Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio as a novel predictor of long-term ischemic heart disease risk in overweight men: a nationwide population-based study

Background: The gamma-glutamyl transferase to high-density lipoprotein cholesterol (GGT/HDL-c) ratio is a novel composite index reflecting systemic oxidative stress and metabolic dysfunction. However, its prognostic value for long-term ischemic heart disease (IHD) risk among overweight men—a population with highly heterogeneous metabolic profiles—remains largely unexplored. This study investigated the association between the GGT/HDL-c ratio and incident IHD in this high-risk group. Methods: This retrospective, population-based cohort study utilized data from the Korean National Health Insurance Service. A total of 124,044 overweight men (body mass index ≥23.0 kg/m2) without a history of ischemic heart disease were included and stratified into quartiles according to their GGT/HDL-c ratios. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios (HRs) for incident IHD. The incremental predictive value was evaluated using the C-index and net reclassification improvement (NRI). Results: Over a follow-up period of up to 20 years among the 124,044 participants, those in the highest GGT/HDL-c quartile (Q4) exhibited a significantly increased risk of IHD compared to the lowest quartile (Q1) (fully adjusted HR, 1.65; 95% confidence interval (CI), 1.49–1.83). A significant interaction with physical activity was observed (p < 0.001); the elevated IHD risk in Q4 was more pronounced among physically inactive men (HR, 1.82; 95% CI, 1.61–2.06) than among those engaging in regular exercise (HR, 1.42; 95% CI, 1.21–1.67). The addition of the GGT/HDL-c ratio to traditional risk models significantly improved risk reclassification (NRI = 0.058). Conclusions: An elevated GGT/HDL-c ratio is a potent and independent predictor of IHD in overweight men. Integrating this simple, cost-effective biomarker into routine assessments may improve clinical risk stratification. Furthermore, regular physical activity may serve as an important intervention to mitigate the elevated cardiovascular risk associated with this metabolic imbalance.