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.     

Influence of treatment on leptin levels in patients with obstructive sleep apnoea.

Obstructive sleep apnoea syndrome (OSAS) is a common disorder in obesity. Leptin, an adipocyte-derived signalling factor, plays an important role in metabolic control. There is growing evidence that leptin regulation is altered in OSAS. Therefore, the aim of this study was to test the hypothesis that effective treatment will influence leptin levels in OSAS patients. Serum leptin levels were determined in 86 consecutive patients (aged 57.5 +/- 11.0 yrs) with polysomnographically verified OSAS. In addition, leptin levels were reassessed and treatment efficacy was evaluated by polysomnography after 6 months of therapy. Patients were treated with continuous or bilevel positive airway pressure, a mandibular advancement device or conservatively, depending on the clinical symptoms. Mean serum leptin levels did not change with treatment in the whole study group (7.3 +/- 5.0 versus 7.5 +/- 4.8 ng.mL-1), however, leptin levels decreased in effectively treated patients (8.5 +/- 5.0 versus 7.4 +/- 5.1 ng.mL-1) while they increased in ineffectively treated patients (5.0 +/- 4.0 versus 7.7 +/- 4.1 ng.mL-1). Furthermore, not only was there a significant and independent correlation between the change in leptin levels with treatment and the change in body mass index, but also with the change in apnoea/hypopnoea index. Effective treatment of sleep-disordered breathing may have significant effects on leptin levels in obstructive sleep apnoea syndrome patients. Changes in leptin levels are related to changes in apnoea/hypopnoea index in obstructive sleep apnoea syndrome patients.     

Predicting sleep apnoea syndrome from heart period: a time-frequency wavelet analysis.

Heart rate fluctuations are a typical finding during obstructive sleep apnoea, characterised by bradycardia during the apnoeic phase and tachycardia at the restoration of ventilation. In this study, a time-frequency domain analysis of the nocturnal heart rate variability (HRV) was evaluated as the single diagnostic marker for obstructive sleep apnoea syndrome (OSAS). The predictive accuracy of time-frequency HRV variables (wavelet (Wv) decomposition parameters from level 2 (Wv2) to level 256 (Wv256)) obtained from nocturnal electrocardiogram Holter monitoring were analysed in 147 consecutive patients aged 53.8+/-11.2 yrs referred for possible OSAS. OSAS was diagnosed in 66 patients (44.9%) according to an apnoea/hypopnoea index > or = 10. Using receiver-operating characteristic curves analysis, the most powerful predictor variable was Wv32 (W 0.758, p<0.0001), followed by Wv16 (W 0.729, p<0.0001) and Wv64 (W 0.700, p<0.0001). Classification and Regression Trees methodology generated a decision tree for OSAS prediction including all levels of Wv coefficients, from Wv2 to Wv256 with a sensitivity reaching 92.4% and a specificity of 90.1% (percentage of agreement 91.2%) with this nonparametric analysis. Time-frequency parameters calculated using wavelet transform and extracted from the nocturnal heart period analysis appeared as powerful tools for obstructive sleep apnoea syndrome diagnosis.     

Overdrive atrial pacing does not improve obstructive sleep apnoea syndrome.

The aim of this study was to assess the ability of overdrive atrial pacing to reduce sleep apnoea severity. A total of 17 unselected patients (12 males; mean+/-SD age 71+/-10 yrs; body mass index 27+/-3 kg x m(-2)) who had received permanent atrial-synchronous ventricular pacemakers for symptomatic bradyarrhythmias and not known to have central or obstructive sleep apnoea syndrome (OSAS) were studied. Using a crossover study design, patients were or were not in pacing mode with atrial overdrive (15 beats x min(-1) faster than mean baseline nocturnal cardiac frequency) for 1 month. Patients were paced only during sleep periods, identified by a specific algorithm included in the pacemaker. Patients underwent three overnight polysomnographic evaluations 1 month apart. The first was performed for baseline evaluation. The patients were then randomly assigned to either 1 night in spontaneous rhythm or to 1 night in pacing mode with atrial overdrive. Two patients refused to continue the study after the first polysomnographic evaluation. OSAS was highly prevalent in this population: 10 of the 15 (67%) patients exhibited an apnoea-hypopnoea index of >30 events x h(-1). The nocturnal spontaneous rhythm was 59+/-7 beats x min(-1) at baseline, compared to 75+/-10 beats x min(-1) with atrial overdrive pacing. The apnoea-hypopnoea index was 46+/-29 events x h(-1) in spontaneous rhythm, compared to 50+/-24 events x h(-1) with atrial overdrive pacing. Overdrive pacing changed none of the respiratory indices, or sleep fragmentation or sleep structure parameters. In conclusion, atrial overdrive pacing has no significant effect on obstructive sleep apnoea.     

Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up.

An increased incidence of cardiovascular disease has previously been reported in middle-aged males during a follow-up period of 7 yrs. The aim of the present study was to address the incidence of coronary artery disease (CAD) in a larger sample without any heart disease at baseline. The population comprised 308 snorers (245 males and 63 females) with a mean +/- sd age of 49.0 +/- 9.9 yrs in 1991. Data were collected via the Swedish Hospital Discharge Register, National Cause of Death Registry, clinical charts and questionnaires. Over 7 yrs, CAD was observed in 17 (16.2%) of 105 patients with obstructive sleep apnoea (OSA; overnight (6 h) oxygen desaturations > or =30 events) compared with 11 (5.4%) of 203 snorers without OSA. OSA diagnosis at baseline was associated with an increased risk of development of CAD in a multivariate model. In the OSA group, CAD was confirmed in 16 (24.6%) of 65 incompletely treated patients compared with one (3.9%) of 26 efficiently treated subjects. Efficient treatment of OSA reduced this risk. It is concluded that middle-aged sleep apnoeics are at high risk of developing coronary artery disease if they are not treated efficiently, which should be considered in cardiovascular disease prevention models.     

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.     

Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities.

Considerable evidence is available in support of an independent association between obstructive sleep apnoea syndrome (OSAS) and cardiovascular disease, which is particularly strong for systemic arterial hypertension and growing for ischaemic heart disease, stroke, heart failure, atrial fibrillation and cardiac sudden death. The pathogenesis of cardiovascular disease in OSAS is not completely understood but likely to be multifactorial, involving a diverse range of mechanisms including sympathetic nervous system overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormal coagulation and metabolic dysregulation, the latter particularly involving insulin resistance and disordered lipid metabolism. The present report, which arose out of a European Union Cooperation in the field of Scientific and Technical Research (COST) action on OSAS (COST B26), reviews the current evidence for an independent association and proposes research priorities to identify the underlying mechanisms involved, with a view to identifying novel therapeutic strategies. Large-scale collaborative studies of carefully defined patient populations with obstructive sleep apnoea syndrome, adequately controlled for potential confounders, are needed. Such studies carry the prospect of evaluating potential interactions between different basic mechanisms operating in obstructive sleep apnoea syndrome and cardiovascular disease, and interactions with other related disorders, such as obesity, diabetes and dyslipidaemia. Furthermore, translational studies involving cell culture and animal models linked to studies of obstructive sleep apnoea syndrome patients are necessary to integrate basic mechanisms with the clinical disorder.     

Daytime sleepiness and polysomnographic variables in sleep apnoea patients.

Excessive daytime sleepiness (EDS) is not invariably present in patients with obstructive sleep apnoea syndrome (OSAS). The aim of the present study was to investigate polysomnographic determinants of EDS in patients with OSAS. EDS was assessed using the Epworth Sleepiness Scale (ESS) and the multiple sleep latency test (MSLT). Patients showed EDS whenever the ESS score was >10 and the MSLT score <5 min. Absence of EDS was defined as having an ESS score of <10 and an MSLT score of >10 min. In total, 23 male patients with EDS (mean+/-sd ESS and MSLT score 17+/-3 and 4+/-1 min, respectively) and 17 without EDS (ESS and MSLT score 5+/-2 and 16+/-3 min, respectively), were studied. Both groups exhibited a similar apnoea/hypopnoea index (62+/-18 versus 60+/-20 events.h(-1)). Patients with EDS exhibited shorter sleep latency (11+/-16 versus 18+/-18 min) and greater sleep efficiency (90+/-7 versus 82+/-13%) than those without EDS. Patients with EDS showed lower oxygenation (lowest arterial oxygen saturation 69+/-12 versus 79+/-8%; mean arterial oxygen saturation 87+/-6 versus 90+/-5%). Sleep stage distribution and arousal index did not differ between the groups. Patients with obstructive sleep apnoea syndrome and excessive daytime sleepiness are characterised by shorter sleep latency, increased sleep efficiency and worse nocturnal oxygenation than those without excessive daytime sleepiness. Nocturnal hypoxaemia can be a major determinant of excessive daytime sleepiness in patients with obstructive sleep apnoea syndrome.     

Homocysteine levels in patients with obstructive sleep apnea syndrome

The exact mechanism of development of cardiovascular disease in patients with obstructive sleep apnea syndrome (OSAS) remains to be unknown. The role of homocysteine in atherosclerotic disease process has become well established over the past ten years. Our aim was to study to compare homoscysteine levels between OSAS and control levels. Sixty-two subjects with OSAS and twelve similar controls in age, gender, body mass index, smoking and coronary heart disease were included in this prospective study. Serum levels of homocysteine (13.5 +/- 6.0 micromol/L vs. 10.2 +/- 2.9 micromol/L, p= 0.03) in the OSAS group were significantly greater than those in the control group. Logistic regression analyses showed that OSAS (Odds ratio: 9.08 95% CI 2.347-35.120; p= 0.001) was independent risk factors for high levels of serum homocysteine in age, smoking status, diabetes mellitus and coronary heart disease. We conclude that homocysteine may be an important factor for development of cardiovascular disease in patients with OSAS.     

Obstructive sleep apnoea syndrome impairs insulin sensitivity independently of anthropometric variables

OBJECTIVES: Obstructive sleep apnoea syndrome (OSAS) is strongly associated with obesity and characterized by endocrine and metabolic changes including impairment of insulin sensitivity. The aim of this study was to further clarify the insulin dynamics and glucose metabolism in this condition. DESIGN, PATIENTS AND MEASUREMENTS: We studied 30 obese patients with OSAS [OSA, 21 males, 9 females; age, mean +/- SEM: 53.1 +/- 1.7 years; body mass index (BMI): 38.6 +/- 1.1 kg/m2; waist-to-hip ratio (WHR): 0.99 +/- 0.07; Apnoea/Hypopnoea Index (AHI): 40.5 +/- 5.8 events/h of sleep] by means of overnight polysomnography and oral glucose tolerance testing. Mathematical models were used to assess: (i) whole-body insulin sensitivity index (ISI composite); (ii) hepatic ISI; (iii) the first phase of insulin secretion (DeltaI30'-0'/DeltaG30'-0'). Results were compared with those in 27 weight-matched patients with simple obesity (OB, 12 males, 15 females; age: 48.1 +/- 2.8 years, BMI: 38.5 +/- 1.4 kg/m2, WHR: 0.94 +/- 0.09; AHI: 2.15 +/- 0.5 events/h of sleep) and with 20 normal subjects (NS, 15 females; 5 males, age: 40.4 +/- 2.9 years; BMI: 22.2 +/- 0.6 kg/m2). RESULTS: ISI composite value was significantly lower in OSAS (1.71 +/- 1.41) than in OB (3.08 +/- 0.27) and in NS (6.1 +/- 0.4) even after age-, BMI- and WHR-adjustment. Similarly, hepatic ISI was significantly different among the three groups (OB = 0.25 +/- 0.02, OSAS = 0.16 +/- 0.014 and NS = 0.55 +/- 0.04). Sex did not affect ISI indices. Insulin secretion estimates were not significantly different among the three groups. DISCUSSION: Obese patients with obstructive sleep apnoea syndrome are more insulin resistant than patients with simple obesity independently of the degree and distribution of adiposity. The worsening in insulin sensitivity in obstructive sleep apnoea syndrome patients could reflect the hypoxic state and would account for the increased vascular risk in this condition.     

An independent association between obstructive sleep apnoea and coronary artery disease.

Previous studies of sleep and breathing suggest an independent association between coronary artery disease (CAD) and obstructive sleep apnoea (OSA) in middle-aged males and females. These studies, however, were criticized because they did not properly adjust for all important confounding factors. In order to better control for the impact of these confounders, a case-control study was performed, matching for age, sex and body mass index (BMI), and additionally adjusting for hypertension, hypercholesterolemia, diabetes mellitus and current smoking. A consecutive selection of 62 patients (44 males and 18 females, mean age 69 yrs, range 44-88 yrs) requiring intensive care for angina pectoris or myocardial infarction at the County Hospital of Skaraborg, Sk?vde, Sweden, as well as 62 age-, sex- and BMI- matched control subjects without history or signs of heart disease underwent an overnight sleep/ventilatory monitoring study. The time interval between discharge from the intensive care unit and the overnight study ranged between 4 and 21 months. OSA, defined as a Respiratory Disturbance Index (RDI) of > or =10 x h(-1), was present in 19 CAD patients but only in eight control subjects (p=0.017). Using a univariate logistic regression analysis, current smoking (odds ratio (OR) 8.1, 95% confidence interval (CI) 2.2-29.0), diabetes mellitus (OR 4.2, 95% CI 1.1-16.1) and OSA (OR 3.0, 95% CI 1.2-7.5), but not hypertension (OR 1.5, 95% CI 0.7-3.2) and hypercholesterolaemia (OR 1.8, 95% CI 0.7-4.1) were significantly correlated with CAD. In a multiple logistic regression model, current smoking (OR 9.8, 95% CI 2.6-36.5), diabetes mellitus (OR 4.2, 95% CI 1.1-17.1) and OSA (OR 3.1, 95% CI 1.2-8.3) all remained independently associated with CAD. In summary, these data suggest a high occurrence of obstructive sleep apnoea in middle-aged and elderly patients with coronary artery disease requiring intensive care, which should be taken into account when considering risk factors for coronary artery disease.     

Angiotensin converting enzyme in patients with sleep apnoea syndrome: plasma activity and gene polymorphisms.

The prevalence of several cardiovascular diseases is increased with obstructive sleep apnoea syndrome (OSAS), due to, as yet, unclear reasons. Angiotensin converting enzyme (ACE) abnormalities have been implicated in the pathogenesis of various cardiovascular diseases. In this study, plasma ACE activity and the distribution of an insertion (I)/deletion (D) polymorphism of the ACE gene were determined in OSAS patients and in healthy controls. A total of 63 patients with OSAS (mean+/-SEM 54.5+/-2.5 apnoea/hypopnoeas.h(-1)) and 32 healthy subjects were studied. To avoid potential confounding factors, patients treated with ACE inhibitors or continuous positive airway pressure were excluded, as well as controls in whom a blood sample was not obtained early in the morning. ACE activity was determined spectrophotometrically in 46 OSAS patients and 25 controls. The I/D ACE polymorphism was determined by polymerase chain reaction in 44 patients and 32 controls. ACE activity was higher in OSAS patients (53.9+/-2.5 IU.L(-1)) than in healthy controls (42.4+/-3.1 IU.L(-1), p<0.01). This was independent of the presence of arterial hypertension. The frequency distribution of the DD, II and ID genotypes in OSAS patients (30%, 16%, 54%, respectively) was not significantly different from that seen in healthy subjects (31%, 28%, 41%, respectively, p=0.356). These results indicate that ACE plasma activity is increased in untreated OSAS patients. This increased activity may contribute to the pathogenesis of the cardiovascular disease in these patients.     

Prognostic value of lung function and pulmonary haemodynamics in OSA patients treated with CPAP.

The aim of the present study was to determine survival rates of obstructive sleep apnoea patients treated with continuous positive airway pressure (CPAP) and to investigate the prognostic value of pretreatment lung function and pulmonary haemodynamics. Two hundred and ninety-six patients, exhibiting > or = 20 apnoeas plus hypopnoeas per hour of sleep, were included. Patients were treated with nasal CPAP and regularly followed up. The cumulative survival rates were 0.96 (95% confidence interval (CI): 0.94-0.99) at 3 yrs and 0.93 (95% CI: 0.91-0.97) at 5 yrs. Most patients died from cardiovascular disease. Apart from age, covariates associated with a lower survival were the presence of a heavy smoking history, a low vital capacity, a low forced expiratory volume in one second (FEV1) and a high mean pulmonary artery pressure. Only three covariates were included by forward stepwise selection in the multivariate analysis, smoking habit (>30 pack-yrs), age and FEV1. The observed survival rates of the group as a whole were similar to those of the general population matched in terms of age, sex and smoking habit, except for patients between 50 and 60 yrs old who had reduced survival. This difference disappeared when patients of the present study with an associated chronic obstructive pulmonary disease were excluded from the comparison. In conclusion, survival of obstructive sleep apnoea patients treated with nasal continuous positive airway pressure is near to that of the general population. The prognosis is worse in subgroups of patients with a history of heavy smoking and with an associated chronic obstructive pulmonary disease.     

Sleep and daytime sleepiness in upper airway resistance syndrome compared to obstructive sleep apnoea syndrome.

This study has investigated differences in the nocturnal sleep and daytime sleepiness among patients with obstructive sleep apnoea syndrome (OSAS), upper airway resistance (UARS), sleep hypopnoea syndrome, and normal control subjects, using sleep scoring and spectral activity analysis of the electroencephalogram (EEG). Twelve nonobese males with UARS aged 30-60 yrs were recruited. These subjects were strictly matched for age and body mass index with twelve OSAS patients, 12 sleep hypopnoea syndrome patients, and 12 normal controls, all male. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS) and the Multiple Sleep Latency Test (MSLT). The macrostructure of sleep was determined using international criteria and spectral analysis of the sleep EEG was obtained from a central lead. The sleep macrostructure of OSAS and UARS patients was significantly different from that of controls. These patients were also sleepier during the daytime than controls. Complaints of tiredness and daytime sleepiness, ESS and MSLT scores were similar in the different patient groups. Mild dysmorphia was present in all three patient groups. However, nocturnal sleep was significantly different among the different groups. OSAS patients had significantly more awake time during sleep than the UARS patients. The spectral activity of the total sleep time of the patient groups also differed significantly from that of controls. When the sleep spectral activity of UARS and OSAS patients were compared, OSAS patients had less slow wave sleep activity than UARS patients. UARS patients had a significantly higher absolute power in the 7-9 Hz bandwidth than OSAS patients. The absolute delta power over the different sleep cycles was also different between controls and patients, and between UARS and OSAS patients. There are clear differences in the macrostructure and spectral activity of sleep between upper airway resistance and obstructive sleep apnoea syndrome patients, demonstrated by differences in the cortical activity recorded in the central lead during sleep. Despite these nocturnal sleep differences, the tests of subjective daytime sleepiness are not significantly different.     

Abnormal lipid peroxidation in patients with sleep apnoea.

The prevalence of cardiovascular diseases is increased in patients with the obstructive sleep apnoea syndrome (OSAS). The fall and rise of arterial oxygenation that follows each apnoea may increase lipid peroxidation and contributes to explaining this association. In the present study, the authors determined lipid peroxidation in patients with OSAS and the effect of treatment with continuous positive airway pressure (CPAP). Fourteen male patients with severe OSAS (59+/-5 apnoea x h(-1)) (+/-SEM) and 13 healthy nonsmoking, male volunteers of similar age were studied. Patients were studied at diagnosis and after treatment with CPAP for more than 1 yr (>4 h x night(-1)). A venous blood sample was obtained early in the morning after fasting all night. In patients with OSAS, a sample before and during sleep was also obtained. Low density lipoprotein (LDL) particles were isolated by sequential ultracentrifugation. Their level of oxidation was determined by the thiobarbituric acid assay (TBARs), and their susceptibility to oxidation by the lag phase measurement. Patients with OSAS showed higher TBARs (28.1+/-2.8 versus 20.0+/-1.8 nmol x malondialdehyde x mgLDL protein(-1), p=0.02) and shorter lag phase values (83.8+/-3.4 versus 99.7+/-3.4 min, p=0.005) than controls. These differences were not due to the smoking status of the patient. Likewise, these values did not change significantly throughout the night yet, the lag phase value was significantly improved by treatment with CPAP (124.9+/-8.5 min; p<0.001). These results indicate that obstructive sleep apnoea syndrome is associated with abnormal lipid peroxidation and that this is improved by chronic use of Continuous positive airway pressure. These results can contribute towards explaining the high prevalence of cardiovascular diseases seen in Obstructive sleep apnoea syndrome.     

Effect of treating severe nasal obstruction on the severity of obstructive sleep apnoea.

An association between mouth breathing during sleep and increased propensity for upper airway collapse is well documented, but the effect of treatment for nasal obstruction on mouth breathing during sleep and simultaneous obstructive sleep apnoea (OSA) severity has not been described previously. A randomised single blind placebo- and sham-controlled crossover study of treatment (topical decongestant and external dilator strip) for nasal obstruction was carried out in 10 patients (nine males; mean+/-SEM 46+/-5 yrs) with nasal obstruction and OSA. All patients had normal acoustic pharyngometry. The effect of treatment on nasal resistance, mouth breathing during sleep and OSA severity was quantified. Treatment of nasal obstruction was associated with a dramatic and sustained reduction in nasal resistance and the oral fraction of ventilation during sleep (mean (95% confidence interval) absolute reduction in oral fraction 30% (12-49)). Improvements in sleep architecture were observed during active treatment, and there was a modest reduction in OSA severity (change in apnoea-hypopnoea index 12 (3-22)). In conclusion, treating nasal obstruction reduced mouth breathing during sleep and obstructive sleep apnoea severity, but did not effectively alleviate obstructive sleep apnoea.     

Metabolic syndrome in Japanese patients with obstructive sleep apnea syndrome.

We investigated the prevalence of metabolic syndrome in patients with obstructive sleep apnea syndrome (OSAS) referred to a tertiary university-based medical center. A cross-sectional study of patients with a definite diagnosis of OSAS was performed using new diagnostic criteria for metabolic syndrome that were designed for the Japanese population. Clinical features and comorbidities related to metabolic syndrome were compared between 819 patients with OSAS (719 men and 100 women) and 89 control subjects without OSAS. Metabolic syndrome was significantly more common in the patients with OSAS than in the controls (49.5% vs. 22.0% for men, p < 0.01; 32.0% vs. 6.7% for women, p < 0.01). Men with OSAS (apnea-hypopnea index [AHI] > or =5/h) had a higher risk of metabolic syndrome compared with controls (odds ratio [OR]: 3.47; 95% confidence interval [CI]: 1.84-6.53). There was a significantly increased risk of metabolic syndrome in men with moderate OSAS (AHI: 15-29.9/h) (OR: 2.83; 95% CI: 1.42-5.66) and men with severe OSAS (AHI > or =30/h) (OR: 5.09; 95% CI: 2.67-9.71). Women with OSAS (AHI> or =5/h) also had an increased risk of metabolic syndrome (OR: 6.59; 95% CI: 1.47-29.38), and the risk was significantly higher in women with severe OSAS (AHI > or =30/h) (OR 14.00; 95% CI: 2.93-66.82). Risk factors for metabolic syndrome differed by gender: in men, age, body mass index (BMI), and OSAS (AHI > or =15/h) were significantly associated with metabolic syndrome, whereas, in women, BMI was the only risk factor for metabolic syndrome. The increase of metabolic syndrome in Japanese OSAS patients suggests that this patient population is burdened with multiple risk factors for cardiovascular disease.     

beta3-Adrenergic receptor Trp64Arg polymorphism and increased body mass index in sleep apnoea.

Obesity is an important risk factor for obstructive sleep apnoea syndrome (OSAS), insulin resistance and cardiovascular disease. The substitution of tryptophan 64 with arginine (Trp64Arg) polymorphism (Arg variant) of the beta(3)-adrenergic receptor (ADRB3) has been associated with obesity. In this study, the prevalence of the Trp64Arg ADRB3 polymorphism in a large group of patients with OSAS and its association with body mass index (BMI), insulin resistance and hypertension were evaluated. ADRB3 genotype was determined in 387 patients with OSAS and 137 healthy subjects recruited from three Spanish tertiary hospitals. The distributions of the ADRB3 genotypes were similar in OSAS and controls, and, in a multivariate model, the risk of OSAS was not associated with the presence of the Arg variant of the ADRB3 gene. However, BMI was higher in those patients with OSAS who carried this genetic variant than in those with the Trp variant. Furthermore, a linear trend for higher BMI was found in those with the Arg variant (56, 75 and 100% for Trp/Trp, Trp/Arg and Arg/Arg, respectively). Insulin resistance, blood pressures and serum levels of lipids and glucose were not associated with the presence of the Arg variant of the ADRB3 gene. The presence of the arginine 64 allele of the beta(3)-adrenergic receptor gene does not increase the risk of obstructive sleep apnoea syndrome, but is associated with the development of obesity in those patients who suffer obstructive sleep apnoea syndrome.     

Validation study of a portable monitoring device for identifying OSA in a symptomatic patient population

Background and objective: Obstructive sleep apnoea syndrome (OSAS) is a common disorder associated with early atherosclerosis, diabetes mellitus, ischaemic heart disease and cerebrovascular disease. The gold standard for confirming OSAS is based on an attended overnight polysomnography (PSG) in a sleep laboratory; however lack of health‐care resources creates long waiting times for patient access to this diagnostic test. This study evaluated the ability of a portable sleep‐monitoring device to identify patients in Hong Kong with suspected OSAS. Methods: Patients with symptoms of OSAS were invited to use the ARES (apnoea risk evaluation system) concurrently with an attended inpatient PSG. Several sets of AHI were generated by the ARES provider based on different oxygen desaturation criteria and surrogate parameters of arousal. The results were compared against PSG to determine the optimal sensitivity and specificity. Results: There were 141 patients who completed the study successfully. Results of AHI from the ARES study were presented in the order of different scoring criteria––4% oxygen desaturation alone, obstructive events with 3% oxygen desaturation and obstructive events with 1% desaturation plus surrogate arousal criteria. The sensitivity was 0.84 (95% confidence interval (CI): 0.77–0.90), 0.89 (95% CI: 0.89–0.94) and 0.97 (95% CI: 0.94–0.99), respectively. The specificity was 1, 1 and 0.63 (95% CI: 0.55–0.71), respectively. The receiver operating curve had an area of 0.96, 0.97 and 0.98, respectively. The kappa coefficient varied from 0.24 to 0.55 for agreement of severity between PSG and ARES. The likelihood ratio positive and the likelihood ratio negative were 2.61, infinity, infinity and 0.16, 0.11, 0.05, respectively, in the order of oxygen desaturation described earlier. Conclusions: The ARES device has reasonable sensitivity and specificity for diagnosing severe OSAS in symptomatic Chinese patients. There is moderate agreement between ARES and PSG in the diagnosis of severe disease, but less agreement in patients with mild/moderate disease.     

Sleep fragmentation: comparison of two definitions of short arousals during sleep in OSAS patients.

The measurement of arousals during sleep is useful to quantify sleep fragmentation. The criteria for electroencephalography (EEG) arousals defined by the American Sleep Disorders Association (ASDA) have recently been criticized because of lack of interobserver agreement. The authors have adopted a scoring method that associates the increase in chin electromyography (EMG) with the occurrence of an alpha-rhythm in all sleep stages (Université Catholique de Louvain (UCL) definition of arousals). The aim of the present study was to compare the two scoring definitions in terms of agreement and repeatability and the time taken for scoring in patients with obstructive sleep apnoea syndrome (OSAS) of varying severity. Two readers using both ASDA and UCL definitions scored twenty polysomnographies (PSGs) each on two occasions. The PSGs were chosen retrospectively to represent a wide range of arousal index (from 6-82) in OSAS patients. There was no difference in the arousal indices between readers and between scoring methods. The mean+/-SD difference between the two definitions (the bias) was 1.1+/-3.76 (95% confidence interval: -0.66-2.86). There was a strong linear relationship between the arousal index scored with the two definitions (r=0.981, p<0.001). Mean+/-SD scoring duration was significantly shorter for UCL than for ASDA definitions (18.5+/-5.4 versus 25.3+/-6.6 min, p<0.001). In conclusion, it has been found that in obstructive sleep apnoea syndrome patients, the American Sleep Disorders Association and Université Catholique de Louvain definitions were comparable in terms of agreement and repeatability.