Association between Gamma-Glutamyltransferase Level and Risk of Stroke: A Systematic Review and Meta-analysis of Prospective Studies

J Stroke Cerebrovasc Dis. 2015 Dec;24(12):2816-23. doi: 10.1016/j.jstrokecerebrovasdis.2015.08.015. Epub 2015 Sep 12.


Background: Stroke is often regulated by a number of modifiable and nonmodifiable risk factors. Recently, studies suggested high gamma-glutamyltransferase (GGT) level may be associated with stroke, but drew inconsistent conclusions. So, we conducted a meta-analysis to evaluate the relationship between GGT level and risk of stroke.

Methods: We systematically searched PubMed, Embase, and Cochrane Library (updated to January 2015) for prospective cohort studies. Then, relative risk (RR) with 95% confidence interval (CI) was used to assess the association. Regression analyses, subgroup analyses, and sensitivity analyses were also performed. The Begg test, Egger test, and the trim-and-fill method were used to assess potential publication bias.

Results: A total of 5707 cases and 926,497 participants in 10 prospective studies were included. Overall, high GGT level has a positive association with increased risk of stroke (RR = 1.28; 95% CI, 1.16-1.43). In the subgroup analyses, a positive association was consistently observed in each subgroup except in the women subgroup (RR = 1.45; 95% CI, .9-2.34) and a large number of stroke events subgroups (≥ 500) (RR = 1.25; 95% CI, .85-1.84). Heterogeneity was significantly reduced in the subgroup analysis by population characteristics. In the publication bias test, the resulting adjusted RR remained significant (RR = 1.10; 95% CI, 1.00-1.21) after using the trim-and-fill method.

Conclusions: Our meta-analysis provides evidence that a high level of GGT is significantly associated with increased risk of stroke independently of alcohol intake. Gender and ethnicity variations may exist in the relationship between high GGT level and risk of stroke.

Keywords: Gamma-glutamyltransferase; meta-analysis; prospective cohort studies; stroke.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Female
  • Humans
  • Risk
  • Stroke / blood*
  • Stroke / epidemiology*
  • gamma-Glutamyltransferase / blood*


  • gamma-Glutamyltransferase