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Dose-response relationship between gamma-glutamyltransferase and the risk of atherosclerotic cardiovascular diseases in Korean adults

  • Jooeun Jeon
    Affiliations
    Department of Public Health, Graduate School, Yonsei University, Seoul, 03722, Republic of Korea

    Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, 03722, Republic of Korea
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  • Dae Hyun Kim
    Affiliations
    Department of Senior Healthcare, Graduate School, Eulji University, Daejeon, 34824, Republic of Korea

    Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Woojin Kim
    Affiliations
    Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
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  • Dong-Woo Choi
    Affiliations
    Department of Public Health, Graduate School, Yonsei University, Seoul, 03722, Republic of Korea

    Institute of Health Services Research, Yonsei University, Seoul, 03722, Republic of Korea
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  • Keum Ji Jung
    Affiliations
    Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, 03722, Republic of Korea
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  • Sung-In Jang
    Correspondence
    Corresponding author. Department of Preventive Medicine & Institute of Health Services Research, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
    Affiliations
    Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

    Institute of Health Services Research, Yonsei University, Seoul, 03722, Republic of Korea
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      Highlights

      • Gamma-glutamyltransferase (GGT) had an independent association and dose-response relationship with atherosclerotic cardiovascular disease (ASCVD) risk.
      • Differences of its relationship trends were shown according to its concentration.
      • A precise relationship was found between hemorrhagic stroke and increasing GGT.

      Abstract

      Background and aims

      The value of gamma-glutamyltransferase (GGT) in the putative mechanisms underlying its association with cardiovascular disease is unclear. This study examined whether serum GGT value has an independent association and dose-response relationship with the risk of atherosclerotic cardiovascular disease (ASCVD).

      Methods

      This observational study included 419,433 subjects from the National Health Insurance Service database. Serum GGT levels were classified into sex-specific quartiles. We used Cox proportional hazard models to examine the effect of serum GGT values on the risk of ASCVD. We quantified associations of the serum GGT quartile groups with risk of ASCVD or each subtype through multivariate sub-distribution hazard models adjusted for covariates at baseline.

      Results

      During 4,572,993.8 person-years of follow-up for ASCVD, we documented 40,359 (9.6%) incident cases of ASCVD. The highest serum GGT group had a significant association with ASCVD in contrast to the lowest serum GGT quartile group (hazard ratio [HR] = 1.23, 95% confidence interval [CI] = 1.19–1.27). Serum GGT quartile groups 2, 3, and 4 had a significantly higher risk for incident hemorrhagic stroke than the serum GGT quartile group 1 (Q 2: HR = 0.92, 95% CI = 0.83–1.02; Q 3: HR = 1.03, 95% CI = 0.93–1.15; Q 4: HR = 1.29, 95% CI = 1.16–1.42; p for trend <0.001). For ischemic heart disease (IHD) and myocardial infarction, non-linear trends were shown according to increasing log-transformed GGT values. In the dose-response trends to assess the interaction effect of obese status, differences of trends were shown between serum GGT level and IHD or hemorrhagic stroke.

      Conclusions

      The serum GGT value, which is known as a factor linked to cardiovascular diseases, has a strong independent association and dose-response relationship with hemorrhagic stroke risk in contrast to that with ischemic stroke or IHD.

      Graphical abstract

      Keywords

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