There Is No Direct Causal Relationship Between Coronary Artery Disease and Alzheimer Disease: A Bidirectional Mendelian Randomization Study

Background The association between poor cardiovascular health and cognitive decline as well as dementia progression has been inconsistent across studies. This study used Mendelian randomization (MR) to investigate the causal relationship between Alzheimer disease (AD), circulating levels of total‐ta...

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Main Authors: Aifang Zhong, Yejun Tan, Yaqiong Liu, Xiangping Chai, Weijun Peng
Format: Article
Language:English
Published: Wiley 2024-08-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.123.032814
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author Aifang Zhong
Yejun Tan
Yaqiong Liu
Xiangping Chai
Weijun Peng
author_facet Aifang Zhong
Yejun Tan
Yaqiong Liu
Xiangping Chai
Weijun Peng
author_sort Aifang Zhong
collection DOAJ
description Background The association between poor cardiovascular health and cognitive decline as well as dementia progression has been inconsistent across studies. This study used Mendelian randomization (MR) to investigate the causal relationship between Alzheimer disease (AD), circulating levels of total‐tau, and coronary artery disease (CAD). Methods and Results This study used MR to investigate the causal relationship between AD or circulating levels of total‐tau and CAD, including ischemic heart disease, myocardial infarction, coronary heart disease, coronary atherosclerosis, and heart failure. The primary analysis used the inverse‐variance weighted method, with pleiotropy and heterogeneity assessed using MR‐Egger regression and the Q statistic. The overall results of the MR analysis indicated that AD did not exhibit a causal effect on heart failure (odds ratio [OR], 0.969 [95% CI, 0.921–1.018]; P=0.209), myocardial infarction (OR, 0.972 [95% CI, 0.915–1.033]; P=0.359), ischemic heart disease (OR, 1.013 [95% CI, 0.949–1.082]; P=0.700), coronary heart disease (OR, 1.005 [95% CI, 0.937–1.078]; P=0.881), or coronary atherosclerosis (OR, 0.987 [95% CI, 0.926–1.052]; P=0.690). No significant causal effect of CAD was observed on AD in the reverse MR analysis. Additionally, our findings revealed that CAD did not influence circulating levels of total‐tau, nor did circulating levels of total‐tau increase the risk of CAD. Sensitivity analysis and assessment of horizontal pleiotropy suggested that these factors did not distort the causal estimates. Conclusions The findings of this study indicate the absence of a direct causal relationship between AD and CAD from a genetic perspective. Therefore, managing the 2 diseases should be more independent and targeted. Concurrently, investigating the mechanism underlying their comorbidity may not yield meaningful insights for advancing treatment strategies.
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spelling doaj-art-65e005fdde5f415da1607aa76c703b9f2025-08-20T03:10:28ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-08-01131510.1161/JAHA.123.032814There Is No Direct Causal Relationship Between Coronary Artery Disease and Alzheimer Disease: A Bidirectional Mendelian Randomization StudyAifang Zhong0Yejun Tan1Yaqiong Liu2Xiangping Chai3Weijun Peng4Department of Emergency Medicine, The Second Xiangya Hospital Central South University Changsha Hunan ChinaSchool of mathematics University of Minnesota Twin Cities Minneapolis MN USACentre for Research in Medical Devices, Biosciences Research Building National University of Ireland Galway Galway IrelandDepartment of Emergency Medicine, The Second Xiangya Hospital Central South University Changsha Hunan ChinaDepartment of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital Central South University Changsha Hunan ChinaBackground The association between poor cardiovascular health and cognitive decline as well as dementia progression has been inconsistent across studies. This study used Mendelian randomization (MR) to investigate the causal relationship between Alzheimer disease (AD), circulating levels of total‐tau, and coronary artery disease (CAD). Methods and Results This study used MR to investigate the causal relationship between AD or circulating levels of total‐tau and CAD, including ischemic heart disease, myocardial infarction, coronary heart disease, coronary atherosclerosis, and heart failure. The primary analysis used the inverse‐variance weighted method, with pleiotropy and heterogeneity assessed using MR‐Egger regression and the Q statistic. The overall results of the MR analysis indicated that AD did not exhibit a causal effect on heart failure (odds ratio [OR], 0.969 [95% CI, 0.921–1.018]; P=0.209), myocardial infarction (OR, 0.972 [95% CI, 0.915–1.033]; P=0.359), ischemic heart disease (OR, 1.013 [95% CI, 0.949–1.082]; P=0.700), coronary heart disease (OR, 1.005 [95% CI, 0.937–1.078]; P=0.881), or coronary atherosclerosis (OR, 0.987 [95% CI, 0.926–1.052]; P=0.690). No significant causal effect of CAD was observed on AD in the reverse MR analysis. Additionally, our findings revealed that CAD did not influence circulating levels of total‐tau, nor did circulating levels of total‐tau increase the risk of CAD. Sensitivity analysis and assessment of horizontal pleiotropy suggested that these factors did not distort the causal estimates. Conclusions The findings of this study indicate the absence of a direct causal relationship between AD and CAD from a genetic perspective. Therefore, managing the 2 diseases should be more independent and targeted. Concurrently, investigating the mechanism underlying their comorbidity may not yield meaningful insights for advancing treatment strategies.https://www.ahajournals.org/doi/10.1161/JAHA.123.032814Alzheimer diseasecoronary artery diseaseMendelian randomization
spellingShingle Aifang Zhong
Yejun Tan
Yaqiong Liu
Xiangping Chai
Weijun Peng
There Is No Direct Causal Relationship Between Coronary Artery Disease and Alzheimer Disease: A Bidirectional Mendelian Randomization Study
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Alzheimer disease
coronary artery disease
Mendelian randomization
title There Is No Direct Causal Relationship Between Coronary Artery Disease and Alzheimer Disease: A Bidirectional Mendelian Randomization Study
title_full There Is No Direct Causal Relationship Between Coronary Artery Disease and Alzheimer Disease: A Bidirectional Mendelian Randomization Study
title_fullStr There Is No Direct Causal Relationship Between Coronary Artery Disease and Alzheimer Disease: A Bidirectional Mendelian Randomization Study
title_full_unstemmed There Is No Direct Causal Relationship Between Coronary Artery Disease and Alzheimer Disease: A Bidirectional Mendelian Randomization Study
title_short There Is No Direct Causal Relationship Between Coronary Artery Disease and Alzheimer Disease: A Bidirectional Mendelian Randomization Study
title_sort there is no direct causal relationship between coronary artery disease and alzheimer disease a bidirectional mendelian randomization study
topic Alzheimer disease
coronary artery disease
Mendelian randomization
url https://www.ahajournals.org/doi/10.1161/JAHA.123.032814
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