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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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Design<\/jats:title>\n            <jats:p>A 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Key Results<\/jats:title>\n            <jats:p>During a median follow-up period of 12.7\u00a0years, 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\u20131.28), 10% (HR 1.10, 95% CI 1.08\u20131.12), 30% (HR 1.30, 95% CI 1.26\u20131.33), and 44% (HR 1.44, 95% CI 1.41\u20131.47) 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\u2009\u2265\u20094 had a 2.67 (95% CI 2.49\u20132.87)-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 (<jats:italic>P<\/jats:italic>-interaction\u2009&lt;\u20090.05).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In 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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11606-024-09335-z","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T12:57:04Z","timestamp":1737550624000},"page":"2207-2217","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Joint Physical-Psychosocial Frailty and Risks of All-Cause and Cause-Specific Premature Mortality"],"prefix":"10.1007","volume":"40","author":[{"given":"Jian","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghao","family":"Kou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoriko","family":"Heianza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JoAnn E.","family":"Manson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"issue":"12","key":"9335_CR1","doi-asserted-by":"publisher","first-page":"e650","DOI":"10.1016\/S2468-2667(20)30113-4","volume":"5","author":"J Fan","year":"2020","unstructured":"Fan J, Yu C, Guo Y, Bian Z, Sun Z, Yang L, Chen Y, Du H, Li Z, Lei Y, Sun D, Clarke R, Chen J, Chen Z, Lv J, Li L. 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