Ischemic stroke and sarcopenia have an asymmetric bidirectional relationship based on a two-sample Mendelian randomization study

Background: We investigated the potential relationship between age-related conditions, particularly sarcopenia and ischemic stroke (IS), through a two-sample Mendelian randomization (MR) study.

Methods: We conducted a two-sample bidirectional MR study to investigate the relationship between sarcopenia and stroke. Genetic instruments for sarcopenia were derived from the UK Biobank, while data on IS and its subtypes were obtained from the MEGASTROKE consortium. Inverse variance weighting (IVW) served as the primary analytical method. Additionally, heterogeneity and pleiotropy were assessed to ensure the robustness of the findings.

Results: The analysis indicates a negative correlation between appendicular lean mass (ALM) and small vessel stroke (SVS; OR = 0.790, 95% CI: 0.703-0.888, p < 0.001), a positive correlation with cardioembolic stroke (CES; OR = 1.165, 95% CI: 1.058-1.284, p = 0.002), and no causal relationship with any ischemic stroke (AIS) or large artery stroke (LAS). Additionally, SVS is negatively associated with right-hand grip strength (OR = 0.639, 95% CI: 0.437-0.934, p = 0.021), while AIS, LAS, and CES do not exhibit a causal relationship with grip strength. Furthermore, no causal relationship was identified between left-hand grip strength, usual walking pace, and IS or its subtypes. MR analysis reveals only a negative association between CES and usual walking pace (OR = 0.989, 95% CI: 0.980-0.998, p = 0.013), with no associations found between other IS subtypes and sarcopenia-related traits.

Conclusion: This study demonstrates that a reduction in ALM and right-hand grip strength is associated with SVS, whereas decreased ALM may serve as a protective factor against CES. Conversely, our analysis suggests that CES can impact walking speed. Overall, these findings provide valuable insights into the prevention and treatment of these conditions.