Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study
Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study
复制标题
探索从缺血性中风到心房颤动的因果途径：网络孟德尔随机化研究
DOI：
10.1186/s10020-019-0133-y
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发表时间：
2020-01-15
影响因子：
5.7
通讯作者：
Xue, Fuzhong
中科院分区：
文献类型：
--
作者：
Hou, Lei;Xu, Mingqing;Xue, Fuzhong
背景和目的既往研究发现缺血性脑卒中与心房颤动有关。然而，缺血性卒中和房颤之间的因果关系尚不清楚。缺血性脑卒中、房颤及其危险因素之间的网络关系有待进一步关注。本研究旨在探讨缺血性卒中与房颤之间的潜在因果关系，并进一步探讨缺血性卒中至房颤因果通路中的潜在介质。（病例= 10，307和对照= 19，326）被用作缺血性卒中遗传工具，AFGen Consortium数据（病例组= 65，446，对照组= 522，744）用于房颤，其他联合数据用于潜在介质（空腹胰岛素、白色血细胞计数、降钙素原、收缩压和舒张压、体重指数、腰围和身高）。在网络孟德尔随机化的框架下，使用多个全基因组关联研究的汇总统计量进行双样本孟德尔随机化研究。逆方差加权法进行估计因果effect. Results血压介导的因果途径从缺血性中风到心房颤动。缺血性卒中与房颤的总比值比为1.05（95%置信区间[CI]，1.02 - 1.07;P= 1.3 × 10−5）。遗传决定的缺血性卒中每增加1个单位，收缩压和舒张压上限值为0.02（DBP：95%CI，0.001 ~ 0.034，P = 0.029; SBP：95%CI，0.006 ~ 0.034，P = 0.003）。较高的遗传决定的收缩压和舒张压水平与较高的房颤风险相关（DBP：RR，1.18; 95%CI，1.03至1.35;P= 0.012）。SBP：RR，1.18; 95% CI，1.01 - 1.38;P= 0.04）。特别是，我们还发现血压与缺血性脑卒中之间存在双向因果关系。结论本研究为脑卒中患者血压升高增加房颤的风险，主动急性降压可改善缺血性脑卒中患者的预后提供了有力的证据。
Background and purposePrevious studies have found ischemic stroke is associated with atrial fibrillation. However, the causal association between ischemic stroke and atrial fibrillation is not clear. Furthermore, the network relationship among ischemic stroke, atrial fibrillation and its risk factors need further attention. This study aims to examine the potential causal association between ischemic stroke and atrial fibrillation and further to explore potential mediators in the causal pathway from ischemic stroke to atrial fibrillation.MethodsSummary statistics from the ISGC (case = 10,307 and control = 19,326) were used as ischemic stroke genetic instruments, AFGen Consortium data (case = 65,446 and control = 522,744) were used for atrial fibrillation, and other consortia data were used for potential mediators (fasting insulin, white blood cell count, procalcitonin, systolic and diastolic blood pressure, body mass index, waist circumference, and height). Under the framework of network Mendelian randomization, two-sample Mendelian randomization study was performed using summary statistics from several genome-wide association studies. Inverse-variance weighted method was performed to estimate causal effect.ResultsBlood pressure mediates the causal pathways from ischemic stroke to atrial fibrillation. The total odds ratio of ischemic stroke on atrial fibrillation was 1.05 (95% confidence interval [CI], 1.02 to 1.07;P= 1.3 × 10−5). One-unit increase of genetically determined ischemic stroke was associated with 0.02 (DBP: 95% CI, 0.001 to 0.034,P= 0.029; SBP: 95% CI, 0.006 to 0.034,P= 0.003) upper systolic and diastolic blood pressure levels. Higher genetically determined systolic and diastolic blood pressure levels were associated with higher atrial fibrillation risk (DBP: RR, 1.18; 95% CI, 1.03 to 1.35;P= 0.012. SBP: RR, 1.18; 95% CI, 1.01 to 1.38;P= 0.04). Specially, we also found the bidirectional causality between blood pressure and ischemic stroke.ConclusionsOur study provided a strong evidence that raised blood pressure in stroke patients increases the risk of atrial fibrillation and active acute blood pressure lowering can improve the outcome in ischemic stroke patients.