8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may compromise oxidative balance. Oxidative stress is increased in the blood and in the airways of OSA patients. DESIGN: The aim of this study was to investigate whether oxidative stress is determined by nocturnal apneas and could be reduced by CPAP therapy, and whether there is a relation between local and systemic oxidative stress in these patients. PATIENTS AND METHODS: Eighteen patients with OSA (13 men; mean [+/- SD] age, 48 +/- 3 years) and 12 healthy age-matched and weight-matched subjects (8 men; mean age, 46 +/- 7 years) were recruited. 8-Isoprostane was measured in exhaled breath condensate and blood by a specific enzyme immunoassay. Measurements and results: Higher concentrations of 8-isoprostane were found in the morning exhaled condensate (9.5 +/- 1.9 pg/mL) and plasma (9.7 +/- 1.5 pg/mL) of OSA patients compared to healthy obese subjects (6.7 +/- 0.2 and 7.1 +/- 0.3 pg/mL, respectively; p < 0.0001). Elevated mean concentrations of exhaled 8-isoprostane were observed in the OSA patients at 8:00 AM (9.5 +/- 1.9 pg/mL) but not at 8:00 PM (7.6 +/- 0.8 pg/mL; p < 0.0005), and a significant reduction was seen after continuous positive airway pressure (CPAP) therapy (7.7 +/- 0.9 pg/mL; before treatment, 9.6 +/- 1.7 pg/mL; p < 0.005). A positive correlation was found between morning exhaled 8-isoprostane levels and the apnea-hypopnea index (r = 0.8; p < 0.0001), and 8-isoprostane levels and neck circumference (r = 0.6; p < 0.0001). CONCLUSIONS: These findings suggest that systemic and local oxidative stress are increased in OSA patients, and that they are higher after nocturnal apnea and reduced by CPAP therapy.     

Sympathetic activity is reduced by nCPAP in hypertensive obstructive sleep apnoea patients.

There is increasing evidence that nasal continuous positive airway pressure (nCPAP) lowers blood pressure in obstructive sleep apnoea (OSA) patients, not only during sleep but also in the daytime. However, both the mechanisms of blood pressure reduction and the considerable differences in the magnitude of the effect in the studies presented to date are not fully understood. Therefore, the authors prospectively studied the effect of nCPAP on noradrenaline plasma levels (NApl), blood pressure and heart rate (HR) in 10 normotensive and eight hypertensive OSA patients before and after 41.6 +/- 16.9 days of nCPAP therapy. Polysomnography and invasive blood pressure were continuously monitored over 24 h in the supine position before and with nCPAP. NApl were analysed every 15 min. In hypertensives, nCPAP reduced NApl by 36 +/- 25%, lowered mean arterial blood pressure substantially (night-time: -8.89 +/- 14.09 mmHg; daytime: -7.94 +/- 10.47 mmHg) and decreased HR by 6.6 +/- 5.4 beats x min(-1), whereas in normotensives there were only minor changes. The decrease in heart rate was associated with a decrease in mean arterial blood pressure and noradrenaline plasma levels, suggesting a causal effect of nasal continuous positive airway pressure therapy. This nasal continuous positive airway pressure effect occurs mainly in hypertensive obstructive sleep apnoea patients, whereas the effect is small in normotensives. This may explain, at least in part, some of the discrepant results in previous treatment studies.     

Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex.

This study was undertaken to determine whether abolition of obstructive sleep apnoea (OSA) by continuous positive airway pressure (CPAP) could reduce blood pressure (BP) in patients with refractory hypertension. In 11 refractory hypertensive patients with OSA, the acute effects of CPAP on nocturnal BP were studied during sleep and its longer term effects on 24-h ambulatory BP after 2 months. During a single night's application, CPAP abolished OSA and reduced systolic BP in stage 2 sleep from 138.3 +/- 6.8 to 126.0 +/- 6.3 mmHg. There was also a trend towards a reduction in average diastolic BP (from 77.7 +/- 4.5 to 72.9 +/- 4.5). CPAP usage for 2 months was accompanied by an 11.0 +/- 4.4 mmHg reduction in 24-h systolic BP. In addition, both the nocturnal and daytime components of systolic BP fell significantly by 14.4 +/- 4.4 and 9.3 +/- 3.9 mmHg, respectively. Diastolic BP was reduced significantly at night by 7.8 +/- 3.0 mmHg. In patients with refractory hypertension, acute abolition of obstructive sleep apnoea by continuous positive airway pressure reduces nocturnal blood pressure. These data also suggest that continuous positive airway pressure may reduce nocturnal and daytime systolic blood pressure chronically. Randomised trials are needed to confirm the latter results.     

Impact of CPAP on asthmatic patients with obstructive sleep apnoea.

The impact of continuous positive airway pressure (CPAP) treatment on the airway responsiveness of asthmatic subjects with obstructive sleep apnoea (OSA) has scarcely been studied. A prospective study was performed comparing the changes in airway responsiveness and quality of life in stable asthmatic OSA patients, before and 6 weeks after their nocturnal CPAP treatment. A total of 20 subjects (11 males and nine females) participated in the study. With the nocturnal CPAP treatment, the apnoea/hypopnoea index dropped from 48.1 +/- 23.6 x h(-1) to 2.6 +/- 2.5 x h(-1). There were no significant changes in airway responsiveness after CPAP treatment (provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV(1); PC(20) 2.5 mg x mL(-1) (1.4-4.5)) compared with baseline (PC(20) 2.2 mg x mL(-1) (1.3-3.5)). There was no significant change in FEV(1) either. However, the asthma quality of life of the subjects improved from 5.0 +/- 1.2 at baseline to 5.8 +/- 0.9 at the end of the study. In conclusion, nocturnal continuous positive airway pressure treatment did not alter airway responsiveness or forced expiratory volume in one second in subjects with stable mild-to-moderate asthma and newly diagnosed obstructive sleep apnoea. However, nocturnal continuous positive airway pressure treatment did improve asthma quality of life.     

Reduced larger von Willebrand factor multimers at dawn in OSA plasmas reflect severity of apnoeic episodes

Plasma von Willebrand factor (VWF), produced in and released from vascular endothelial cells by various stimuli including hypoxia, induces platelet aggregation under high shear stress and plays dual pivotal roles in haemostasis and thrombosis within arterioles, which are regulated by the size of vWF multimers (VWFMs). Patients with obstructive sleep apnoea (OSA) have increased risk of thrombotic cardiovascular events, but the pathogenesis is unclear. We examined the relationship between VWF and OSA by measuring VWF antigen (VWF:Ag), VWFMs, VWF collagen binding activity (VWF:CB) and a disintegrin-like, metalloproteinase, and thrombospiondin type 1 motifs 13. A total of 58 OSA patients were enrolled. Blood samples were collected before sleep, after sleep, and after one night of nasal continuous positive airway pressure therapy. Based on VWFM analysis, OSA patients were classified into three groups; consistently normal VWFMs (group 1, n=29), increased high molecular weight (HMW)-VWFMs at 06:00 h (group 2, n=18), and decreased or absent HMW-VWFMs at 06:00 h (group 3, n=11). Patients in group 3 had significantly worse apnoea/hypopnoea index; VWF:CB followed a similar pattern. We observed a significant decrease in platelet count between 21:00 h and 06:00 h in OSA patients, potentially associated with reduced larger VWFMs together with decreased VWF:Ag levels. Severe OSA may contribute to an arterial pro-thrombotic state.     

Efficacy of flow- vs impedance-guided autoadjustable continuous positive airway pressure: a randomized cross-over trial

STUDY OBJECTIVES: Autoadjustable continuous positive airway pressure (CPAP) devices are increasingly used in the treatment of obstructive sleep apnea (OSA). Since different measurements of upper airway obstruction are applied, it is uncertain whether these devices are equally effective in controlling sleep-disordered breathing. Hypothesizing that differences in therapeutic efficacy were to come out, we compared the performance of the AutoSet device (ResMed; Sydney, Australia), which features autoadjustable positive airway pressure (APAP) guided by detection of flow limitation (APAPfl), with the SOMNOsmart device (Weinmann; Hamburg, Germany), which features APAP guided by the forced oscillation technique (APAPfot). DESIGN: A double-blind, randomized, cross-over trial. SETTING: The sleep disorders center and sleep laboratory of a university hospital. PATIENTS AND INTERVENTIONS: An overnight CPAP autotitration procedure was performed in 30 patients with OSA. A split-night protocol allowed that each patient used both devices. MEASUREMENTS AND RESULTS: Using polysomnography, sleep, indexes of sleep-disordered breathing, snoring, and CPAP levels were recorded. No significant differences were found in conventional sleep variables. While the apnea-hypopnea index (AHI) was lower with APAPfl (3.5 +/- 5.6/h) as compared to APAPfot (9.9 +/- 31.0/h), the difference was not statistically significant (mean +/- SD). The snoring index, however, was significantly lower with APAPfl (35.3 +/- 53.7/h vs 111.6 +/- 175.4/h, respectively; p = 0.01). The median and 95th percentile pressure levels rose from wakefulness to sleep in APAPfl, but decreased in APAPfot. Higher pressure variability was present in the latter method. CONCLUSIONS: These findings suggest that the APAPfl is superior to APAPfot in the control of snoring. While a lower AHI was achieved with APAPfl, at the expense of a higher median pressure but less pressure variability, the difference with APAPfot was not statistically significant.     

Use of heated humidification during nasal CPAP titration in obstructive sleep apnoea syndrome.

Nasal symptoms associated with the use of nasal continuous positive airway pressure (nCPAP) in obstructive sleep apnoea (OSA) can adversely impact on patients' tolerance, acceptance and adherence to nCPAP therapy. Regular use of heated humidification is effective in alleviating these symptoms and improve patient comfort. In a randomised, parallel, double-blinded, controlled study, the present authors examined the use of heated humidification during a single night laboratory nCPAP titration in untreated OSA patients and its effect on nasal symptoms, nasal airway resistance (NAR), effective pressure and treatment tolerability and acceptance. Baseline characteristics of subjects (n=70) receiving placebo and humidification were (mean+/-sem): age 51.2+/-2.2 versus 50.6+/-1.6 yrs; body mass index 33.6+/-0.9 versus 35.2+/-0.9 kg.m-2; Epworth Sleepiness Scale 10.8+/-1.0 versus 11.3+/-0.7; and apnoea-hypopnoea index 43.5+/-4.6 versus 44.4+/-4.1 events.h-1. Total inspiratory NAR, before (0.36+/-0.09 (placebo) versus 0.33+/-0.09 kPa.L-1.s-1) and after nCPAP (0.47+/-0.11 versus 0.29+/-0.04 kPa.L-1.s-1) were not significantly different between the groups. No difference was found in the frequency and severity of nasopharyngeal symptoms, therapeutic pressure and subjective response to nCPAP. In conclusion, heated humidification during the initial nasal continuous positive airway pressure titration offers no additional benefit in nasal physiology, symptoms or subjective response to nasal continuous positive airway pressure, and, therefore, should not be routinely recommended.     

Obstructive sleep apnoea and its therapy influence high-density lipoprotein cholesterol serum levels.

Recent studies suggest an association of obstructive sleep apnoea (OSA) with cardiovascular risk factors, such as dyslipidaemia. The present study analyses the effects of OSA and its therapy on serum lipid concentrations in 470 OSA patients in a single centre study. Multivariate regression showed a significant association between the apnoea-hypopnoea index and high-density lipoprotein cholesterol (HDL-C) serum levels (n = 366), independent of age, sex, body mass index, diabetes and lipid lowering medication. There were no independent associations with total cholesterol, triglyceride and low-density lipoprotein cholesterol serum levels. During follow-up (6 months) with effective bilevel or continuous positive airway pressure therapy in 127 patients (lipoproteins: n = 86) without change in their lipid lowering therapy, the mean HDL-C serum level increased significantly by 5.8% from 46.9+/-15.8 to 49.6+/-15.3 mg x dL(-1) (mean+/-SD). An independent relationship was found between the change of apnoea-hypopnoea index and the change of high-density lipoprotein cholesterol or triglycerides, respectively. All patients with abnormal serum lipid/lipoprotein levels improved significantly under bilevel or continuous positive airway pressure therapy. This study demonstrates an influence of obstructive sleep apnoea and its therapy on high-density lipoprotein cholesterol levels.     

Platelet function in patients with obstructive sleep apnoea syndrome.

Patients with obstructive sleep apnoea syndrome (OSAS) are subject to an increased cardiovascular morbidity including myocardial infarction and stroke. Platelets play an important role in the pathogenesis and triggering of acute cardiovascular syndromes. So far, the influence of OSAS on platelet function is not fully understood. Platelet aggregability to epinephrine, collagen, arachidonic acid, and adenosine diphosphate in vitro was measured in 17 consecutive male patients (53.0+/-2.1 yrs) with polysomnographically verified OSAS and compared with that of 15 male controls (50.1+/-3.6 yrs) at 20:00 h, 24:00 h, and 06:00 h. In addition, the long-term effects of continuous positive airway pressure (CPAP) therapy on platelet aggregability was assessed after 6 months. Platelet aggregation in vitro induced by epinephrine showed a slight increase overnight in the untreated OSAS patients (NS) whereas it decreased slightly (NS) in the controls and in the treated OSAS patients. Pretherapeutic platelet aggregability was significantly lowered by CPAP therapy both at 24:00 h (64.0+/-6.5 versus 55.3+/-6.7%, p<0.05) and at 06:00 h (64.1+/-6.5 versus 45.8+/-7.6%; p=0.01). Platelet aggregability during sleep in the controls resembled that found in patients with OSAS during CPAP therapy. The results suggest that obstructive sleep apnoea syndrome contributes, at least in part, to platelet dysfunction and that long-term continuous positive airway pressure treatment may reduce platelet aggregability.     

Pulmonary hypertension in obstructive sleep apnoea: effects of continuous positive airway pressure: a randomized, controlled cross-over study.

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.     

Treatment of obstructive sleep apnoea with nasal continuous positive airway pressure in stroke.

The prevalence of obstructive sleep apnoea (OSA) following stroke is high and OSA is associated with increased morbidity, mortality and poor functional outcome. Nasal continuous positive airway pressure (nCPAP) is the treatment of choice for OSA, but its effects in stroke patients are unknown. The effectiveness and acceptance of treatment with nCPAP in 105 stroke patients with OSA, admitted to rehabilitation was prospectively investigated. Subjective wellbeing was measured with a visual analogue scale in 41 patients and 24-h blood pressure was determined in 16 patients before and after 10 days of treatment. Differences were compared between patients who did and did not accept treatment. There was an 80% reduction of respiratory events with concomitant increase in oxygen saturation and improvement in sleep architecture. No serious side-effects were noticed. Seventy-four patients (70.5%) continued treatment at home. Nonacceptance was associated with a lower functional status, as measured by the Barthel Index, and the presence of aphasia. Ten days after initiation of nCPAP, compliant users showed a clear improvement in wellbeing (differences in visual analogue scale (deltaVAS) mean+/-SD 26+/-26 mm) versus noncompliant patients (deltaVAS 2+/-25 mm, p=0.021). Only the compliant group had a reduction in mean nocturnal blood pressure (deltaBP; -8+/-7.3 mmHg versus 0.8+/-8.4 mmHg, p=0.037). Stroke patients with obstructive sleep apnoea can be treated effectively with nasal continuous positive airway pressure and show a similar improvement and primary acceptance to obstructive sleep apnoea patients without stroke. Continuous positive airway pressure acceptance is associated with improved wellbeing and decreased nocturnal blood pressure.     

Determinants of continuous positive airway pressure compliance in a group of Chinese patients with obstructive sleep apnea.

OBJECTIVE: To assess continuous positive airway pressure (CPAP) compliance and factors associated with CPAP compliance among Chinese patients with obstructive sleep apnea (OSA). DESIGN: A prospective study of 112 consecutive patients with newly diagnosed OSA commencing CPAP treatment. SETTING: A university teaching hospital. Measurements and results: The following factors were evaluated for any correlation with objective CPAP compliance (effective mask pressure [hours per day]) at 1 month and 3 months: age, baseline apnea-hypopnea index (AHI), common OSA symptoms, minimum arterial oxygen saturation (SaO(2)), mean SaO(2), arousal index (AI), Epworth sleepiness scale (ESS), education level, CPAP levels, satisfaction with CPAP, side effects, and machine cost. There were 101 male and 11 female patients, with a mean (+/- SD) age of 45.6 +/- 1.2 years; body mass index, 29.3 +/- 5.2 kg/m(2); AI, 60 +/- 18/h; AHI, 48 +/- 24/h; minimum SaO(2) of 70 +/- 17%; and mean SaO(2) of 86 +/- 7%. ESS fell from 12.9 +/- 4.0 (baseline) to 5.2 +/- 4.7 at 3 months (p < 0.001). Objective CPAP compliance was 5.4 +/- 1.6 h/d and 5.3 +/- 1.6 h/d, while 75% and 72% of our patients were using CPAP objectively for > or = 4 h/d and at least 70% of the nights per week at 1 month and 3 months, respectively. Following univariate analysis of variance, a high baseline AHI (p = 0.006 and p = 0.004) was associated with higher objective CPAP compliance at 1 month and 3 months, respectively. CONCLUSION: CPAP usage and compliance were high in this patient population. A high baseline AHI was the only significant independent predictor of better CPAP compliance.     

Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure

OBJECTIVES: This study was designed to determine whether reductions in morning systolic blood pressure (BP) elicited by treatment of moderate to severe obstructive sleep apnea (OSA) in heart failure (HF) patients are associated with a reduction in sympathetic vasoconstrictor tone. BACKGROUND: Daytime muscle sympathetic nerve activity (MSNA) is elevated in HF patients with coexisting OSA. In our recent randomized trial in HF, abolition of OSA by continuous positive airway pressure (CPAP) increased left ventricular ejection fraction (LVEF) and lowered morning systolic BP. METHODS: Muscle sympathetic nerve activity, BP, and heart rate (HR) of medically treated HF patients (EF <45%) and OSA (apnea-hypopnea index > or =20/h of sleep) were recorded on the morning after overnight polysomnography, and again one month after patients were randomly allocated nocturnal CPAP treatment or no CPAP (control). RESULTS: In nine control patients, there were no significant changes in the severity of OSA, MSNA, systolic BP, or HR. In contrast, in the 8 CPAP-treated patients, OSA was attenuated, and there were significant reductions in daytime MSNA (from 58 +/- 4 bursts/min to 48 +/- 5 bursts/min; 84 +/- 4 bursts/100 heart beats to 72 +/- 5 bursts/100 heart beats; p < 0.001 and p = 0.003, respectively), systolic BP (from 135 +/- 5 mm Hg to 120 +/- 6 mm Hg, p = 0.03), and HR (from 69 +/- 2 min(-1) to 66 +/- 2 min(-1); p = 0.013). CONCLUSIONS: Treatment of coexisting OSA by CPAP in HF patients lowers daytime MSNA, systolic BP, and HR. Inhibition of increased central sympathetic vasoconstrictor outflow is one mechanism by which nocturnal CPAP reduces awake BP in HF patients with moderate to severe OSA.     

Studies on the pathogenesis of the dawn phenomenon in insulin-dependent diabetic patients

To assess the role of hormonal factors in the pathogenesis of the dawn phenomenon, nocturnal (9:00 PM to 9 AM) concentrations of blood glucose, free insulin, and counterregulatory hormones were determined in eight insulin-dependent diabetic patients under feedback-controlled and continuous insulin infusions after previous blood glucose normalization. Under feedback control, mean insulin requirements, necessary for maintenance of euglycemia rose significantly in the early morning (11:00 PM to 3 AM: 8.4 +/- 1.4; 5 AM to 9 AM: 12.6 +/- 1.5 mU/kg/h; P less than 0.01). Mean free-insulin concentrations did not increase simultaneously. Correspondingly, mean insulin-clearance rates under continuous insulin infusion were higher in the morning (11:00 AM to 3 AM: 359 +/- 58; 5 AM to 9 AM: 459 +/- 72 mL/min/m2; P less than 0.05). Increases of insulin clearance rates were most marked (greater than 15%) in patients whose blood glucose rose during continuous insulin administration. Glucagon and norepinephrine concentrations were stable throughout both parts of the study. Cortisol and growth hormone exhibited the known nocturnal rhythms. Epinephrine levels were at the lower limit of detection at night and rose to normal basal concentrations at 9:00 AM. We conclude that increases of insulin clearance rates may be an important factor for the development of the dawn phenomenon while the role of most counter-regulatory hormones is still uncertain.     

Circadian variation of plasma fibrinopeptide A level in patients with variant angina

Plasma levels of fibrinopeptide A (FPA), beta-thromboglobulin (BTG), and platelet factor 4 (PF4) were examined on venous plasma samples taken every 4 hours for 24 hours in 20 patients with variant angina and 20 patients with stable exertional angina together with 24-hour Holter recordings. The mean plasma FPA levels (ng/ml) at 2:00 PM, 6:00 PM, 10:00 PM, 2:00 AM, 6:00 AM, and 10:00 AM were 4.6 +/- 1.0, 3.1 +/- 0.5, 6.1 +/- 1.6, 9.9 +/- 2.4, 8.7 +/- 1.4, and 4.2 +/- 0.8 in patients with variant angina (p less than 0.01) and 1.8 +/- 0.2, 2.3 +/- 0.3, 1.9 +/- 0.3, and 2.3 +/- 0.2 in those with stable exertional angina. In seven patients with variant angina, we also examined the effects of heparin (3,000 units), given subcutaneously at 6:00 PM, 10:00 PM, and 2:00 AM, on the plasma FPA levels and the anginal attacks. Although heparin suppressed the elevation and circadian variation of plasma FPA levels, it did not suppress the attacks and their circadian variation in these patients. Plasma FPA levels increased significantly from 3.7 +/- 0.5 to 12.5 +/- 2.7 ng/ml during or immediately after an attack in the seven patients with no heparin. On the other hand, the plasma levels of BTG and PF4 were increased in patients with variant angina as compared with those with stable exertional angina but did not show a significant circadian variation in both groups. We conclude that 1) plasma levels of FPA, BTG, and PF4 were increased in patients with variant angina as compared with those with stable exertional angina; 2) there was a significant circadian variation in the plasma levels of FPA in parallel with that of the frequency of the attacks with the peak level occurring from midnight to early morning in patients with variant angina; and 3) elevated levels of plasma FPA are the result and not the cause of coronary spasm.     

Circadian rhythm of blood pressure in patients with obstructive sleep apnea.

AIMS: The aims of this study were to examine the circadian variation in blood pressure (BP) in obstructive sleep apnea (OSA) and to compare this between normotensive and hypertensive subjects. METHODS: We measured 24-hour ambulatory BP (ABP) in 72 men (mean age 51 +/- 8 years), with OSA diagnosed on overnight sleep study. Measurements of BP were made at 15 min intervals for 24 h using either an Oxford Medilog ABP or Spacelabs 90207 recorder. All recordings were performed after > or = 3 week washout of anti-hypertensive drugs. The day-time monitoring period was defined as 07:00 hrs to 22:00 and night-time 22:00 to 07:00. The ratio of night:day systolic and diastolic BP was calculated. RESULTS: The patients were obese (mean body mass index 33 +/- 5 kg/m2) with a central pattern of obesity (waist:hip ratio 0.99 +/- 0.14, normal < 0.94). The mean 24-h ABP (systolic/diastolic) was 138 +/- 18/88 +/- 12 mmHg. The mean daytime ABP was 143 +/- 18/93 +/- 12 and night-time ABP 128 +/- 20/80 +/- 12 Hg. The night:day BP ratio was 0.90 +/- 0.07 (systolic) and 0.87 +/- 0.09 (diastolic) indicating that average BP was lower during the night. This pattern was similar in normotensive and hypertensive subjects. In contrast there was a significant relationship between increasing BMI and night:day blood pressure ratio (r = 0.56, p < 0.001) independent of the effects of OSA. CONCLUSION: In contrast to previous studies, men with OSA have a normal diurnal pattern of blood pressure levels. These findings suggest that any influence of OSA on BP is manifested throughout the 24-h period.     

Serum leptin and vascular risk factors in obstructive sleep apnea

STUDY OBJECTIVES: To define the metabolic profile relevant to vascular risks in obstructive sleep apnea (OSA) and the role of leptin resistance in this risk profile. DESIGN: Case control study. SETTING: Sleep Laboratory, Queen Mary Hospital, University of Hong Kong, China. METHODS: Thirty OSA subjects were matched with 30 non-OSA subjects for body mass index (BMI), age, sex, and menopausal status. Neck, waist, and hip girth, skinfold thickness, and fasting serum levels of lipids, glucose, insulin, and leptin were compared between these two groups. RESULTS: Compared with control subjects with a similar BMI but without OSA, the OSA group had a significantly more adverse vascular risk factor profile, including dyslipidemia, higher diastolic BP, insulin resistance, and greater adiposity reflected by skinfold thickness. OSA subjects also had higher circulating leptin levels (9.18+/-4.24 ng/mL vs 6.54+/-3.81 ng/mL, mean +/- SD, p = 0.001). Serum leptin levels correlated positively with BMI, skinfold thickness, serum cholesterol, low-density lipoprotein cholesterol, insulin, insulin/glucose ratio, apnea-hypopnea index, and oxygen desaturation time; multiple stepwise regression analysis identified skinfold thickness, waist/hip ratio, serum low-density lipoprotein cholesterol, and diastolic BP as independent correlates, while only serum insulin and diastolic BP were independent correlates in OSA subjects. After treatment with nasal continuous positive airway pressure for 6 months, there was a significant decrease in circulating leptin (p = 0.01) and triglyceride levels (p = 0.02) without change in other parameters. CONCLUSION: Despite controlling for BMI, OSA subjects showed distinct profiles with clustering of vascular risk factors. Hyperleptinemia was present in the OSA subjects, but it can be normalized by treatment with nasal continuous positive airway pressure, suggesting that increased leptin resistance was not the cause of OSA or its associated vascular risks.     

Falls in blood pressure in patients with obstructive sleep apnoea after long-term nasal continuous positive airway pressure treatment

OBJECTIVES: Effective treatment of obstructive sleep apnoea (OSA) with nasal continuous positive airway pressure (nCPAP) lowers blood pressure (BP). The long-term effects of nCPAP treatment on BP in OSA patients are not well known. The time period of such treatment sufficient to lower BP in OSA patients is also not known. We investigated compliance with long-term nCPAP therapy and its effects on BP. METHODS: This observational study involved 66 OSA patients [59 men, seven women; mean age, 51 (48-54) years; body mass index (BMI), 28.7 (27.7-29.7) kg/m; apnoea and hypopnoea, 50.3 (45.6-55.0)/h; 95% confidence intervals]. BP and BMI were measured before the study and at two checkpoints after usage of nCPAP [620 (552-688) and 1071 (1000-1143) days]. RESULTS: The different times between the first and second checkpoints for detecting objective compliance were 17 (4-30) min (P = 0.003). Diastolic BP decreased by 5.9 (3.1-8.7) mmHg after 600 days nCPAP treatment and by 4.6 (2.0-7.2) mmHg after 1000 days (P = 0.0006). Systolic BP and BMI did not change significantly. Usage of nCPAP treatment for a daily average of 3 h was needed to achieve a significant decrease in diastolic BP [7.4 (4.3-10.6) mmHg, P < 0.0001]. Diastolic BP of normotensive OSA patients did not change significantly by nCPAP treatment, but that of hypertensive OSA patients decreased significantly within 1 month-3 years of nCPAP treatment whether or not medication was used. CONCLUSIONS: In patients with severe OSA, the use of nCPAP for a daily average of 3 h would be sufficient to decrease the diastolic BP of hypertensive OSA patients.     

An auto-continuous positive airway pressure device controlled exclusively by the forced oscillation technique.

The forced oscillation technique (FOT) has been demonstrated to be a very sensitive tool for the assessment of upper airway obstruction during nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA). The present study was designed to evaluate the therapeutic efficacy of a novel auto-CPAP device based exclusively on the FOT. Following manual CPAP titration, 18 patients with OSA (mean apnoea/hypopnoea index (AHI) 48.0+/-28.1) were allocated to conventional CPAP and auto-CPAP treatment under polysomnographic control in randomized order. The patients were asked to assess their subjective daytime sleepiness using the Epworth Sleepiness Scale (ESS). The mean AHI during auto-CPAP treatment was 3.4+/-3.4 and was comparable with that obtained during conventional CPAP treatment (4.2+/-3.6). The analysis of sleep architecture, the arousal index (6.6+/-2.1 versus 7.3+/-4.4) or the ESS (5.6+/-1.8 versus 7.3+/-4.4) did not reveal any significant differences. However, the mean CPAP pressure during auto-CPAP treatment (0.84+/-0.26 kPa) and in particular the pressure applied in the lateral body position (0.74+/-0.35 kPa), was significantly lower than that employed in conventional CPAP treatment (0.93+/-0.16 kPa, both comparisons: p<0.05). The auto-continuous positive airway pressure device proved equally as effective as conventional continuous positive airway pressure. However, the mean treatment pressure was significantly reduced, especially when patients were sleeping in the lateral position.     

Effects of augmented continuous positive airway pressure education and support on compliance and outcome in a Chinese population

OBJECTIVES: To study the effects of augmentation of continuous positive airway pressure (CPAP) education and support on compliance and outcome in patients with obstructive sleep apnea (OSA). DESIGN: A randomized, controlled, parallel study of basic vs augmented CPAP education and support. SETTING: A university teaching hospital. PATIENTS: A total of 108 OSA patients randomized into basic-support (BS) and augmented-support (AS) groups. INTERVENTIONS: Patients in the BS group (n = 54) were given educational brochures on OSA and CPAP, CPAP education by nurses, CPAP acclimatization, and were reviewed by physicians and nurses at weeks 4 and 12. Patients in the AS group (n = 54) received more education, including a videotape, telephone support by nurses, and early review at weeks 1 and 2. MEASUREMENTS: Objective CPAP compliance, Calgary sleep apnea quality of life index (SAQLI), and cognitive function after 1 month and 3 months; and Epworth sleepiness scale (ESS) after 3 months of CPAP treatment. RESULTS: At 4 weeks, CPAP usage was 5.3 +/- 0.2 h/night (mean +/- SEM) vs 5.5 +/- 0.2 h/night in the BS and AS groups, respectively (p = 0.4). At 12 weeks, CPAP usage was 5.3 +/- 0.3 h/night vs 5.3 +/- 0.2 h/night in the two groups, respectively (p = 0.98). There was greater improvement of SAQLI at 4 weeks (p = 0.008) and at 12 weeks (p = 0.047) in the AS group. There was no significant difference between BS and AS groups in terms of improvement of ESS and cognitive function. CONCLUSION: Augmentation of CPAP education and support does not increase CPAP compliance, but leads to a greater improvement of quality of life during the reinforced period.