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.

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 UKBiobank 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 (FEV₁) 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.

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. FEV₁ and airflow obstruction do not appear to cause increased cardiovascular events; confounding and collider bias may explain previous findings of a causal association.

观察性研究表明，肺功能降低与冠状动脉疾病和缺血性中风的风险之间存在关联，与吸烟等共同的心血管风险因素无关。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。

孟德尔随机化使用遗传变异作为工具变量来研究因果关系。初步分析使用具有肺功能单核苷酸多态性的两样本孟德尔随机化。为避免对撞机偏差，主要分析使用了从 UKBiobank 确定的肺功能单核苷酸多态性，在多变量孟德尔随机模型中对身高、体重指数和吸烟进行调节。

多变量孟德尔随机化显示强有力的证据表明，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/标准差）。减少 1 秒用力呼气量 (FEV ₁ ) 不太可能导致冠状动脉疾病的风险增加，因为其影响的证据在调整身高后变得微弱 (OR 1.08, 95% CI 0.89–1.30)。有微弱的证据表明肺功能下降会增加缺血性中风的风险。

有强有力的证据表明，FVC 降低与冠状动脉疾病独立且因果相关。尽管机制尚不清楚，但在评估心血管风险时可以考虑 FVC，并被认为是减少心血管事件的潜在目标。FEV ₁和气流阻塞似乎不会导致心血管事件增加；混杂和对撞机偏差可以解释以前的因果关系发现。