Ulla Anttalainen

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.

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.

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.

Reimbursed drugs in patients with sleep-disordered breathing: A static-charge-sensitive bed study

BACKGROUND Co-morbidities in men and women with sleep-disordered breathing (SDB) were compared retrospectively to an age-standardized, general Finnish population. The prevalence of diseases was based on the reimbursement refunds of medications. METHODS Two hundred thirty-three age- and BMI-matched male-female pairs and 368 consecutive women identified from our sleep recording database were included. Data on medication were gathered from the National Agency for Medicines and Social Insurance Institution database. RESULTS Men with SDB had three-fold prevalence of reimbursed medication for diabetes and two-fold prevalence of reimbursed medication for chronic arrhythmia. Women with SDB had three-fold prevalence of reimbursed medication for thyroid insufficiency, and postmenopausal women had two-fold prevalence of reimbursed medication for psychosis. BMI and age did not explain prevalence of reimbursed medications for chronic arrhythmia or psychosis. In both genders with SDB, prevalence of reimbursed medications compared to the general population was two-fold for hypertension and seven-fold for asthma and/or chronic obstructive pulmonary disease (COPD). Partial upper airway obstruction was associated with three-fold prevalence of reimbursed medication for asthma and/or COPD in both genders and 60% reduced prevalence of reimbursed medication for hypertension in females matched for age and BMI. CONCLUSIONS Co-morbidity profile differed between genders. Our results emphasize the importance of diagnosis and treatment of co-morbidities and partial upper airway obstruction.

Short-term medroxyprogesterone acetate in postmenopausal women with sleep-disordered breathing: a placebo-controlled, randomized, double-blind, parallel-group study.

ObjectiveMenopause predisposes women to sleep-disordered breathing (SDB) and sleep disturbances. Progestin has a potential to stimulate breathing and to induce sleep. Our goal was to test these effects objectively and to compare them with the effects of nasal continuous positive airway pressure (CPAP), which is the standard treatment of SDB. MethodsIn a placebo-controlled, double-blind, parallel-group trial, we investigated 34 postmenopausal women (17 in the placebo group and 17 in the medroxyprogesterone acetate [MPA] group) whose SDB had been treated with nasal CPAP for 6 months to 8 years prior to study entry. The 6-week trial included measurements with CPAP at baseline, after 14 days of placebo or MPA (60 mg daily), and after a 3-week washout. The participants discontinued their nasal CPAP therapy 1 week after baseline measurements and went on with study medication. ResultsTwo weeks after discontinuation of CPAP therapy, nightly oxygen saturation was sustained higher (P = 0.004) and arterial carbon dioxide tension was lower (P < 0.001) with MPA than with placebo. Carbon dioxide was also lower than during CPAP (P < 0.001), and this effect was sustained beyond 3 weeks after the cessation of MPA (P < 0.001). However, the apnea-hypopnea index of CPAP increased and sleep deteriorated similarly on MPA and placebo after withdrawal of CPAP therapy. ConclusionsIn postmenopausal women with SDB, MPA induces a long-lasting stimulatory effect on breathing without improving sleep quality or the apnea-hypopnea index.

Women with partial upper airway obstruction are not less sleepy than those with obstructive sleep apnea

PurposeSleep-disordered breathing (SDB) differs between genders in terms of the type, signs, and symptoms of the disease. Partial upper airway obstruction is underdiagnosed and undertreated.MethodsIn this study, we retrospectively investigated respiratory sleep recordings of 601 women, ending up with 240 women for the final statistical analyses. We hypothesized that there are differences between the signs and symptoms of sleep-disordered breathing whether women had partial upper airway obstruction or obstructive sleep apnea.ResultsThe results showed no difference in sleepiness between women with partial upper airway obstruction or obstructive sleep apnea. Also, the other main symptoms of SDB were the same between the groups. Micrognathia was more common in women with partial upper airway obstruction than with obstructive sleep apnea.ConclusionThese results indicate that partial upper airway obstruction in women should be clinically recognized like obstructive sleep apnea.

Is ‘MILD’ sleep-disordered breathing in women really mild?

Sleep‐disordered breathing (SDB) consists of episodes of periodic obstructive or central sleep apnea and partial upper airway obstruction. The first two are well recognized and diagnosed, although still underdiagnosed. Traditionally, research in SDB has focused mainly on male patients with obstructive sleep apnea using apnea/hypopnea index (AHI) as a measure of severity. This has led to overrating of AHI as the only marker of SDB and underestimating of SDB in women. However, recently, partial upper airway obstruction has been acknowledged to be pathological and it may cause symptoms of SDB. There is a growing body of evidence that women suffer from SDB more than thought before and they especially have partial upper airway obstruction. Co‐morbidities such as cardiovascular diseases seem to be more prevalent in patients with SDB. This commentary points out some differences of SDB between genders in terms of symptoms and findings and emphasizes the clinical relevance of partial upper airway obstruction, especially in women.

Relationship between habitual sleep duration, obesity and depressive symptoms in patients with sleep apnoea

OBJECTIVES Short sleep duration has been linked with obesity in general population, but this issue has not been addressed in patients with obstructive sleep apnoea syndrome (OSAS) separately. Depressive symptoms are frequent in OSAS and may affect sleep and energy balance. Our purpose was to assess the association of habitual sleep duration, psychological distress, depressive symptoms, and excessive daytime sleepiness with measures of obesity in patients with OSAS. METHODS 210 middle aged consecutive patients (111 men and 99 women) referred for evaluation of suspected OSAS were divided into subgroups based on apnoea-hypopnoea index (AHI) and treatment suggested by a sleep physician. RESULTS OSAS (AHI>5/h plus symptoms) was diagnosed in 75.7% of the patients. Their sleep duration correlated negatively with psychological distress (r=-0.22, p=0.043) and depressive symptoms (r=-0.27, p=0.013) in men. No association was found between self-reported habitual sleep duration and measures of obesity or subjective sleepiness. In patients considered for CPAP therapy, sleep duration associated inversely with depressive symptoms both in men (r=-0.28, p=0.024) and women (r=-0.33, p=0.037). After adjusting for age and Epworth Sleepiness Score, the results remained essentially similar. CONCLUSIONS Our results suggest that self-reported habitual sleep duration does not associate with obesity in patients with OSAS. Shorter habitual sleep duration seems to associate with higher scores of depressive symptoms and psychological distress.