Causal Effects of Sarcopenia-related Traits on Ischemic Stroke: A Two-sample Mendelian Randomization Study

Objective: The stroke itself can cause sarcopenia, loss of muscle, and weaker strength is commonly experienced in some patients after ischemic stroke. However, the causal effect of sarcopenia on stroke is unclear, and previous studies focusing on ischemic stroke, particularly in its types were rare. Methods: We propose that sarcopenia is a risk factor for stroke, suggesting that maintaining skeletal muscle mass may help prevent stroke. Using a two-sample Mendelian randomization (MR) approach, we analyzed sarcopenia-related traits and their impact on ischemic stroke. This analysis utilized summary-level data from publicly available genome-wide association studies (GWAS) focusing on European populations. Results: In the results, inverse variance weighted analysis showed that sarcopenia-related traits were significant with ischemic stroke: whole body fat-free mass may increase risk for cardioembolic stroke (OR: 1.28 per SD increase in genetically determined left handgrip strength, 95% CI: 1.11-1.49, P=1.14×10-3) and reduce risk for large-artery atherosclerosis and small vessel stroke (OR: 0.76, 95% CI: 0.61-0.95, P=0.014, OR: 0.79, 95% CI: 0.65-0.97, P=0.026, respectively), and handgrip strength may reduce risk for small vessel stroke (OR: 0.60, 95% CI: 0.41-0.87, P=7.29×10-3; OR: 0.57, 95% CI: 0.40-0.82, P=2.30×10-3, left handgrip strength and right handgrip strength respectively). Conclusion: We concluded that there was an overall inverse association of sarcopenia-related traits with large-artery atherosclerosis and small-vessel stroke and a positive association with cardiogenic embolism.