Long-term nasal CPAP does not ameliorate obstructive sleep apnoea

Fifty-seven patients with obstructive sleep apnoea (OSA) were treated for at least six months with nasal continuous positive airway pressure (CPAP). At follow-up, sleep studies were performed in which CPAP was not used for the first half of the night. We compared the severity of OSA at follow-up without CPAP to the severity of OSA during the patient's initial diagnostic study. Apnoea and hypopnoea index (AHI) fell from 41.4 ± 7.5 (mean ±95% CI) to 34.8 ± 7.9 (p= 0.06 by Wilcoxon test) and minimum oxygen saturation rose from 71.6 ± 3.2 to 78.5 ± 2.6 (p<0.001). Some of this change may have been due to reduced REM sleep in the follow-up study (10.5±2.1% Total Sleep Time vs 7.4±2.4% TST, p<0.05). Long-term nasal CPAP was not associated with any reduction of obesity (BMI before CPAP 31.9 ± 1.0, after CPAP 31.7 ± 1.0 (p= 0.39). Systolic arterial pressure fell (before CPAP 143.0 ±4.5 mmHg, after CPAP 136.3 ± 4.6, p < 0.05) but diastolic pressure did not (before CPAP 88.5 ± 3.0 mmHg, after CPAP 85.6 ±2.9 mmHg, p = 0.11). We concluded that the effect of CPAP treatment for six or more months was a small fall in AHI and a small rise in minimum Sa0₂, but that this would be of marginal clinical significance, and may be artefactual. (Aust NZ J Med 1991; 21: 235–238.)     

Atrial overdrive pacing compared to CPAP in patients with obstructive sleep apnoea syndrome.

AIMS: Obstructive sleep apnoea (OSA) is associated with oxygen desaturation, blood pressure increase, and neurohumoral activation, resulting in possible detrimental effects on the cardiovascular system. Continuous positive airway pressure (CPAP) is the therapy of choice for OSA. In a recent study, nocturnal atrial overdrive pacing (pacing) reduced the severity of sleep apnoea in pacemaker patients. We compared the effects of CPAP with those of pacing in patients with OSA but without pacemaker indication or clinical signs of heart failure. METHODS AND RESULTS: Ten patients with OSA on CPAP therapy were studied for three nights by polysomnography. During the nights that followed a night without any treatment (baseline), the patients were treated with CPAP or pacing in a random order. Pacing was performed with a temporary pacing lead. The pacing frequency was 15 b.p.m. higher than the baseline heart rate. The apnoea-hypopnoea index was 41.0 h(-1) (12.0-66.6) at baseline and was significantly lower during CPAP [2.2 h(-1) (0.3-12.4)] compared with pacing [39.1 h(-1) (8.2-78.5)]. Furthermore, duration and quality of sleep were significantly improved during CPAP when compared with pacing. CONCLUSION: Nocturnal atrial overdrive pacing is no alternative therapeutic strategy to CPAP for the treatment of OSA in patients without clinical signs of heart failure and without conventional indication for anti-bradycardia pacing.     

Hypercapnia in obstructive sleep apnoea syndrome

BACKGROUND: The reports on the prevalence of hypercapnia in Obstructive Sleep Apnoea Syndrome (OSAS) are conflicting. We studied the prevalence of hypercapnia in a population of OSAS patients referred to a Department of Respiratory Medicine and the mechanism of the respiratory failure in OSAS associated with Obesity Hypoventilation Syndrome (OHS) or with Chronic Obstructive Pulmonary Disease (COPD) (Overlap syndrome). METHODS: We studied 219 consecutive OSAS patients during a period of 3 years. We recorded age and anthropomorphic data and performed polysomnography and pulmonary function tests. In relation to the value of PaCO(2), the patients were divided in hypercapnic (PaCO(2)>45 mmHg) patients and normocapnic patients. They were also divided into three groups in relation to the presence of "simple" or "pure" OSAS, to the presence of OSAS associated with COPD, to the presence of OSAS associated with OHS. RESULTS: Seventeen per cent of the patients were hypercapnic. They were significantly heavier, had more severe lung function test abnormalities and more severe nocturnal oxyhemoglobin desaturations than the normocapnic ones, while Forced Expiratory Volume in one second as a percentage of Forced Vital Capacity (FEV1/FVC %) and Apnoea/Hypopnoea Index (AHI) were similar. OHS patients (13%) were significantly younger and heavier, had lower PaO(2) and higher PaCO(2) than "simple" OSAS patients (77%) and Overlap patients (10%) and had more severe restrictive defect. There was no difference in terms of AHI among the three groups, but nocturnal oxyhemoglobin desaturations were more severe in OHS group. In OHS group hypercapnia was correlated to FVC% of predicted and FEV1% of predicted and to the mean nocturnal oxyhemoglobin saturation; in Overlap patients PaCO(2) was correlated to Forced Expiratory Flow rate at low Vital Capacity. CONCLUSION: Seventeen per cent of OSAS patients referred to a Department of Respiratory Medicine were hypercapnic. Hypercapnia in OHS patients correlates to the restrictive ventilatory defect whereas in Overlap patients it seems to correlate to peripheral airways obstruction. The distinction between patients with "simple" or "pure" OSAS and patients affected by OSAS associated with OHS or COPD could be important not only for clinical and prognostic implications, but also for the consequences in terms of ventilatory treatment.     

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.     

QT dispersion in childhood obstructive sleep apnoea syndrome

The difference between maximal and minimal QT interval and corrected QT interval defined as QT dispersion and corrected QT dispersion may represent arrhythmogenic risks. This study sought to evaluate QT dispersion and corrected QT dispersion in childhood obstructive sleep apnoea syndrome. Forty-four children (34 male) with obstructive sleep apnoea syndrome, aged 6.2 plus or minus 3.5 years along with 38 healthy children (25 male), 6.6 plus or minus 2.1 years underwent electrocardiography to measure QT and RR intervals. Means QT dispersion and corrected QT dispersion were significantly higher in obstructive sleep apnoea syndrome than controls, 52 plus or minus 27 compared to 40 plus or minus 14 milliseconds (p equal to 0.014), and 71 plus or minus 29 compared to 57 plus or minus 19 milliseconds (p equal to 0.010), respectively. Interestingly, QT dispersion and corrected QT dispersion in obstructive sleep apnoea syndrome with obesity, 57 plus or minus 30 and 73 plus or minus 31 milliseconds, were significantly higher than in control, 40 plus or minus 14 and 57 plus or minus 19 milliseconds (p equal to 0.009 and 0.043, respectively). However, QT dispersion and corrected QT dispersion in obstructive sleep apnoea syndrome without obesity, 43 plus or minus 20 and 68 plus or minus 26 milliseconds, were not significantly different. In conclusion, QT dispersion and corrected QT dispersion were significantly increased only in childhood obstructive sleep apnoea syndrome with obesity. Obesity may be the factor affecting the increased QT dispersion and corrected QT dispersion.     

Obesity, obstructive sleep apnoea and metabolic syndrome

OSA is increasingly recognized as a major health problem in developed countries. Obesity is the most common risk factor in OSA and hence, the prevalence of OSA is undoubtedly rising given the epidemic of obesity. Recent data also suggest that OSA is highly associated with the metabolic syndrome, and it is postulated that OSA contributes to cardiometabolic dysfunction, and subsequently vasculopathy. Current evidence regarding the magnitude of impact on ultimate cardiovascular morbidity or mortality attributable to OSA-induced metabolic dysregulation is scarce. Given the known pathophysiological triggers of intermittent hypoxia and sleep fragmentation in OSA, the potential mechanisms of OSA-obesity-metabolic syndrome interaction involve sympathetic activation, oxidative stress, inflammation and neurohumoral changes. There is accumulating evidence from human and animal/cell models of intermittent hypoxia to map out these mechanistic pathways. In spite of support for an independent role of OSA in the contribution towards metabolic dysfunction, a healthy diet and appropriate lifestyle modifications towards better control of metabolic function are equally important as CPAP treatment in the holistic management of OSA.     

Impaired glucose-insulin metabolism in males with obstructive sleep apnoea syndrome.

The aim of this cross-sectional study was to evaluate the frequency of type-2 diabetes and impaired glucose tolerance (IGT) in a large clinic-based male population presenting various degrees of obstructive sleep apnoea syndrome (OSAS) and to analyse the relationship between OSAS and glucose-insulin metabolism. Male patients (n=595) with suspected OSAS underwent both nocturnal polysomnography and a 2-h oral glucose-tolerance test with measurements of fasting and postload blood glucose and plasma insulin. Insulin sensitivity was evaluated by the ratio of fasting glucose to fasting insulin. OSAS was diagnosed in 494 patients, while 101 patients were nonapnoeic snorers. Type-2 diabetes was present in 30.1% of OSAS patients and 13.9% of nonapnoeic snorers. IGT was diagnosed in 20.0% of OSAS patients and 13.9% of nonapnoeic snorers. Fasting and postload blood glucose increased with severity of sleep apnoea. Insulin sensitivity decreased with increasing severity of sleep apnoea. In addition to body mass index and age, the apnoea/hypopnoea index independently influenced postload blood glucose and insulin sensitivity. The authors conclude that in a clinic-based sample of patients, obstructive sleep apnoea syndrome is associated with a high frequency of type-2 diabetes and impaired glucose tolerance. The relationship between sleep-disordered breathing and impaired glucose-insulin metabolism is independent of obesity and age.     

Cardiovascular risk factors in patients with obstructive sleep apnoea syndrome.

Cardiovascular disorders are common in patients with obstructive sleep apnoea syndrome (OSAS) but there is debate as to whether OSAS is an independent risk factor for their development, since OSAS may be associated with other disorders and risk factors that predispose to cardiovascular disease. In an effort to quantify the risk of OSAS patients for cardiovascular disease arising from these other factors, the authors assessed the future risk for cardiovascular disease among a group of 114 consecutive patients with established OSAS prior to nasal continuous positive airway pressure therapy, using an established method of risk prediction employed in the Framingham studies. Patients were 100 males, aged (mean+/-SD) 52+/-9.0 yrs, and 14 females, aged 51+/-10.4 yrs, with an apnoea/hypopnoea index of 45+/-22 x h(-1). Based on either a prior diagnosis, or a mean of three resting blood pressure recordings >140 mmHg systolic and/or 90 diastolic, 68% of patients were hypertensive. Only 18% were current smokers, while 16% had either diabetes mellitus or impaired glucose tolerance, and 63% had elevated fasting cholesterol and/or triglyceride levels. The estimated 10-yr risk of a coronary heart disease (CHD) event in males was (mean+/-SEM) 13.9+/-0.9%, 95% confidence interval (95% CI) 12.1-16.0, and for a stroke was 12.3+/-1.4%; 95% CI 9.4-15.1, with a combined 10 yr risk for stroke and CHD events of 32.9+/-2.7%; 95% CI 27.8-38.5 in males aged >53 yrs. These findings indicate that obstructive sleep apnoea syndrome patients are at high risk of future cardiovascular disease from factors other than obstructive sleep apnoea syndrome, and may help explain the difficulties in identifying a potential independent risk from obstructive sleep apnoea syndrome.     

Total energy expenditure in children with obstructive sleep apnoea syndrome.

Childhood obstructive sleep apnoea syndrome (OSAS) acts as a check on growth and nutritional status. An increase in sleeping energy expenditure has been proposed as a possible mechanism, but to date, no studies have determined whether energy requirements (total energy expenditure; TEE) are raised in OSAS. The aim of this study was to test the hypothesis that OSAS is associated with increased TEE. Eleven children (mean+/-SD 5.8+/-2.2 yrs of age) with OSAS confirmed by nocturnal polysomnography were each matched with a pair of healthy controls (n=22) of the same age and sex. TEE was measured using the doubly-labelled water method in all subjects. In 10/11 patients TEE was also measured after adenotonsillectomy and changes in TEE assessed. There was no significant difference in TEE between patients (mean+/-SD 325+/-44 kJ x kg(-1) x day(-1)) and controls (339+/-48 kJ x kg(-1) x day(-1)), nor between patients and age- and sex-specific literature data on TEE, using the doubly-labelled water method. Differences in TEE within patients, before versus after surgery, were minor and not statistically significant. This study does not support the hypothesis that obstructive sleep apnoea syndrome in childhood is associated with increased energy requirements, and suggests that alternative explanations for the effect of this syndrome on growth and energy balance should be sought.     

Severe obstructive sleep apnoea syndrome in an adult patient with Laron syndrome.

A 68 year old patient with Laron syndrome (primary growth hormone (GH) resistance-insensitivity due to a molecular defect of the GH receptor) and severe obstructive sleep apnoea syndrome is described. Treatment with continuous positive air pressure therapy resulted in improved nocturnal sleep, daytime alertness and cognitive functions.     

Progression of obstructive sleep apnoea syndrome in Japanese patients

Sleep and Breathing - The aggravation of obstructive sleep apnoea syndrome (OSAS) is reportedly associated with weight gain. The present study investigated the factors associated with worsening of...     

Plasma homocysteine in obstructive sleep apnoea.

AIMS: Whether increased homocysteine is one mechanism linking obstructive sleep apnoea (OSA) to cardiovascular abnormalities is unclear. We hypothesised that plasma homocysteine would be higher in OSA patients than in control subjects, would increase further during sleep, and decrease after treatment with continuous positive airway pressure (CPAP). METHODS AND RESULTS: For study A, homocysteine was measured in 22 OSA patients and 20 controls first before sleep, then after 5 h of untreated OSA, and then in the morning after CPAP treatment. Homocysteine was similar in the OSA and control subjects at all three time points, and declined overnight in both groups (P=0.0017, P=0.036, respectively). To further assess this diurnal variation, we studied plasma homocysteine under a full-night protocol in 10 OSA patients and 12 controls (study B). Homocysteine was measured before sleep, in the morning after sleep, and at noon. Results in both OSA and control groups showed an overnight decline in homocysteine which was reversed by noon (repeated measures ANOVA: OSA, P=0.04; controls, P=0.02). Study C showed that disturbed sleep did not affect homocysteine levels in normal subjects. CONCLUSION: There is a significant diurnal variation in plasma homocysteine, so that homocysteine is lower in the morning after waking. Neither OSA nor disturbed sleep elicit acute or chronic changes in homocysteine.     

Oxidative stress in obstructive sleep apnoea.

AIMS: Any sustained elevation of oxidative stress in patients with obstructive sleep apnoea (OSA) might help explain their increased risk for cardiovascular diseases. We tested the hypothesis that measures of oxidative stress are increased in otherwise healthy subjects with OSA when compared to closely matched OSA-free control subjects. METHODS AND RESULTS: Plasma indices of oxidative stress and lipid peroxidation [thiobarbituric acid-reactive substances (TBARS), oxidized LDL (oxLDL), isoprostanes] were measured in 41 moderate-severe OSA males without other diseases and in 35 matched controls first before sleep, then after 4 h of untreated OSA, and again in the morning after 4 h of effective treatment with continuous positive airway pressure (CPAP). Plasma levels of oxLDL, TBARS, and isoprostanes in OSA patients (n=34, 26, 17, respectively) were comparable to the controls (n=28, 27, 15 for the three markers, respectively). Neither untreated OSA nor CPAP treatment nor normal sleep affected levels of any of the three measures of oxidative stress. There was no association between the severity of sleep apnoea and any measure of oxidative stress. CONCLUSION: Otherwise healthy OSA patients, without any other co-morbidities, do not manifest evidence for higher oxidative stress and lipid peroxidation. Thus, oxidative stress and lipid peroxidation do not appear to be key mediators of increased cardiovascular disease in OSA patients.     

NT-proBNP is not elevated in patients with obstructive sleep apnoea

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-ProBNP) has emerged as an important marker of cardiac stress and may reflect the severity of underlying cardiac dysfunction, which is thought to be associated with obstructive sleep apnoea syndrome (OSAS). METHODS: This study evaluated the plasma concentration of NT-ProBNP in 60 consecutive patients (median age 55.7 years, median body mass index (BMI) 31.8) who were referred to a sleep laboratory with a suspicion of OSAS. Each subject underwent measurement of morning NT-ProBNP plasma levels, polysomnography and echocardiography. Patients were treated with nasal continuous or bilevel positive airway pressure ventilation (nCPAP/BIPAP) or without mechanical respiratory support, depending on clinical symptoms and results of polysomnography. Three months after treatment of OSAS 28 of the patients were reassessed for re-evaluation of NT-ProBNP and polysomnography. RESULTS: Low or high levels of NT-proBNP were not associated with AHI and other sleep related indices (p>0.3). There was no correlation between NT-proBNP and AHI or other sleep related indices. In multiple regression analysis, NT-proBNP was significantly correlated with left ventricular ejection fraction, creatinine clearance and the presence of systemic arterial hypertension but not with AHI. CONCLUSIONS: Our results show by a robust multiple regression analysis, that NT-pro BNP is not associated with OSAS and NT-pro BNP cannot be used as a sensitive marker for underlying cardiovascular abnormalities in patients with OSAS.     

QT interval dispersion in obstructive sleep apnoea syndrome patients without hypertension.

QT interval dispersion (QT(d)) reflects inhomogeneity of repolarisation. Delayed cardiac repolarisation leading to the prolongation of the QT interval is a well-characterised precursor of arrhythmias. Obstructive sleep apnoea syndrome (OSAS) can cause cardiovascular complications, such as arrhythmias, myocardial infarction, and systemic and pulmonary hypertension. The aim of this study was to assess QT(d) in OSAS patients without hypertension. A total of 49 subjects without hypertension, diabetes mellitus, any cardiac or pulmonary diseases, or any hormonal, hepatic, renal or electrolyte disorders were referred for evaluation of OSAS. An overnight polysomnography and a standard 12-lead ECG were performed in each subject. According to the apnoea-hypopnoea index (AHI), subjects were divided into control subjects (AHI <5, n = 20) and moderate-severe OSAS patients (AHI > or =15, n = 29). QT(d) (defined as the difference between the maximum and minimum QT interval) and QT-corrected interval dispersion (QT(cd)) were calculated using Bazzet's formula. In conclusion, the QT(cd) was significantly higher in OSAS patients (56.1+/-9.3 ms) than in controls (36.3+/-4.5 ms). A strong positive correlation was shown between QT(cd) and AHI. In addition, a significantly positive correlation was shown between QT(cd) and the desaturation index (DI). The AHI and DI were significantly related to QT(cd) as an independent variable using stepwise regression analysis. The QT-corrected interval dispersion is increased in obstructive sleep apnoea syndrome patients without hypertension, and it may reflect obstructive sleep apnoea syndrome severity.     

Two months auto-adjusting versus conventional nCPAP for obstructive sleep apnoea syndrome.

Autoadjusting nasal continuous positive airway pressure (CPAP) greatly reduces the apnoea/hypopnoea index (AHI), and affords a significant reduction in median pressure (P50) compared-with manually titrated conventional nasal CPAP. The aim of the present study was to test whether these benefits were maintained in the medium term at home, in a double-blind crossover study. Ten sequential subjects (mean AHI 52.9 x h(-1)) were enrolled. After a manual titration, subjects were randomly allocated to 2 months autoadjusting nasal CPAP (AutoSet), followed by 2 months with the AutoSet device in fixed pressure mode at the manually titrated pressure, or vice versa. The machine-scored AHI, P50, and median leak were recorded on 12 nights in each arm, and averaged. Mean+/-SEM AHI was 4.0+/-0.3 x h(-1) in auto mode, and 3.7+/-0.3 x h(-1) in manual mode (NS). Mean+/-SEM P50 was 7.2+/-0.4 cmH2O auto, 9.4+/-0.6 cmH2O manual, average reduction 23+/-4% (p<0.0001). Auto "recommended" pressure was (mean+/-SEM) 10.1+/-0.5 cmH2O (p=0.04 with respect to manual) and peak pressure typically 1 cmH2O higher. Median (+/-SEM) leak was 0.181+/-0.006 L x s(-1) auto (and uncorrelated with AHI or pressure), 0.20+/-0.006 L x s(-1) manual (p=0.003). Compliance was 6.3+/-0.4 h in auto mode and 6.1+/-0.5 h in fixed mode (NS). Apnoea/hypopnoea index during 2 months of home autoadjusting nasal continuous positive airway pressure is comparable to that during conventionally titrated fixed pressure continuous positive airway pressure, while affording a 23% reduction in median pressure but no increase in compliance. Leak did not importantly affect autoadjustment.