Chen Xingyu, Li Aiping, Zhou Wensheng, Yao Liping
Department of Neurology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.
Department of Neurology, The Third Hospital of Changsha, Changsha, China.
Front Neurol. 2024 Aug 19;15:1408758. doi: 10.3389/fneur.2024.1408758. eCollection 2024.
Observational researches have suggested a connection between iron deficiency anemia (IDA) and an increased likelihood of ischemic stroke (IS), yet establishing causality is challenging owing to the inherent limitations of such studies, including their vulnerability to confounding factors and the potential for reverse causation. This study employs a bidirectional two-sample Mendelian randomization (MR) approach to assess the causal linkage between IDA and IS and its subtypes.
Identifiable single nucleotide polymorphisms (SNPs) with significant links to either IDA or IS and its subtypes were employed as instrumental variables (IVs). The relationship between IDA and any IS, small vessel stroke (SVS), cardioembolic stroke (CES), and large artery stroke (LAS), was quantified using the inverse variance weighted (IVW) method. Complementary analyses utilizing MR-Egger and weighted median methods further supplemented the IVW findings. Moreover, the leave-one-out analysis, MR-Egger intercept test, MR-PRESSO global test, and Cochrane's Q test were conducted for sensitivity analyses.
This study revealed no correlation between IDA and any IS (IVW method: OR [95% CI] = 0.977 [0.863-1.106]; = 0.716), LAS (OR [95% CI] = 1.158 [0.771-1.740]; = 0.479), CES (OR [95% CI] = 1.065 [0.882-1.285]; = 0.512), or SVS (OR [95% CI] = 1.138 [0.865-1.498]; = 0.357). Conducting a reverse MR analysis, it was determined that there is no causal connection between any IS, LAS, CES, SVS, and IDA (all > 0.05). Sensitivity analysis indicated that heterogeneity was not significant and no evidence of horizontal pleiotropy was detected.
This MR study suggested no causal effect of IDA on IS, LAS, CES, and SVS. Through reverse MR analyses, it was determined that IS and its subtypes did not exert a causal impact on IDA.
观察性研究表明缺铁性贫血（IDA）与缺血性中风（IS）风险增加之间存在关联，但由于此类研究存在固有局限性，包括易受混杂因素影响以及存在反向因果关系的可能性，因此确定因果关系具有挑战性。本研究采用双向两样本孟德尔随机化（MR）方法来评估IDA与IS及其亚型之间的因果联系。
将与IDA或IS及其亚型有显著关联的可识别单核苷酸多态性（SNP）用作工具变量（IV）。使用逆方差加权（IVW）方法量化IDA与任何IS、小血管性中风（SVS）、心源性栓塞性中风（CES）和大动脉粥样硬化性中风（LAS）之间的关系。利用MR-Egger和加权中位数方法进行的补充分析进一步补充了IVW的结果。此外，进行了留一法分析、MR-Egger截距检验、MR-PRESSO全局检验和Cochrane's Q检验以进行敏感性分析。
本研究表明IDA与任何IS（IVW方法：OR[95%CI]=0.977[0.863-1.106]；P=0.716）、LAS（OR[95%CI]=1.158[0.771-1.740]；P=0.479）、CES（OR[95%CI]=1.065[0.882-1.285]；P=0.512）或SVS（OR[95%CI]=1.138[0.865-1.498]；P=0.357）之间无相关性。进行反向MR分析时，确定任何IS、LAS、CES、SVS与IDA之间均无因果关系（所有P>0.05）。敏感性分析表明异质性不显著，未检测到水平多效性的证据。
本MR研究表明IDA对IS、LAS、CES和SVS无因果效应。通过反向MR分析，确定IS及其亚型对IDA无因果影响。
