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.