Elsevier

International Journal of Cardiology

Volume 245, 15 October 2017, Pages 149-155
International Journal of Cardiology

Association between γ-glutamyltransferase level and incidence of atrial fibrillation: A nationwide population-based study

https://doi.org/10.1016/j.ijcard.2017.07.067Get rights and content

Abstract

Background

Information on the association between γ-glutamyltransferase (GGT) and the incidence of atrial fibrillation (AF) is scarce. We evaluated the association between GGT and AF incidence, and the interaction between GGT and obesity on developing AF in a large population-based cohort.

Methods

We evaluated 266,550 individuals (mean age, 53 ± 11; men, 48.4%) who underwent the national insurance health checkup between 2004 and 2008. Subjects were categorized in accordance with quartiles of GGT levels (range: Q1, 0–15 U/L; Q2, 16–22 U/L; Q3, 23–38 U/L; Q4, ≥ 39 U/L). The association between GGT levels and AF incidence was analyzed by using multivariable Cox proportional-hazards regression models.

Results

During a median of 8 years' follow-up, 5034 individuals (1.9%) were newly diagnosed with AF. The crude AF incidence gradually increased with increases in GGT level (1.9, 2.5, 2.8, and 3.1 per 1000 person-years in the Q1, Q2, Q3, and Q4 GGT groups, respectively; p for trend < 0.001). In the multivariable Cox proportional hazard models, GGT level showed a dose-response relationship with AF incidence. The subjects with the highest quartile of GGT levels had a significantly higher risk of AF (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.18–1.45; p < 0.001). When the analysis was stratified by body mass index (BMI), GGT level showed good discrimination for AF incidence only in the non-obese population (BMI < 25 kg/m2), and not in the obese population (BMI  25 kg/m2; p interaction < 0.001).

Conclusions

In this large population-based study, elevated GGT level showed a significant association with increased risk of AF, especially in a non-obese population.

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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