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Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization

Ville Karhunen1,2,3, Mark K Bakker4, Ynte M Ruigrok4

  • 1Department of Epidemiology and Biostatistics School of Public Health Imperial College London London United Kingdom.

Journal of the American Heart Association
|November 3, 2021
PubMed

Insights

Smoking, insomnia, and high blood pressure significantly increase the risk of intracranial aneurysms and subarachnoid hemorrhage. These modifiable lifestyle and cardiometabolic factors are key targets for prevention strategies.

Area of Science:

  • Neuroscience
  • Genetics
  • Cardiovascular Medicine

Background:

  • Intracranial aneurysms (IAs) and aneurysmal subarachnoid hemorrhage (aSAH) are significant causes of morbidity and mortality.
  • Understanding the influence of modifiable lifestyle and cardiometabolic factors on IA and aSAH risk is crucial for prevention.

Purpose of the Study:

  • To investigate the causal associations between modifiable lifestyle factors (smoking, coffee consumption, sleep, physical activity) and cardiometabolic factors (BMI, glycemic traits, blood pressure, lipids, inflammation, kidney function) with the risk of IA and aSAH.
  • To utilize Mendelian randomization to infer causality between these factors and cerebrovascular diseases.

Main Methods:

  • Employed Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS).
  • Utilized the inverse-variance weighted (IVW) method as the primary MR analysis.
  • Conducted sensitivity analyses using methods robust to horizontal pleiotropy to ensure result validity.

Main Results:

  • Genetic predisposition to smoking, insomnia, and elevated diastolic blood pressure showed significant associations with increased risk of both IA and aSAH.
  • Specific odds ratios indicated substantial risk increases per unit increase in smoking index, insomnia, and diastolic blood pressure.
  • Weak evidence suggested potential associations for decreased physical activity, higher triglycerides, higher BMI, and lower LDL cholesterol, though with overlapping confidence intervals for at least one outcome.

Conclusions:

  • Smoking, insomnia, and hypertension are identified as major risk factors for intracranial aneurysms and aneurysmal subarachnoid hemorrhage.
  • These findings highlight the importance of addressing these modifiable factors in clinical practice and public health initiatives for cerebrovascular disease prevention.
  • The study provides strong genetic evidence supporting the causal role of smoking, insomnia, and high blood pressure in the pathogenesis of IAs and aSAHs.

Keywords:
Mendelian randomizationintracranial aneurysmlifestylerisk factorssingle‐nucleotide polymorphismssubarachnoid hemorrhage

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