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

Autor: Li C; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China.; Clinical Trial Research Center, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China., Gu L; Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China., Shi FY; Key Laboratory of Luzhou City for Aging Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China., Xiong SY; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China., Wu GS; Key Laboratory of Luzhou City for Aging Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.; Central Nervous System Drug Key Laboratory of Sichuan Province, Luzhou, Sichuan, China., Peng JH; Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China., Wang RL; Clinical Trial Research Center, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China., Yuan Y; Clinical Trial Research Center, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China., Jiang Y; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China.; Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China.; Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China., Huang C; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China., Luo HR; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China.; Key Laboratory of Luzhou City for Aging Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.; Central Nervous System Drug Key Laboratory of Sichuan Province, Luzhou, Sichuan, China.
Jazyk: angličtina
Zdroj: European journal of neurology [Eur J Neurol] 2024 Dec; Vol. 31 (12), pp. e16506. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1111/ene.16506
Abstrakt: 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.
(© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)
Databáze: MEDLINE
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