• Li-Rui Dai, Liang Lyu, Wen-Yi Zhan, Shu Jiang, and Pei-Zhi Zhou.
• Department of Neurosurgery, West China Hospital of Sichuan University, Sichuan University, Chengdu, Sichuan, China.
• World Neurosurg. 2025 Jan 29: 123649123649.

BackgroundMendelian randomization was employed to investigate the impact of circulating lipids, specifically residual lipids, on the risk of susceptibility to cerebral hemorrhage and ischemic stroke.MethodsAccording to previously studies, we chose 19 circulating lipids, comprising 6 regular lipids and 13 residual lipids, to investigate their potential causal relationship with intracranial hemorrhage and ischemic stroke. The effect estimates were computed utilizing the random-effects inverse-variance-weighted methodology.ResultsThe findings revealed negative correlations between HDL-C and cerebral hemorrhage and large artery stroke. HDL-C, Apo A1, XS.VLDL.TG, and IDL.TG were found to be negatively correlated with any ischemic stroke. Apo B, TG, LDL-C, L.VLDL-TG, M.VLDL-TG, and S.VLDL-TG exhibited positive correlations with large artery stroke. XL.HDL-TG and IDL.TG were positively correlated with cardioembolic stroke. No significant causal relationship was observed between circulating lipids, with the exception of HDL-C, and cerebral hemorrhage. No causal relationship was identified between any circulating lipids and small vessel stroke. Furthermore, the causal relationships were only found between residual lipids and ischemic stroke.ConclusionThis study provides evidence for the beneficial impact of Apo A1 and HDL-C in reducing the risk of ischemic stroke, as well as the protective effect of HDL-C against cerebral hemorrhage. It highlights the detrimental effects of Apo B, TG, and LDL-C in increasing the risk of ischemic stroke, particularly in cases of large artery stroke. Furthermore, the study underscores the heterogeneity and two-sided effects of the causal relationship between triglyceride-rich lipoproteins and ischemic stroke, offering a promising avenue for the treatment of ischemic stroke.Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.

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