Association Between Systemic and Pulmonary Vascular Dysfunction in COPD

Lucilla Piccari,1 Roberto Del Pozo,1 Isabel Blanco,1,2 Jessica García-Lucio,1 Yolanda Torralba,1,2 Olga Tura-Ceide,1,2 Jorge Moises,1,2 Marta Sitges,3,4 Víctor Ivo Peinado,1,2 Joan Albert Barberà1,2 1Department of Pulmonary Medicine, Hospital Clínic, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; 2Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), Madrid, Spain; 3Department of Cardiology, Hospital Clínic, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Barcelona, Spain; 4Biomedical Research Networking Centre on Cardiovascular Diseases (CIBERCV), Madrid, SpainCorrespondence: Joan Albert BarberàDepartment of Pulmonary Medicine, Hospital Clínic, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), University of Barcelona, Villarroel 170, Barcelona 08036, SpainTel +34 932275779Email jbarbera@clinic.catIntroduction: In chronic obstructive pulmonary disease (COPD), endothelial dysfunction and stiffness of systemic arteries may contribute to increased cardiovascular risk. Pulmonary vascular disease (PVD) is frequent in COPD. The association between PVD and systemic vascular dysfunction has not been thoroughly evaluated in COPD.Methods: A total of 108 subjects were allocated into four groups (non-smoking controls, smoking controls, COPD without PVD and COPD with PVD). In systemic arteries, endothelial dysfunction was assessed by flow-mediated dilation (FMD) and arterial stiffness by pulse wave analysis (PWA) and pulse wave velocity (PWV). PVD was defined by a mean pulmonary artery pressure (PAP) ≥ 25 mmHg at right heart catheterization or by a tricuspid regurgitation velocity > 2.8 m/s at doppler echocardiography. Biomarkers of inflammation and endothelial damage were assessed in peripheral blood.Results: FMD was lower in COPD patients, with or without PVD, compared to non-smoking controls; and in patients with COPD and PVD compared to smoking controls. PWV was higher in COPD with PVD patients compared to both non-smoking and smoking controls in a model adjusted by age and the Framingham score; PWV was also higher in patients with COPD and PVD compared to COPD without PVD patients in the non-adjusted analysis. FMD and PWV correlated significantly with forced expiratory volume in the first second (FEV1), diffusing capacity for carbon monoxide (DLCO) and systolic PAP. FMD and PWV were correlated in all subjects.Discussion: We conclude that endothelial dysfunction of systemic arteries is common in COPD, irrespective if they have PVD or not. COPD patients with PVD show increased stiffness and greater impairment of endothelial function in systemic arteries. These findings suggest the association of vascular impairment in both pulmonary and systemic territories in a subset of COPD patients.Keywords: COPD, pulmonary circulation and pulmonary hypertension, emphysema, cardiovascular diseases