta, which can potentially be fatal due to exsanguination following rupture. Although AAA is less prevalent in women, women with AAA have a more severe AAA progression compared to men as reflected by enhanced aneurysm growth rates and a higher rupture risk. Women are diagnosed with AAA at an older age than men, and in line with increased osteoporosis and cardiovascular events, the delayed AAA onset has been attributed to the reduction of the protective effect of oestrogens during the menopausal transition. However, new insights have shown that a high follicle stimulating hormone (FSH) level during menopause may also play a key role in those diseases. In this report we hypothesize that FSH may aggravate AAA development and progression in postmenopausal women via a direct and/or indirect role, promoting aorta pathology. Since FSH receptors (FSHR) are reported on many other cell types than granulosa cells in the ovaries, it is feasible that FSH stimulation of FSHR-bearing cells such as aortic endothelial cells or inflammatory cells, could promote AAA formation directly. Indirectly, AAA progression may be influenced by an FSH-mediated increase in osteoporosis, which is associated with aortic calcification. Also, an FSH-mediated decrease in cholesterol uptake by the liver and an increase in cholesterol biosynthesis will increase the cholesterol level in the circulation, and subsequently promote aortic atherosclerosis and inflammation. Lastly, FSH-induced adipogenesis may lead to obesity-mediated dysfunction of the microvasculature of the aorta and/or modulation of the periaortic adipose tissue. Thus the long term increased plasma FSH levels during the menopausal transition may contribute to enhanced AAA disease in menopausal women and could be a potential novel target for treatment to lower AAA-related events in women

Inadequate detection of the FSHR complicates future research on extragonadal FSHR localization

Introduction: Recently, follicle stimulating hormone (FSH) through interaction with its receptor (FSHR) has been proposed to play a role in postmenopausal osteoporosis and cardiovascular disease, rather than the loss of estrogen. To explore this hypothesis, unravelling which cells express extragonadal FSHR on protein level is key. Methods: We used two commercial anti-FSHR antibodies and validated them by performing immunohistochemistry on positive (ovary, testis) and negative controls (skin). Results: The monoclonal anti-FSHR antibody could not identify the FSHR in ovary or testis. The polyclonal anti-FSHR antibody stained the granulosa cells (ovary) and Sertoli cells (testis), yet there was equally intense staining of other cells/extracellular matrix. Furthermore, the polyclonal anti-FSHR antibody also stained skin tissue extensively, suggesting that the antibody stains more than just FSHR. Discussion: The findings in this study may add accuracy to literature on extragonadal FSHR localization and warrants attention to the use of inadequate anti-FSHR antibodies to value the potential role of FSH/FSHR in postmenopausal disease

Inadequate detection of the FSHR complicates future research on extragonadal FSHR localization

Introduction: Recently, follicle stimulating hormone (FSH) through interaction with its receptor (FSHR) has been proposed to play a role in postmenopausal osteoporosis and cardiovascular disease, rather than the loss of estrogen. To explore this hypothesis, unravelling which cells express extragonadal FSHR on protein level is key. Methods: We used two commercial anti-FSHR antibodies and validated them by performing immunohistochemistry on positive (ovary, testis) and negative controls (skin). Results: The monoclonal anti-FSHR antibody could not identify the FSHR in ovary or testis. The polyclonal anti-FSHR antibody stained the granulosa cells (ovary) and Sertoli cells (testis), yet there was equally intense staining of other cells/extracellular matrix. Furthermore, the polyclonal anti-FSHR antibody also stained skin tissue extensively, suggesting that the antibody stains more than just FSHR. Discussion: The findings in this study may add accuracy to literature on extragonadal FSHR localization and warrants attention to the use of inadequate anti-FSHR antibodies to value the potential role of FSH/FSHR in postmenopausal disease