{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:12:10Z","timestamp":1789661530088,"version":"4.0.1"},"reference-count":47,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiology"],"abstract":"<jats:p>Introduction: In this two-sample, two-step Mendelian randomization (MR) study, we aimed to elucidate the causal associations between sarcopenia-related characteristics and heart failure (HF) risk, and to identify the factors mediating these associations, with a particular focus on the mediating roles of obesity and sedentary habits. Methods: Genetic instruments for appendicular lean mass (ALM), hand grip strength (HGS), walking pace (WP), and potential mediators were extracted from genome-wide association studies. Inverse\u2010variance weighting (IVW) was used as the primary analytical method, supplemented by MR\u2010Egger regression, weighted median, and weighted mode analyses. Sensitivity analyses including Cochran\u2019s Q test and MR-Egger intercept method were performed to assess heterogeneity and pleiotropy. Bidirectional MR was conducted to exclude reverse causation. Results: IVW revealed that a faster genetically predicted WP was associated with lower HF risk (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.33\u20130.60, p = 5.806 \u00d7 10\u22127). The mediation analysis indicated that body mass index (BMI) accounted for 32% of this effect, while time spent watching television accounted for 14%. Elevated ALM showed a slight but significant positive association with HF risk (OR 1.06, 95% CI 1.03\u20131.09, p = 5.437 \u00d7 10\u22124). However, multivariable MR adjusting for BMI completely attenuated this association (p = 0.693), suggesting ALM reflects overall body composition rather than isolated muscle mass. No significant associations were found between HGS and HF. Bidirectional MR showed no robust reverse effects. Conclusions: These findings suggest that genetically predicted increased WP exerts beneficial effects against HF, partially mediated by obesity and sedentary habits. Targeting weight management and anti-sedentary interventions may mitigate HF risk in individuals with sarcopenia-related characteristics.<\/jats:p>","DOI":"10.1159\/000553480","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:00:48Z","timestamp":1784649648000},"page":"1-12","source":"Crossref","is-referenced-by-count":0,"title":["Causal Associations and Potential Mediating Factors between Sarcopenia-Related Traits and Heart Failure Risk: A Mendelian Randomization 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