Novel insights into causal effects of serum lipids, lipid metabolites, and lipid-modifying targets on the risk of intracerebral aneurysm.

IF 5.8 3区医学 Q1 CLINICAL NEUROLOGY

European Stroke Journal Pub Date : 2024-07-30 DOI:10.1177/23969873241265019

Youjia Qiu, Bingyi Song, Ziqian Yin, Menghan Wang, Yuchen Tao, Minjia Xie, Aojie Duan, Zhouqing Chen, Ke Si, Zhong Wang

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引用次数: 0

Abstract

Introduction: Different serum lipid and lipid-lowering agents are reported to be related to the occurrence of intracerebral aneurysm (IA). However, the causal relationship between them requires further investigation.

Patients and methods: Mendelian randomization (MR) analysis was performed on IA and its subtypes by using instrumental variants associated with six serum lipids, 249 lipid metabolic traits, and 10 lipid-lowering agents that were extracted from the largest genome-wide association study. Phenome-wide MR analyses were conducted to identify potential phenotypes associated with significant lipid-lowering agents.

Results: After multiple comparison adjustments (p < 0.0083), genetically proxied triglyceride (TG) (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.07-1.47, p = 0.005) and high-density lipoprotein cholesterol (HDL-C) levels (OR 0.93, 95% CI 0.89-0.98, p = 0.008) showed causal relationships with the risk of IA. Four lipid metabolic traits showed a causal relationship with the risk of IA (p < 0.0002). As confirmed by drug target MR, the causal relationship between the HMGCR target and IA, HMGCR target and subarachnoid hemorrhage (SAH), ANGPTL3 target and SAH, CETP target, and SAH remained statistically significant after multiple adjustments (p < 0.005). Additionally, phenome-wide MR did not identify other diseases linked to the significant lipid-lowering agent (p < 6.39 × 10^-5).

Discussion and conclusion: This study not only supports that serum lipids (TG and HDL-C) are associated with IA but also confirms the positive effect and absence of safety concerns of intervening HMGCR, ANGPTL3, and CETP targets in IA and its subtypes, opening new avenues for IA treatment.

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血清脂质、脂质代谢物和脂质修饰靶标对脑内动脉瘤风险因果效应的新见解。

导言：据报道，不同的血清脂质和降脂药与脑内动脉瘤（IA）的发生有关。然而，它们之间的因果关系还需要进一步研究：利用从最大规模的全基因组关联研究中提取的与六种血清脂质、249种脂质代谢特征和10种降脂药相关的工具变异，对脑内动脉瘤及其亚型进行了孟德尔随机化（MR）分析。进行了全表型MR分析，以确定与重要降脂药相关的潜在表型：经多重比较调整后（p p = 0.005），高密度脂蛋白胆固醇（HDL-C）水平（OR 0.93，95% CI 0.89-0.98，p = 0.008）与内脏癌风险呈因果关系。四种脂质代谢特质与胰腺癌风险存在因果关系（p p p -5）：本研究不仅支持血清脂质（TG 和 HDL-C）与内脏癌相关，还证实了干预内脏癌及其亚型的 HMGCR、ANGPTL3 和 CETP 靶点具有积极作用且无安全问题，为内脏癌治疗开辟了新途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Stroke Journal Multiple-

CiteScore

7.50

自引率

6.60%

发文量

102

期刊介绍： Launched in 2016 the European Stroke Journal (ESJ) is the official journal of the European Stroke Organisation (ESO), a professional non-profit organization with over 1,400 individual members, and affiliations to numerous related national and international societies. ESJ covers clinical stroke research from all fields, including clinical trials, epidemiology, primary and secondary prevention, diagnosis, acute and post-acute management, guidelines, translation of experimental findings into clinical practice, rehabilitation, organisation of stroke care, and societal impact. It is open to authors from all relevant medical and health professions. Article types include review articles, original research, protocols, guidelines, editorials and letters to the Editor. Through ESJ, authors and researchers have gained a new platform for the rapid and professional publication of peer reviewed scientific material of the highest standards; publication in ESJ is highly competitive. The journal and its editorial team has developed excellent cooperation with sister organisations such as the World Stroke Organisation and the International Journal of Stroke, and the American Heart Organization/American Stroke Association and the journal Stroke. ESJ is fully peer-reviewed and is a member of the Committee on Publication Ethics (COPE). Issues are published 4 times a year (March, June, September and December) and articles are published OnlineFirst prior to issue publication.