Gender-Based Patterns in Intracranial Aneurysm Site and Rupture Risk: A Single-Center Retrospective Cohort Study from the Caucasus region

doi:10.21203/rs.3.rs-6992239/v1

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Gender-Based Patterns in Intracranial Aneurysm Site and Rupture Risk: A Single-Center Retrospective Cohort Study from the Caucasus region

https://doi.org/10.21203/rs.3.rs-6992239/v1

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Background

Intracranial aneurysms (IAs) are vascular abnormalities characterized by localized dilation of cerebral arteries, with a higher prevalence in females. Ruptured IAs can lead to subarachnoid hemorrhage, a life-threatening condition. The purpose of this study is to investigate gender-based differences in aneurysm distribution and rupture risk, focusing on the role of anatomical, hemodynamic, and hormonal factors.

Results:

Among 164 patients, 85 were women (51.83%) and 79 were men (48.17%). The anterior communicating artery (ACA) was the most common site (34.76%), followed by the internal carotid artery (ICA) (30.49%) and middle cerebral artery (MCA) (18.29%). Women had a higher prevalence of ICA aneurysms (25.91% vs. 24.09%), while men showed a greater occurrence in the ACA (27.46% vs. 29.54%). Age-related differences were observed, with women experiencing ruptures at older ages.

Conclusions:

Gender disparities in IA distribution highlight the influence of anatomical and hormonal factors. Women exhibit a higher prevalence in ICA aneurysms, whereas men are more affected in the ACA. These findings emphasize the need for sex-specific risk assessment, preventive strategies, and tailored clinical management. Future research should focus on predictive modeling for improved early detection and intervention.

Intracranial aneurysms

gender differences

rupture risk

aneurysm site

An intracranial aneurysm (IA), also known as a cerebral aneurysm, is a cerebrovascular disorder characterized by a localized dilation or ballooning of a blood vessel in the brain due to a weakness in the vessel wall. IAs can be divided into four main types: saccular, fusiform, dissecting, and mycotic type. The most common type of IA is the saccular and 85% of cases occur in the Circle of Willis. (^1,2) When the aneurysm ruptures, it may bleed into the subarachnoid space, leading to a subarachnoid hemorrhage (SAH). Females are approximately three times more likely to have an unruptured IA and are also 1.6 times more prone to aneurysm rupture, which leads to subarachnoid hemorrhage, compared to men. (^1–3)

The most frequent anatomical predisposition for IA is the anterior communicating artery (35% of the cases), the internal carotid artery (30%—including the carotid artery itself, the posterior communicating artery, and the ophthalmic artery). The middle cerebral artery has a case prevalence of 22%, and finally, the posterior circulation sites, most commonly the basilar artery tip. (¹) The unique characteristics of these arteries suggest the blood flow at these arterial junctions is more turbulent due to abrupt vascular angles or bifurcations with wider angles which inadvertently results in greater shear stress in these areas. These factors induce endothelial cell damage, thinning of the intima media and smooth muscle degeneration which degrade the extracellular matrix giving rise to the formation of an aneurysm. (⁴)

Risk factors for unruptured intracranial aneurysms include demographics, aneurysm characteristics (size, shape, and location), multiple aneurysms, prior subarachnoid hemorrhage, family history of smoking, and hypertension. These factors also play a critical role in guiding treatment decisions.[^5,6] The prevalence of unruptured IAs in women reached 6% while the overall prevalence in the study population was reportedly 3%-4%. Smoking has a greater impact on women than on men and has a relationship with low levels of 15-PGDH which could serve as a pro-oxidative damaging action of smoking in women.[^7,8].

Researchers suggest that hormones also play a role in IAs pathogenesis with a decline in the concentration of estrogen in peri- and post-menopause periods leading to structure and function changes in the cerebral artery which favor the formation and rupture of IAs. Estrogens have a mediated protection mechanism towards the first step of IA formation: hemodynamic injury-induced endothelial dysfunction at the intracranial artery bifurcation. [^7,9–12]

Research shows unruptured IAs have a preferred location on the internal carotid artery (ICA) in women (54% vs 38% in men). In contrast, in men, it frequently occurs in the anterior cerebral artery (ACA) (29% vs 15% in women) and anterior communicating artery. This sex-specific distinction may be attributed to the measurement of the diameter of arteries of the circle of Willis revealed that ICA, ACA, posterior cerebral artery and basilar artery were substantially smaller in women than in men, with the most pronounced difference found in ICA. [^7,13]

This retrospective, single-institutional cohort study included patients admitted to the High Technology Medical Center, University Clinic, in Tbilisi, Georgia, between January 2022 and December 2024. The study was approved by the High Technology Medical Center's institutional review board, and data were anonymized to maintain patient confidentiality.

The study included patients aged 40 to 60 who were diagnosed with intracranial aneurysms and confirmed through imaging techniques. Most importantly, patients consented to the use of their clinical data for research purposes. The study identified patients with intracranial aneurysms using CT angiography (CTA) and Magnetic Resonance Angiography (MRA) as primary diagnostic tools. In certain cases, Digital Subtraction Angiography (DSA) was utilized to verify the diagnosis.

Exclusion criteria comprised individuals with inadequate or incomplete documentation.

Data collection:

Information was extracted retrospectively from electronic health records and imaging databases. The collected variables encompassed patient demographics (age, gender) and aneurysm characteristics (site, rupture status)

Data sources and confidentiality:

The study period was selected based on the availability of the complete medical records and consistency in diagnosing aneurysms using CTA, MRA, and DSA within the timeframe. Data was extracted from the High Technology Medical Center database, and all data were anonymized using patient record numbers to ensure confidentiality.

Statistical analysis:

Univariate and multivariate logistic regression analyses were performed to identify gender specific differences associated with intracranial aneurysms. Categorical variables within the study were compared using chi square tests. P-values less than 0.05 were considered to be statistically significant.

Outcome measures

The main outcome variable assessed was the occurrence of Intracranial Aneurysms, categorized by gender (male, female) and anatomical site (ICA, MCA, AComA), as well as the incidence of ruptured and unruptured aneurysms across both sexes and specific locations. The additional outcome measure evaluated the relationship between aneurysm rupture and patient age (for both sexes) as well as aneurysm location.

The rationale for exclusion criteria

The study focused on the 40–60 age group as it represented the most consistently available and complete dataset within our institution's medical records, ensuring statistical power and reducing missing data bias.

The study included a total of 164 patients diagnosed with intracranial aneurysms, with 79 men (48.17%) and 85 women (51.83%). Demographic details, including the distribution of aneurysm sites according to gender is presented in Table 1. Aneurysm sites varied in prevalence across the study population. The anterior communicating artery (ACA) was the most commonly affected site, comprising 57 cases (34 men, 27.46%; 23 women, 29.54%). This was followed by the internal carotid artery (ICA) with 50 cases, of which a higher proportion was observed in women (34 cases, 25.91%) compared to men (16 cases, 24.09%). Middle cerebral artery (MCA) aneurysms were also notable, with 30 cases reported; these were more frequent in men (19 cases, 14.45%) than in women (11 cases, 15.55%). Aneurysms located in the posterior communicating artery (PCommA) and other sites were less prevalent, collectively contributing to 27 cases (16.47% of total cases).

Table 1
Distribution of Aneurysm Sites by Gender
Aneurysm Site	Total Cases	Men (n)	Men (%)	Women (n)	Women (%)
Anterior Communicating Artery (ACA)	57	34	27.46	23	29.54
Internal Carotid Artery (ICA)	50	16	24.09	34	25.91
Middle Cerebral Artery (MCA)	30	19	14.45	11	15.55
Posterior Communicating Artery (PCommA)	7	2	3.31	5	3.63
Other Sites	20	8	9.36	12	10.37

Among the 164 aneurysms analyzed, 25 (15.24%) were ruptured, and 139 (84.76%) were unruptured. Rupture status varied by gender, as shown in Table 2. A slightly higher proportion of ruptures was observed in women (13%) compared to men (12%). Conversely, unruptured aneurysms were more prevalent in both men (67%) and women (72%). The relationship between gender and rupture status was assessed using a chi-square test, revealing a statistically significant association (χ² = 12.62, df = 4, p = 0.013). This suggests gender-based differences in rupture risk within the studied population.

Table 2
Rupture Status by Gender
Rupture Status	Total Cases	Men (%)	Women (%)
Ruptured	25	12	13
Unruptured	139	67	72
Total	164	79	85

The frequency of ruptures varied significantly depending on aneurysm location, as shown in Table 3. The ACA was associated with the highest number of ruptured aneurysms (13 cases, 8.69%), followed by the MCA and other sites (5 cases each). Ruptures were least common in the PCommA, with only 1 case (1.07%). Unruptured aneurysms were more prevalent across all sites, particularly in the ACA (44 cases, 48.31%) and ICA (49 cases, 42.38%). A chi-square test of independence revealed a significant association between aneurysm site and rupture frequency (χ² = 10.84, df = 4, p = 0.028). This indicates that rupture frequencies differ significantly across aneurysm sites (p < 0.05).

Table 3
Rupture Status by Aneurysm Site
Aneurysm Site	Total Cases	Ruptured (n)	Ruptured (%)	Unruptured (n)	Unruptured (%)
Anterior Communicating Artery (ACA)	57	13	8.69	44	48.31
Internal Carotid Artery (ICA)	50	1	7.62	49	42.38
Middle Cerebral Artery (MCA)	30	5	4.57	25	25.43
Other Sites	20	5	3.06	15	16.95
Posterior Communicating Artery (PCommA)	7	1	1.07	6	5.93

These findings underscore significant gender and site-specific differences in aneurysm distribution and rupture risk. The ACA exhibited the highest rupture frequency, while the PCommA showed the lowest. Gender disparities in both rupture and unruptured aneurysm prevalence further highlight the need for tailored clinical assessment and management strategies.

Hemodynamic stress is a significant risk factor for intracranial aneurysm (IA) formation, with anatomical variations in the circle of Willis between men and women playing a critical role. Differences in arterial diameters and bifurcation geometry increase hemodynamic forces in women, leading to greater endothelial shear stress and vascular wall remodeling. This elevated stress contributes to endothelial dysfunction, increased inflammatory response, and degradation of the extracellular matrix, promoting IA formation and progression, This aligns with our study, which included 164 patients diagnosed with intracranial aneurysms (IAs). The prevalence of IAs was higher in women (51.83%) compared to men (48.17%) [14 ].

1. Difference in Common Aneurysm Sites Between Men and Women

The distribution of aneurysm sites demonstrates distinct gender-based patterns. In this study, men exhibited a higher prevalence of anterior communicating artery (ACA) aneurysms (34 cases) compared to women (23 cases). Conversely, women were more likely to have aneurysms in the internal carotid artery (ICA), with 34 cases versus 16 in men. These findings align with prior research that identifies a significantly higher proportion of ACA aneurysms in men and ICA aneurysms in women (p < 0.001) [¹⁵]. Similarly, it has also been reported that ACA aneurysms accounted for 81% of male cases and only 49% of female cases, while ICA aneurysms were predominant in females (64% vs. 24% in males) [¹⁶]. Additionally, it was stated that women had double the amount of aneurysms in the ICA compared to men[¹⁷].

The physiological basis for these differences may include hormonal effects, such as the vascular protective properties of estrogen, and gender-specific anatomical variations in vessel size and geometry. For example, women’s smaller vessel diameters may predispose them to aneurysms in regions like the ICA, where shear stress and wall tension are more concentrated. Lifestyle factors and comorbidities unique to each gender may also play a role.[²⁰]

2. Difference in Ruptured vs. Unruptured Aneurysms Between Men and Women

Rupture trends further underscore gender distinctions in aneurysm presentation. While both sexes showed a higher prevalence of unruptured aneurysms, women experienced slightly more ruptured aneurysms (13 cases) compared to men (12 cases). Notably, ruptured aneurysms in women were predominantly located at the ICA (42%), consistent with Watt et al. (2020), who observed a higher frequency of ICA ruptures in females [¹⁷]. In contrast, ruptured ACA aneurysms were more common in men (47%), reflecting findings by Ghods et al [¹⁵].

Women’s heightened rupture risk may stem from hormonal changes post-menopause and lower aneurysm size thresholds for rupture. Additionally, women were more likely to present with multiple aneurysms, which occurred in 11% of female cases compared to 6% in males [¹⁸].

The average age of rupture differed between genders, with men presenting at 53 years and women at 59 years. These findings are consistent with the results of Park et al. (2008), who attributed the younger age of rupture in men to lifestyle factors such as smoking and hypertension. [¹⁹]

3. Aneurysm Site and Rupture Likelihood

The risk of rupture was strongly associated with the aneurysm site. ACA aneurysms exhibited the highest rupture frequency (22.8%), followed by MCA aneurysms (16.7%). ICA aneurysms, despite their prevalence in women, demonstrated a notably low rupture rate (2.0%). These findings reinforce the conclusions of Kongable et al. (1996), who identified site-specific hemodynamic stress and vascular wall structure as critical determinants of rupture risk. [¹²]

This study’s chi-square analysis (p = 0.028) confirmed a statistically significant relationship between aneurysm location and rupture likelihood [²⁰]. The higher rupture risk in ACA aneurysms may be due to their exposure to complex hemodynamic forces at bifurcation points, whereas ICA aneurysms may benefit from more stable flow patterns.

Implications for Clinical Practice

These findings underscore the necessity of site-specific management solutions. ACA aneurysms, given their higher rupture potential, warrant more frequent monitoring and earlier intervention in both men and women. For women, especially postmenopausal women, ICA aneurysms may require tailored surveillance protocols to address their unique distribution and rupture characteristics. Future research should focus on integrating hormonal, anatomical, and hemodynamic factors into predictive models to improve patient outcomes.

This study serves to highlight the gender-based differences in various aspects of aneurysms, especially regarding aneurysm location and frequency of rupture. Women had a higher prevalence of aneurysms in the ICA, whereas men had more frequent aneurysms in the ACA. These differences extend to aneurysm rupture rates as well, with women having higher rupture tendency, especially in the ICA aneurysms. Meanwhile, men exhibit more ruptured ACA aneurysms.

These distinctions could be attributed to a combination of hemodynamic, anatomical, and hormonal factors; so there's a need for personalized treatment and monitoring strategies. The association between aneurysm site and rupture risk underscores the importance of targeted surveillance, especially for ACA aneurysms, which showed the highest rupture frequency. The study also highlights the role of age; women experience ruptures at older ages than men on average, suggesting the role of hormonal changes post-menopause.

Further research on the subject is required to formulate predictive models to improve the diagnosis and management of IAs. By taking these gender differences into account, clinicians can formulate better algorithms to optimize patient care and minimize risks.

Future Research Suggestions

More investigating on the impact of hormones and hormonal changes, on aneurysm formation and rupture risk would add depth to our understanding of gender differences in aneurysm pathophysiology.

Future research should look into how differences in vascular anatomy, such as arterial width and branching patterns, affect gender-specific aneurysm distribution and rupture rates.

Consent for publication: Informed consent was obtained from all patients.

Availability of data and materials: All the variables that were used in this study are available.

Ethics approval and consent to participate

The ethical approval was obtained from the High Technology Medical Center University Clinic with number:03-7/O-1 We have anonymized the patient information that could identify an individual.

Limitations

This study has several limitations. First, it was conducted at a single medical center, which may limit the generalizability of the findings to broader populations. Second, the sample size, although adequate for exploratory analysis, was relatively small, particularly in subgroup comparisons of rupture status across aneurysm sites and genders. This limits the statistical power to detect more subtle associations. Additionally, the retrospective design may carry the risk of missing or incomplete data, although efforts were made to minimize this through rigorous chart review and inclusion criteria.

However, this study represents the first dataset from Georgia—and more broadly, the entire Caucasus region—to examine gender-based patterns in intracranial aneurysm distribution and rupture risk. This regional uniqueness adds valuable insight to the global literature and provides a foundation for future multicenter research in underrepresented populations

Competing interests: There are none.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors

Authors' contributions

AQ and AA, the team leader, was instructing the subteams and was reviewing and editing their work.
Dr. EE was the supervisor and the source of the data.
TT, under the supervision of Dr. EE and the ethical committee, translated the data from Georgian to English.
ASJ, CP and MA wrote the introduction.
JG and AH wrote the methodology.
GG has worked on the results.
RS and NM and AZ wrote the discussion.
RGR is the author of the conclusion and abstract.

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No competing interests reported.

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You are reading this latest preprint version

Gender-Based Patterns in Intracranial Aneurysm Site and Rupture Risk: A Single-Center Retrospective Cohort Study from the Caucasus region

Status:

Version 1

Abstract

Background

Results:

Conclusions:

INTRODUCTION

Materials and Methods

Data collection:

Data sources and confidentiality:

Statistical analysis:

Outcome measures

The rationale for exclusion criteria

Results

Discussion

1. Difference in Common Aneurysm Sites Between Men and Women

2. Difference in Ruptured vs. Unruptured Aneurysms Between Men and Women

3. Aneurysm Site and Rupture Likelihood

Implications for Clinical Practice

Conclusion

Declarations

Ethics approval and consent to participate

References

Additional Declarations

Status:

Version 1