TyG-WC as a composite marker of metabolic dysfunction and central obesity predicts all-cause and cardiovascular mortality in overweight and obese adults

Simple and scalable tools for mortality risk stratification in individuals with overweight or obesity remain limited. The triglyceride–glucose–waist circumference (TyG-WC) index integrates insulin resistance and central adiposity, but its prognostic value for mortality in this high-risk population is not well established. We analyzed 11,560 adults with overweight or obesity from the National Health and Nutrition Examination Survey (1999–2018) with mortality follow-up through 2019. Associations between TyG-WC and all-cause and cardiovascular mortality were assessed using multivariable Cox proportional hazards models and restricted cubic spline analyses. Subgroup, exploratory mediation, and sensitivity analyses, including propensity score matching and competing risk models, were performed. Over a median follow-up of 7.6 years, 1,098 deaths occurred, including 294 from cardiovascular disease. Compared with participants in the lowest TyG-WC quartile (Q1), those in the highest quartile (Q4) had significantly higher risks of all-cause mortality (HR 1.589, 95% CI 1.308–1.929) and cardiovascular mortality (HR 1.728, 95% CI 1.158–2.579). When analyzed as a continuous variable, higher TyG-WC levels were also independently associated with increased risks of all-cause mortality (adjusted HR 1.135, 95% CI 1.063–1.211) and cardiovascular mortality (adjusted HR 1.168, 95% CI 1.031–1.324). The associations showed an overall positive dose–response pattern and remained generally consistent across multiple sensitivity analyses. Exploratory mediation analysis suggested that white blood cell count partially mediated the observed relationships. TyG-WC is associated with increased mortality risk among individuals with overweight or obesity and may represent a complementary marker for risk assessment, pending further prospective validation.