Associations between γ-glutamyltransferase (GGT) and biomarkers of atherosclerosis: The multi-ethnic study of atherosclerosis (MESA)

Objective: To evaluate associations between total serum γ-glutamyltransferase activity (GGT) and biomarkers of arteriosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA), including 6783 participants from four ethnic subgroups, i.e., White, Chinese, Black and Hispanic. Methods: Associations between fasting total serum GGT activity and oxidized low-density lipoproteins (oxLDL), interleukin-6 (IL-6), C-reactive protein (CRP), and soluble intercellular adhesion molecule-1 (sICAM-1) were assessed. Following evaluation of linear trends between GGT and biomarkers of interest, multivariable linear regression models were serially adjusted for age, gender, site, ethnicity (M1); M1. +. lifestyle variables (M2); M2. +. traditional cardiovascular risk factors plus medications (M3); and M3. +. metabolic status (M4). Interactions were evaluated between GGT and age and ethnicity in all models. Results: Linear trends were positive and significant between GGT and oxLDL, IL-6, CRP and sICAM-1 in crude models, and trends remained significant in all ethnic subgroups for CRP (p<. 0.0001) and sICAM-1 (p<. 0.001), and for IL-6 except in the Chinese. Trends between GGT and oxLDL were significant in the entire cohort and the White subgroup (p<. 0.0001), but not in other ethnic subgroups. Multivariable models demonstrated continuous strong, positive associations between GGT and CRP, IL-6 and sICAM-1. Associations between GGT and oxLDL were attenuated upon adjustment for LDL-C and other traditional risk factors. All models were attenuated with adjustment for metabolic status. No age interactions were evident. Conclusions: Our findings support the hypothesis that total serum GGT activity represents the impact of metabolic disease on vascular injury and atherosclerosis.