Association between walking pace and heart failure: A Mendelian randomization analysis

Abstract

Background and aimThe relationship between walking pace and heart failure (HF) has been recognized, yet the directionality and underlying mediating risk factors remain unclear. Methods and resultsThis study utilized bidirectional two-sample Mendelian randomization (MR) with genome-wide association studies (GWAS) summary statistics to assess the causal relationships between walking pace and HF. Additionally, we employed a two-step Multivariable Mendelian Randomization (MVMR) to explore potential mediating factors. We further validated our findings by conducting two-sample MR with another available GWAS summary data on heart failure. Results indicated that genetically predicted increases in walking pace were associated with a reduced risk of HF (odds ratio (OR), 0.589, 95% confidence interval (CI): 0.417–0.832). Among the considered mediators, the waist-to-hip ratio (WHR) accounts for the largest proportion of the effect (45.7%, 95% CI: 13.2%, 78.2%). This is followed by type 2 diabetes at 24.4% (95% CI: 6.7%, 42.0%) and triglycerides at 18.6% (95% CI: 4.5%, 32.7%). Furthermore, our findings reveal that genetically predicted HF risk (OR, 0.975, 95% CI: 0.960–0.991) is associated with a slower walking pace. Validated findings were consistent with the main results. ConclusionsIn conclusion, MR analysis demonstrates that a slow walking pace is a reliable indicator of an elevated risk of HF, and the causal relationship is bidirectional. Interventions focusing on waist-to-hip ratio, type 2 diabetes, and triglycerides may provide valuable strategies for HF prevention in individuals with a slow walking pace.