Lung function and cardiovascular disease: a two-sample Mendelian randomisation study
Lung function and cardiovascular disease: a two-sample Mendelian randomisation study
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DOI：
10.1183/13993003.03196-2020
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发表时间：
2021-09-01
影响因子：
24.3
通讯作者：
Dodd, James W.
中科院分区：
文献类型：
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作者：
Higbee, Daniel H.;Granell, Raquel;Dodd, James W.
背景观察性研究表明，肺功能下降与冠状动脉疾病和缺血性中风的风险之间存在联系，与吸烟等共同的心血管危险因素无关。我们使用最新的遗传流行病学方法来确定肺功能受损是否与心血管疾病风险增加有因果关系。方法和结果孟德尔随机化使用遗传变异作为工具变量来调查因果关系。初步分析使用两个样本孟德尔随机化与肺功能单核苷酸多态性。为了避免碰撞偏倚，主要分析使用了UKBiohank的单核苷酸多态性，在多变量孟德尔随机化模型中对身高、体重指数和吸烟进行了调节。多变量孟德尔随机化显示了强有力的证据表明，用力肺活量（FVC）降低会导致冠状动脉疾病风险增加（OR 1.32，95%CI 1.19-1.46，每个标准差）。1秒用力呼气量（FENT 1）减少不太可能导致冠状动脉疾病风险增加，因为在身高条件化后，其影响的证据变得较弱（OR 1.08，95% CI 0.89-1.30）。有微弱的证据表明，肺功能下降增加缺血性stroke.Conclusion的风险，有强有力的证据表明，减少FVC是独立的和因果关系与冠状动脉疾病。尽管机制尚不清楚，但在评估心血管风险时可考虑FVC，并将其视为减少心血管事件的潜在目标。FEV和气流阻塞似乎不会引起心血管事件的增加;混杂和碰撞偏倚可能解释先前的因果关系研究结果。
Background Observational studies suggest an association between reduced lung function and risk of coronary artery disease and ischaemic stroke, independent of shared cardiovascular risk factors such as cigarette smoking. We use the latest genetic epidemiological methods to determine whether impaired lung function is causally associated with an increased risk of cardiovascular disease.Methods and findings Mendelian randomisation uses genetic variants as instrumental variables to investigate causation. Preliminary analysis used two-sample Mendelian randomisation with lung function single nucleotide polymorphisms. To avoid collider bias, the main analysis used single nucleotide polymorphisms for lung function identified from UKBiohank in a multivariable Mendelian randomisation model conditioning for height, body mass index and smoking.Multivariable Mendelian randomisation shows strong evidence that reduced forced vital capacity (FVC) causes increased risk of coronary artery disease (OR 1.32, 95% CI 1.19-1.46 per standard deviation). Reduced forced expiratory volume in 1 s (FENT1) is unlikely to cause increased risk of coronary artery disease, as evidence of its effect becomes weak after conditioning for height (OR 1.08, 95% CI 0.89-1.30). There is weak evidence that reduced lung function increases risk of ischaemic stroke.Conclusion There is strong evidence that reduced FVC is independently and causally associated with coronary artery disease. Although the mechanism remains unclear, FVC could be taken into consideration when assessing cardiovascular risk and considered a potential target for reducing cardiovascular events. FEV, and airflow obstruction do not appear to cause increased cardiovascular events; confounding and collider bias may explain previous findings of a causal association.