What is the clinical evidence from this study?

Study design: Observational. Population: Cardiovascular disease (n=12591). Intervention: Resistance exercise vs. No resistance exercise. Primary outcome: Total CVD events (CVD morbidity and mortality combined) (HR 0.44, 95% CI 0.36-0.54).

August 6, 2021Open Access

Causal mediation analysis between resistance exercise and reduced risk of cardiovascular disease based on the Aerobics Center Longitudinal Study

Key Result

Resistance exercise significantly reduced the risk of total cardiovascular disease events with a natural direct effect hazard ratio of 0.44 compared to no resistance exercise.

Study Design

Type

Observational (n=12,591)

Multicenter

Structured PICO

Does resistance exercise reduce total CVD events in adults without preexisting cardiovascular disease?

Population

12,591 adults aged 18 to 89 (21% female), free of preexisting cardiovascular disease, cancer, and diabetes, followed longitudinally to assess the effect of resistance exercise on cardiovascular disease risk.

Exposure

Resistance exercise (RE) at least once per week

Comparator

No resistance exercise (RE frequency = 0)

Outcome

Total CVD events (CVD morbidity and mortality combined)hard clinical

Resistance exercise significantly reduces the risk of total cardiovascular disease events primarily through direct effects rather than indirect mediation via traditional risk factors like BMI, glucose, cholesterol, and blood pressure.

Main Result

Hazard Ratio: 0.44 (95% CI 0.36–0.54)

Limitations

Total CVD events were rare (205 out of 12,591 subjects), limiting statistical power.
The inverse probability weighting method for causal mediation analysis leads to large variation and reduced statistical power.
Aerobic exercise amount and alcohol consumption were self-reported and subject to large recall errors.
Resistance exercise in the baseline data was subject to measurement errors.

Abstract

Health benefits of resistance exercise (RE), particularly in lowering cardiovascular disease (CVD) risks, are less understood in comparison to aerobic exercise (AE). Motivated by big data from the Aerobics Center Longitudinal Study (ACLS), we study the direct and indirect effects of RE on CVD risks. The primary outcome in our study, total CVD events (CVD morbidity and mortality combined), is modeled as a survival outcome. To investigate the pathway from RE to CVD outcome through potential mediators, we first conduct causal mediation analysis based on marginal structural models (MSMs). To fully account the information from repeated measurements of the mediators, we also adopt a joint model of the CVD survival outcome and multiple longitudinal trajectories of the mediators. Results show statistically significant direct effects of RE and AE on lowering the risk of total CVD events under each pathway. The causal effect of RE and AE on CVD risk is also studied across different age and gender groups. Furthermore, we produce a ranking for the relative importance of the potential risk factors for CVD, with total cholesterol ranking the highest.

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