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Causal Associations and Potential Mediating Factors Between Sarcopenia-related Traits and Heart Failure Risk: A
Cardiology
|July 21, 2026
Summary
Faster walking pace (WP) genetically predicted reduces heart failure (HF) risk, with obesity and sedentary habits partially mediating this effect. Interventions for weight management and reduced sedentary behavior may lower HF risk in individuals with sarcopenia-related characteristics.
Area of Science:
- Cardiovascular Genetics
- Metabolic Health
- Aging Research
Background:
- Sarcopenia, characterized by loss of muscle mass and function, is a growing concern in aging populations.
- Understanding the link between sarcopenia-related traits and heart failure (HF) risk is crucial for preventative strategies.
- Obesity and sedentary lifestyles are suspected mediators in the relationship between sarcopenia and HF.
Purpose of the Study:
- To investigate the causal relationship between sarcopenia-related characteristics (appendicular lean mass, hand grip strength, walking pace) and heart failure (HF) risk.
- To identify potential mediating factors, specifically obesity and sedentary habits, in the sarcopenia-HF association.
- To apply Mendelian randomization (MR) to elucidate these complex relationships.
Main Methods:
- Utilized a two-sample, two-step Mendelian randomization (MR) design.
- Employed genome-wide association study (GWAS) data for genetic instruments.
- Applied inverse-variance weighting (IVW) as the primary analysis, with sensitivity analyses and bidirectional MR to ensure robustness and exclude reverse causation.
Main Results:
- A faster genetically predicted walking pace (WP) was significantly associated with reduced HF risk (OR 0.44).
- Body mass index (BMI) and television viewing time mediated 32% and 14% of the WP-HF association, respectively.
- Elevated appendicular lean mass (ALM) showed a positive association with HF risk, but this was attenuated when adjusting for BMI, suggesting it reflects overall body composition.
Conclusions:
- Genetically predicted faster walking pace (WP) confers a protective effect against heart failure (HF).
- Obesity and sedentary behaviors partially mediate the beneficial effect of WP on HF risk.
- Weight management and anti-sedentary interventions are potential strategies to mitigate HF risk in individuals with sarcopenia-related traits.
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