支气管哮喘与冠心病：一项观察性孟德尔随机研究
2023/11/23
摘要
背景：观察性研究表明，支气管哮喘（以下简称哮喘）是冠状动脉心脏病（以下简称冠心病）的危险因素之一，且性别会影响风险性，但该结果可能受到方法学的限制。
方法：为克服上述问题，本研究采用“三角测量法”，采用多种具有不同潜在偏倚的方法来增强研究结果的可信度。首先，本研究采用英国病历记录进行了一项观察性研究，按年龄、性别和全科医生医疗行为，将哮喘患者与普通人群进行1:1匹配。本研究通过最小充分调整来分析哮喘与冠心病（心肌梗死：住院/死亡）之间的关系：模型1：吸烟、体重指数、是否口服皮质类固醇、变应性和经济情况；模型2：额外调整医疗行为（全科医生咨询频率）。其次，本研究采用来自英国生物库、跨国家哮喘遗传联盟和冠状动脉疾病全基因组复制和荟萃分析联盟的数据进行孟德尔随机（MR）研究。针对64个哮喘SNPs，通过反向方差加权荟萃分析和多效性调整方法评估哮喘对冠心病的影响。
结果：观察性研究（N=1 522 910）发现哮喘与冠心病风险上升（6%）相关（模型1:HR=1.06，95%CI=1.01-1.13），而纳入医疗行为后，未发现任何关联（模型2:HR=0.99，95%CI=0.94-1.05）。哮喘严重程度未改变上述关联，且性别无影响（女性：HR=1.11，95%CI=1.01-1.21；男性：HR=0.91，95%CI=0.84-0.98）。MR研究（N=589875）发现哮喘与冠心病之间无关联（OR=1.01；95%CI=0.98-1.04），且性别无影响。
结论：本研究结果表明，哮喘不是冠心病的危险因素。既往相关研究可能存在检测偏倚或残余混淆。
Asthma and incident coronary heart disease: an observational and Mendelian randomisation study.
Valencia-Hernández CA, Del Greco M F, Sundaram V, Portas L, Minelli C, Bloom CI.
Abstract
BACKGROUND:Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations.
METHODS:To overcome these, we applied a "triangulation approach", where different methodologies, with different potential biases, were leveraged to enhance confidence in findings. First, we conducted an observational study using U.K. medical records to match asthma patients, by age, sex and GP practice, 1:1 to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian Randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium, and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium. Using 64 asthma SNPs, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy.
RESULTS:In our observational study (N=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR=1.06, 95%CI=1.01-1.13), after accounting for healthcare behaviour, we found no association (model 2: HR=0.99, 95% CI=0.94-1.05). Asthma severity did not modify the association, but sex did (females: HR=1.11, 95%CI=1.01-1.21; males: HR=0.91, 95%CI=0.84-0.98). Our MR study (N=589 875) found no association between asthma and CHD (OR=1.01; 95%CI=0.98-1.04) and no modification by sex.
CONCLUSION:Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding.
背景：观察性研究表明，支气管哮喘（以下简称哮喘）是冠状动脉心脏病（以下简称冠心病）的危险因素之一，且性别会影响风险性，但该结果可能受到方法学的限制。
方法：为克服上述问题，本研究采用“三角测量法”，采用多种具有不同潜在偏倚的方法来增强研究结果的可信度。首先，本研究采用英国病历记录进行了一项观察性研究，按年龄、性别和全科医生医疗行为，将哮喘患者与普通人群进行1:1匹配。本研究通过最小充分调整来分析哮喘与冠心病（心肌梗死：住院/死亡）之间的关系：模型1：吸烟、体重指数、是否口服皮质类固醇、变应性和经济情况；模型2：额外调整医疗行为（全科医生咨询频率）。其次，本研究采用来自英国生物库、跨国家哮喘遗传联盟和冠状动脉疾病全基因组复制和荟萃分析联盟的数据进行孟德尔随机（MR）研究。针对64个哮喘SNPs，通过反向方差加权荟萃分析和多效性调整方法评估哮喘对冠心病的影响。
结果：观察性研究（N=1 522 910）发现哮喘与冠心病风险上升（6%）相关（模型1:HR=1.06，95%CI=1.01-1.13），而纳入医疗行为后，未发现任何关联（模型2:HR=0.99，95%CI=0.94-1.05）。哮喘严重程度未改变上述关联，且性别无影响（女性：HR=1.11，95%CI=1.01-1.21；男性：HR=0.91，95%CI=0.84-0.98）。MR研究（N=589875）发现哮喘与冠心病之间无关联（OR=1.01；95%CI=0.98-1.04），且性别无影响。
结论：本研究结果表明，哮喘不是冠心病的危险因素。既往相关研究可能存在检测偏倚或残余混淆。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(Eur Respir J. 2023 Nov 9:2301788. doi: 10.1183/13993003.01788-2023.)
(Eur Respir J. 2023 Nov 9:2301788. doi: 10.1183/13993003.01788-2023.)
Asthma and incident coronary heart disease: an observational and Mendelian randomisation study.
Valencia-Hernández CA, Del Greco M F, Sundaram V, Portas L, Minelli C, Bloom CI.
Abstract
BACKGROUND:Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations.
METHODS:To overcome these, we applied a "triangulation approach", where different methodologies, with different potential biases, were leveraged to enhance confidence in findings. First, we conducted an observational study using U.K. medical records to match asthma patients, by age, sex and GP practice, 1:1 to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian Randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium, and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium. Using 64 asthma SNPs, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy.
RESULTS:In our observational study (N=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR=1.06, 95%CI=1.01-1.13), after accounting for healthcare behaviour, we found no association (model 2: HR=0.99, 95% CI=0.94-1.05). Asthma severity did not modify the association, but sex did (females: HR=1.11, 95%CI=1.01-1.21; males: HR=0.91, 95%CI=0.84-0.98). Our MR study (N=589 875) found no association between asthma and CHD (OR=1.01; 95%CI=0.98-1.04) and no modification by sex.
CONCLUSION:Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding.
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