Fig. 1: Overview of the study design.

A total of 2144 TwinsUK participants were analysed to explore biological links between social deprivation, frailty, and cardiovascular risk. Random Forest with SHapley Additive explanation (SHAP) identified the top 20 proteomic features distinguishing the most deprived frail and least deprived non-frail individuals. These proteins were examined for associations with the IMD, frailty, and ASCVD risk in TwinsUK, and validated in an independent replication cohort. Associations of replicated proteins with 10-year ischaemic heart disease risk were assessed in age-matched TwinsUK participants. Mediation analyses were performed to examine whether shared inflammatory proteins linked deprivation, frailty, and cardiovascular risk.