Association of gamma-glutamyltransferase levels with total mortality, liver-related and cardiovascular outcomes: A prospective cohort study in the UK Biobank

Background Gamma-glutamyltransferase (GGT) levels in the blood can be a sensitive marker of liver injury but the extent to which they give insight into risk across multiple outcomes in a clinically useful way remains uncertain. Methods Using data from 293,667 UK Biobank participants, the relationship of GGT concentrations to self-reported alcohol intake and adiposity markers were investigated. We next investigated whether GGT predicted liver-related, cardiovascular (CV) or all-cause mortality, and potentially improved CV risk prediction. Findings Higher alcohol intake and greater waist circumference (WC) were associated with higher GGT; the associa-tion was stronger for alcohol with evidence of a synergistic effect of WC. Higher GGT concentrations were associated with multiple outcomes. Compared to a GGT of 14.5 U/L (lowest decile), values of 48 U/L for women and 60 U/L for men (common upper limits of 'normal') had hazard ratios (HRs) for liver-related mortality of 1.83 (95% CI 1.60 - 2.11) and 3.25 (95% CI 2.38-4.42) respectively, for CV mortality of 1.21 (95% CI 1.14-1.28) and 1.43 (95% CI 1.27 - 1.60) and for all-cause mortality of 1.15 (95% CI 1.12-1.18) and 1.31 (95% CI 1.24-1.38). Adding GGT to a risk algo-rithm for CV mortality reclassified an additional 1.24% (95% CI 0.14-2.34) of participants across a binary 5% 10-year risk threshold. Interpretation Our study suggests that a modest elevation in GGT levels should trigger a discussion with the indi-vidual to review diet and lifestyle including alcohol intake and consideration of formal liver disease and CV risk assessment if not previously done. Copyright (C) 2022 The Authors. Published by Elsevier Ltd.

Automated summary

This study found that elevated GGT levels were associated with self-reported alcohol intake and adiposity markers. Higher GGT concentrations were related to liver-related, cardiovascular, and all-cause mortality. Adding GGT to risk algorithms improved the classification of cardiovascular mortality risk.