Association of Longitudinal Repeated Measurements of Frailty Index with Mortality: Cohort Study Among Community-dwelling Older Adults

Background: Frailty indices (FIs), defined by accumulation of health deficits, have been shown to be strongly related to mortality in older adults. However, previous studies mostly relied on FI measurement at a single point of time. We aimed to investigate the association of frailty with mortality according to longitudinal repeated measurements of FI in a large population-based cohort study in Germany.

Methods: Among 9912 men and women aged 50-75 years living in Saarland, Germany and recruited in the ESTHER study in 2000-2002, a FI based on 30 deficits was determined at baseline, 2-, 5-, 8-, and 11-year follow-up. Hazard ratios (HRs) were calculated to assess the associations of FI with all-cause mortality and cause-specific mortality during 14 years of follow-up using Cox proportional hazards models that included FI as a time-varying covariate.

Findings: During the 14-year follow-up, a total of 2483 deaths were observed, of which 859 and 863 were due to cancer and cardiovascular diseases (CVD), respectively. The time-varying FI showed consistently strong associations with mortality throughout 14 years of follow-up, with HRs (95% confidence intervals) for frail (FI≥ 0·35) versus non-frail (FI≤ 0·11) participants of 4·72 (4.05-5.51), 2·55 (1·95-3·34) and 7·52 (5·69-9·94) for all-cause, cancer, and CVD mortality, respectively. Gradually decreasing associations with increasing length of follow-up would have been obtained by using baseline FI only.

Interpretation: Longitudinal repeated measures of FI show strong, consistent associations with mortality, especially CVD mortality, throughout extended periods of follow-up among community-dwelling older adults.

Funding: The ESTHER study was funded by grants from the Baden-Württemberg state Ministry of Science, Research and Arts (Stuttgart, Germany), the Federal Ministry of Education and Research (Berlin, Germany), the Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany), and the Saarland State Ministry of Health, Social Affairs, Women and the Family (Saarbrücken, Germany).