Li Quan, Yan Shijiao, Li Yan, Kang Hai, Zhu Huadong, Lv Chuanzhu
Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Emergency Medicine Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Front Cardiovasc Med. 2022 Apr 7;9:844733. doi: 10.3389/fcvm.2022.844733. eCollection 2022.
Whether heart failure (HF) is an independent risk factor of ischemic stroke (IS) and hemorrhagic stroke remains controversial. We employed a multivariable Mendelian randomization (MR) to further investigate the causal effects of HF on the risk of stroke and stroke subtypes.
Genetically predicted HF was selected as an instrumental variable (IV) from published genome-wide association studies (GWAS) meta-analyses. Stroke data with different etiologies were extracted as outcome variables from another two GWAS meta-analyses. The random-effects inverse variance-weighted (IVW) model was applied as the main method, along with sensitivity analysis. Atrial fibrillation (AF), coronary heart disease (CHD), and systolic blood pressure (SBP) were controlled for mediating effects in multivariable MR.
Genetically predicted HF was significantly associated with any IS [odds ratio (OR), 1.39; 95% CI, 1.12-1.74; = 0.03], large artery stroke (LAS; OR, 1.84; 95% CI, 1.27-2.65; = 0.001), and cardioembolic stroke (CES; OR, 1.73; 95% CI, 1.21-2.47; = 0.003), but without small vessel stroke (SVS; OR, 1.1; 95% CI, 0.80-1.52; = 0.56) and intracerebral hemorrhage (ICH; OR, 0.86; 95% CI, 0.41-1.83; = 0.699) in univariable MR. However, these significant associations were attenuated to the null after adjusting for confounding factor in multivariable MR.
There was no direct causal association between HF and stroke in our study. The association between HF and IS can be driven by AF, CHD, and SBP.
心力衰竭（HF）是否为缺血性卒中（IS）和出血性卒中的独立危险因素仍存在争议。我们采用多变量孟德尔随机化（MR）方法进一步研究HF对卒中和卒中亚型风险的因果效应。
从已发表的全基因组关联研究（GWAS）荟萃分析中选择基因预测的HF作为工具变量（IV）。从另外两项GWAS荟萃分析中提取不同病因的卒中数据作为结果变量。采用随机效应逆方差加权（IVW）模型作为主要方法，并进行敏感性分析。在多变量MR中控制心房颤动（AF）、冠心病（CHD）和收缩压（SBP）的中介效应。
在单变量MR中，基因预测的HF与任何IS显著相关[优势比（OR），1.39；95%置信区间（CI），1.12 - 1.74；P = 0.03]，与大动脉卒中（LAS；OR，1.84；95% CI，1.27 - 2.65；P = 0.001）和心源性栓塞性卒中（CES；OR，1.73；95% CI，1.21 - 2.47；P = 0.003）显著相关，但与小血管卒中（SVS；OR，1.1；95% CI，0.80 - 1.52；P = 0.56）和脑出血（ICH；OR，0.86；95% CI，0.41 - 1.83；P = 0.699）无关。然而，在多变量MR中调整混杂因素后，这些显著关联减弱至无统计学意义。
在我们的研究中，HF与卒中之间不存在直接因果关联。HF与IS之间的关联可能由AF、CHD和SBP驱动。
