Trajectories of frailty preceding incident cardiovascular diseases among middle-aged and older adults

Background: The longitudinal dynamics of frailty during the preclinical stages of cardiovascular disease (CVD) remain poorly understood.

Objectives: We aimed to delineate frailty trajectories before CVD onset to elucidate the temporal sequence between deficit accumulation and disease onset, uncovering optimal preclinical windows for prevention.

Methods: Drawing on data from the English Longitudinal Study of Ageing (ELSA) and the Health and Retirement Study (HRS). Frailty was quantified using a Frailty Index (FI), and CVD was ascertained by self-reported physician-diagnosed heart disease or stroke. Bayesian generalized linear mixed models with a backward timescale were applied to reconstruct FI trajectories. Time-stratified Cox models were employed to assess phase-specific FI-CVD associations.

Results: This analysis included 10,237 ELSA and 24,534 HRS participants. Over median follow-ups of 9 and 8 years (maximum 17 and 21 years), 21.4% and 26.5% developed CVD, respectively. FI scores for the incident CVD and CVD-free groups began to diverge significantly 15 years (in ELSA) and 11 years (in HRS) prior to diagnosis. Inflection points for accelerated frailty accumulation emerged at 7 and 4 years before diagnosis, respectively. Notably, the association between baseline frailty and CVD was stronger during the pre-acceleration period than in the acceleration phase (P for interaction < 0.01), indicating early-stage frailty serves as an upstream risk factor.

Conclusions: Frailty trajectories diverge and accelerate years before CVD onset. This extended preclinical window establishes early frailty screening and multidomain interventions as actionable targets for cardiovascular prevention.