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

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.

Keywords: Atherosclerotic cardiovascular disease; Cohort; Dose-response relationship; Obesity; γ-Glutamyltransferase.