Abstract
BACKGROUND: Whether leisure-time physical activity modifies the association between frailty and mortality in older adults is unclear. METHODS: We analyzed the interactions between physical activity and frailty status on all-cause mortality risk using Cox proportional hazards models across five nationally representative cohorts: Survey of Health, Ageing and Retirement in Europe (56,555 participants, median follow-up 6.5 years), China Health and Retirement Longitudinal Study (12,271 participants, 9.0 years); Health and Retirement Study (13,729 participants, 11.9 years); English Longitudinal Study of Ageing (9100 participants, 9.8 years); and Mexican Health and Aging Study (11,262 participants, 19.3 years). Frailty status was classified as robust, prefrail, and frail based on deficit accumulation models, including common disease, functional, locomotor, sensory, mental, and cognitive deficit. Physical activity was classified as regular (meeting World Health Organization recommendations) or inactive. FINDINGS: Across five cohorts (median age 58.0-65.0 years), physical activity consistently interacted with frailty on all-cause mortality (all P(interaction) ≤ 0.036). In pooled analyses, frailty was associated with higher risks of mortality in inactive participants (multivariable-adjusted HR: 3.72, 95% CI: 2.54-5.45 for frailty) than in regularly active participants (2.40, 1.71-3.36 for frailty; P(interaction) < 0.001); results of each cohort were meta-analyzed by random-effects models (I(2) within-subgroup >78.7%, P < 0.001). Whereby, the inverse association between regular activity and mortality was more evident in frail participants (0.56; 0.53-0.59) than in robust participants (0.80, 0.73-0.87); results were meta-analyzed by fixed effects models (I(2) within-subgroup >18.6%, P > 0.296). Such interaction patterns remained between each deficit of frailty and physical activity in at least one cohort. INTERPRETATION: Consistent findings across five cohorts demonstrated that regular physical activity mitigates frailty-associated mortality, and frail adults might gain more survival benefits from regular activity than robust adults. FUNDING: The Noncommunicable Chronic Diseases-National Science and Technology Major Project, the National Natural Science Foundation of China, the National Key R&D Program of China, the "Shu-Guang Scholar Programme" from Shanghai Municipal Education Commission, the "Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support" from Shanghai Jiao Tong University School of Medicine, and the Innovative Research Team of High-level Local Universities in Shanghai.