European Journal of Vascular & Endovascular Surgery
Volume 39, Issue 5 , Pages 555-558, May 2010

Evaluation of Sex Differences in Relative Dilatation of Thoracic Aortic Aneurysms

Division of Vascular Surgery, London Health Sciences Center & The University of Western Ontario, London ON, Canada

Received 23 December 2009; accepted 19 February 2010. published online 12 March 2010.

Article Outline

Abstract 

Objectives

Treatment recommendations based on thoracic aortic aneurysm (TAA) diameter (D) ignore differences in proportional dilatation between patients of different body habitus and sex. This study's goal is to compare TAA diameters between sexes as a function of relative aortic size as determined by aortic size index (ASI).

Methods

This is a retrospective review of all TAA's treated between 2003 and 2008. ASI was calculated for each patient, which considers aneurysm diameter, patient's height and weight. Values for males and females were plotted separately (TAA diameter vs ASI) and the resulting linear regression equations permitted comparison of proportional dilatation between sexes.

Results

In 40 patients (25 males, 15 females) mean TAA diameter did not differ between sexes (6.56 ± 0.99 vs 7.03 ± 1.14, P = 0.18), while ASI was larger in females than males (4.21 ± 0.85 vs 3.24 ± 0.63, P = 0.0003). Values for ruptured and intact aneurysms did not differ. Linear regression analysis permitted comparison of TAA diameter with ASI between sexes resulting in the following equation: DFemale = 0.91DMale − 0.49. This correlates a 6 cm TAA in a male with a 4.97 cm TAA in a female.

Conclusions

TAA of equal diameter represent a larger proportional dilatation in females compared to males. This could influence repair thresholds that are historically diameter based.

Keywords: Thoracic aneurysms, Relative dilatation, Sex differences

 

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Introduction 

Maximum aortic diameter has traditionally been used as a predictive tool for aneurysm rupture, and is the basis for most commonly used treatment recommendations and guidelines. In contrast to the thoracic aorta, this diameter-rupture risk relationship has been more thoroughly evaluated with abdominal aortic aneurysms (AAA) and has resulted in validated and widely used treatment recommendations based on randomized controlled trials.1

Information regarding the natural history of TAA's and repair thresholds has not been validated to the extent of the abdominal aorta.2

As in the abdominal aorta, repair thresholds of TAA have predominantly been diameter based. A descending TAA over 6 cm in diameter has a 14.1% yearly risk of rupture, dissection or death.3 As a result, most investigators would recommend a repair threshold of 6.0–6.5 cm for descending TAA's.3, 4, 5, 6 However, diameter measurements can simplify the rupture risk determination at the expense of ignoring proportional dilatation of TAA's between individuals of different body configurations and sexes.

The goal of the present study is to expand on previous work in the abdominal aorta7 by comparing TAA diameters between sexes as a function of relative aortic size as reflected by aortic size index.8

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Materials and methods 

Our vascular surgery database was retrospectively reviewed to identify all patients who underwent elective or emergent repair of a descending TAA over a recent five year period (2003–2008) by one of four vascular surgeons. Demographic information and maximum aortic diameter was obtained. Aneurysm diameter was determined perpendicular to the centerline using an Aquarius APS server (TeraRecon Inc, San Mateo, CA, USA). Patients with aortic arch, visceral aortic involvement, connective tissue disorders or aortic dissection were excluded from subsequent analysis, limiting this series to those who underwent repair of a degenerative aneurysm of the descending thoracic aorta.

The aortic size index (ASI) was calculated for each patient. This is a previously described measure of relative aortic size that takes into account body surface area [Aortic Size Index(cm/m2) = Aortic Diameter(cm) ÷ Body Surface Area (m2)].8 Several equations can be used to calculate body surface area but many are complicated and not intuitive. A recently simplified version of this equation uses the Mosteller formula for body surface area calculation resulting in the following,9 which was used in this study:

ASI = 60D(HW)−0.5, where D is largest aortic diameter (cm), H is patient's height (cm), W is patient's weight (kg).

Information regarding height and weight was obtained from hospital charts and operative records. All data is presented as means ± standard deviation and analyzed with unpaired t-tests with a P < 0.05 level of statistical significance.

Linear regression analysis was performed and sex specific linear regression plots and equations were developed comparing thoracic aneurysm diameter and ASI (GraphPad Prism version 5.02, GraphPad Software Inc, San Diego, CA). The male and female linear regression equations were combined using equivalent ASI's resulting in a single formula and graph equating aneurysm diameters between sexes.

This study received approval from the University of Western Ontario's Research Ethics Board for Health Sciences Research involving Human Subjects.

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Results 

During this time period 45 patients underwent repair of their descending TAA at our university affiliated medical center. Data was complete for 40 patients who comprise the study cohort. All patients underwent endovascular repair, and the clinical results and outcomes have been reported previously.2 The majority of these patients were male (25 patients, 64.4%) and the mean TAA diameters did not differ between females (7.03 ± 1.14 cm) and males (6.56 ± 0.99 cm), (P = 0.18). Aortic size index was appreciably larger in females compared to males (4.21 ± 0.85 versus 3.24 ± 0.63, P = 0.0003), (Table 1). Most of these patients underwent elective repair of their TAA (32 patients, 80%) and the mean thoracic aortic diameter and ASI did not differ between those treated for ruptured or intact aneurysms (Table 2). However, there were only eight patients with ruptured aneurysms in this series (5 males, 3 females).

Table 1. Thoracic Aortic Aneurysms (N = 40) (data presented as mean ± standard deviation).
Male95% CIFemale95% CIP-value
Number/%25/62.5 15/37.5
TAA diameter (cm)6.56 (0.99)6.14, 6.977.03 (1.14)6.40, 7.660.18
ASI (cm/m2)3.24 (0.63)2.98, 3.514.21 (0.85)3.70, 4.620.0003
Table 2. Ruptured versus Intact TAA (data presented as mean ± standard deviation).
IntactRupturedP-value
Number/%32/80.08/20.0
TAA diameter (cm)6.73 (1.09)6.78 (0.84)0.93
ASI (cm/m2)3.63 (0.88)3.21 (0.26)0.35

Aortic size index was plotted against aneurysm diameter for both sexes for each individual patient (Figure 1, Figure 2), resulting in the linear regression equations listed in Table 3. These were then combined for equivalent ASI values to arrive at an equation and plot comparing TAA diameters between sexes (Table 3 and Fig. 3). For example, a 6.5 cm TAA in a male corresponds to a 5.4 cm aneurysm in a female.

Table 3. Linear regression equations.
SexEquationCorrelation coefficient (r)
MaleASI = −0.15 + 0.52D0.82
FemaleASI = 0.13 + 0.57D0.78
CombinedDFemale = 0.91DMale–0.49

ASI = aortic size index, D = TAA diameter.

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Discussion 

Vascular surgeons continue to attempt to prevent aneurysm rupture because of its high mortality rate. However, the prediction of this complication remains far from accurate. As in the abdominal aorta, diameter measurements of TAA's are the basis of most commonly used treatment guidelines and have resulted in recommendations for repair of a descending TAA once it reaches 6.0–6.5 cm.3, 4, 5 There is concern, however, that this might over simplify the situation and fails to consider differences in TAA relative, or proportional dilatation, and differences between males and females.

Females constitute a minority of patients in most series of TAA, but some investigators have reported a higher risk of rupture in female patients.6, 8 It remains debatable whether this can be explained simply by differences in aortic size and proportional dilatation between sexes10, 11 (i.e. a 6.0 cm TAA is proportionately larger in a female compared to a male), or by biological differences. These biological factors might include estrogen derived affects on inflammation12 and increased stiffness of the thoracic aorta in females.13 It's likely that both anatomic and biologic factors play a role in these differences in behavior of TAA's between sexes.

This issue of relative aortic dilatation has been explored previously by our group in the abdominal aorta.7 Briefly, a measure of proportional dilatation was developed for each patient by comparing the AAA diameter with that of the nonaneurysmal suprarenal aorta. As with the present study, linear regression analyses resulted in plots that compared these measurements between males and females. As a result, a 5.5 cm AAA in a male was proportionately similar to a 5.2 cm AAA in a female, thereby providing further validation for a lower repair threshold in women than men. Using a segment of the aorta as a reference diameter in a similar study with TAA's proved problematic given the wide range of thoracic aortic diameters and the probable pan-aortic involvement in patients with TAA. As a result, a comparison to the patient's body surface area was used to provide a measure of relative dilatation.

The predictive value of the ASI has been previously validated through a retrospective review and analysis of over four hundred patients with thoracic aneurysms.8 This combination of aneurysm diameter and body surface area was evaluated with respect to a composite endpoint of death, aneurysm rupture or dissection. Three levels of risk were observed with patients having an ASI less than 2.75 cm/m2 having a risk of 4% per year, and those with an ASI greater than 4.25 cm/m2 having a 20% risk per year. The intermediate risk group had an 8% annual risk of this composite outcome. This has yet to be prospectively validated, and in the present study neither aortic diameter, nor ASI differed between ruptured and intact TAA's (Table 2). Meaningful conclusions are difficult, however, given that there were only eight ruptured aneurysms in this series and the numbers were too small (5 males, 3 females) to determine sex differences.

Even though TAA diameters were similar in males and females in this study, ASI was significantly larger in our female patients (Table 1). Although this may seem fairly intuitive, it supports the notion that thoracic aneurysms of equivalent diameters are proportionately larger in women than in men. With further statistical manipulation a graph was plotted that compares aneurysm diameters between sexes (Fig. 3), revealing that TAA's in females are proportionally similar to aneurysms in males that are approximately 1 cm larger. Although ASI can be calculated fairly quickly, most TAA treatment guidelines remain diameter based and the present study, along with clarifying this relative dilatation relationship between sexes, might suggest an approximately 1 cm lower treatment threshold in women than in men. Further validation is required, however, prior to adoption of this recommendation.

This study has several limitations, including its relatively small number of patients. Females are underrepresented but this is consistent with other studies of this predominantly male disease. Additionally, application of this study's conclusions should be restricted to degenerative aneurysms of the descending thoracic aorta, and should not include patients with connective tissue disorders. Further clarification and validation of these diameter relationships will require a larger series of patients. Also, a prospective evaluation of this diameter-rupture relationship would likely involve multiple centers, given the relatively modest number of TAA's presenting to any one institution.

Additionally, any recommendation regarding diameter threshold for repair needs to consider the repair options available. Despite the absence of randomized trials, as opposed to the abdominal aorta, endovascular repair has replaced open surgery as the preferred method of repair of descending TAA's at many centers,14, 15 including ours.2 As a result of this lower rate of major morbidity and mortality some would suggest a smaller repair diameter with endovascular repair then used previously. However, the promise of further technological improvements and the uncertainty regarding durability would support the continued use of the 6.0–6.5 cm diameter threshold for endovascular repair. The results of the present study suggest a somewhat smaller (5.4 cm) diameter at which point repair should be considered in women.

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Conclusions 

The decision to treat a descending TAA requires a complex decision making process weighing the natural history of the disease, the patient's life expectancy and the risk of intervention. The present study confirms that TAA's in men and women are not equivalent regarding relative dilatation when considering body surface area. Those in men are proportionally similar to aneurysms in women that are approximately 1 cm smaller. How this might impact repair thresholds, that are historically diameter based, remains to be seen.

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Conflict of Interest/Funding 

None.

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References 

  1. The United Kingdom Small Aneurysm Trial Participants . Long-term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346:1445–1452
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PII: S1078-5884(10)00117-6

doi:10.1016/j.ejvs.2010.02.011

European Journal of Vascular & Endovascular Surgery
Volume 39, Issue 5 , Pages 555-558, May 2010

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