The role of lifestyle in the association between frailty and all-cause mortality amongst older adults: a mediation analysis in the UK Biobank.

OBJECTIVE: frailty is a syndrome characterised by increased vulnerability to stressors, which manifests as higher death risk. Whilst guidelines for frailty management usually entails lifestyle modifications (e.g. physical exercise, diet), the mediating role of lifestyle on the excess mortality associated with frailty is unclear. This study estimates the death risk due to frailty that could be avoided with a healthy lifestyle in older adults. SUBJECTS AND METHODS: we analysed data from 91,906 British individuals aged ≥60 years recruited between 2006 and 2010. At baseline, frailty was identified according to Fried's phenotype, and a four-item Healthy Lifestyle Index (HLS) was calculated based on physical activity, diet, smoking and alcohol consumption. Mortality was ascertained from baseline through 2021. A mediation analysis under the counterfactual framework was performed adjusting for the main confounders. RESULTS: during a median follow-up of 12.5 years, 9,383 deaths occurred. Frailty was directly associated with all-cause mortality (hazard ratio: 2.30 [95% confidence interval {CI} 2.07, 2.54]), and inversely associated with the HLS (ß: -0.45 points [-0.49, -0.40]). The hazard ratio [95%CI] for the direct effect of frailty on mortality was 2.12 [1.91, 2.34], whilst for the indirect effect (mediated by HLS) was 1.08 [1.07, 1.10]. The mediated proportion of HLS on mortality was 13.55% [11.26, 16.20], with physical activity having the highest proportion amongst the four HLS items (7.69% [5.00, 10.40]). CONCLUSIONS: a healthy lifestyle partly mediates the association between frailty and mortality in British older adults. Since this was an exploratory mediation analysis, these results should be specifically tested in future research.