Metabolic and inflammatory burden modifies muscle cardiovascular association across aging cohorts within an intrinsic capacity framework

This study evaluates the association between intrinsic capacity domains and incident cardiovascular disease across three nationally representative aging cohorts from the United States, the United Kingdom, and China. Harmonized data from HRS, ELSA, and CHARLS were analyzed using multivariable cause-specific Cox models with time-varying covariates where available. Among intrinsic capacity domains, muscle function showed the most consistent inverse association with cardiovascular risk across cohorts. Higher levels of systemic inflammatory and metabolic burden, including elevated C-reactive protein, diabetes, and non-HDL cholesterol, were associated with higher risk and with attenuation of the modeled muscle-cardiovascular association, with the strongest modification observed in CHARLS. A three-dimensional Metabolism-Inflammation-Muscle surface was used to visualize this interaction structure. These findings support muscle function as a cross-cohort marker of lower cardiovascular risk while highlighting its context-dependent magnitude under systemic stress. The proposed surface is descriptive and requires external validation before clinical application.