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Related Experiment Video

Updated: Apr 12, 2026

Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
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Genetically proxied appendicular lean mass and stroke risk: A two-step mendelian randomization study.

Zhiming Li1, Xueyun Liu1, Jianshang Wen2

  • 1Department of Neurology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, China.

Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association
|August 4, 2024
PubMed
Summary

Lower appendicular lean mass (ALM) is linked to increased stroke risk. Higher ALM may protect against stroke, with hypertension and blood pressure playing a mediating role.

Keywords:
Appendicular lean massMendelian randomizationSarcopeniaStrokeVascular damage

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Area of Science:

  • Genetics
  • Neurology
  • Gerontology

Background:

  • Observational studies suggest sarcopenia and stroke are linked, but causality is unclear.
  • Sarcopenia, characterized by muscle mass loss, impacts aging populations.
  • Stroke remains a leading cause of disability and mortality worldwide.

Purpose of the Study:

  • To investigate the causal relationship between genetically predicted sarcopenia-related traits and stroke.
  • Utilize a two-step Mendelian randomization (MR) approach for robust genetic analysis.
  • Examine potential mediating factors in the ALM-stroke association.

Main Methods:

  • Acquired genome-wide association study (GWAS) data for sarcopenia traits from UK Biobank.
  • Selected genetic associations for ischemic stroke (IS) subtypes from MEGASTROKE and cerebral hemorrhage from FinnGen.
  • Employed inverse-variance weighted (IVW) method for MR estimates and assessed SNP heterogeneity and pleiotropy.

Main Results:

  • Higher appendicular lean mass (ALM) showed a potential protective association with large artery atherosclerosis (LAA) and small vessel disease (SVD).
  • Multivariable MR indicated that body fat and physical activity modified the ALM-stroke and ALM-intracerebral hemorrhage (ICH) associations.
  • Hypertension and systolic blood pressure (SBP) were identified as significant mediators (>10%) in the ALM-stroke relationship.

Conclusions:

  • Lower ALM is associated with an elevated risk of stroke.
  • Higher ALM may confer protection against stroke, warranting further investigation.
  • Understanding the mechanisms of ALM's protective effects is crucial for stroke prevention strategies.