Results:
A total of 1538 patients were hospitalized to either hospital with a diagnosis of AAA. About 92% of the sample (1417 patients) were excluded and 117 patients were included for final analysis (figure 1) as the sample was restricted to ruptured aneurysms only. Out of the 117 patients, 79 were male (67.6%) and 38 were female patients (32.4%) admitted with a AAA rupture.
Table 1 demonstrates the demographic characters of the sample. 100% of the sample were Caucasian. Obesity was more prevalent in the male patients with a significant statistical difference (p=0.02) but there was no difference in the distribution of tobacco use, hypertension, other major cardiovascular co-morbidities or use of any cardio-protective medications.
Gender was identified as an independent predictor of age of rupture after adjusting the effects of hypertension, co-morbidities, smoking, use of medications and previous history of aneurysms (p=0.005). The mean age of rupture in males was 75.8 years (S.D.=10) and in females, it was 82.4 years (S.D.=8.6). We evaluated the age specific incidence of the aneurysm ruptures and it was noted that 65.8% of the male patients were under 85 years age and 65.7% of the female patients were over 85 years old (figure 2).
Table 2 describes the characteristics of the ruptured aneurysms in male and female patients. There was no difference in the pattern of the location of the rupture, whether they are supra-renal, infra-renal or both, whether they are located on the left, right or both sides. There were 75 males (94.9%) and 34 females (89.5%) with an infra-renal aneurysm. However, there was a significant difference in the size of the aneurysm rupture between the two groups. Female patients tend to have a significantly smaller size of aneurysm at the time of rupture (mean=7.46 cm, S.D.=2.09) as compared to the males (mean=8.23 cm, S.D. 1.84), p=0.04. About 58% of the male patients had a known previous diagnosis of AAA and 29% of them had their aneurysms repaired on an elective basis. In the female patients, AAA was a known diagnosis in only 50% of the cases and surgical repair was performed only in 10.5% of the cases. At their previous diagnosis, the mean size of the aneurysm was significantly smaller in males (4.0 cm, S.D. 3.3), as compared to the females (5.0 cm, S.D. 2.6), p=0.03. The AAA was found in either routine screening or as an incidental finding.
Table 3 explains the characteristics describing hospital course and mortality of the ruptured AAAs and the post-operative complications. The overall mortality (irrespective of surgery or not) was significantly higher in women (68.4%) as compared to men (31.6%), p<0.001. The post-operative mortality was also higher in females which is 50% versus 21.2% in males, p=0.05. The overall mortality and post-operative mortality were adjusted for tobacco use, age, major co-morbidities and use of cardio-protective medications using a logistic regression model.
Out of the 79 male patients in the sample, 74 of them (93.7%) had an operative management of the ruptured AAA as compared to only 24 of the 38 females (63.2%), p=0.03. Endo-vascular repair of the ruptured AAA was performed more frequently in both males and females (72.2% vs 42.1%) than open repair, p<0.01. The post-operative complications (ventilator dependent respiratory failure, requirement of vasopressors and other unexpected complications like blood loss, renal failure etc.) tend to happen more frequently in females as compared to males at a statistically significant level (p<0.001) even when adjusted for age, comorbidities, tobacco use and use of medications. The length of stay in the intensive care unit (ICU) was significantly longer in females as compared to males (5.5 days versus 4.1 days) using the same model, p=0.02.
Figure 3 shows the long-term survival of the patients discharged alive after the AAA repair. The available sample for this analysis was 27 patients; out of them 21 were male and 6 were female patients. Males survived an average of 11.0 months (S.D.=2.2) as compared to 9.3 months (S.D.=2.9) in females, though not at a significant level (p-value=0.41). The sample available for this analysis was only 27 patients, 21 males and 6 females.
Discussion :
Cardiovascular disease is the number one cause of death for both men and women in the United States.3 Traditionally, all the cardiovascular diseases were considered as “men’s diseases.” Our study concludes that there was a significant effect of gender on the age of death from AAA rupture and there was a significant difference in the size of AAA rupture between males and females.  Women tend to present at an advanced age and have a smaller size of the ruptured aneurysm though the overall incidence of AAA rupture was higher in males. The probability of undergoing surgery for ruptured AAA was significantly lower for women. Female gender was also identified as an independent predictor of longer length of ICU stay, higher incidence of postoperative complications, more frequent use of vasopressors and ventilators.
There are a few previous studies which showed the disparities of risks and outcomes of AAAs in males and females and our study adds to the literature that even ruptured aneurysms tend to fare worse in females. Females are usually protected from the development of AAAs, but behave aggressively with faster growth, frequency of rupture, and higher mortality rate.5
100% of the patients included in our study were Caucasian. AAAs are commonly seen in Caucasian population and few studies have reported differences in the development of AAA in Caucasians and African-American populations.9 Out of 117 patients included in the study, 92 (78.6%) of them have at least smoked 100 cigarettes in their lifetime. Smoking and genetics play a key role in the development of AAA.10 Among all the cardiovascular diseases, AAA has the strongest association with smoking, precisely current smoking. In a study by Ulug et al on the prevalence of screening-detected AAAs in women, it was found that smoking had a greater impact on prevalence of AAA in females than in males.11 As seen in our study, there is also a strong correlation between obesity with high waist circumference and AAA. This is probably due to the release of adipokines and obesity induced aortic inflammation leading to weakening of the vessel and further aneurysmal formation.12 We wanted to neutralize the effect of current use of medications on AAA outcomes as there is evidence suggesting that use of cardio-protective medications like aspirin,13clopidogrel,14 statins15 and beta blockers16 have protective effects against AAA. 93% of our sample presented with infrarenal aneurysm which is consistent with the data that 85% of the AAAs are infrarenal.17Though estrogen has a protective effect in the development of AAA in females, hormonal replacement therapy increases the risk of AAA development after menopause18. Overall, the development of AAA, its progression and outcome are a combination of genetic predispositions and environmental factors10.
In our sample, mean diameter at the time of rupture in males is 8.23 cm with (SD 1.84) while that of females is 7.46 cm (SD 2.09).  Few authors believe that discrepancy in geometric and biomechanical properties are the reasons for faster growth of AAA and increased rate of rupture than that of males in spite of low prevalence. Females also exhibit higher proportion of aneurysms with high peak wall stress.19In males, the average infrarenal diameter of aorta at the age of 65 years or more is 2.02 cm, whereas in females it is 1.75cm.11 The intuitive thought for smaller diameters of AAA in females when compared to males is that females inherently have smaller aortas.19 These innate differences could call for gender specific guidelines in screening and elective surgical repair of AAAs in females.
AAA is usually asymptomatic and diagnosis is usually made as an incidental finding on imaging for other medical complaints.20 65 patients (55.5%) in our sample had the previous diagnosis of AAA who were diagnosed as part of routine screening or as an incidental finding on imaging for other medical illnesses. Few studies suggest that non-specific inflammatory markers like D-dimer levels are elevated in patients with AAA,21 but there are no other diagnostic and prognostic markers for the diagnosis of AAA20 and there is also no drug therapy to limit the progression of AAA.22 The only effective way of diagnosis and follow up of a AAA is abdominal ultrasound. No repeat ultrasound is recommended if the AAA is less than 3 cm but if the initial size is 3 to 4 cm, an ultrasound is recommended every 2-3 years and for a AAA sized 4 to 5.5 cm, ultrasound is recommended every 6 months to one year.20
50% of the females in our sample who had a previous diagnosis of AAA had a mean diameter of 5 cm. Considering the worse outcomes in females with higher mortality and delayed age at presentation, a threshold of 5.5 cm might be too high for females though this has been the recommended size of elective repair in males.23 The current indications for elective AAA repair include diameter of 5.5 cm for a patient with symptomatic AAA (irrespective of the size) and rapid expansion like 1 cm in one year irrespective of the size. Though elective AAA repair is associated with decreased morbidity and mortality, overall operative mortality and long-term survival mainly depends on the patient’s age and other risk factors. Hence, the decision to perform an elective AAA repair must weigh the patient’s risk of rupture depending on AAA diameter against the individual risk of surgery.24 Endo-vascular repair (72.2% and 42.1%) for ruptured AAA is performed more frequently than open repair (21.5% and 21.1%) in both males and females.25 In spite of advanced ICU and techniques for repair, mortality still remains high following repair of ruptured AAA.5 We adjusted our sample for age, cardio-protective medications and comorbidities and still found that the post-operative complications, overall mortality and morbidity remain higher in females.
Post-operative complications tend to happen more commonly in females as compared to males at a statistically significant level (p<0.0001) when adjusted for age, comorbidities, tobacco use and use of medications. Hence, very close post-procedural surveillance and prompt correction of complications are required to avoid fatal outcomes.26 24 out of 38 female patients had undergone surgical repair, either EVAR or open repair. Of these, 18 (75%) patients required ventilator, 17 (70.8%) required vasopressors and 10 (58.3%) had other unexpected postoperative complications like blood loss, renal failure, etc. Females (12 out of 24, 50%) who received EVAR or open repair have postoperative complications and are more likely to die than males. Differences in diagnosis and treatment rates or inherent anatomical dissimilarities and lack of screening for females are the reasons for high mortality rate in females after EVAR or open repair.5 Hence, there is a need to focus on improving ruptured AAA outcomes in females with a repair at a smaller size and earlier age.