Sex and age-specific gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio: a potential marker of subclinical arterial stiffness elevation

Introduction The gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio (GGT/HDL-C) integrates oxidative stress and lipid dysregulation, but its relationship with subclinical arterial stiffness elevation (SASE) and potential sex- and age-specific differences remains unclear. This study examined the association between GGT/HDL-C and SASE, assessed using brachial-ankle pulse wave velocity (baPWV), in an asymptomatic adult population. Methods This cross-sectional study included 10,518 adults who underwent routine self-paid health examinations at Xiamen Chang Gung Hospital between 2013 and 2016. Clinical, biochemical, and vascular parameters were assessed. SASE was defined as a mean baPWV >1,700 cm/s. Participants were stratified by sex and age (≤50 and >50 years) and categorized into sex- and age-specific tertiles of GGT/HDL-C. Hierarchical logistic regression models were adjusted for age, fasting glucose, triglycerides, low-density lipoprotein cholesterol, alcohol intake, and lipid-lowering medication use. Receiver operating characteristic analyses were performed to evaluate discriminatory performance. Results The study included 5,877 men and 4,641 women, with a median age of 46 years; 799 participants (7.6%) had SASE. Higher GGT/HDL-C tertiles were associated with less favorable cardiometabolic profiles and progressively higher baPWV. In the fully adjusted model, the highest versus lowest GGT/HDL-C tertile was associated with increased odds of SASE in men >50 years (odds ratio [OR], 1.823; 95% confidence interval [CI], 1.303–2.550), women ≤50 years (OR, 4.620; 95% CI, 1.012–21.101), and women >50 years (OR, 1.435; 95% CI, 1.009–2.040). In men ≤50 years, the association was positive but of borderline statistical significance (OR, 1.877; 95% CI, 0.994–3.544). Sensitivity analyses yielded generally consistent findings. GGT/HDL-C alone demonstrated modest discriminatory performance, which was better in women than in men. Discussion Higher GGT/HDL-C ratios were associated with SASE, with variations in the magnitude and statistical precision of the associations across sex and age groups. The GGT/HDL-C ratio may serve as an adjunctive biomarker for preliminary vascular risk stratification. However, its modest stand-alone discriminatory performance and the cross-sectional, single-center study design warrant cautious interpretation and external validation.