Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Roflumilast on Endothelial Function in Patients With Chronic Obstructive Pulmonary Disease

Inclusion Criteria: * Signed informed consent * 55-75 years of age * Current and former smokers \>20 cigarettes pack-yr (if former smokers withdrawn \>1 year) * Diagnosis COPD (GOLD criteria1 for more than a year before V0) * Presence of chronic bronchitis (cough and/or expectoration for more that 3 months/yr for more than 2 consecutive yrs. in the absence of other potential cause) * Post-bronchodilator FEV1\<70% reference * Presence of established CVD, CVD equivalent or diabetes mellitus * Presence of chronic systemic inflammation, determined on: 1. Serum CRP ≥ 2 and \< 10 mg/l or 2. Serum fibrinogen \> 518 mg/dl and Leucocytes \> 8,6\*106 /mm3 Exclusion Criteria: * Episode of COPD exacerbation and/or COPD treatment change during the last 2 months before V0 * History of asthma, significant residual lung lesions or bronchiectasis on chest x-ray * Apnea-hypopnea syndrome * Poorly controlled CVD risk factors (Table 2) and/or change in their treatment during the last 3 months before V0 * Clinically significant cardiac arrhythmias or valve disease * Severe concomitant immunological, inflammatory, infectious or neoplastic diseases * Moderate or severe hepatic insufficiency (B or C class, following Child-Pugh scale) * Severe neurologic and/or psychiatric disorder, including depression with suicidal ideas * Alcohol and/or drug abuse during the last 12 months before V0 * Hypersensitivity to roflumilast or to any of its excipients * Pregnancy or potential pregnancy * Participation in other clinical trial during the last 30 days before V0 * Language difficulties to follow the instructions of the study