{"title":"Causal relationship between cardiovascular diseases and vestibular dysfunction: A 2-sample Mendelian randomization study.","authors":"Huiguo Liu, Liu Shihan, Luo Wenlong","doi":"10.1097/MD.0000000000043091","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"104 29","pages":"e43091"},"PeriodicalIF":1.4000,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/MD.0000000000043091","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
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.
观察性研究已经确定了心血管疾病(cvd)和前庭功能障碍之间的关联,但潜在的因果机制尚不清楚。本研究首次采用孟德尔随机化(Mendelian randomization, MR)方法系统评估多种心血管疾病与前庭功能障碍之间的潜在因果关系,为其病理机制提供新的见解。使用全基因组关联研究的心血管疾病数据集和FinnGen数据库的前庭功能障碍数据集(N = 4,08,645),通过2样本MR分析暴露(房颤、心绞痛、心力衰竭、心肌梗死、高血压和冠状动脉粥样硬化)与结果(前庭功能障碍)之间的相关性,并进行反向MR研究。采用方差反加权(IVW)法、MR-Egger法和加权中位数法,并辅以各种敏感性分析,以保证结果的稳健性和可靠性。MR分析显示,心绞痛(IVW: P = 4.71E-06)、心衰(IVW: P = 0.017)、心肌梗死(IVW: P = 4.09E-05)、高血压(IVW: P = 0.029)、冠状动脉粥样硬化(IVW: P = 7.76E-07)和前庭功能障碍具有遗传因果关系。然而,磁共振分析显示心房颤动和前庭功能障碍之间没有遗传因果关系(P = 0.27)。在可逆性研究中,在任何MR分析结果中,前庭功能障碍与结果(心房颤动、心绞痛、心力衰竭、心肌梗死、高血压和冠状动脉粥样硬化)之间均未发现显著关联。敏感性分析显示没有水平多效性,但在一些结果中存在异质性。本研究首次利用磁共振分析证明多发性心血管疾病可增加前庭功能障碍的风险,为高危人群的早期临床筛查提供遗传证据。未来的研究应进一步探索其分子机制,特别是心血管-前庭轴的具体通路,并开展介入性研究,以验证有针对性的预防措施。这些发现为开发新的诊断和治疗策略奠定了理论基础,为临床翻译提供了重要的潜力。
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