Oxidative stress mediates the association between triglyceride-glucose index and risk of cardiovascular and all-cause mortality in metabolic syndrome: evidence from a prospective cohort study.

Abstract

The aim of this study was to investigate the relationship between triglyceride-glucose (TyG) index and cardiovascular disease (CVD) and all-cause mortality in adults with metabolic syndrome (MeS) and explore the mediating role of oxidative stress. This study included 6131 adults with MeS from the National Health and Nutrition Examination Survey (NHANES). The relationships between TyG index and mortality were elucidated using multivariate Cox proportional hazards models, restricted cubic splines (RCS) Fine-Gray competing risk model. In addition, mediation analysis was used to test the indirect effect of oxidative stress indicators. Over a median 106-month follow-up, a total of 357 CVD and 1292 all-cause deaths were recorded. After multivariate adjustment, there was a J-type relationship between TyG index and CVD and all-cause mortality, with optimal inflection point of 9.13 and 8.92. After the threshold point, TyG index was positively associated with CVD (HR: 4.21, 95%CI: 1.82, 9.78) and all-cause mortality(HR: 2.93, 95%CI: 2.05, 4.18). Even using non-cardiovascular mortality as a competitive risk, the Fine-Gray model also illustrated that the cumulative CVD mortality incidence was higher in MeS with TyG index >9.13 (Fine-Gray P< 0.01). Mediation analysis revealed that biomarkers of oxidative stress, including gamma-glutamyl transferase and uric acid, collectively mediated 10.53% of the association between the TyG index and CVD mortality, and 8.44% of the association with all-cause mortality (P < 0.05). In the cohort study, TyG index was found to have a J-shaped association with CVD mortality and all-cause mortality in MeS population and oxidative stress may play a key mediating role in this relationship.