Abstract
BACKGROUND: Cardiovascular disease (CVD) and frailty are interrelated conditions prevalent in aging populations, yet their dynamic temporal relationship remains underexplored. This study investigates longitudinal changes in frailty trajectories before and after incident CVD across diverse cohorts. METHODS: Utilizing data from four longitudinal, multinational cohorts (ELSA, HRS, CHARLS, SHARE; n = 66,537), we constructed the frailty index (FI) based on age-related health deficits, using 40, 40, 42, and 44 items from ELSA, HRS, CHARLS and SHARE, respectively. Linear mixed models assessed FI changes pre- and post-CVD, adjusting for demographics, lifestyle, and baseline FI. Sensitivity analyses excluded hypertension, diabetes, and arthritis to mitigate confounding. RESULTS: Frailty increased steadily before CVD onset (pre-CVD slope: ELSA β = 0.005, HRS β = 0.005, CHARLS β = 0.012, SHARE β = 0.007; all P < 0.001), with an acute FI spike at diagnosis (post-CVD acute change: ELSA β = 0.024, HRS β = 0.031, CHARLS β = 0.046, SHARE β = 0.038; all P < 0.001). Post-CVD, frailty progression further accelerated (ELSA β = 0.008, HRS β = 0.005, CHARLS β = 0.017, SHARE β = 0.010; all P < 0.001). Sensitivity analyses confirmed robustness across age strata and FI definitions. CONCLUSIONS: This first multinational study demonstrates bidirectional acceleration of frailty around CVD onset, highlighting their close temporal interplay. These findings suggest that incorporating frailty assessment into CVD management may help identify high-risk individuals and support timely, multidimensional care in aging populations.