Associations of Folate and Homocysteine Levels with Futile Recanalization in Acute Ischemic Stroke After Successful Endovascular Thrombectomy

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INTRODUCTION: Our preliminary study identified two metabolically distinct thrombus subtypes, demonstrating enhanced lipid metabolic signatures but downregulated folate biosynthesis pathways associated with poor prognosis. This study aimed to assess the prognostic value of routine laboratory parameters involved in lipid and folate metabolism for predicting 90-day futile recanalization (FR) in patients with anterior circulation acute ischemic stroke caused by large vessel occlusion (AIS-LVO) who achieved successful recanalization by endovascular thrombectomy. METHODS: Consecutive patients with anterior circulation AIS-LVO who achieved successful recanalization (modified Thrombolysis in Cerebral Infarction score of 2b-3) were retrospectively screened from April 2019 to February 2024. Admission serum levels of traditional and non-traditional lipid parameters, folate, and homocysteine (Hcy) were measured. FR was defined as a 90-day modified Rankin Scale score of 3-6, despite successful recanalization. Multivariable logistic regression was performed to identify predictors for FR, which were incorporated into a predictive nomogram. RESULTS: Among 446 enrolled patients [median age 65 (IQR, 56-72.75) years; 32.1% female], 210 (47.1%) experienced 90-day FR. Multivariate logistic regression analysis revealed that lower admission serum folate and higher Hcy levels were independently associated with increased 90-day FR risk. In contrast, neither admission traditional or non-traditional lipid parameters were independent predictors. The addition of folate and Hcy, individually or combined, significantly improved the predictive performance of conventional clinical factor-based model, as reflected by significant increases in net reclassification improvement and integrated discrimination improvement. Finally, a predictive nomogram was developed incorporating age, admission National Institute of Health Stroke Scale, puncture-to-recanalization time, and admission serum glucose, folate, and Hcy levels. CONCLUSIONS: Admission serum folate and Hcy levels are independent predictors of 90-day FR risk and may enhance risk stratification and guide personalized secondary prevention strategies in patients with successfully recanalized AIS-LVO.

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