Fig. 4: Predictive performance of frailty- and metabolomic-augmented risk models for all-cause and cause-specific mortality.

A–E show model performance based on physical frailty (PF) and its associated metabolomic signature (MS-PF), and (F–J) show performance based on the frailty index (FI) and its associated metabolomic signature (MS-FI). Each dot represents the Harrell’s concordance index (C-index), with vertical error bars indicating 95% confidence intervals. Colors differentiate the eight model specifications. AgeSex refers to models adjusted only for age and sex. PANEL denotes multivariable models including age and sex, body mass index, Townsend Deprivation Index, ethnicity, education, smoking status, alcohol consumption frequency, physical activity, fruit and vegetable intake, oily and non-oily fish consumption, red meat (beef, lamb, or pork) intake, poultry intake, and processed meat consumption. For each outcome—including all-cause mortality (A, F), cancer-related mortality (B, G), CVD-related mortality (C, H), respiratory-related mortality (Panels D and I), and digestive-related mortality (E, J)—C-indices were compared across the following eight models: (1) AgeSex; (2) AgeSex + Frailty (PF or FI); (3) AgeSex + Metabolic Signature (MS-PF or MS-FI); (4) AgeSex + Frailty + Metabolic Signature; (5) PANEL; (6) PANEL + Frailty; (7) PANEL + Metabolic Signature; (8) PANEL + Frailty + Metabolic Signature. PF physical frailty, FI frailty index, MS-PF PF-associated metabolomic signature, MS-FI FI-associated metabolomic signature, C-index, Harrell’s concordance index, CVD cardiovascular disease.