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
{"title":"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。","authors":"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","doi":"10.1111/ene.16506","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background and purpose</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"31 12","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555028/pdf/","citationCount":"0","resultStr":"{\"title\":\"Serum liver enzymes and risk of stroke: Systematic review with meta-analyses and Mendelian randomization studies\",\"authors\":\"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\",\"doi\":\"10.1111/ene.16506\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background and purpose</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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. 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Serum liver enzymes and risk of stroke: Systematic review with meta-analyses and Mendelian randomization studies
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.
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).
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