Triglyceride-glucose waist-to-height ratio in relation to prevalent and incident multimorbidity: cross-sectional and prospective evidence from four national studies.

BACKGROUND: The triglyceride-glucose waist-to-height ratio (TyG-WHtR) integrates insulin resistance and central adiposity, but its association with generalized multimorbidity across populations and its dose-response threshold remain uncertain. METHODS: We analyzed adults aged ≥ 50 years from five analytic samples derived from four national studies. Cross-sectional analyses included the National Health and Nutrition Examination Survey (NHANES; n = 1842) and the Health and Retirement Study (HRS; n = 4310), whereas prospective analyses included the China Health and Retirement Longitudinal Study (CHARLS; n = 4114), the English Longitudinal Study of Ageing (ELSA; n = 1310), and HRS (n = 971). Multimorbidity was defined as the presence of at least two of eight harmonized chronic conditions. Multivariable logistic regression and Cox proportional hazards models were used to evaluate prevalent and incident multimorbidity, respectively. Restricted cubic spline and two-piecewise regression models were used to assess nonlinear associations, and receiver operating characteristic curves were used to compare TyG-WHtR with five alternative TyG-related anthropometric indices. RESULTS: In the cross-sectional analyses, the fully adjusted ORs comparing the highest with the lowest TyG-WHtR quartile were 5.04 (95% CI 3.02-8.42) in NHANES and 3.63 (95% CI 2.70-4.90) in HRS. In the prospective analyses, the fully adjusted HRs comparing the highest with the lowest quartile were 1.87 (95% CI 1.59-2.21) in CHARLS, 1.67 (95% CI 1.30-2.15) in ELSA, and 1.57 (95% CI 1.08-2.29) in HRS. Prospective dose-response associations were nonlinear, with inflection points of 5.92, 5.80, and 6.69, respectively; risk increased predominantly below these values. TyG-WHtR had the largest area under the curve in both cross-sectional samples and in CHARLS and ELSA. Lagged analyses and alternative multimorbidity definitions yielded consistent results. CONCLUSIONS: Higher TyG-WHtR was associated with prevalent multimorbidity in both cross-sectional samples and with incident multimorbidity in quartile-based analyses across all three prospective cohorts, although the continuous association was not statistically significant in prospective HRS. The cohort-specific inflection points suggest a provisional candidate risk-alert interval of approximately 5-7. This interval requires independent external validation and should not be interpreted as a diagnostic or treatment threshold.