Hyperlipidaemia prevalence and cholesterol control in obstructive sleep apnoea: Data from the European sleep apnea database (ESADA).

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) and hyperlipidaemia are independent risk factors for cardiovascular disease. This study investigates the association between OSA and prevalence of hyperlipidaemia in patients of the European Sleep Apnea Database (ESADA) cohort. METHODS: The cross-sectional analysis included 11 892 patients (age 51.9 ± 12.5 years, 70% male, body mass index (BMI) 31.3 ± 6.6 kg/m2 , mean oxygen desaturation index (ODI) 23.7 ± 25.5 events/h) investigated for OSA. The independent odds ratio (OR) for hyperlipidaemia in relation to measures of OSA (ODI, apnoea-hypopnoea index, mean and lowest oxygen saturation) was determined by means of general linear model analysis with adjustment for important confounders such as age, BMI, comorbidities and study site. RESULTS: Hyperlipidaemia prevalence increased from 15.1% in subjects without OSA to 26.1% in those with severe OSA, P < 0.001. Corresponding numbers in patients with diabetes were 8.5% and 41.5%, P < 0.001. Compared with ODI quartile I, patients in ODI quartiles II-IV had an adjusted OR (95% CI) of 1.33 (1.15-1.55), 1.37 (1.17-1.61) and 1.33 (1.12-1.58) (P < 0.001), respectively, for hyperlipidaemia. Obesity was defined as a significant risk factor for hyperlipidaemia. Subgroups of OSA patients with cardio-metabolic comorbidities demonstrated higher prevalence of HL. In addition, differences in hyperlipidaemia prevalence were reported in European geographical regions with the highest prevalence in Central Europe. CONCLUSION: Obstructive sleep apnoea, in particular intermittent hypoxia, was independently associated with the prevalence of hyperlipidaemia diagnosis.

Insomnia symptoms combined with nocturnal hypoxia associate with cardiovascular comorbidity in the European sleep apnea cohort (ESADA).

PURPOSE: The aim of the current study was to further investigate the concept of previously reported high occurrence of comorbidities in obstructive sleep patients (OSA) with insomnia-like symptoms. We hypothesized that this finding at least partly is mediated by nocturnal hypoxia. Moreover, we speculated that the spectrum of the clinical OSA phenotypes differs between European geographical regions. METHODS: Cohort of the European Sleep Apnea Database (n = 17,325; 29.9% females) was divided into five subcohorts according to geographical region (North, East, South, West, Central) and further into four clinical presentation phenotypes based on daytime symptoms (EDS) and characteristics suggestive of insomnia. RESULTS: The insomnia phenotype (alone or together with EDS) dominated in all European regions. Isolated insomnia, however, was less common in the West. Insomnia phenotype was associated with the highest proportion of cardiovascular comorbidity (51.7% in the insomnia vs. 43.9% in the EDS type). Measures of nocturnal hypoxemia were independently associated with cardiovascular comorbidity in phenotypes with insomnia-like symptoms. The burden of comorbidities was high across all geographical regions and clinical phenotypes. Regional differences were clinically relevant for age (48 vs. 54 years), BMI (29 vs. 34 kg/m2), and ODI (15 vs. 32/h). CONCLUSION: High prevalence of particularly cardiovascular comorbidity among patients with insomnia-like symptoms was linked to nocturnal hypoxemia. Considerable differences in clinical presentation were found among OSA patients across Europe. Our data underline that physicians should ask their patients with suspected OSA also for insomnia symptoms. It remains to be explored if a reduction of nocturnal hypoxemia predicts the improvement of insomnia symptoms.

Measures of bronchodilator response of FEV1, FVC and SVC in a Swedish general population sample aged 50-64 years, the SCAPIS Pilot Study.

BACKGROUND: Data are lacking from general population studies on how to define changes in lung function after bronchodilation. This study aimed to analyze different measures of bronchodilator response of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and slow vital capacity (SVC). MATERIALS AND METHODS: Data were derived from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) Pilot study. This analysis comprised 1,050 participants aged 50-64 years from the general population. Participants were investigated using a questionnaire, and FEV1, FVC and SVC were recorded before and 15 minutes after inhalation of 400 µg of salbutamol. A bronchodilator response was defined as the relative change from baseline value expressed as the difference in units of percent predicted normal. Predictors of bronchodilator responses were assessed using multiple linear regression models. Airway obstruction was defined as FEV1/FVC ratio below lower limit of normal (LLN) before bronchodilation, and COPD was defined as an FEV1/FVC ratio below LLN after bronchodilation. Physician-diagnosed asthma was defined as an affirmative answer to "Have you ever had asthma diagnosed by a physician?". Asymptomatic never-smokers were defined as those not reporting physician-diagnosed asthma, physician-diagnosed COPD or emphysema, current wheeze or chronic bronchitis and being a lifelong never-smoker. RESULTS: Among all subjects, the greatest bronchodilator responses (FEV1, FVC and SVC) were found in subjects with asthma or COPD. The upper 95th percentile of bronchodilator responses in asymptomatic never-smokers was 8.7% for FEV1, 4.2% for FVC and 5.0% for SVC. The bronchodilator responses were similar between men and women. In a multiple linear regression model comprising all asymptomatic never-smokers, the bronchodilator response of FEV1 was significantly associated with airway obstruction and height. CONCLUSION: When the bronchodilator response in asymptomatic never-smokers is reported as the difference in units of predicted normal, significant reversibility of FEV1, FVC and SVC to bronchodilators is ~9%, 4% and 5%, respectively.

Attention deficits detected in cognitive tests differentiate between sleep apnea patients with or without a motor vehicle accident.

OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased motor vehicle accident (MVA) risk. Conventional measures of OSA severity do not predict individual risk. Cognitive function tests have failed to incorporate outcomes in risk prediction. We aimed to identify markers of cognitive function for MVA risk prediction in OSA. METHODS: OSA patients [n = 114, 75% male, median age 51 (43-61) years, body mass index (BMI) 30 (27-33) kg/m2, apnea-hypopnea index 25 (6-49) n/h, and Epworth Sleepiness (ESS) score 11 (8-16)] were recruited from a sleep laboratory. Two cognitive function tests, the Attention Network Test (ANT) and a modified Oxford Sleep Resistance Test (OSLER) test (GOSLING), were assessed. RESULTS: OSA patients with (n = 11) or without (n = 103) a MVA record in the Swedish traffic accident registry were identified. In patients with a MVA, 64% were commercial drivers. In patients with a MVA history, more lapses [42 (5-121) vs. 5 (1-25), P = 0.02] and fewer responses [238 (158-272) vs. 271 (256-277), P = 0.03] to stimuli in the ANT were found. In the GOSLING, the number of lapses was higher (29 (10-97) vs. 7 (2-19), P = 0.01) and the reaction time was longer [462 (393-551) vs. 407 (361-449) ms, P = 0.05]. OSA severity and ESS score poorly predicted MVAs (P > 0.2). CONCLUSIONS: We have demonstrated that deficit in sustained attention, assessed by daytime neurocognitive function tests, was associated with MVA risk in OSA patients. We were unable to detect an association between MVA history and severity of OSA or the ESS score. The findings provide a rationale for further development of objective MVA risk assessment tools in OSA.

High prevalence of restless legs syndrome among women with multi-site pain: a population-based study in Dalarna, Sweden.

BACKGROUND: The chronic pain (CP) and chronic multi-site pain (CMP) condition is a highly prevalent health problem. Several studies have reported a high (31-64%) prevalence of co-morbid restless legs syndrome (RLS) in patients with fibromyalgia, one specifically defined form of chronic widespread pain. The current study explored the association between CMP and RLS. METHOD: The study included 4040 respondents to a postal questionnaire sent to 10,000 women in the age range of 18-64 years and randomly selected from the general population. Complete questionnaire data on type (acute/chronic), degree (mild to severe) and spreading (0-5 body zones) of pain, as well as RLS symptoms (validated questionnaire), were obtained from 3060 subjects. Information on lifestyle, anthropometrics, co-morbidities and medication was collected. RESULTS: RLS prevalence increased from 9.6% in subjects with no report of pain to 23,9%, 26.4%, 39.2%, 44.9% and 54.8% in those reporting one, two, three, four and five pain areas, respectively (p < 0.001). Further, RLS prevalence increased from 9.6% (no pain) to 27.9%, 37.9% and 42.4% in subjects with mild, moderate and severe chronic pain (p < 0.001). Multi-site pain, pain localized in the leg, extended pain duration and co-morbid psychiatric disorder were all independently associated with a RLS diagnosis in a multiple regression analysis. CONCLUSION: The prevalence of RLS increased progressively with pain severity and even more sharply with the degree of pain spreading in women recruited from the general population. Both acute and chronic pain was associated with RLS-related symptoms.

Night-time symptoms: a forgotten dimension of COPD.

Sleep quality is often poor in patients with chronic obstructive pulmonary disease (COPD), but these night-time symptoms are frequently unnoticed by physicians and/or not reported by patients themselves. Therefore, the prevalence and clinical impact of sleep disturbances and night-time symptoms in COPD is not well understood and has not been a clinical focus to date. To address this gap, an expert panel meeting was convened in Barcelona, Spain, in March 2011 to discuss the aetiology, evolution, burden, long-term clinical consequences and optimal management of night-time symptoms in COPD. The term "night-time symptoms" in COPD has not been distinctly defined in an objective sense but epidemiological data suggests that the prevalence of nocturnal symptoms and symptomatic sleep disturbance may exceed 75% in patients with COPD. The panel concluded that night-time symptoms in COPD are prevalent and bothersome; that their cause(s) are multiple and include demographic factors, such as age and obesity, pharmacotherapy, disease-specific symptoms and the presence of comorbid sleep disorders, and other medical conditions; and that potential long-term consequences can include lung function changes, increased exacerbation frequency, emergence or worsening of cardiovascular disease, cognitive effects, depression, impaired quality of life and increased mortality. To date, few interventional studies have investigated them, but emerging data suggest that bronchodilator therapy can improve them if deployed appropriately. In summary, night-time symptoms in COPD warrant further clinical investigation with validated tools.

The European Sleep Apnoea Database (ESADA): report from 22 European sleep laboratories.

The European Sleep Apnoea Database (ESADA) reflects a network of 22 sleep disorder centres in Europe enabled by a COST action B26 programme. This ongoing project aims to describe differences in standard clinical care of patients with obstructive sleep apnoea (OSA) and to establish a resource for genetic research in this disorder. Patients with suspected OSA are consecutively included and followed up according to local clinical standards. Anthropometrics, medical history, medication, daytime symptoms and sleep data (polysomnography or cardiorespiratory polygraphy) are recorded in a structured web-based report form. 5,103 patients (1,426 females, mean±sd age 51.8±12.6 yrs, 79.4% with apnoea/hypopnoea index (AHI) ≥5 events·h(-1)) were included from March 15, 2007 to August 1, 2009. Morbid obesity (body mass index ≥35 kg·m(-2)) was present in 21.1% of males and 28.6% of females. Cardiovascular, metabolic and pulmonary comorbidities were frequent (49.1%, 32.9% and 14.2%, respectively). Patients investigated with a polygraphic method had a lower AHI than those undergoing polysomnography (23.2±23.5 versus 29.1±26.3 events·h(-1), p<0.0001). The ESADA is a rapidly growing multicentre patient cohort that enables unique outcome research opportunities and genotyping. The first cross-sectional analysis reveals a high prevalence of cardiovascular and metabolic morbidity in patients investigated for OSA.

Self-reported sleep apnoea and mortality in patients from the Swedish Obese Subjects study.

Sleep apnoea is associated with increased mortality in sleep clinic and community population groups. It is unclear whether a clinical report of sleep apnoea results in additional mortality risk in patients with severe obesity. The Swedish Obese Subjects (SOS) study is a nonrandomised controlled trial of bariatric surgery versus conventional treatment for the treatment of severe obesity and its complications (mean ± SD body mass index 41 ± 5 kg · m(-2)). The presence or absence of sleep apnoea (witnessed pauses in breathing) was determined by self-reporting at baseline in 3,953 patients who were observed for 54,236 person-yrs (mean 13.5 maximum 21.0 yrs). Sleep apnoea was reported by 934 (23.6%) patients at baseline and was a significant univariate predictor of mortality (hazard ratio (95% CI) 1.74 (1.40-2.18)). In a range of multivariate models of mortality risk, controlling for ≤ 16 other potential confounders and established mortality risk factors, sleep apnoea remained a significant prognostic factor (fully adjusted model 1.29 (1.01-1.65)). Self-reported sleep apnoea is an independent prognostic marker of all-cause mortality in obese patients.

Management of obstructive sleep apnea in Europe.

OBJECTIVES: In Europe, the services provided for the investigation and management of obstructive sleep apnoea (OSA) varies from country to country. The aim of this questionnaire-based study was to investigate the current status of diagnostic pathways and therapeutic approaches applied in the treatment of OSA in Europe, qualification requirements of physicians involved in diagnosis and treatment of OSA, and reimbursement of these services. METHODS: Two questionnaires were sent to 39 physicians in 22 countries in Europe. In order to standardize the responses, the questionnaire was accompanied by an example. RESULTS: Sleep centers from 21 countries (38 physicians) participated. A broad consistency among countries with respect to the following was found: pathways included referral to sleep physicians/sleep laboratories, necessity for objective diagnosis (primarily by polysomnography), use of polygraphic methods, analysis of polysomnography (PSG), indications for positive airway pressure (PAP) therapy, application of standard continuous PAP (CPAP) therapy (100% with an CPAP/APAP ratio of 2.24:1), and the need (90.5%) and management of follow-up. Differences were apparent in reimbursement of the diagnostic procedures and follow-up, in the procedures for PAP titration from home APAP titration with portable sleep apnea monitoring (38.1%) up to hospital monitoring with PSG and APAP (85.7%), and in the qualification requirements of sleep physicians. CONCLUSIONS: Management of OSA in different European countries is similar except for reimbursement rules, qualification of sleep specialists and procedures for titration of the CPAP treatment. A European network (such as the one accomplished by the European Cooperation in Science and Technology [COST] B26 Action) could be helpful for implementing these findings into health-service research in order to standardize management in a cost effective perspective.

Medico-legal implications of sleep apnoea syndrome: driving license regulations in Europe.

BACKGROUND: Sleep apnoea syndrome (SAS), one of the main medical causes of excessive daytime sleepiness, has been shown to be a risk factor for traffic accidents. Treating SAS results in a normalized rate of traffic accidents. As part of the COST Action B-26, we looked at driving license regulations, and especially at its medical aspects in the European region. METHODS: We obtained data from Transport Authorities in 25 countries (Austria, AT; Belgium, BE; Czech Republic, CZ; Denmark, DK; Estonia, EE; Finland, FI; France, FR; Germany, DE; Greece, GR; Hungary, HU; Ireland, IE; Italy, IT; Lithuania, LT; Luxembourg, LU; Malta, MT; Netherlands, NL; Norway, EC; Poland, PL; Portugal, PT; Slovakia, SK; Slovenia, SI; Spain, ES; Sweden, SE; Switzerland, CH; United Kingdom, UK). RESULTS: Driving license regulations date from 1997 onwards. Excessive daytime sleepiness is mentioned in nine, whereas sleep apnoea syndrome is mentioned in 10 countries. A patient with untreated sleep apnoea is always considered unfit to drive. To recover the driving capacity, seven countries rely on a physician's medical certificate based on symptom control and compliance with therapy, whereas in two countries it is up to the patient to decide (on his doctor's advice) to drive again. Only FR requires a normalized electroencephalography (EEG)-based Maintenance of Wakefulness Test for professional drivers. Rare conditions (e.g., narcolepsy) are considered a driving safety risk more frequently than sleep apnoea syndrome. CONCLUSION: Despite the available scientific evidence, most countries in Europe do not include sleep apnoea syndrome or excessive daytime sleepiness among the specific medical conditions to be considered when judging whether or not a person is fit to drive. A unified European Directive seems desirable.

The influence of patent foramen ovale on oxygen desaturation in obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is associated with oxygen desaturation to a varying degree. A patent foramen ovale (PFO) may allow interatrial right-to-left shunting. The hypothesis of the current study was that oxygen desaturation will occur more often, in proportion to the frequency of respiratory disturbances, in OSA subjects with PFO than in those without. In a group of 209 subjects diagnosed with OSA, the proportion of desaturation to respiratory events was calculated as the ratio of oxygen desaturation index (ODI)/apnoea-hypopnoea index (AHI). A total of 15 cases with high proportional desaturation (ODI/AHI >or=0.66) were individually matched with 15 controls with low proportional desaturation (ODI/AHI or=20 bubbles passed over from the right to the left atrium after a single injection. The prevalence of large PFO was nine out of 15 (60%) in the high proportional desaturation group versus two out of 15 (13%) in the low proportional desaturation group. The median number of passing bubbles was positively correlated to minimum oxygen saturation among those with PFO. In conclusion, oxygen desaturation occurs more often, in proportion to the frequency of respiratory disturbances, in obstructive sleep apnoea subjects with a patent foramen ovale than in those without.

The effect of sibutramine-assisted weight loss in men with obstructive sleep apnoea.

OBJECTIVE: Obstructive sleep apnoea (OSA) occurs frequently in obese patients and may be reversible with weight loss. Obstructive sleep apnoea and obesity are both independent risk factors for hypertension and increased sympathetic activity. Sibutramine has been increasingly used in the management of obesity, but is relatively contraindicated in patients with hypertension. No studies have investigated the effect of sibutramine on OSA, blood pressure and heart rate. We aimed to assess the changes in OSA and cardiovascular parameters in obese men with OSA enrolled in a sibutramine-assisted weight loss programme (SIB-WL). DESIGN: Open uncontrolled cohort study of obese male subjects with OSA in an SIB-WL. SUBJECTS: Eighty-seven obese (body mass index =34.2+/-2.8 kg/m(2)) middle-aged (46.3+/-9.3 years) male subjects with symptomatic OSA (Epworth score 13.4+/-3.6; respiratory disturbance index (RDI) 46.0+/-23.1 events/h) completed the study. RESULTS: At 6 months, there was significant weight loss (8.3+/-4.7 kg, P<0.0001), as well as a reduction in waist and neck circumference and sagittal height (all P<0.0001). These changes were accompanied by a reduction in OSA severity (RDI fell by 16.3+/-19.4 events/h and Epworth score by 4.5+/-4.6), both P<0.0001). There was no significant change to systolic (P=0.07) or diastolic blood pressure (P=0.87); however, there was a mild rise in resting heart rate (P<0.0001). CONCLUSION: Moderate (approximately 10%) weight loss with SIB-WL results in improvement in OSA severity without increase in blood pressure in closely monitored OSA subjects.

Sleep apnoea and quality of life in growth hormone (GH)-deficient adults before and after 6 months of GH replacement therapy.

OBJECTIVE: To investigate the sleep architecture and breathing as well as quality of life (QoL) in adults with GH deficiency (GHD) before and 6 months after GH replacement therapy. DESIGN: A prospective observational study. PATIENTS: Nineteen consecutive adults with GHD (11 men, eight women; mean age 53, range 21-73 years) were studied. MEASUREMENTS: An overnight sleep study was performed and the Minor Symptom Evaluation Profile (MSEP), Functional Outcome of Sleep Questionnaire (FOSQ), Short Form 36 (SF-36) and Epworth Sleepiness Scale (ESS) questionnaires were applied at baseline and after the treatment period. RESULTS: For the whole group, there were no significant changes in mean total sleep time (TST; 370 min vs. 374 min), proportion of slow-wave sleep (SWS; 17.8%vs. 18.4%) and rapid eye movement (REM) sleep (12.1%vs. 13.9%) on GH replacement. Mean apnoea-hypopnoea index (AHI) was high and remained unchanged (28.2/h before vs. 28.0/h following GH replacement). Twelve patients (63%) were found to have obstructive sleep apnoea (OSA; AHI >or= 10/h) at baseline. Compared with GH-deficient patients without OSA (AHI 3.9/h), the OSA patients (AHI 42.4/h) had less SWS (11.4%vs. 28.6%, P = 0.010) and REM sleep (10.1%vs. 15.5%, P = 0.036). A marginal increase was observed in REM sleep time (10.1% before vs. 12.7% after GH; P = 0.048) while SWS was unchanged in this group. Moreover, MSEP for General Well-being and Responsiveness, FOSQ scores for General Productivity, Activity Level and Vigilance as well as SF-36 domains for Vitality and Mental Health were improved. CONCLUSIONS: Contrary to some previous observations in a smaller group of patients, our data suggest that GH therapy does not induce or aggravate OSA in GH-deficient adults. Moreover, GH therapy may improve some of the QoL dimensions in these patients.

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.

Hypertension prevalence in obstructive sleep apnoea and sex: a population-based case-control study.

Obstructive sleep apnoea (OSA) is a recognised risk factor for hypertension (HT). The current authors investigated confounders of this association in a sex-balanced community-based sample of patients with HT (n=161) from the Skaraborg Hypertension and Diabetes Project (n=1,149) and normotensive controls (n=183) from an age and sex stratified community-based population sample (n=1,109). All participants underwent ambulatory home polysomnography. Severe OSA (apnoea-plus-hypopnoea index (AHI)>or=30 events.h-1) was found in 47 and 25% of hypertensive and normotensive males, respectively. The corresponding numbers in females were 26 and 24%, respectively. The odds ratio (OR) for HT increased across AHI tertiles from 1.0 to 2.1 (95% confidence interval: 0.9-4.5) and 1.0 to 3.7 (95% CI: 1.7-8.2) in males, but not in females where the OR increased from 1.0 to 1.8 (95% CI: 0.8-3.9) and 1.0 to 1.6 (95% CI: 0.7-3.5). Regression analysis correcting for age, body mass index (or waist-hip ratio) and smoking did not eliminate the association between OSA and HT in males. The present data suggest that obstructive sleep apnoea is highly prevalent in both the general population and in patients with known hypertension. The contribution of obstructive sleep apnoea to hypertension risk may be sex dependent and higher in males than in females.

Low serum concentration of sulfatide and presence of sulfated lactosylceramid are associated with Type 2 diabetes. The Skaraborg Project.

AIMS: The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of beta-cell secretory granules, activates K(ATP)-channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes. METHODS: A case-control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey. RESULTS: Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently). CONCLUSIONS: We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors.

Intracerebroventricular administration of the angiotensin II receptor antagonist saralasin reduces respiratory rate and tidal volume variability in freely moving Wistar rats.

The possible importance of intra-individual variations in respiratory rate and tidal volume has recently gained interest in psychiatric research, as a result of the observations that patients with panic disorder or premenstrual dysphoric disorder display enhanced respiratory variability as compared to controls. Although the role of brain neurotransmitters in the regulation of breathing has been extensively studied, as yet data on the central regulation of respiratory variability is sparse. Prompted by previous studies indicating that angiotensin II (ANG II) may influence ventilation as well as anxiety, we have studied the effect of intracerebroventricular administration of an ANG II receptor antagonist, saralasin, on respiratory variability in unrestrained, freely moving male Wistar rats. Treatment with saralasin, 5 mug dissolved in 1 mul saline followed by 9 mul saline in each lateral cerebral ventricle, did not influence tidal volume, but markedly reduced tidal volume variability (p=0.0005), as compared to saline injections (10 mul). Respiratory rate was reduced by saralasin (p=0.02), and there was also a non-significant tendency for a reduction in respiratory rate variability. Both minute volume (p=0.005) and volume/10 s variability (p=0.0006) were reduced. It is suggested that ANG II in the brain of Wistar rats may regulate respiratory rate and tidal volume variability.

Obstructive sleep apnoea and urine catecholamines in hypertensive males: a population-based study.

Studies addressing the relationship between obstructive sleep apnoea (OSA) and sympathoadrenal activity have been criticized for poor control of factors known to confound sympathetic function, including hypertension. The aim of this study was to investigate the relationship between OSA and urinary catecholamines in a population-based sample of hypertensive males. In 1994, 2,668 males aged 40-79 yrs answered a questionnaire regarding sleep disorders and somatic diseases. Of those who reported hypertension, an age-stratified sample of 116 was selected for monitoring of breathing during sleep and overnight urine analysis. Subjects with OSA, defined as apnoea-hypopnoea index > or = 10 x h(-1), had higher concentrations of urinary normetanephrine (182+/-57 versus 141+/-45 micromol x mol(-1) creatinine, p<0.001) and metanephrine (70+/-28 versus 61+/-28 micromol mol(-1) creatinine, p<0.05) in comparison to subjects without OSA. In a multiple regression analysis, there was an association between variables of sleep-disordered breathing and normetanephrine and metanephrine concentrations, independent of major confounding factors. The authors concluded that, in a population-based sample of hypertensive males, obstructive sleep apnoea is associated with increased urinary concentrations of extraneuronal metabolites of catecholamines independent of major confounding factors, suggesting increased sympathoadrenal activity. Elevated sympathoadrenal activity may explain the increased cardiovascular morbidity associated with obstructive sleep apnoea.

Therapeutic electrical stimulation of the hypoglossal nerve in obstructive sleep apnea.

BACKGROUND: Hypoglossal nerve stimulation has been demonstrated to relieve upper airway obstruction acutely, but its effect on obstructive sleep apnea is not known. OBJECTIVE: To determine the response in obstructive sleep apnea to electrical stimulation of the hypoglossal nerve. METHODS: Eight patients with obstructive sleep apnea were implanted with a device that stimulated the hypoglossal nerve unilaterally during inspiration. Sleep and breathing patterns were examined at baseline before implantation and after implantation at 1, 3, and 6 months and last follow-up. RESULTS: Unilateral hypoglossal nerve stimulation decreased the severity of obstructive sleep apnea throughout the entire study period. Specifically, stimulation significantly reduced the mean apnea-hypopnea indices in non-rapid eye movement (mean +/- SD episodes per hour, 52.0 +/- 20.4 for baseline nights and 22.6 +/- 12.1 for stimulation nights; P<.001) and rapid eye movement (48.2 +/- 30.5 and 16.6 +/- 17.1, respectively; P<.001) sleep and reduced the severity of oxyhemoglobin desaturations. With improvement in sleep apnea, a trend toward deeper stages of non-rapid eye movement sleep was observed. Moreover, all patients tolerated long-term stimulation at night and did not experience any adverse effects from stimulation. Even after completing the study protocol, the 3 patients who remained free from stimulator malfunction continued to use this device as primary treatment. CONCLUSION: The findings demonstrate the feasibility and therapeutic potential for hypoglossal nerve stimulation in obstructive sleep apnea.

Blood pressure, cardiac structure and severity of obstructive sleep apnea in a sleep clinic population.

OBJECTIVES: We investigated whether the severity of obstructive sleep apnea (OSA) predicts blood pressure or cardiac left ventricular thickness in a clinical population of OSA patients, if adjustments are made for age, gender, use of antihypertensive agents, smoking, body mass index, history of coronary artery disease, hypercholesterolemia and circulating C-peptide concentrations. DESIGN: Relationships in this cross-sectional study were investigated with correlation analysis and multiple regression procedures. PATIENTS AND METHODS: Apnea-hypopnea index (AHI, polysomnography) and office systolic and diastolic blood pressures (SBP and DBP) were measured in 81 subjects referred to a university hospital sleep laboratory. Ambulatory blood pressures were recorded during one 24 h cycle. Left ventricular (LV) muscle size was quantified as two-dimensionally directed M-mode-derived end-diastolic thickness of interventricular septum and posterior chamber wall. RESULTS: After adjustment for separate or the entire set of covariates, AHI predicted office SBP and DBP as well as daytime ambulatory DBP and night-time ambulatory SBP and DBP, but not daytime ambulatory SBP. In contrast, associations between AHI and LV muscle thickness reflected complex inter-relationships with confounding variables. Smoking and age suppressed, whereas body mass index (BMI) and hypertension inflated the relationship between OSA severity and LV muscle thickness in this study. CONCLUSIONS: AHI is an independent predictor of several measures of blood pressure. OSA severity and LV muscle thickness appear to be primarily linked via increased blood pressure.