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Purpose <p>Examine sex-specific differences in Intracranial Aneurysms (IA) rupture <i>at presentation</i> and to retrospectively benchmark sex-stratified versus pooled classification models for their ability to discriminate rupture status, using a cross-sectional cohort.</p> Methods <p>We retrospectively analyzed 203 patients (46 males, 157 females) with 303 IAs from a single-center, IRB-approved registry. Of these, 76 IAs were ruptured and 227 unruptured at presentation. Clinical data and lesion characteristics were summarized into patient-level variables and used to develop sex-specific logistic regression models. Adjusted Odds ratios (ORs) were produced for clinical covariates. Cross-application assessed generalizability across sexes.</p> Results <p>Among females, 58.7% of ruptures were &lt; 5&#xa0;mm, with a median ruptured size of 4.2&#xa0;mm at Anterior Communicating Artery (ACOM). Rupture likelihood in females peaked between ages 40 and 59 (aORs = 2.8 and 1.7), coinciding with perimenopause. In males, ACOM was the most frequent rupture site; although males had higher mean hemoglobin levels (14.1 vs. 12.5&#xa0;g/dL, <i>p</i> &lt; 0.0001), hemoglobin contributed less to rupture compared to sex-specific models incorporating age, location, and metabolic factors (hemoglobin concentration, blood glucose). Metabolic factors contributed significantly to the female-specific model, achieving strong discrimination (AUC-ROC: 0.80), while the male-specific model underperformed (AUC-ROC: 0.50), due to limited rupture events (<i>n</i> = 19). Cross-application of features between sexes drastically reduced performance, providing the first computational evidence that male and female rupture mechanisms represent distinct biological feature spaces requiring separate modeling architectures</p> Conclusion <p>Women in this cohort more often presented with rupture IAs at smaller sizes and at midlife ages than men. These sex-specific patterns, though strictly cross-sectional and associative rather than predictive, highlight potential biological and clinical contributors to rupture presentation and may partly explain misclassification by pooled risk models. Future longitudinal, multicenter studies with balanced cohorts are required to validate these findings and to develop robust rupture-risk prediction tools that incorporate sex as a biological variable.</p>

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Sex-Specific Differences in Intracranial Aneurysm Rupture Presentation and Model Performance: Evidence from a Retrospective Cohort

  • 期刊论文

  • 发表日期：

    2025年12月11日

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  • Hemanth Krishna Taduka,
  • Prithvinath Reddy Garigapuram,
  • Srushti Katore,
  • Alia Zeid,
  • Albert S. Favate

摘要

Purpose

Examine sex-specific differences in Intracranial Aneurysms (IA) rupture at presentation and to retrospectively benchmark sex-stratified versus pooled classification models for their ability to discriminate rupture status, using a cross-sectional cohort.

Methods

We retrospectively analyzed 203 patients (46 males, 157 females) with 303 IAs from a single-center, IRB-approved registry. Of these, 76 IAs were ruptured and 227 unruptured at presentation. Clinical data and lesion characteristics were summarized into patient-level variables and used to develop sex-specific logistic regression models. Adjusted Odds ratios (ORs) were produced for clinical covariates. Cross-application assessed generalizability across sexes.

Results

Among females, 58.7% of ruptures were < 5 mm, with a median ruptured size of 4.2 mm at Anterior Communicating Artery (ACOM). Rupture likelihood in females peaked between ages 40 and 59 (aORs = 2.8 and 1.7), coinciding with perimenopause. In males, ACOM was the most frequent rupture site; although males had higher mean hemoglobin levels (14.1 vs. 12.5 g/dL, p < 0.0001), hemoglobin contributed less to rupture compared to sex-specific models incorporating age, location, and metabolic factors (hemoglobin concentration, blood glucose). Metabolic factors contributed significantly to the female-specific model, achieving strong discrimination (AUC-ROC: 0.80), while the male-specific model underperformed (AUC-ROC: 0.50), due to limited rupture events (n = 19). Cross-application of features between sexes drastically reduced performance, providing the first computational evidence that male and female rupture mechanisms represent distinct biological feature spaces requiring separate modeling architectures

Conclusion

Women in this cohort more often presented with rupture IAs at smaller sizes and at midlife ages than men. These sex-specific patterns, though strictly cross-sectional and associative rather than predictive, highlight potential biological and clinical contributors to rupture presentation and may partly explain misclassification by pooled risk models. Future longitudinal, multicenter studies with balanced cohorts are required to validate these findings and to develop robust rupture-risk prediction tools that incorporate sex as a biological variable.