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Association of cardiovascular disease and urate levels with aortic aneurysm: a bilateral mendelian randomization

Yuanyuan Xiao1, Tao Xiang2,3

  • 1Department of Emergency, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China.

Scientific Reports
|October 14, 2024
PubMed

Insights

Coronary artery disease and myocardial infarction causally increase the risk of aortic aneurysm and abdominal aortic aneurysm. No causal link was found between these conditions and thoracic aortic aneurysm or urate levels.

Area of Science:

  • Cardiovascular Genetics
  • Aortic Diseases
  • Epidemiology

Background:

  • Coronary artery disease (CAD) and myocardial infarction (MI) are leading causes of mortality worldwide.
  • Aortic aneurysms (AA), including abdominal (AAA) and thoracic (TAA) types, and aortic dissection (AD) represent serious vascular conditions.
  • The etiological relationship between CAD/MI and various aortic pathologies, including urate levels, remains incompletely understood.

Purpose of the Study:

  • To investigate potential causal relationships between coronary artery disease (CAD), myocardial infarction (MI), and urate levels with aortic aneurysm (AA), abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA), and aortic dissection (AD).
  • To employ Mendelian randomization (MR) to assess these causal links in individuals of European ancestry.

Main Methods:

  • Two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data for CAD, MI, and urate levels.
  • Genetic instruments for AA, AAA, TAA, and AD were sourced from the FinnGen cohort.
  • Primary analysis utilized the inverse-variance weighted (IVW) method, with sensitivity analyses including MR-Egger, weighted median MR, and MR-PRESSO; MR-Egger intercept and Cochran's Q statistics assessed pleiotropy and heterogeneity, respectively. Bidirectional MR was performed to address reverse causation.

Main Results:

  • A statistically significant positive causal relationship was identified between CAD/MI and the risk of AA (OR: 1.309; 95% CI: 1.150-1.490) and AAA (OR: 1.383; 95% CI: 1.189-1.609).
  • Sensitivity analyses confirmed the robustness of these findings.
  • No significant causal links were observed between CAD, MI, urate levels, and TAA or AD.

Conclusions:

  • CAD and MI are established causal risk factors for the development of AA and AAA.
  • The findings suggest that interventions targeting CAD/MI risk factors may also benefit aortic health.
  • Urate levels and CAD/MI do not appear to have a causal role in TAA development.

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