Background: Previous studies present contradictory data concerning obstructive sleep apnea syndrome (OSAS), lipid oxidation and nitric oxide (NO) bioavailability. This study was aimed: (1) to compare the concentration of 8-isoprostane and total nitrate and nitrite (NOx) in plasma of middle aged males with OSAS and no other known comorbidity and carefully matched healthy controls of the same age and gender; and (2) to test the hypothesis that nasal continuous positive airway pressure (CPAP) therapy, might attenuate oxidative stress and nitrate deficiency.

We performed a single-center, prospective, randomized, double-blind, placebo-controlled and cross-over clinical study, in which patients received CPAP and sham therapy for two 12-week periods. Baseline measurements in healthy controls matched for age and gender were also obtained. At recruitment, 24-h blood pressure monitoring (ABPM), an echocardiogram (to rule out any cardiac dysfunction) and a sleep study was obtained in all participants . After fasting overnight, a venous blood sample (anti-coagulated with dipotassium EDTA, for 8-isoprostane and total nitrate and nitrite concentration (NOx) determinations) and a urine sample were collected in all of them between 08:00 and 10:00 hours. Within 30 minutes of blood collection, plasma was obtained by centrifugation at 3000 rpm for 15 min. All plasma samples were stored at -60°C until analysis. Patients with OSAS underwent a full-night CPAP titration study using an automated pressure setting device (Auto Set; ResMed, Sydney, Australia). Compliance with therapy was obtained from a built-in run-time counter. After 12 weeks, CPAP device was switched to the alternate mode of therapy and ABPM,, plasma and urine sampling were repeated in patients

Inclusion Criteria:

• apnea-hypopnea index (AHI) ≥10 h-1
• excessive daytime sleepiness defined by an Epworth scale score ≥11 points
• no treatment for OSAS. Inclusion criteria for healthy control subjects were AHI <5 h-1 and Epworth sleepiness scale <10.

Exclusion Criteria:

• unwillingness or inability to participate in the study
• obstructive or restrictive lung disease as identified by pulmonary function testing
• use of cardioactive drugs
• cardiac rhythm disturbances, including sinus bradycardia and sinus tachycardia
• known arterial hypertension, or 24-hour mean blood pressure of 135 and/or 85 mm Hg or more
• left ventricular ejection fraction <50%, ischemic or valve heart disease, hypertrophic, restrictive or infiltrative cardiomyopathy, pericardial disease or stroke, by history, physical examination, ECG, chest radiography, conventional exercise stress testing, and echocardiography
• diabetes mellitus, by history or 2 random blood glucose levels ≥126 mg/dl
• morbid obesity (body mass index >40 Kg/m2)
• daytime hypoxemia (PaO2 <70 mm Hg) or hypercapnia (PaCO2 >45 mm Hg)
• need to change medication
• hospital admission for 10 or more days
• average nightly CPAP usage less than 3.5 hours.