Relationship between ischemic stroke and calcific aortic valve stenosis evaluated using Mendelian randomization and transcriptomic analysis

Abstract

Introduction: Aortic valve stenosis (AVS) is clinically associated with an increased risk of stroke and ischemic cerebrovascular events. However, previous studies on the relationship between aortic valve calcification and stroke have yielded inconsistent findings, and the causal link between ischemic stroke (IHS) and calcified AVS (CAVS) remains unclear due to confounding factors.

Objective: This study aimed to investigate the relationship between IHS and CAVS.

Methods: In the first part of the study, we explored the bidirectional causal relationship between IHS and CAVS using Mendelian randomization (MR). In the second part, we identified shared diagnostic biomarkers for the two diseases through differential gene expression analysis, weighted gene co-expression network analysis, and least absolute shrinkage and selection operator regression. Based on these biomarkers, an artificial neural network (ANN) diagnostic model was established to aid the diagnosis of both diseases.

Results: MR analysis suggested that genetically predicted IHS was associated with an increased risk of CAVS (p=0.0003, odds ratio [OR] = 1.2701, 95% confidence interval [CI]: 1.1153-1.4465), whereas CAVS did not exert a significant causal effect on IHS (p=0.2254, OR = 0.9751, 95% CI: 0.9361-1.0158). FCGR2A, RBMS2, MAP1S, RCN3, HCK, and SLPIwere identified as shared diagnostic biomarkers for IHS and CAVS. Based on these six genes, an ANN diagnostic model was developed and demonstrated reliable diagnostic performance for both diseases.

Conclusion: Genetically predicted IHS appears to be associated with an increased risk of CAVS, while CAVS does not demonstrate a significant causal effect on IHS. FCGR2A, RBMS2, MAP1S, RCN3, HCK, and SLPIserve as shared diagnostic biomarkers for IHS and CAVS. The ANN-based diagnostic model incorporating these biomarkers showed strong predictive capability for both diseases.

Keywords

Ischemic stroke / Calcific aortic valve stenosis / Mendelian randomization / Biomarker / Diagnostic model

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