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

Background: Elevated gamma-glutamyl transferase (gamma-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high gamma-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 gamma-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 gamma-GTP quartile (0-4), and the sum of quartiles (0-12) was defined as cumulative gamma-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 gamma-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 gamma-GTP (all P for trend < 0.0001). Subjects younger than 65 years, with a body mass index < 25 kg/m(2), and without hypertension or fatty liver showed a stronger relationship between cumulative gamma-GTP and the incidence of MI, CVD, and death. Conclusion: Cumulative.-GTP elevation is associated with CVD. gamma-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.