• Jian Zhou, Minghao Kou, Rui Tang, Xuan Wang, Xiang Li, Yoriko Heianza, JoAnn E Manson, and Lu Qi.
• Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, Suite 1724, New Orleans, LA, 70112, USA.
• J Gen Intern Med. 2025 Jan 22.

BackgroundThe importance of integrating physical and psychosocial factors in assessing frailty -health outcomes has been increasingly acknowledged, while the related evidence is lacking. We sought to investigate the associations of joint physical-psychosocial frailty with risk of premature mortality and evaluate the relative importance of individual physical and psychosocial factors.DesignA total of 381,295 participants with no history of cancer or cardiovascular disease (CVD) were recruited from the UK Biobank cohort. The physical-psychosocial frailty was evaluated based on seven indicators including weight loss, exhaustion, physical activity, walking pace, grip strength, social isolation, and loneliness. The outcomes were premature mortality from all causes, cancer, CVD, and other causes. Cox proportional hazards models were used to assess the associations between the physical-psychosocial frailty and premature mortality.Key ResultsDuring a median follow-up period of 12.7 years, we recorded 20,328 premature deaths. Each additional increment in the physical-psychosocial frailty index was associated with a 26% (HR 1.26, 95% CI 1.24-1.28), 10% (HR 1.10, 95% CI 1.08-1.12), 30% (HR 1.30, 95% CI 1.26-1.33), and 44% (HR 1.44, 95% CI 1.41-1.47) higher risk of all-cause, cancer, cardiovascular, and other-cause premature mortality, respectively. Compared with participants with the physical-psychosocial frailty index of 0, those with the index ≥ 4 had a 2.67 (95% CI 2.49-2.87)-fold higher risk of all-cause premature mortality. Slow walking pace and social isolation were the top two strongest predictors for all-cause premature mortality. In addition, we found that lower body mass index (BMI), age, smoking status, and dietary quality modified the associations of physical-psychosocial frailty with all-cause premature mortality (P-interaction < 0.05).ConclusionsIn this cohort study of UK Biobank participants, joint physical-psychosocial frailty is significantly associated with risks of all-cause and cause-specific premature mortality, highlighting the importance to jointly assess physical and psychosocial factors in determining aging-related health.© 2025. The Author(s).

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