Physical activity across mid-life and mortality outcomes in Australian women: A target trial emulation using a prospective cohort

by Binh Nguyen, Katherine B. Owen, Mengyun Luo, Wendy Brown, Gregore I.

Mielke, Philip J. Clare, Ding Ding Background Long-term causal evidence comparing different physical activity patterns and mortality outcomes is needed.

Using observational data to emulate an RCT, this study compared different physical activity patterns over 15 years in relation to mortality from all causes, cardiovascular disease (CVD) and cancer in mid-aged Australian women. Methods and findings A target trial emulation framework was used to emulate an RCT, based on data collected every 3 years (nine surveys between 1996 and 2019) from 11,169 women in the Australian Longitudinal Study on Women’s Health (ALSWH; 1946−51 cohort).

Two emulated interventions were compared against consistent non-adherence (control) to WHO moderate-to-vigorous physical activity (MVPA) recommendations during the 15-year ‘exposure period’: (1) consistent adherence to recommendations (at least 150 min/week) over 15 years (2001−2016; women were 50−55–65−70 years); and (2) starting to meet the recommendations at age 55, 60, or 65 years. Analyses were adjusted for sociodemographic and health variables using marginal structural models with the assumptions of conditional exchangeability, positivity, consistency, and no interference.

Mortality outcomes that occurred between surveys 4−9 (women were 53−58 to 68−73 years), were ascertained from Australian death registries. Comparing consistent adherence to MVPA recommendations with consistent non-adherence, there was evidence (Bayes factor [BF] = 5.71) for a protective effect for all-cause mortality (risk ratio [RR]: 0.50, 99.5% CI [0.27, 0.94]; risk difference [RD]: −5.2%, 99.5% CI [−10.5%, 0.1%]).

Findings for CVD (BF = 2.05; RR: 0.50, 99.5% CI [0.19, 1.30]; RD: −2.1%, 99.5% CI [−5.3%, 1.1%]) and cancer mortality (BF = 2.26; RR: 0.35, 99.5% CI [0.10, 1.17]; RD: −3.3%, 99.5% CI [−8.4%, 1.9%]) were more uncertain and less conclusive, as were those for an effect of starting to meet MVPA recommendations in the mid-fifties on mortality outcomes. The main study limitations included reliance of self-reported physical activity and that findings may not be generalisable to all mid-aged Australian women.

Conclusions Based on findings from this target trial emulation, women should be encouraged to meet physical activity recommendations throughout mid-age to derive mortality benefits.