γ-Glutamyltransferase Variability and the Risk of Mortality, Myocardial Infarction, and Stroke: A Nationwide Population-Based Cohort Study

Although it has been suggested that the gamma-glutamyltransferase (GGT) level is an indicator of cardiometabolic disorders, there is no previous study to evaluate the implication of GGT variability on the development of myocardial infarction (MI), stroke, all-cause mortality, and cardiovascular disease (CVD)-related mortality. GGT variability was measured as the coefficient variance (GGT-CV), standard deviation (GGT-SD), and variability independent of the mean (GGT-VIM). Using the population-based Korean National Health Insurance Service-Health Screening Cohort, we followed 158,736 Korean adults over a median duration of 8.4 years. In multivariable Cox proportional hazard analysis, the risk of mortality, MI, and stroke showed a stepwise increase according to the quartiles of GGT-CV, GGT-SD or GGT-VIM. In the highest quartile of GGT-CV compared to the lowest quartile after adjusting for confounding variables including mean GGT, the hazard ratios (HRs) for incident MI, stroke, mortality, and CVD-related mortality were 1.19 (95% confidence interval (CI), 1.06-1.34; p < 0.001), 1.20 (95% CI, 1.10-1.32; p < 0.001), 1.41 (95% CI, 1.33-1.51; p < 0.001), and 1.52 (95% CI, 1.30-1.78; p < 0.001), respectively, which were similar or even higher compared with those associated with total cholesterol variability. This is the first study to demonstrate that high GGT variability is associated with increased risk of MI, stroke, all-cause mortality, and CVD-related mortality in the general population.