Background— The purpose of this study was to determine the role of obstructive sleep apnea syndrome (OSAS) as an independent risk factor for the development of left ventricular diastolic abnormalities. Moreover, we tested the hypothesis that nasal continuous positive airway pressure (nCPAP) improves such alterations in OSAS patients by eliminating apneic events. Methods and Results— In this prospective, randomized, placebo-controlled, double-blind crossover study, 27 consecutive newly diagnosed middle-aged OSAS men with neither controllable factors nor conditions affecting left ventricular diastolic function and 15 healthy control subjects were selected. OSAS patients were randomized to 12 weeks on sham nCPAP and 12 weeks on effective nCPAP application. Echocardiographic parameters, blood pressure recordings, and urinary catecholamine levels were obtained at baseline and after both treatment modalities. At baseline, an abnormal left ventricular filling pattern was present in 15 of the 27 OSAS patients and only in 3 of the 15 control subjects ( P =0.020). Impaired relaxation was by far the most common abnormal pattern in both groups (11 and 3 patients, respectively). In OSAS patients, 12 weeks on effective nCPAP induced a significant increase in E/A ratio ( P <0.01), as well as reductions in mitral deceleration ( P <0.01) and isovolumic relaxation ( P <0.05) times. Conclusions— OSAS can affect left ventricular diastolic function independently of other possible factors. Chronic application of nCPAP could avoid the progression of diastolic abnormalities, and indeed, it might reverse these alterations, at least in the initial stages before severe structural changes can be developed.

Aims We tested the hypothesis that: (i) obstructive sleep apnoea (OSA) by itself originates pulmonary hypertension (PH); and (ii) the application of continuous positive airway pressure (CPAP) can reduce pulmonary pressure. Methods and results In this randomized and cross-over trial, 23 middle-aged OSA (apnoea–hypopnoea index, 44.1±29.3 h⁻¹) and otherwise healthy patients and 10 control subjects were included. OSA patients randomly received either sham or effective CPAP for 12 weeks. Echocardiographic parameters, blood pressure recordings, and urinary catecholamine levels were obtained at baseline and after both treatment modalities. At baseline, OSA patients had higher pulmonary artery systolic pressure than control subjects (29.8±8.8 vs. 23.4±4.1 mmHg, respectively, P=0.036). Ten out of 23 patients [43%, (95% CI: 23–64%)] and none of the control subjects had PH at baseline (P=0.012). Two patients were removed from the study because of inadequate CPAP compliance. Effective CPAP induced a significant reduction in the values for pulmonary systolic pressure (from 28.9±8.6 to 24.0±5.8 mmHg, P<0.0001). The reduction was greatest in patients with either PH or left ventricular diastolic dysfunction at baseline. Conclusion Severe OSA is independently associated with PH in direct relationship with disease severity and presence of diastolic dysfunction. Application of CPAP reduces pulmonary systolic pressure levels.

Background: Previous studies have presented contradictory data concerning obstructive sleep apnoea syndrome (OSAS), lipid oxidation and nitric oxide (NO) bioavailability. This study was undertaken to (1) compare the concentration of 8-isoprostane and total nitrate and nitrite (NOx) in plasma of middle-aged men with OSAS and no other known co-morbidity and healthy controls of the same age, gender and body mass index; and (2) test the hypothesis that nasal continuous positive airway pressure (CPAP) therapy attenuates oxidative stress and nitrate deficiency. Methods: A prospective, randomised, placebo controlled, double-blind, crossover study was performed in 31 consecutive middle-aged men with newly diagnosed OSAS and 15 healthy control subjects. Patients with OSAS were randomised to receive sham CPAP or effective CPAP for 12 weeks. Blood pressure, urinary catecholamine levels and plasma 8-isoprostane and NOx concentrations were obtained before and after both treatment modalities. Results: Patients with OSAS had significantly higher 8-isoprostane levels (median (IQR) 42.5 (29.2–78.2) vs 20.0 (12.5–52.5) pg/ml, p = 0.041, Mann-Whitney test) and lower NOx levels (264 (165–650) vs 590 (251–1465) μmol/l, p = 0.022) than healthy subjects. Body mass index, blood pressure and urinary catecholamines were unchanged by CPAP therapy, but 8-isoprostane concentrations decreased (38.5 (24.2–58.7) pg/ml at baseline vs 22.5 (16.2–35.3) pg/ml on CPAP, p = 0.0001) and NOx levels increased (280 (177–707) vs 1373 (981–1517) μmol/l, p = 0.0001) after CPAP. Conclusions: OSAS is associated with an increase in oxidative stress and a decrease in NOx that is normalised by CPAP therapy.

There is increasing evidence that inflammation plays an important role in the development of cardiovascular complications in patients with obstructive sleep apnoea (OSA).No previous works have studied levels of soluble tumour necrosis factor-α receptor (sTNFR)-1 in patients with OSA. The aims of the present study were to examine serum levels of sTNFR-1 and the effect of nasal continuous positive airway pressure (CPAP) in patients with OSA.A prospective, randomised, placebo-controlled crossover study was performed. In total, 30 consecutive newly diagnosed OSA patients (apnoea/hypopnoea index 43.8±27.0 events·h⁻¹) and 15 healthy obese patients were selected. Urinary levels of norepinephrine and epinephrine, as well as plasma sTNFR-1, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and leukotriene (LT)B₄levels were obtained at baseline and after 3 months of CPAP or sham CPAP.Nocturnal urinary levels of norepinephrine, epinephrine and sTNFR-1 (1,053±269versus820±166 pg·mL⁻¹) were significantly higher in OSA patients. There were no significant differences in plasma levels of IL-6, LTB₄, or TNF-α between the two study groups. There were no significant differences in blood pressure, urinary catecholamine levels, or plasma IL-6, LTB₄and TNF-α levels after both treatment modalities. However, after 3 months of effective CPAP usage, sTNFR-1 levels were significantly reduced (1,053±269versus899±254 pg·mL⁻¹).Obstructive sleep apnoea patients have higher levels of soluble tumour necrosis factor-α receptor 1 than individuals without OSA; soluble tumour necrosis factor-α receptor 1 levels are lowered by continuous positive airway pressure therapy. These findings further corroborate a potential role of inflammation in the natural history of obstructive sleep apnoea.