Background Alpha 1 Antitrypsin Deficiency (AATD) is a rare, inherited lung disease which shares features with Chronic Obstructive Pulmonary Disease (COPD) but has a greater burden of proteinase related tissue damage. These proteinases are associated with cardiovascular disease (CVD) in the general population. It is unclear whether patients with AATD have a greater risk of CVD compared to usual COPD, how best to screen for this, and whether neutrophil proteinases are implicated in AATD-associated CVD. This study had three aims. To compare CVD risk in never-augmented AATD patients to non-AATD COPD and healthy controls (HC). To assess relationships between CVD risk and lung physiology. To determine if neutrophil proteinase activity was associated with CVD risk in AATD. Cardiovascular risk was assessed by QRISK2® score and aortic stiffness measurements using carotid-femoral (aortic) pulse wave velocity (aPWV). Medical history, computed tomography scans and post-bronchodilator lung function