The frailty mortality link in people with chronic diseases pertaining to 13 body organ systems: findings from the UK Biobank study

Frailty in older adults, particularly those with chronic diseases, has a robust association with risk of mortality, but whether this is the case in middle-aged adults is unclear. We examined the frailty-mortality association in middle-aged adults with chronic diseases and multimorbidity. Data on Fried's frailty phenotype (robust, prefrail, frail) and 47 chronic diseases, mapped to 13 body organ systems, was available on 230,960 participants of the UK Biobank study (mean age 57.8, range 38.0-72.0). The mortality follow-up was 13.3 (± 2.1) years, and associations with mortality were examined using Cox regression, adjusted for socio-demographic factors and health behaviours. Compared to the robust group, frailty (HR, 2.32 (95% confidence intervals, 2.21; 2.43)) and prefrailty (1.35 (1.31; 1.39)) in those with diseases in any body organ system had a higher risk of mortality. Frailty was associated with a higher mortality risk for all 13 groups (all p < 0.01); estimates ranged from 2.25 (2.12; 2.39) for circulatory system diseases to 2.97 (2.60; 3.39) for the eye system. The same was the case for prefrailty; estimates ranged from 1.33 (1.23; 1.43) to 1.61 (1.03; 2.51). Between 19 and 34% of the mortality risk in the 13 disease groups could potentially be explained by frailty/prefrailty. Frailty (p < 0.01) and prefrailty (p < 0.01) had stronger associations with mortality in those with diseases affecting multiple organ systems. These findings highlight the importance of frailty in middle-aged adults with chronic diseases, suggesting that a third of the excess risk of mortality could potentially be addressed by improving frailty status.