Serum liver enzymes and risk of stroke: Systematic review with meta-analyses and Mendelian randomization studies

IF 4.5 2区医学 Q1 CLINICAL NEUROLOGY European Journal of Neurology Pub Date : 2024-10-10 DOI:10.1111/ene.16506

Chun Li, Long Gu, Fu-Yi Shi, Shi-Ying Xiong, Gui-Sheng Wu, Jian-Hua Peng, Ruo-Lan Wang, Yuan Yuan, Yong Jiang, Chen Huang, Huai-Rong Luo

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Abstract

Background and purpose

Previous observational studies have identified correlations between liver enzyme levels and stroke risk. However, the strength and consistency of these associations vary. To comprehensively evaluate the relationship between liver enzymes and stroke risk, we conducted meta-analyses complemented by Mendelian randomization (MR) analyses.

Methods

Following the PRISMA guidelines, we performed meta-analyses of prospective studies and conducted subgroup analyses stratified by sex and stroke subtype. Subsequently, adhering to the STROBE-MR guidelines, we performed two-sample bidirectional univariable MR (UVMR) and multivariable MR (MVMR) analyses using the largest genome-wide association studies summary data. Finally, the single-nucleotide polymorphisms associated with liver enzymes on sex differences underwent gene annotation, gene set enrichment, and tissue enrichment analyses.

Results

In the meta-analyses of 17 prospective studies, we found the relative risks for serum γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were 1.23 (95% CI: 1.16–1.31) and 1.3 (95% CI: 1.19–1.43), respectively. Subgroup analyses revealed sex and stroke subtype differences in liver enzyme-related stroke risk. Bidirectional UVMR analyses confirmed that elevated GGT, alanine aminotransferase, and aspartate aminotransferase levels were associated with increased stroke occurrence. The primary results from the MVMR analyses revealed that higher ALP levels significantly increased the risk of stroke and ischemic stroke. Gene set and tissue enrichment analyses supported genetic differences in liver enzymes across sexes.

Conclusions

Our study provides evidence linking liver enzyme levels to stroke risk, suggesting liver enzymes as potential biomarkers for early identification of high-risk individuals. Personalized, sex-specific interventions targeting liver enzymes could offer new strategies for stroke prevention.

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血清肝酶与中风风险：荟萃分析和孟德尔随机研究的系统综述。

背景和目的：以往的观察性研究发现肝酶水平与中风风险之间存在相关性。然而，这些关联的强度和一致性各不相同。为了全面评估肝酶与中风风险之间的关系，我们进行了荟萃分析，并辅以孟德尔随机分析（MR）：按照 PRISMA 指南，我们对前瞻性研究进行了荟萃分析，并按性别和中风亚型进行了亚组分析。随后，根据 STROBE-MR 指南，我们利用最大的全基因组关联研究汇总数据进行了双样本双向单变量 MR（UVMR）和多变量 MR（MVMR）分析。最后，对与肝酶性别差异相关的单核苷酸多态性进行了基因注释、基因组富集和组织富集分析：在对17项前瞻性研究的荟萃分析中，我们发现血清γ-谷氨酰转移酶（GGT）和碱性磷酸酶（ALP）的相对风险分别为1.23（95% CI：1.16-1.31）和1.3（95% CI：1.19-1.43）。亚组分析显示，肝酶相关中风风险存在性别和中风亚型差异。双向 UVMR 分析证实，谷丙转氨酶、丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平升高与中风发生率增加有关。MVMR 分析的主要结果显示，较高的 ALP 水平会显著增加中风和缺血性中风的风险。基因组和组织富集分析支持不同性别间肝酶的遗传差异：我们的研究提供了肝酶水平与中风风险相关的证据，表明肝酶是早期识别高危人群的潜在生物标志物。针对肝酶的个性化、性别特异性干预可为中风预防提供新策略。

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来源期刊

European Journal of Neurology 医学-临床神经学

CiteScore

9.70

自引率

2.00%

发文量

418

审稿时长

1 months

期刊介绍： The European Journal of Neurology is the official journal of the European Academy of Neurology and covers all areas of clinical and basic research in neurology, including pre-clinical research of immediate translational value for new potential treatments. Emphasis is placed on major diseases of large clinical and socio-economic importance (dementia, stroke, epilepsy, headache, multiple sclerosis, movement disorders, and infectious diseases).