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The frailty index is a predictor of cause-specific mortality independent of familial effects from midlife onwards

By Xia Li, Alexander Ploner, Ida K. Karlsson, Xingrong Liu, Patrik K.E. Magnusson, Nancy Pedersen, Sara Hagg, Juulia Jylhävä

Posted 07 Dec 2018
bioRxiv DOI: 10.1101/486845 (published DOI: 10.1186/s12916-019-1331-8)

Background: Frailty index (FI) is a well-established predictor of all-cause mortality, but less is known for cause-specific mortality and whether familial effects influence the associations. Furthermore, the population mortality impact of frailty remains understudied. Objectives: To estimate the predictive value of frailty for all-cause and cause-specific mortality, and to test whether the associations are time-dependent. We also assessed the proportion of deaths that are attributable to increased levels of frailty. Methods: We analyzed 42,953 participants from the Screening Across the Lifespan Twin Study (aged 41-95 years at baseline) with up to 20-years' mortality follow-up. The FI was constructed using 44 health-related items. Deaths due to cardiovascular disease (CVD), respiratory-related causes and cancer were considered in the cause-specific analysis. Generalized survival models were used in the analysis. Results: Increased FI was associated with higher risks of all-cause, CVD, and respiratory-related mortality. No significant associations were observed for cancer mortality. No attenuation of the mortality associations was found in unrelated individuals when adjusting for familial effects in twin pairs. The associations were time-dependent with relatively greater effects observed in younger ages. The proportion of deaths attributable to FI levels >0.10 were 13.0% of all-cause deaths, 14.7% of CVD deaths and 12.5% of respiratory-related deaths in men, and 12.2% of all-cause deaths, 9.9% of CVD deaths and 21.9% of respiratory-related deaths in women. Conclusions: Increased FI predicts higher risks of all-cause, CVD, and respiratory-related mortality independent of familial effects. Increased FI levels have a significant population mortality impact in both men and women.

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