Association of gamma-glutamyltransferase levels with total mortality, liver-related and cardiovascular outcomes: a prospective cohort study in the UK Biobank
Open accessAbstract
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).
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GGT reflects liver adiposity in addition to alcohol intake signals.
“liver adiposity in addi tion to alcohol intake signals (GGT)”
From Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide (2026) · cites this paper as [30]
Leptin reflects total obesity or percent fat mass.
“consistent with their roles as biomarkers reflecting total obesity or percent fat mass (leptin)”
From Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide (2026) · cites this paper as [30]
The Methods section describes BMI, waist circumference and liver-marker measurements, but does not identify leptin as a biomarker of obesity or percent fat mass. Searches of our copy for “leptin” and “percent fat mass” found no passage addressing that relationship. (LLM, conf=0.75)
Experimental — accuracy not yet measuredHOMA-IR reflects insulin resistance and ectopic and total fat.
“insulin resistance and ectopic and total fat (HOMA-IR). 2,29-31”
From Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide (2026) · cites this paper as [30]
The Methods (Study design and participants; Statistical analysis, pages unavailable) describe BMI, waist measurements, diabetes status, and liver markers, but do not discuss HOMA-IR. Searches for HOMA-IR, insulin resistance, and ectopic or total fat found no passage stating that HOMA-IR reflects those measures. (LLM, conf=0.75)
Experimental — accuracy not yet measured
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- Authors
- Ho, F. K., Ferguson, L. D., Celis-Morales, C. A., Gray, S. R., Forrest, E., Alazawi, W., Gill, J. M., Katikireddi, S. V., Cleland, J. G., Welsh, P., Pell, J. P., & Sattar, N.
- Affiliations
- University of Glasgow (GB)
- Glasgow Royal Infirmary (GB)
- Queen Mary University of London (GB)
- Corresponding author
- Sattar, Naveed
- ORCID
- Venue
- EClinicalMedicine
- Publisher
- Elsevier BV
- Published
- 2022-06
- Volume
- 48
- Pages
- 101435
- ISSN
- 2589-5370 (ISSN-L)
- PMC
- PMC9112033
- OpenAlex
- W4280524821
- Cited by
- 41
- References
- 52
- Citations by year
- 2026: 13 · 2025: 8 · 2024: 8 · 2023: 12
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- EClinicalMedicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Medical Research Council (MC_UU_00022/2)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- gamma-glutamyl transferase, liver injury biomarkers, liver-related mortality, cardiovascular mortality, all-cause mortality, alcohol consumption, waist circumference, adiposity, cardiovascular risk prediction, risk reclassification, UK Biobank, sex differences, lifestyle risk factors, liver disease screening, cardiovascular disease prevention
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