Causal relationship between cardiovascular diseases and vestibular dysfunction: A 2-sample Mendelian randomization study

Observational studies have identified an association between cardiovascular diseases (CVDs) and vestibular dysfunction, but the underlying causal mechanisms remain unclear. This study employs Mendelian randomization (MR) to systematically evaluate, for the first time, the potential causal relationships between multiple CVDs and vestibular dysfunction, providing new insights into the pathological mechanisms involved. Correlations between exposures (atrial fibrillation, angina pectoris, heart failure, myocardial infarction, high blood pressure and coronary atherosclerosis) and outcomes (vestibular dysfunction) were analyzed by 2-sample MR using a dataset of cardiovascular diseases from the Genome-Wide Association Study and a vestibular dysfunction dataset from a FinnGen database (N = 4,08,645) and a reverse MR study was also performed. The inverse variance weighting (IVW) method, MR-Egger method, and weighted median method were chosen, supplemented by various sensitivity analyses to ensure the robustness and reliability of the results. MR analysis showed that angina pectoris (IVW: P = 4.71E–06), heart failure (IVW: P = .017), myocardial infarction (IVW: P = 4.09E–05), high blood pressure (IVW: P = .029), coronary atherosclerosis (IVW: P = 7.76E–07) and vestibular dysfunction were genetically causally associated. However, MR analysis showed no genetic causality between atrial fibrillation and vestibular dysfunction (P = .27). In the reversibility study, no significant associations were found between vestibular dysfunction and outcomes (atrial fibrillation, angina pectoris, heart failure, myocardial infarction, high blood pressure and coronary atherosclerosis) in any of the MR analysis results. Sensitivity analyses showed no horizontal pleiotropy, but there was heterogeneity in some of the results. This study is the first to use MR analysis to demonstrate that multiple CVDs can increase the risk of vestibular dysfunction, providing genetic evidence for early clinical screening of high-risk populations. Future research should further explore the molecular mechanisms, particularly the specific pathways of the cardiovascular-vestibular axis, and conduct interventional studies to validate targeted preventive measures. These findings lay a theoretical foundation for developing novel diagnostic and therapeutic strategies, offering significant potential for clinical translation.