Systemic Vascular Dysfunction in Patients with Mild Chronic Obstructive Pulmonary Disease

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular disease, a finding that might be mechanistically linked to systemic vascular abnormalities. In fact, coexistent cardiovascular disease is a major cause of disability and death in COPD patients with only mild airflow obstruction. It remains unknown however whether these patients may present with systemic vascular dysfunction. Moreover, it remains unclear whether specific lung structural abnormalities (i.e., emphysema versus airway disease) would be associated with greater systemic vascular dysfunction. We hypothesized that patients with mild COPD, particularly those with larger emphysema burden, would present with abnormalities in systemic vascular function compared to controls. Methods: In an observational and prospective study, we measured central and peripheral pulse wave velocity (PWV), flow mediated dilation (FMD) of the brachial artery, systemic levels of plasma interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) in 16 COPD patients (FEV1=8613 % predicted) and 16 age- and gender-matched sedentary controls. Emphysema and airway disease burden were quantified by chest computed tomography in patients. Results: Patients and controls were well-matched by comorbidities burden, including cardiovascular disease. Patients presented with greater central aortic stiffness (aPWV=9.571.39m/s versus 7.741.30m/s; p=0.002) but preserved peripheral arterial compliance (p =0.43) compared to controls. Patients had impaired shear rate-corrected FMD (- 1.86-fold; p=0.03) and delayed maximum vasodilatory response (-16.5 s; p<0.01). Emphysema extent (but not airway disease) and lung transfer factor for carbon monoxide (DLCO) were significantly related to higher central arterial stiffness and both impaired and slowed flow-mediated dilation of the brachial artery (r values ranging from 0.50 to 0.66; p<0.05). Conclusion: Systemic vascular dysfunction is present in patients with mild COPD, particularly in patients with greater emphysema burden and low DLCO. These patients might be at higher risk of negative cardiovascular events thereby deserving more detailed screening and closer longitudinal follow-up.