Sex differences in risk factor relationships with subarachnoid haemorrhage and intracranial aneurysms: A Mendelian randomization study.

IF 5.8 3区医学 Q1 CLINICAL NEUROLOGY European Stroke Journal Pub Date : 2024-07-30 DOI:10.1177/23969873241265224

Lena Tschiderer, Mark K Bakker, Dipender Gill, Stephen Burgess, Peter Willeit, Ynte M Ruigrok, Sanne Ae Peters

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Abstract

Background: The prevalence of intracranial aneurysms (IAs) and incidence of aneurysmal subarachnoid haemorrhage (aSAH) is higher in women than in men. Although several cardiometabolic and lifestyle factors have been related to the risk of IAs or aSAH, it is unclear whether there are sex differences in causal relationships of these risk factors.

Aims: The aim of this study was to determine sex differences in causal relationships between cardiometabolic and lifestyle factors and risk of aSAH and IA.

Methods: We conducted a sex-specific two-sample Mendelian randomization study using summary-level data from genome-wide association studies. We analysed low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, non-HDL-C, total cholesterol, fasting glucose, systolic and diastolic blood pressure, smoking initiation, and alcohol use as exposures, and aSAH and IA (i.e. aSAH and unruptured IA combined) as outcomes.

Results: We found statistically significant sex differences in the relationship between genetically proxied non-HDL-C and aSAH risk, with odds ratios (ORs) of 0.72 (95% confidence interval 0.58, 0.88) in women and 1.01 (0.77, 1.31) in men (p-value for sex difference 0.044). Moreover, genetic liability to smoking initiation was related to a statistically significantly higher risk of aSAH in men compared to women (p-value for sex difference 0.007) with ORs of 3.81 (1.93, 7.52) and 1.12 (0.63, 1.99), respectively, and to a statistically significantly higher IA risk in men compared to women (p-value for sex difference 0.036) with ORs of 3.58 (2.04, 6.27) and 1.61 (0.98, 2.64), respectively. In addition, higher genetically proxied systolic and diastolic blood pressure were related to a higher risk of aSAH and IA in both women and men.

Conclusions: Higher genetically proxied non-HDL-C was related to a lower risk of aSAH in women compared to men. Moreover, genetic liability to smoking initiation was associated with a higher risk for aSAH and IA in men compared to women. These findings may help improve understanding of sex differences in the development of aSAH and IA.

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蛛网膜下腔出血和颅内动脉瘤风险因素的性别差异：孟德尔随机化研究

背景：女性颅内动脉瘤（IAs）的患病率和动脉瘤性蛛网膜下腔出血（aSAH）的发病率均高于男性。尽管一些心脏代谢和生活方式因素与颅内动脉瘤或蛛网膜下腔出血的风险有关，但目前尚不清楚这些风险因素的因果关系是否存在性别差异：我们利用全基因组关联研究的汇总数据进行了一项性别特异性双样本孟德尔随机研究。我们将低密度脂蛋白胆固醇、高密度脂蛋白胆固醇[HDL-C]、甘油三酯、非高密度脂蛋白胆固醇、总胆固醇、空腹血糖、收缩压和舒张压、开始吸烟和饮酒作为暴露因素，将aSAH和IA（即aSAH和未破裂IA的总和）作为结果进行了分析：我们发现，非高密度脂蛋白胆固醇（non-HDL-C）基因代用值与非室间隔缺血性心肌梗死风险之间存在统计学意义上的性别差异，女性的几率比（ORs）为 0.72（95% 置信区间为 0.58，0.88），男性为 1.01（0.77，1.31）（性别差异的 p 值为 0.044）。此外，与女性相比，男性开始吸烟的遗传易感性与男性发生 aSAH 的风险显著相关（性别差异的 p 值为 0.007），OR 分别为 3.81 (1.93, 7.52) 和 1.12 (0.63, 1.99)；与女性相比，男性发生 IA 的风险显著相关（性别差异的 p 值为 0.036），OR 分别为 3.58 (2.04, 6.27) 和 1.61 (0.98, 2.64)。此外，在女性和男性中，较高的基因代偿收缩压和舒张压与较高的非心源性休克和心肌梗死风险有关：结论：与男性相比，女性较高的非高密度脂蛋白胆固醇（non-HDL-C）与较低的非心源性脑缺血风险有关。此外，与女性相比，男性开始吸烟的遗传易感性与较高的 aSAH 和 IA 风险相关。这些研究结果可能有助于人们更好地了解aSAH和IA发病过程中的性别差异。

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.