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Causal relationship between stable angina and bone mineral density: A two-sample bidirectional Mendelian

Yuewei Song1,2, Hao Tian Li1,2, Yaxin Pan1,2

  • 1Beijing University of Chinese Medicine, Beijing, China.

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|November 8, 2025
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Summary

This study found a causal link between higher bone mineral density (BMD) and an increased risk of stable angina pectoris (SAP). Increased BMD may contribute to the development of this heart condition.

Keywords:
Mendelian randomizationbone mineral densitycausalitysingle nucleotide polymorphismstable angina pectoris

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Area of Science:

  • Cardiovascular Disease Epidemiology
  • Bone Metabolism Research
  • Genetic Epidemiology

Background:

  • Observational studies suggest a link between bone mineral density (BMD) and stable angina pectoris (SAP), but causality remains unclear.
  • Understanding the relationship between bone health and cardiovascular conditions is crucial for public health.
  • Mendelian randomization offers a robust method to investigate potential causal pathways.

Purpose of the Study:

  • To investigate the causal relationship between genetically predicted bone mineral density (BMD) and the risk of developing stable angina pectoris (SAP).
  • To explore the potential causal effect of SAP on BMD.
  • To assess the influence of BMD at specific skeletal sites on SAP risk.

Main Methods:

  • Utilized Mendelian randomization (MR) analysis with large-scale genome-wide association study (GWAS) data for BMD and SAP.
  • Employed the inverse variance weighted (IVW) method as the primary analysis, supported by weighted median, MR-Egger, and simple weighted models for robustness.
  • Performed sensitivity analyses including Cochran Q test to assess heterogeneity and potential pleiotropy.

Main Results:

  • MR analysis indicated a significant positive causal association between genetically predicted BMD and the risk of SAP.
  • Higher genetically predicted BMD was associated with an increased risk of developing stable angina pectoris.
  • Analysis considering left heel BMD as exposure showed a positive correlation with SAP; however, other BMD sites did not show significant associations.
  • When SAP was the exposure, left and right heel BMD showed a negative correlation, suggesting a complex, potentially bidirectional relationship.

Conclusions:

  • Genetically predicted higher bone mineral density is causally associated with an increased risk of stable angina pectoris.
  • The findings suggest a potential role for bone metabolism in the pathogenesis of stable angina.
  • Further research is warranted to elucidate the underlying mechanisms and explore therapeutic implications.