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Aortic stenosis intricacies beyond the valve: A bidirectional Mendelian randomization study

Dihui Cai1, Jianhui Liu1

  • 1Department of Cardiology, Ningbo Medical Center of Lihuili Hospital, Ningbo, China.

ESC Heart Failure
|June 13, 2025
PubMed

Insights

Calcific aortic valve stenosis (CAVS) causally increases the risk of heart failure, stroke, and atrial fibrillation. Hypertension also increases the risk of CAVS, highlighting the need for blood pressure management in cardiovascular disease prevention.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Epidemiology

Background:

  • Observational studies suggest an association between calcific aortic valve stenosis (CAVS) and increased risk of other cardiovascular diseases (CVDs).
  • The causal nature of this association remains uncertain.

Purpose of the Study:

  • To investigate the potential causal relationship between calcific aortic valve stenosis (CAVS) and the risk of seven common cardiovascular diseases (CVDs).
  • To explore the causal relationship between hypertension and CAVS.

Main Methods:

  • A bidirectional Mendelian randomization (MR) analysis was employed.
  • Meta-analysis was used to combine multiple MR results and estimate causal effects.
  • Genetic variants were used as instrumental variables to infer causality.

Main Results:

  • Genetically predicted CAVS was causally associated with an increased risk of heart failure, large-artery stroke, cardioembolic stroke, and atrial fibrillation.
  • Hypertension was found to causally increase the risk of CAVS.
  • The analyses showed no significant heterogeneity or pleiotropy.

Conclusions:

  • This study establishes a causal link between CAVS and increased risks of various CVDs, including heart failure, stroke, and atrial fibrillation.
  • A causal relationship between hypertension and CAVS risk was also identified.
  • Prioritizing CVD prevention and management in individuals with CAVS, alongside blood pressure control, is crucial.
Abstract

Keywords:
Calcific aortic valve stenosisHeart failureHypertensionMendelian randomizationStroke

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