Obstructive sleep apnoea syndrome (OSAS) causes nocturnal chronic intermittent hypoxia (IH) that contributes to excess cardiovascular morbidity. To explore the consequences of IH, we used our recently developed model of nocturnal IH in healthy humans to characterise the profile of this blood pressure increase, to determine if it is sustained and to explore potential physiological mechanisms.We performed 24-h ambulatory monitoring of blood pressure in 12 healthy subjects before and after 2 weeks of IH exposure. We also assessed systemic haemodynamics, muscle sympathetic nerve activity (MSNA), ischaemic calf blood flow responses and baroreflex gain. We obtained blood samples for inflammatory markers before, during and after exposure. IH significantly increased daytime ambulatory blood pressure after a single night of exposure (3 mmHg for mean and diastolic) and further increased daytime pressures after 2 weeks of exposure (8 mmHg systolic and 5 mmHg diastolic). Mean±sdMSNA increased across the exposure (17.2±5.1versus21.7±7.3 bursts·min⁻¹; p<0.01) and baroreflex control of sympathetic outflow declined from -965.3±375.1 to -598.4±162.6 AIU·min⁻¹·mmHg⁻¹(p<0.01). There were no evident changes in either vascular reactivity or systemic inflammatory markers.These data are the first to show that the arterial pressure rise is sustained throughout the waking hours beyond the acute phase immediately after exposure. Moreover, they may suggest that sympathoactivation induced by IH likely contributes to blood pressure elevation and may derive from reduced baroreflex inhibition. These mechanisms may reflect those underlying the blood pressure elevation associated with OSAS.

Rationale: Randomized controlled trials (RCTs) have shown that continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA) reduces blood pressure (BP). CPAP treatment has never been compared with antihypertensive medications in an RCT. Objectives: To assess the respective efficacy of CPAP and valsartan in reducing BP in hypertensive patients with OSA never treated for either condition. Methods: In this 8-week randomized controlled crossover trial, 23 hypertensive patients (office systolic BP/diastolic BP: 155 ± 14/102 ± 11 mm Hg) with OSA (age, 57 ± 8 yr; body mass index, 28 ± 5 kg/m2; apnea–hypopnea index, 29 ± 18/h) were randomized first to either CPAP or valsartan (160 mg). The second 8-week period consisted of the alternative treatment (crossover) after a 4-week washout period. Measurements and Main Results: Office BP and 24-hour BP were measured before and at the end of the two active treatment periods. Twenty-four–hour mean BP was the primary outcome variable. There was an overall significant difference in 24-hour mean BP between treatments: the change in 24-hour mean BP was −2.1 ± 4.9 mm Hg (P < 0.01) with CPAP, and −9.1 ± 7.2 mm Hg with valsartan (P < 0.001), with a difference of −7.0 mm Hg (95% confidence interval, −10.9 to −3.1 mm Hg; P < 0.001). The difference was significant not only during daytime but also during nighttime: the change in nighttime mean BP with CPAP was −1.3 ± 4.6 mm Hg (not significant), and −7.4 ± 8.4 mm Hg with valsartan (P < 0.001), with a difference of −6.1 mm Hg (P < 0.05) (95% confidence interval, −10.8 to −1.4 mm Hg). Conclusions: In an RCT, although the BP decrease was significant with CPAP treatment, valsartan induced a fourfold higher decrease in mean 24-hour BP than CPAP in untreated hypertensive patients with OSA. Clinical trial registered with www.clinicaltrials.gov (NCT00409487).

Summary: Hypoxic brain damage might explain persistent sleepiness in some continuous positive airway pressure‐compliant obstructive sleep apnea called residual excessive sleepiness. Although continuous positive airway pressure may not be fully efficient in treating this symptom, wake‐promoting drug prescription in residual excessive sleepiness is no longer allowed by the European Medicines Agency. The aim of this study is to describe residual excessive sleepiness phenotypes in a large prospective sample of patients with obstructive sleep apnea. Residual excessive sleepiness was defined by an Epworth Sleepiness Scale score ≥ 11. Eligible patients from the French National Sleep Registry attending follow‐up continuous positive airway pressure visits numbered 1047. Patients using continuous positive airway pressure < 3 h (n = 275), with residual apnea–hypopnea index > 15 h⁻¹ (n = 31) or with major depression were excluded (n = 150). Residual excessive sleepiness prevalence in continuous positive airway pressure‐treated obstructive sleep apnea was 13% (18% for those with an initial Epworth Sleepiness Scale score > 11), and significantly decreased with continuous positive airway pressure use (9% in ≥ 6 h night⁻¹ continuous positive airway pressure users, P < 0.005). At the time of diagnosis, patients with residual excessive sleepiness had worse subjective appreciation of their disease (general health scale, Epworth Sleepiness Scale and fatigue score), and complained more frequently of continuous positive airway pressure side‐effects. Residual excessive sleepiness prevalence was lower in severe obstructive sleep apnea than in moderate obstructive sleep apnea (11% when AHI > 30 h⁻¹ versus 18% when AHI 15–30, P < 0.005). There was no relationship between residual excessive sleepiness and body mass index, cardiovascular co‐morbidities or diabetes. Continuous positive airway pressure improved symptoms in the whole population, but to a lower extent in patients with residual excessive sleepiness (fatigue scale: −5.2 versus −2.7 in residual excessive sleepiness− and residual excessive sleepiness+ patients, respectively, P < 0.001). Residual excessive sleepiness prevalence decreased with continuous positive airway pressure compliance. Hypoxic insult is unlikely to explain residual excessive sleepiness as obstructive sleep apnea severity does not seem to be critical. Residual symptoms are not limited to sleepiness, suggesting a true ‘continuous positive airway pressure‐resistant syndrome’, which may justify treatment by wake‐promoting drugs.

Study Objectives:. The American Academy of Sleep Medicine (AASM) guidelines for polysomnography (PSG) scoring are increasingly being adopted worldwide,

There are three major types of sleep-disordered breathing (SDB) with respect to prevalence and health consequences,i.e.obstructive sleep apnoea syndrome (OSAS), Cheyne–Stokes respiration and central sleep apnoea (CSR-CSA) in chronic heart failure, and obesity hypoventilation syndrome (OHS). In all three conditions, hypoxia appears to affect body functioning in different ways. Most of the molecular and cellular mechanisms that occur in response to SDB-related hypoxia remain unknown.In OSAS, an inflammatory cascade mainly dependent upon intermittent hypoxia has been described. There is a strong interaction between haemodynamic and inflammatory changes in promoting vascular remodelling. Moreover, during OSAS, most organ, tissue or functional impairment is related to the severity of nocturnal hypoxia. CSR-CSA occurring during heart failure is primarily a consequence of cardiac impairment. CSR-CSA has deleterious consequences for cardiac prognosis and mortality since it favours sympathetic activation, ventricular ectopy and atrial fibrillation. Although correction of CSR-CSA seems to be critical, there is a need to establish therapy guidelines in large randomised controlled trials.Finally, OHS is a growing health concern, owing to the worldwide obesity epidemic and OHS morbidities. The pathophysiology of OHS remains largely unknown. However, resistance to leptin, obesity and severe nocturnal hypoxia lead to insulin resistance and endothelial dysfunction. In addition, several adipokines may be triggered by hypoxia and explain, at least in part, OHS morbidity and mortality.Overall, chronic intermittent hypoxia appears to have specific genomic effects that differ notably from continuous hypoxia. Further research is required to fully elucidate the molecular and cellular mechanisms.