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  • Endothelin Polymorphisms as a Risk Factor for Cerebral Aneurysm Rebleeding Following Aneurysmal Subarachnoid Hemorrhage

    Final Number:

    Paul M. Foreman; Robert M. Starke; Philipp Hendrix; Mark R. Harrigan; Winfield S. Fisher; Nilesh A. Vyas; Robert Lipsky; Minkuan Lin; Beverly C. Walters; Jean-Francois Pittet; Mali Mathru; Christoph J. Griessenauer

    Study Design:

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2017 Annual Meeting

    Introduction: Aneurysm rebleeding following presentation with aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and poor functional outcome. While a substantial genetic contribution to aneurysm formation and rupture is known, the genetic influence on the risk of rebleeding is poorly understood.

    Methods: Blood sample from all patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study were used for genetic evaluation. The CARAS study prospectively enrolled aSAH patients at two academic institutions in the United States from 2012-2015. Common endothelin SNPs were detected using 5’exonnuclease (Taqman) genotyping assays. Analysis of associations between endothelin single nucleotide polymorphisms (SNP) and aneurysm rebleeding was performed.

    Results: One hundred and forty-nine aSAH patients were included. Aneurysm rebleeding occurred in 7 (4.6%) patients. Multivariable analysis identified increasing Hijdra grade (OR 1.342, 95% CI 1.010-1.783, p = 0.042) and the TT genotype for EDN1 G/T SNP (rs2070699; OR 29.281, 95% CI 2.730-314.055, p = 0.005) as risk factors for aneurysm rebleeding. Aneurysm rebleeding was identified as an independent predictor of unfavorable functional outcome (mRS 3-6) at last follow up (OR 62.005, 95% CI 3.037-1265.997, p = 0.007).

    Conclusions: Aneurysm rebleeding following presentation with aSAH was independently associated with increasing Hijdra grade, the TT genotype of the EDN1 G/T SNP, and poor functional outcome at last follow up.

    Patient Care: This research seeks to further define the genetic influence on the risk of aneurysm rebleeding in patients presenting with aneurysmal subarachnoid hemorrhage. This is a small step in the ongoing process of individualizing the practice of medicine. Patients that are identified as high risk for aneurysm rebleeding might benefit from anti-fibrinolytics, aggressive blood pressure control, and prompt aneurysm obliteration, while those at a low risk might not require these more aggressive measures.

    Learning Objectives: By the conclusion of this session, participants should be able to 1) identify risk factors associated with aneurysm rebleeding, 2) understand the risk of rebleeding associated with certain endothelin polymorphisms, and 3) recognize the impact of aneurysm rebleeding on functional outcome.


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