Threshold Effect Analysis.

ObjectiveThis study aimed to investigate the independent and synergistic effects of social isolation and multidimensional biomarkers (cardiovascular, metabolic, renal, muscular, and frailty) on physical dysfunction in middle-aged and older Chinese adults by utilizing an integrated sociobiological framework to address the limitations of the current research.MethodA cross-sectional analysis was conducted using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS 2015; N = 3,756 participants aged ≥45 years). Physical dysfunction was defined as difficulty in ≥1 of 9 basic activities of daily living. Core exposures included social isolation (composite score), cardiovascular–kidney–metabolic (CKM) syndrome stage (0–4), vascular ageing (estimated pulse wave velocity [EPWV]), renal function (eGFR), body composition (appendicular skeletal muscle mass [ASM]), metabolic status (visceral adiposity index [VAI] and C-reactive protein triglyceride glucose index [CTI]), and frailty (frailty index). Multivariable logistic regression adjusted for demographic, lifestyle, and socioeconomic factors. Threshold effect models revealed nonlinear relationships. Causal mediation analysis (1000 bootstraps) was used to quantify pathway effects.ResultsSocial isolation independently increased physical dysfunction risk by 38% (adjusted odds ratio [aOR]=1.380; 95% CI: 1.132–1.683; P = 0.002), with stronger effects in those aged P P = 0.021). A frailty index of P P P = 0.008).Sensitivity analyses using E-values indicated that unmeasured confounding was unlikely to fully explain the observed associations.ConclusionSocial isolation and multidimensional biomarkers (particularly CKM severity, vascular stiffness, and frailty) synergistically drive physical dysfunction in ageing Chinese adults. Frailty is a critical mediator of the impact of vascular dysfunction. The identified biomarker thresholds (e.g., EPWV = 7.178 m/s) offer intervention windows. Integrated strategies combining social connections (e.g., community support) with biomarker screening and targeted interventions (e.g., anti-frailty training for elevated EPWV) are essential to disrupt the “isolation–comorbidity–dysfunction” cycle.