Endocrinol Metab.  2023 Dec;38(6):770-781. 10.3803/EnM.2023.1726.

Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study

• Baek HS
• Kim B
• Lee SH
• Lim DJ
• Kwon HS
• Chang SA
• Han K
• Yun JS

• KMID: 2549270
• DOI: http://doi.org/10.3803/EnM.2023.1726

Abstract

Background
Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population.
Methods
Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0–4), and the sum of quartiles (0–12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model.
Results
During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m², and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death.
Conclusion
Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

Keyword

Gamma-glutamyltransferase; Cardiovascular diseases; Metabolic syndrome; Nation-wide study

Figure

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  Fig. 1. Survival curve analysis for (A) myocardial infarction (MI), (B) stroke, (C) cardiovascular disease (CVD), and (D) death according to number of exposures to high γ-glutamyl transferase (γ-GTP). HR, hazard ratio; CI, confidence interval.

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  Fig. 2. Association between cumulative sum of γ-glutamyl transferase (γ-GTP) quartiles and the development of myocardial infarction (MI), stroke, cardiovascular disease (CVD) and death. The hazard ratio was adjusted for age, sex, status of smoking, drinking, physical activity, and alanine transaminase. CI, confidence interval.

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  Fig. 3. Association between cumulative number of exposures to high γ-glutamyl transferase (γ-GTP) and the development of myocardial infarction (MI), stroke, cardiovascular disease (CVD), and death according to age, sex, smoking and drinking. CI, confidence interval.

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  Fig. 4. Association between cumulative number of exposures to high γ-glutamyl transferase (γ-GTP) and the development of myocardial infarction (MI), stroke, cardiovascular disease (CVD), and death according to diabetes mellitus (DM), hypertension (HTN), dyslipidemia (DLP), body mass index (BMI), and fatty liver index (FLI). CI, confidence interval.

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