Lung Function and Coronary Artery Disease Risk
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Observational studies have consistently shown associations between impaired lung function and increased risk of coronary artery disease (CAD) that persist after adjustment for possible confounders, such as height, smoking, and age.1,2 Evidence of a causal effect of lung function on CAD risk could have implications for cardiovascular prevention. Smoking is a leading modifiable cause of reduced lung function, and evidence of causality would further strengthen the public health antismoking message, particularly because the noncancer-related harmful effects of even low-volume cigarette smoking have only recently gained attention.3 Apart from its direct cardiovascular benefits, regular physical activity might also contribute to maintaining healthy lung function,4 and the potential added cardiovascular health benefits could be an additional incentive to motivate the public for regular physical exercise.
Establishing causality in observational studies is problematic because of bias from confounding and reverse causation.5 Impaired lung function might increase cardiovascular risk through, for example, raised inflammation, ventilation–perfusion mismatch, or impaired toxic waste removal. The association could, on the contrary, also be driven by reverse causation, where (initially asymptomatic) cardiovascular disease worsens lung function, perhaps because of physical weakness or inadequate pulmonary circulation. Yet a third mechanism linking CAD and lung function might be confounding from factors such as height, which is associated with increased lung function and lower cardiovascular risk,6 or from smoking, which is related to impaired lung function and raised cardiovascular risk.3
In epidemiology, prospective studies with randomization to exposures followed by sufficient follow-up to record outcome events are difficult to implement, as evident in the case of lung function. Mendelian randomization (MR) analysis provides a strategy to obtain causal estimates in epidemiological settings in the absence of …