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

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Title: Serum liver enzymes and risk of stroke: Systematic review with meta‐analyses and Mendelian randomization studies.
Authors: Li, Chun (AUTHOR), Gu, Long (AUTHOR), Shi, Fu‐Yi (AUTHOR), Xiong, Shi‐Ying (AUTHOR), Wu, Gui‐Sheng (AUTHOR), Peng, Jian‐Hua (AUTHOR), Wang, Ruo‐Lan (AUTHOR), Yuan, Yuan (AUTHOR), Jiang, Yong (AUTHOR), Huang, Chen (AUTHOR), Luo, Huai‐Rong (AUTHOR)
Source: European Journal of Neurology. Dec2024, Vol. 31 Issue 12, p1-14. 14p.
Subjects: Liver enzymes, Ischemic stroke, Alanine aminotransferase, Aspartate aminotransferase, Alkaline phosphatase, Mendelian randomization
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. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Serum liver enzymes and risk of stroke: Systematic review with meta‐analyses and Mendelian randomization studies.
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  Data: <searchLink fieldCode="AR" term="%22Li%2C+Chun%22">Li, Chun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gu%2C+Long%22">Gu, Long</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shi%2C+Fu‐Yi%22">Shi, Fu‐Yi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xiong%2C+Shi‐Ying%22">Xiong, Shi‐Ying</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wu%2C+Gui‐Sheng%22">Wu, Gui‐Sheng</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Peng%2C+Jian‐Hua%22">Peng, Jian‐Hua</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Ruo‐Lan%22">Wang, Ruo‐Lan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yuan%2C+Yuan%22">Yuan, Yuan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jiang%2C+Yong%22">Jiang, Yong</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Huang%2C+Chen%22">Huang, Chen</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Luo%2C+Huai‐Rong%22">Luo, Huai‐Rong</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neurology%22">European Journal of Neurology</searchLink>. Dec2024, Vol. 31 Issue 12, p1-14. 14p.
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  Data: <searchLink fieldCode="DE" term="%22Liver+enzymes%22">Liver enzymes</searchLink><br /><searchLink fieldCode="DE" term="%22Ischemic+stroke%22">Ischemic stroke</searchLink><br /><searchLink fieldCode="DE" term="%22Alanine+aminotransferase%22">Alanine aminotransferase</searchLink><br /><searchLink fieldCode="DE" term="%22Aspartate+aminotransferase%22">Aspartate aminotransferase</searchLink><br /><searchLink fieldCode="DE" term="%22Alkaline+phosphatase%22">Alkaline phosphatase</searchLink><br /><searchLink fieldCode="DE" term="%22Mendelian+randomization%22">Mendelian randomization</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of European Journal of Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1111/ene.16506
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        Text: English
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      – SubjectFull: Liver enzymes
        Type: general
      – SubjectFull: Ischemic stroke
        Type: general
      – SubjectFull: Alanine aminotransferase
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      – SubjectFull: Aspartate aminotransferase
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      – SubjectFull: Alkaline phosphatase
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      – SubjectFull: Mendelian randomization
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              Text: Dec2024
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