Association between γ-glutamyltransferase level and incidence of atrial fibrillation: A nationwide population-based study☆
Introduction
γ-Glutamyltransferase (GGT) level is a marker of liver function, regarded as an indicator of alcohol consumption, and commonly included in health checkup diagnostic tests. Previous studies reported that it is associated with increased risk of cardiovascular disease (CVD) and associated with poor outcome from CVD [1], [2], [3]. Serum GGT levels showed independent correlation with the occurrence of coronary heart disease and stroke, which suggests that the linkage between GGT level and atherosclerosis would be the underlying mechanism [2], [4]. Furthermore, GGT level was demonstrated as an independent predictor of CVD mortality and showed a strong dose-response relationship [2]. In addition, GGT level is a potential marker of the preclinical development of metabolic syndrome (MetS). Serum GGT levels were independently associated with the development of obesity, hypertension, and insulin resistance, which are components of MetS [5], [6], [7]. Furthermore, GGT level is positively and strongly associated with the risk of developing MetS [8], [9]. The pathophysiological mechanisms of the associations of GGT level with MetS and CVD could potentially be explained by GGT level being an indicator of excessive alcohol intake and the cluster of cardiometabolic risk factors. However, after adjustment for these factors, GGT level was independently associated with the incidence of MetS and CVD, suggesting that alternative mechanisms exist such as oxidative stress and subclinical level of inflammation [10], [11].
Atrial fibrillation (AF) is the most common cardiac arrhythmia and a growing public health issue that shares risk factors with metabolic and CVD [12], [13], [14], [15]. Only a few data have been reported on the association between GGT level and the incidence of AF in a large population [16]. Therefore, we aimed to assess whether GGT level is associated with AF incidence in a large population-based cohort who participated in the national insurance health checkup program.
Section snippets
Data source
Most (97%) of the Korean population (approximately 50 million people) are covered by the mandatory social National Health Insurance Service (NHIS), except the remaining 3%, who are low-income earners covered by the Medical Aid program. The NHIS claims database includes individuals' socio-demographic information, disease diagnoses, use of inpatient and outpatient services, procedures, and pharmacy dispensing claims. Diagnoses were confirmed based on the International Classification of Disease,
Baseline characteristics
We evaluated 266,550 individuals (mean age, 53.4 ± 10.7 years; 48.4% male). The mean GGT level was 37.2 ± 53.2 U/L (median, 23 U/L; interquartile range, 15–39 U/L). The distribution of the GGT levels in the total study population is presented in Supplementary Fig. 3. For evaluation of the association between serum GGT levels and AF incidence, we divided the total study population into 4 groups according to GGT quartile values (first quartile [Q1], 0–15 U/L; second quartile [Q2], 16–22 U/L; third quartile
Main findings
The main findings of our study in a large population-based cohort are as follows: (1) a strong correlation between GGT level and risk of AF; (2) although the population in higher GGT quartile group tended to be subjects with the cluster of cardiometabolic risk factors, GGT level showed an independent and dose-response association with AF incidence; and (3) the association between GGT level and incident AF was observed only in the non-obese population, and not in the obese population.
GGT and AF in the general population
After the
Conclusion
In conclusion, our findings demonstrated that GGT level showed an independent association and dose-response relationship with AF incidence. However, the impact of GGT level on AF development was only observed in the non-obese population, whereas this impact was attenuated in the obese population, who were already at high risk for AF development. GGT level might be a useful marker for risk stratification of future AF as an indicator of early-stage MetS in non-obese populations.
Sources of funding
This study was supported by grant no 0620160680 from the SNUH Research Fund, a Korea National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2014R1A1A2A16055218) and the Korean Healthcare technology R&D project funded by the Ministry of Health & Welfare (HI15C1200).
Conflicts of interest
None
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