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

## TL;DR

This study shows that consistently meeting physical activity guidelines in midlife reduces all-cause mortality in Australian women, though effects on cancer and heart disease were less clear.

## Contribution

The study uses a target trial emulation to provide causal evidence on long-term physical activity patterns and mortality in midlife women.

## Key findings

- Consistent adherence to physical activity recommendations over 15 years was associated with a 50% lower risk of all-cause mortality.
- Findings for cardiovascular and cancer mortality were less conclusive, possibly due to limited statistical power.
- Starting physical activity in midlife (e.g., by age 55) showed uncertain benefits for mortality outcomes.

## Abstract

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.

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.

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

The evidence for an association between physical activity and mortality outcomes has generally been based on epidemiological studies relying on a single measurement of physical activity and not examining causal effects.

Studies that examine the effect of longer-term patterns of physical activity on mortality outcomes are needed.

Using a causal inference framework to imitate a randomised controlled trial based on observational data, this study offers long-term evidence comparing different physical activity patterns during mid-life in relation to all-cause, cardiovascular disease and cancer mortality in a cohort of Australian women.

In this emulated target trial (n = 11,169), consistently meeting the World Health Organization’s recommendations of moderate-to-vigorous physical activity over 15 years was protective for all-cause mortality compared to consistent non-adherence to recommendations. Findings were uncertain and not conclusive for cardiovascular disease and cancer mortality, possibly due to insufficient statistical power from the smaller number of observed deaths from cardiovascular disease and cancer.

Findings were also more uncertain and inconclusive for whether starting to meet guidelines earlier in mid-life (e.g., by the mid-fifties) resulted in lower risks of all-cause, cardiovascular disease and cancer mortality by the end of the study.

Staying physically active at recommended levels throughout midlife provides protective benefits against premature mortality in women.

This study supports the growing evidence that maintaining an active lifestyle in midlife provides health benefits.

Limitations of the study included the use of self-reported physical activity, and findings may not apply to all mid-aged Australian women.

In a target trial emulation study, Binh Nguyen and colleagues use longitudinally collected data to investigate the impact of physical activity during mid-life on mortality of Australian women later in life.