Tarja Saaresranta

Diabetes Mellitus Prevalence and Control in Sleep-Disordered Breathing: The European Sleep Apnea Cohort (ESADA) Study

BACKGROUND OSA is associated with an increased risk of cardiovascular morbidity. A driver of this is metabolic dysfunction and in particular type 2 diabetes mellitus (T2DM). Prior studies identifying a link between OSA and T2DM have excluded subjects with undiagnosed T2DM, and there is a lack of population-level data on the interaction between OSA and glycemic control among patients with diabetes. We assessed the relationship between OSA severity and T2DM prevalence and control in a large multinational population. METHODS We performed a cross-sectional analysis of 6,616 participants in the European Sleep Apnea Cohort (ESADA) study, using multivariate regression analysis to assess T2DM prevalence according to OSA severity, as measured by the oxyhemoglobin desaturation index. Patients with diabetes were identified by previous history and medication prescription, and by screening for undiagnosed diabetes with glycosylated hemoglobin (HbA1c) measurement. The relationship of OSA severity with glycemic control was assessed in diabetic subjects. RESULTS T2DM prevalence increased with OSA severity, from 6.6% in subjects without OSA to 28.9% in those with severe OSA. Despite adjustment for obesity and other confounding factors, in comparison with subjects free of OSA, patients with mild, moderate, or severe disease had an OR (95% CI) of 1.33 (1.04-1.72), 1.73 (1.33-2.25), and 1.87 (1.45-2.42) (P < .001), respectively, for prevalent T2DM. Diabetic subjects with more severe OSA had worse glycemic control, with adjusted mean HbA1c levels 0.72% higher in patients with severe OSA than in those without sleep-disordered breathing (analysis of covariance, P < .001). CONCLUSIONS Increasing OSA severity is associated with increased likelihood of concomitant T2DM and worse diabetic control in patients with T2DM.

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 program. 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. 5103 patients (1426 females, age 51.8±12.6 years, 79.4% with AHI≥5 events·hr−1) were included from March 15, 2007 to August 1, 2009. Morbid obesity (BMI≥35 kg·m−2) was present in 21.1% of males and 28.6% of women. 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 vs. 29.1±26.3 events·hour−1, p<0.0001). The ESADA is a rapidly growing multicentric 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 OSAS.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.

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.

Impact of menopause on the manifestation and severity of sleep‐disordered breathing

Background. Decreased production of female hormones might explain the increased prevalence of sleep‐disordered breathing in postmenopausal women. Objectives. We evaluated, whether menopause has an impact on the manifestation of sleep‐disordered breathing in terms of signs, symptoms, and breathing pattern. Methods. The study was a cross‐sectional study utilizing a patient database, hospital records, sleep studies, and questionnaires. The hospital records and sleep studies were reviewed in 601 consecutive women studied between 1994 and 1998 in a university hospital pulmonary clinic. The records were completed with questionnaires. Results. Nocturnal breathing abnormalities covered a greater proportion of the night in postmenopausal than in premenopausal women (68.1% versus 35.8% of time in bed, p<0.0001), and the prevalence of sleep‐disordered breathing tended to be higher (86.2% versus 79.4% of time in bed, p = 0.057). The body mass indices and the major symptoms of sleep‐disordered breathing were similar in pre‐ and postmenopausal women. Postmenopausal women had less nasal congestion (p<0.001) than premenopausal ones. Body mass index was a significant explanatory factor of daytime sleepiness. Conclusions. Post‐ and premenopausal women present with similar signs and symptoms when referred to sleep studies. However, sleep‐disordered breathing is more severe in postmenopausal than in premenopausal women.

CPAP adherence and partial upper airway obstruction during sleep.

Nasal continuous positive airway pressure (CPAP) is the treatment of choice in severe obstructive sleep-disordered breathing (SDB). Partial obstruction is usually considered as mild SDB with poor CPAP adherence. In a retrospective study, we investigated the occurrence of partial obstruction in 233 age and BMI-matched male–female pairs and its impact on CPAP adherence after one year using static-charge-sensitive bed. Women had less SDB compared with men (21.8 vs 31.7% of time in bed (TIB), p < 0.001), less periodic breathing (5.8 vs 15.6%, p < 0.001) but tended to have more partial obstruction (10.5 vs 7.5%, p = 0.174). In women, partial obstruction accounted for 50.2% of breathing abnormalities, in men 37.2% (p < 0.001). CPAP adherence was 60.5% in women and 56.9% in men. When taking into account the proportion of partial obstruction (≤5 vs >5% of TIB) or periodic breathing, there were no differences in women’s CPAP adherence (p = 0.130 and p = 0.148, respectively). Men with periodic breathing over 5% of TIB tended to be more adherent to CPAP, (p = 0.052). The high occurrence of partial obstruction in both genders and particularly in women suggests that the apnea–hypopnea index underestimates the occurrence of SDB. There are no concerns of low adherence when treating symptomatic partial obstruction during sleep. Partial obstruction may not represent mild SDB but a different entity.

Glucose Homeostasis in Hypertensive Subjects

The objective of this study was to estimate the prevalence of undiagnosed impaired glucose homeostasis in hypertensive subjects in the general population. The most reasonable screening strategy for glucose disorders was also assessed. We carried out an oral glucose tolerance test for 1106 hypertensive subjects aged 45 to 70 years without previously diagnosed diabetes or cardiovascular disease. Blood pressure, waist circumference, body mass index, and plasma lipids were also measured. Type 2 diabetes was found in 66 (6%) of the subjects, impaired glucose tolerance in 220 (20%), and impaired fasting glucose in 167 (15%). If we had carried out an oral glucose tolerance test only for those hypertensive subjects with fasting plasma glucose ≥5.6 mmol/L, we would have missed ≈40% of the patients with impaired glucose tolerance. The International Diabetes Federation criteria of metabolic syndrome identified 96% of all the cases of type 2 diabetes and 88% of all the cases of impaired glucose tolerance. The prevalence of central obesity was alarming: 90% of the women and 82% of the men had a waist circumference ≥80 cm or ≥94 cm, respectively. Impaired glucose homeostasis and central obesity are common in hypertensive subjects. An oral glucose tolerance test is reasonable to carry out at least for the hypertensive subjects with metabolic syndrome. Weight stabilization is an important goal to treat hypertensive patients.

Sleep apnoea severity independently predicts glycaemic health in nondiabetic subjects: the ESADA study

Obstructive sleep apnoea (OSA) is associated with increased risk of dysglycaemia but the intimate link of these conditions with obesity makes discerning an independent relationship between them challenging. Glycosylated haemoglobin (HbA1c) levels predict adverse cardiovascular outcomes in nondiabetics but there is a lack of population-level data exploring the relationship of HbA1c with OSA. A cross-sectional analysis of 5294 participants in the multinational European Sleep Apnoea Cohort (European Sleep Apnoea Database) study was performed, assessing the relationship of OSA severity with HbA1c levels in nondiabetic subjects, with adjustment for confounding factors. HbA1c levels correlated significantly with OSA severity in univariate analysis. Following adjustment for confounding factors, apnoea–hypopnoea index (AHI) (standardised &bgr; 0.158; p<0.001), along with nocturnal hypoxaemia, predicted HbA1c. Adjusted mean HbA1c levels were lower in the lowest AHI quartile (5.24%, 95% CI 5.21–5.27%) than in the second (5.37%, 95% CI 5.34–5.40%), third (5.44%, 95% CI 5.41–5.47%) or highest (5.50%, 95% CI 5.46–5.53%) quartiles. Subjects in the higher quartiles had significantly greater adjusted odds ratios of HbA1c level ≥6.0% than those in the first quartile. In stratified analyses, OSA severity predicted glycaemic health irrespective of sleep study modality, sex, obesity or daytime sleepiness. OSA severity independently predicts glycaemic health in nondiabetic subjects. Further studies should assess the impact of OSA treatment on glycaemic health and elucidate underlying mechanisms. Increasing sleep apnoea severity was associated with elevated HbA1c levels in a nondiabetic multinational cohort http://ow.ly/u1RLR

Clinical Phenotypes and Comorbidity in European Sleep Apnoea Patients

Background Clinical presentation phenotypes of obstructive sleep apnoea (OSA) and their association with comorbidity as well as impact on adherence to continuous positive airway pressure (CPAP) treatment have not been established. Methods A prospective follow-up cohort of adult patients with OSA (apnoea-hypopnoea index (AHI) of ≥5/h) from 17 European countries and Israel (n = 6,555) was divided into four clinical presentation phenotypes based on daytime symptoms labelled as excessive daytime sleepiness (“EDS”) and nocturnal sleep problems other than OSA (labelled as “insomnia”): 1) EDS (daytime+/nighttime-), 2) EDS/insomnia (daytime+/nighttime+), 3) non-EDS/non-insomnia (daytime-/nighttime-), 4) and insomnia (daytime-/nighttime+) phenotype. Results The EDS phenotype comprised 20.7%, the non-EDS/non-insomnia type 25.8%, the EDS/insomnia type 23.7%, and the insomnia phenotype 29.8% of the entire cohort. Thus, clinical presentation phenotypes with insomnia symptoms were dominant with 53.5%, but only 5.6% had physician diagnosed insomnia. Cardiovascular comorbidity was less prevalent in the EDS and most common in the insomnia phenotype (48.9% vs. 56.8%, p<0.001) despite more severe OSA in the EDS group (AHI 35.0±25.5/h vs. 27.9±22.5/h, p<0.001, respectively). Psychiatric comorbidity was associated with insomnia like OSA phenotypes independent of age, gender and body mass index (HR 1.5 (1.188–1.905), p<0.001). The EDS phenotype tended to associate with higher CPAP usage (22.7 min/d, p = 0.069) when controlled for age, gender, BMI and sleep apnoea severity. Conclusions Phenotypes with insomnia symptoms comprised more than half of OSA patients and were more frequently linked with comorbidity than those with EDS, despite less severe OSA. CPAP usage was slightly higher in phenotypes with EDS.

Gender differences in age and BMI distributions in partial upper airway obstruction during sleep

The obstructive sleep apnea-hypopnea syndrome occurs more frequently and with higher apnea-hypopnea indices in men than in women. To investigate the gender differences we extended our respiratory analyses during sleep to cover not only periodic obstruction (apnea and hypopnea) but also nonperiodic partial upper airway obstruction during sleep and their associations with increasing age or body mass index (BMI). The clinical sleep recordings with the static-charge-sensitive bed (SCSB) and oximeter were reviewed in 233 age and BMI-matched men-women pairs. Periodic obstruction increased with increasing BMI only in men. Nonperiodic partial obstruction increased with moderate to morbid obesity in women and men after the age of 65 years. Our findings suggest that while partial upper airway obstruction increases with increasing age and BMI in both genders, men have a gender specific BMI dependent predisposition for periodic obstruction (obstructive sleep apnea). The apnea-hypopnea index is likely to underestimate the impact of sleep-disordered breathing, particularly in elderly patients.

Sleep in midlife women: effects of menopause, vasomotor symptoms, and depressive symptoms.

ObjectiveThis study aims to evaluate subjective sleep quality in premenopausal and postmenopausal women and to study its association with night sweats, hot flashes, and depressive symptoms. MethodsA total of 158 healthy women were recruited; 107 were premenopausal (44-48 y) and 51 were postmenopausal (53-58 y). Sleep quality was evaluated with the Basic Nordic Sleep Questionnaire, night sweats and hot flashes were evaluated with a specific symptom questionnaire, and depressive symptoms were evaluated with the Beck Depression Inventory. ResultsPostmenopausal women had poorer general sleep quality (P < 0.001), slept more restlessly (P = 0.020), and had more nocturnal awakenings (P = 0.015). However, the frequency of difficulty falling asleep, snoring, witnessed apnea, or use of sleep medication was similar between the groups. Furthermore, sleep latency, morning tiredness, or daytime tiredness did not differ between the groups. Postmenopausal women did not report more unintentional falling asleep at work or during leisure time; however, when not active, they dozed off more easily than premenopausal women (P < 0.001). Postmenopausal women had more night sweats (P < 0.001), hot flashes (P < 0.001), and depressive symptoms (P < 0.001). Even a low frequency of night sweats disturbed sleep in postmenopausal women, whereas only frequent night sweats were disturbing in premenopausal women. Depressive symptoms disturbed sleep regardless of menopause status. ConclusionsMaintenance insomnia, most evidently because of night sweats and hot flashes, seems to be the major type of insomnia in postmenopausal women and has to be considered when choosing insomnia treatment for this group. Initiation of sleep and daytime vitality are not, in general, affected by menopause.