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

Ho, F. K. et al. (2022) Association of gamma-glutamyltransferase levels with total mortality, liver-related, and cardiovascular outcomes: a prospective cohort study in the UK Biobank. EClinicalMedicine, 48, 101435. (doi: 10.1016/j.eclinm.2022.101435)

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Abstract

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 association 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 algorithm 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 individual to review diet and lifestyle including alcohol intake and consideration of formal liver disease and CV risk assessment if not previously done. Funding: British Heart Foundation Centre of Research Excellence Grant (grant number RE/18/6/34217), NHS Research Scotland (grant number SCAF/15/02), the Medical Research Council (grant number MC_UU_00022/2); and the Scottish Government Chief Scientist Office (grant number SPHSU17).

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Katikireddi, Professor Vittal and Celis, Dr Carlos and Gray, Dr Stuart and Gill, Professor Jason and Ferguson, Dr Lyn and Ho, Dr Frederick and Welsh, Dr Paul and Forrest, Dr Ewan and Pell, Professor Jill and Cleland, Professor John and Sattar, Professor Naveed
Authors: Ho, F. K., Ferguson, L. D., Celis-Morales, C. A., Gray, S. R., Forrest, E., Alazawi, W., Gill, J. M.R., Katikireddi, S. V., Cleland, J. G.F., Welsh, P., Pell, J. P., and Sattar, N.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > General Practice and Primary Care
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > MRC/CSO SPHSU
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:EClinicalMedicine
Publisher:Lancet Publishing Group
ISSN:2589-5370
ISSN (Online):2589-5370
Published Online:12 May 2022
Copyright Holders:Copyright © 2022 The Authors.
First Published:First published in EClinicalMedicine 48:101435
Publisher Policy:Reproduced under a Creative Commons Licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science
172690Understanding the impacts of welfare policy on health: A novel data linkage studySrinivasa KatikireddiOffice of the Chief Scientific Adviser (CSO)SCAF/15/02HW - Public Health
3048231Inequalities in healthAlastair LeylandMedical Research Council (MRC)MC_UU_00022/2HW - MRC/CSO Social and Public Health Sciences Unit
3048231Inequalities in healthAlastair LeylandChief Scientist Office (CSO)SPHSU17HW - MRC/CSO Social and Public Health Sciences Unit