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Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study

BACKGROUND AND PURPOSE: Previous 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 fact...

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Autores principales: Hou, Lei, Xu, Mingqing, Yu, Yuanyuan, Sun, Xiaoru, Liu, Xinhui, Liu, Lu, Li, Yunxia, Yuan, Tonghui, Li, Wenchao, Li, Hongkai, Xue, Fuzhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964084/
https://www.ncbi.nlm.nih.gov/pubmed/31941463
http://dx.doi.org/10.1186/s10020-019-0133-y
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author Hou, Lei
Xu, Mingqing
Yu, Yuanyuan
Sun, Xiaoru
Liu, Xinhui
Liu, Lu
Li, Yunxia
Yuan, Tonghui
Li, Wenchao
Li, Hongkai
Xue, Fuzhong
author_facet Hou, Lei
Xu, Mingqing
Yu, Yuanyuan
Sun, Xiaoru
Liu, Xinhui
Liu, Lu
Li, Yunxia
Yuan, Tonghui
Li, Wenchao
Li, Hongkai
Xue, Fuzhong
author_sort Hou, Lei
collection PubMed
description BACKGROUND AND PURPOSE: Previous 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. METHODS: Summary 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. RESULTS: Blood 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. CONCLUSIONS: Our 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.
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spelling pubmed-69640842020-01-22 Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study Hou, Lei Xu, Mingqing Yu, Yuanyuan Sun, Xiaoru Liu, Xinhui Liu, Lu Li, Yunxia Yuan, Tonghui Li, Wenchao Li, Hongkai Xue, Fuzhong Mol Med Research Article BACKGROUND AND PURPOSE: Previous 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. METHODS: Summary 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. RESULTS: Blood 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. CONCLUSIONS: Our 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. BioMed Central 2020-01-15 /pmc/articles/PMC6964084/ /pubmed/31941463 http://dx.doi.org/10.1186/s10020-019-0133-y Text en © The Author(s) 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Hou, Lei
Xu, Mingqing
Yu, Yuanyuan
Sun, Xiaoru
Liu, Xinhui
Liu, Lu
Li, Yunxia
Yuan, Tonghui
Li, Wenchao
Li, Hongkai
Xue, Fuzhong
Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study
title Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study
title_full Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study
title_fullStr Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study
title_full_unstemmed Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study
title_short Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study
title_sort exploring the causal pathway from ischemic stroke to atrial fibrillation: a network mendelian randomization study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964084/
https://www.ncbi.nlm.nih.gov/pubmed/31941463
http://dx.doi.org/10.1186/s10020-019-0133-y
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