SYSTEMATIC REVIEW article
Front. Neurol.
Sec. Neuroepidemiology
Associations between lipoproteins and risk of ischemic stroke: A systematic review and meta-analysis of Mendelian randomization studies
Provisionally accepted
- 1Lanzhou University Second Hospital, Lanzhou, China
- 2The Second People's Hospital of Gansu Province, Lanzhou, China
- 3Lanzhou University, Lanzhou, China
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Objective To systematically evaluate the causal effects of lipoproteins on ischemic stroke (IS) through a systematic review and meta-analysis of Mendelian randomization (MR) studies. Methods A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify MR studies investigating the relationship between lipoproteins and IS, covering all publications up to November 2024. Relevant data were extracted, followed by a quality assessment. Meta-analyses were performed using RevMan software, with evaluations of heterogeneity and publication bias. Results A total of 442 studies were evaluated, and 10 were included. Our meta-analysis showed a significant positive correlation between LDL and IS (OR 1.09, 95% CI 1.07-1.12; P < 0.001, I²= 0), apoB and IS (OR 1.08, 95% CI 1.02-1.14; P = 0.006, I²= 60%), VLDL and IS (OR 1.09, 95% CI 1.01-1.18; P = 0.03). In contrast, apoA1 was significantly negatively associated with IS (OR 0.93, 95% CI 0.89-0.96; P <0.001, I²= 38%). Interestingly, although the association between Lp(a) and IS was not statistically significant (OR 1.01, 95% CI 0.99-1.02; P= 0.26, I²= 57%), combined non-HDL lipoproteins were positively associated with IS (OR 1.03, 95% CI 1.01-1.06; P < 0.001, I²= 93.6%). In contrast, HDL lipoproteins was significantly negatively associated with IS (OR 0.93, 95% CI 0.89-0.97; P < 0.001, I²= 58%). The funnel plot appears generally symmetrical and sensitivity analyses confirmed the robustness of the findings for LDL, apoA1, apoB, HDL, and total cholesterol in relation to IS. Conclusion This meta-analysis provides evidence for a causal relationship between various lipoproteins and ischemic stroke. Most non-HDL lipoproteins (LDL, VLDL, apoB) are associated with an increased risk of IS, while HDL and apoA1 appear to confer a protective effect. The role of Lp(a) in IS remains inconclusive and warrants further investigation.
Keywords: ischemic stroke, Lipoproteins, Mendelian randomization (MR) studies, Meta-analysis, Systematic review
Received: 12 Sep 2025; Accepted: 09 Dec 2025.
Copyright: © 2025 Guo, Guo, Zhu, Xie, Yang and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yanwei Guo
Shouyuan Sun
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