The relationship between periodic limb movement during sleep and dyslipidaemia in patients with obstructive sleep apnea.

Periodic limb movements during sleep and obstructive sleep apnea are both associated with increased sympathetic tone, and have been proposed as risk factors for heart diseases and, in particular, cardiovascular disease. As sympathetic system activation may lead to dyslipidaemia, periodic limb movements during sleep could be an additional risk factor for cardiovascular disease in patients with obstructive sleep apnea. The aim of the study was to determine whether the presence of periodic limb movements during sleep affects serum lipid levels in obstructive sleep apnea. Total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non- high-density lipoprotein cholesterol and triglyceride levels were investigated in 4138 patients with obstructive sleep apnea in the European Sleep Apnea Database (ESADA) cohort, divided into those with periodic limb movements during sleep index ≥ 15 per hr (n = 628) and controls (n = 3510). ANCOVA adjusted for age, sex, body mass index, apnea-hypopnea index, alcohol intake, smoking status, diabetes, insomnia and study site was used to assess differences in lipids between periodic limb movements during sleep and controls. Patients with periodic limb movements during sleep (24% female, 54.4 ± 12.1 years, body mass index 31.9 ± 5.8 kg m-2 , apnea-hypopnea index 36.7 ± 25.4 per hr) had higher triglyceride (1.81 ± 1.04 versus 1.69 ± 0.90 mmol L-1 , p = 0.002) and lower high-density lipoprotein cholesterol (1.19 ± 0.34 versus 1.24 ± 0.37 mmol L-1 , p = 0.002) levels, whilst there was no difference in either total cholesterol (4.98 ± 1.10 versus 4.94 ± 1.07 mmol L-1 ), low-density lipoprotein cholesterol (3.04 ± 0.96 versus 2.98 ± 0.98 mmol L-1 ) or non- high-density lipoprotein cholesterol (3.78 ± 1.10 versus 3.70 ± 1.05 mmol L-1 ) concentrations (all p > 0.05). The results remained unchanged after most sensitivity analyses. Patients with obstructive sleep apnea with periodic limb movements during sleep had more prevalent cardiovascular disease (11% versus 6%, p < 0.01). Periodic limb movements during sleep in obstructive sleep apnea is associated with dyslipidaemia independently of important confounders. Our results highlight periodic limb movements during sleep as an additional risk factor for cardiovascular disease in obstructive sleep apnea.

Bed partner perception of CPAP therapy on relationship satisfaction and intimacy-A European perspective from the ESADA network.

Obstructive sleep apnea increases morbidity and mortality risks. The most common treatment is continuous positive airway pressure, with nasal mask usage being important, but not always optimal. While most research on treatment adherence focuses on the patient, the bed partner's involvement may be detrimental. Our study aim is to obtain a European-wide picture of the bed partner's attitude and support towards continuous positive airway pressure therapy, including effects on relationship satisfaction and intimacy. The English translation of a German bed partner questionnaire, assessing relationship satisfaction and three major components (general attitude, perceived mask looks, intimacy effects) was distributed within the European Sleep Apnea Database Network and translated in participating countries' local language. Data were collected for 2 years. In total, 10 European countries (13 sleep centres) participated with 1546 questionnaires. Overall, 91% of bed partners had a positive attitude towards continuous positive airway pressure therapy, 86% perceived mask looks not negative, 64% stated no negative intimacy effects. More specifically, 71% mentioned improved sleep quality, 68% supported nightly device usage. For 41% of bed partners, relationship satisfaction increased (no change for 47%). These results were significantly more pronounced in Eastern/Southern Europe compared with Middle Europe, especially regarding intimacy effects. However, increased continuous positive airway pressure therapy length affected attitude negatively. These results provide necessary information to improve treatment strategies by including educational couple-focused approaches. Among others, we revealed that negative intimacy effects are not considered a barrier to continuous positive airway pressure adherence. These results may inspire more research identifying regional gaps with need for treatment adjustments.

Polygraphic evaluation of the effects of different rapid maxillary expansion appliances on sleep quality: A randomized clinical trial.

BACKGROUND: The purpose of this clinical study was to assess the effects of different rapid maxillary expansion appliances on the severity of obstructive sleep apnea (OSA). MATERIAL AND METHODS: Patients having a narrow maxilla and identified with OSA were divided randomly into three groups: tooth tissue-borne, tooth-borne, and bone-borne expanders. Changes in sleep parameters at baseline and 3-month follow-up detected by polygraphy were the primary outcome. Treatment of the crossbite was the secondary outcome. Dunn-Bonferroni tests, Kruskal-Wallis, and Wilcoxon analysis were applied for intra- and inter-group differences at p < 0.05 significance level. RESULTS: Among 46 patients randomized, apnea-hypopnea index (AHI) changed from baseline to follow-up in all groups (- 1.6, p = 0.280; 0.6, p = 0.691; - 0.45, p = 0.796, respectively), with no between-group difference (p = 0.631). Oxygen desaturation index (ODI) altered from baseline to follow-up in all groups (0.80, p = 0.977; 0.20, p = 0.932; and - 1.00, p = 0.379, respectively), with no between-group difference (p = 0.858). There was no significant difference in minimum oxygen saturation from baseline to follow-up in all groups (0.00, p = 0.401; - 2.00, p = 0.887; 0.50, p = 0.407, respectively). No significant changes were observed in supine AHI from baseline to follow-up in all groups (0.00, p = 0.581; - 1.00, p = 0.393; 0.00, p = 0.972, respectively). The upper intermolar width increased from baseline to follow-up in all groups (5.04, p = 0.000; 3.15, p = 0.001; 5.41, p = 0.00, respectively) with no between-group difference (p = 0.560). Maxillary width increased from baseline to follow-up in all groups (4.25, p = 0.001; 4.74, p = 0.00; 4.49, p = 0.001, respectively) with no inter-group difference (p = 0.963). CONCLUSIONS: The amount of skeletal and dental expansion obtained in the maxilla was similar in all groups. Rapid maxillary expansion was not found to be effective in OSA treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04604392.

Metabolic dysfunction in OSA: Is there something new under the sun?

The growing number of patients with obstructive sleep apnea is challenging healthcare systems worldwide. Obstructive sleep apnea is characterized by chronic intermittent hypoxaemia, episodes of apnea and hypopnea, and fragmented sleep. Cardiovascular and metabolic diseases are common in obstructive sleep apnea, also in lean patients. Further, comorbidity burden is not unambiguously linked to the severity of obstructive sleep apnea. There is a growing body of evidence revealing diverse functions beyond the conventional tasks of different organs such as carotid body and gut microbiota. Chronic intermittent hypoxia and sleep loss due to sleep fragmentation are associated with insulin resistance. Indeed, carotid body is a multi-sensor organ not sensoring only hypoxia and hypercapnia but also acting as a metabolic sensor. The emerging evidence shows that obstructive sleep apnea and particularly chronic intermittent hypoxia is associated with non-alcoholic fatty liver disease. Gut dysbiosis seems to be an important factor in the pathophysiology of obstructive sleep apnea and its consequences. The impact of sleep fragmentation and intermittent hypoxia on the development of metabolic syndrome may be mediated via altered gut microbiota. Circadian misalignment seems to have an impact on the cardiometabolic risk in obstructive sleep apnea. Dysfunction of cerebral metabolism is also related to hypoxia and sleep fragmentation. Therefore, obstructive sleep apnea may alter cerebral metabolism and predispose to neurocognitive impairment. Moreover, recent data show that obstructive sleep apnea independently predicts impaired lipid levels. This mini-review will provide novel insights into the mechanisms of metabolic dysfunction in obstructive sleep apnea combining recent evidence from basic, translational and clinical research, and discuss the impact of positive airway pressure treatment on metabolic disorders.

Impact of temperature on obstructive sleep apnoea in three different climate zones of Europe: Data from the European Sleep Apnoea Database (ESADA).

Recent studies indicate that ambient temperature may modulate obstructive sleep apnoea (OSA) severity. However, study results are contradictory warranting more investigation in this field. We analysed 19,293 patients of the European Sleep Apnoea Database (ESADA) cohort with restriction to the three predominant climate zones according to the Köppen-Geiger climate classification: Cfb (warm temperature, fully humid, warm summer), Csa (warm temperature, summer dry, hot summer), and Dfb (snow, fully humid, warm summer). Average outside temperature values were obtained and several hierarchical regression analyses were performed to investigate the impact of temperature on the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), time of oxygen saturation <90% (T90) and minimum oxygen saturation (MinSpO2 ) after controlling for confounders including age, body mass index, gender, and air conditioning (A/C) use. AHI and ODI increased with higher temperatures with a standardised coefficient beta (ß) of 0.28 for AHI and 0.25 for ODI, while MinSpO2 decreased with a ß of -0.13 (all results p < .001). When adjusting for climate zones, the temperature effect was only significant in Cfb (AHI: ß = 0.11) and Dfb (AHI: ß = 0.08) (Model 1: p < .001). The presence of A/C (3.9% and 69.3% in Cfab and Csa, respectively) demonstrated only a minor increase in the prediction of the variation (Cfb: AHI, R2 +0.003; and Csa: AHI, R2 +0.007; both p < .001). Our present study indicates a limited but consistent influence of environmental temperature on OSA severity and this effect is modulated by climate zones.

Positive airway pressure (PAP) treatment reduces glycated hemoglobin (HbA1c) levels in obstructive sleep apnea patients with concomitant weight loss: Longitudinal data from the ESADA.

Patients with obstructive sleep apnea (OSA) are at increased risk of developing metabolic disease such as diabetes. The effects of positive airway pressure on glycemic control are contradictory. We therefore evaluated the change in glycated hemoglobin (HbA1c) in a large cohort of OSA patients after long-term treatment with positive airway pressure. HbA1c levels were assessed in a subsample of the European Sleep Apnea Database [n=1608] at baseline and at long-term follow up with positive airway pressure therapy (mean 378.9±423.0 days). In a regression analysis, treatment response was controlled for important confounders. Overall, HbA1c decreased from 5.98±1.01% to 5.93±0.98% (p=0.001). Patient subgroups with a more pronounced HbA1c response included patients with diabetes (-0.15±1.02, p=0.019), those with severe OSA baseline (-0.10±0.68, p=0.005), those with morbid obesity (-0.20±0.81, p<0.001). The strongest HbA1c reduction was observed in patients with a concomitant weight reduction >5 kilos (-0.38±0.99, p<0.001). In robust regression analysis, severe OSA (p=0.038) and morbid obesity (p=0.005) at baseline, and weight reduction >5 kilos (p<0.001) during follow up were independently associated with a reduction of HbA1c following PAP treatment. In contrast, PAP treatment alone without weight reduction was not associated with significant Hb1Ac reduction. In conclusion, positive airway pressure therapy is associated with HbA1c reduction in patients with severe OSA, in morbidly obese patients. and most obviously in those with significant weight lost during the follow-up. Our study underlines the importance to combine positive airway pressure use with adjustments in lifestyle to substantially modify metabolic complications in OSA.

Clusters of sleep apnoea phenotypes: A large pan-European study from the European Sleep Apnoea Database (ESADA).

BACKGROUND AND OBJECTIVE: To personalize OSA management, several studies have attempted to better capture disease heterogeneity by clustering methods. The aim of this study was to conduct a cluster analysis of 23 000 OSA patients at diagnosis using the multinational ESADA. METHODS: Data from 34 centres contributing to ESADA were used. An LCA was applied to identify OSA phenotypes in this European population representing broad geographical variations. Many variables, including symptoms, comorbidities and polysomnographic data, were included. Prescribed medications were classified according to the ATC classification and this information was used for comorbidity confirmation. RESULTS: Eight clusters were identified. Four clusters were gender-based corresponding to 54% of patients, with two clusters consisting only of men and two clusters only of women. The remaining four clusters were mainly men with various combinations of age range, BMI, AHI and comorbidities. The preferred type of OSA treatment (PAP or mandibular advancement) varied between clusters. CONCLUSION: Eight distinct clinical OSA phenotypes were identified in a large pan-European database highlighting the importance of gender-based phenotypes and the impact of these subtypes on treatment prescription. The impact of cluster on long-term treatment adherence and prognosis remains to be studied using the ESADA follow-up data set.

Change in weight and central obesity by positive airway pressure treatment in obstructive sleep apnea patients: longitudinal data from the ESADA cohort.

The effect of positive airway pressure treatment on weight and markers of central obesity in patients with obstructive sleep apnea remains unclear. We studied the change in body weight and anthropometric measures following positive airway pressure treatment in a large clinical cohort. Patients with obstructive sleep apnea with positive airway pressure treatment from the European Sleep Apnea Database registry (n = 1,415, 77% male, age 54 ± 11 [mean ± SD] years, body mass index 31.7 ± 6.4 kg/m2 , apnea-hypopnea index 37 ± 24 n per hr, Epworth Sleepiness Scale 10.2 ± 5.0) were selected. Changes in body mass index and neck/waist/hip circumferences at baseline and at follow-up visit were analysed. Overall, body mass index (0.0 [95% confidence interval, -0.1 to 0.2] kg/m2 ) and neck circumference (0.0 (95% confidence interval, -0.1 to 0.1] cm) were unchanged after positive airway pressure treatment compared with baseline (follow-up duration 1.1 ± 1.0 years and compliance 5.2 ± 2.1 hr per day). However, in non-obese (body mass index <30 kg/m2 ) patients, positive airway pressure treatment was associated with an increased body mass index and waist circumference (0.4 [0.3-0.5] kg/m2 and 0.8 [0.4-1.2] cm, respectively, all p < 0.05), and weight gain was significantly associated with higher positive airway pressure compliance and longer positive airway pressure treatment duration. In the obese subgroup, body mass index was reduced after positive airway pressure treatment (-0.3 [-0.5 to -0.1] kg/m2 , p < 0.05) mainly in patients with a strong reduction in Epworth Sleepiness Scale. In conclusion, positive airway pressure therapy was not found to systematically change body mass index in the European Sleep Apnea Database cohort, but the response was heterogeneous. Our findings suggest that weight gain may be restricted to an obstructive sleep apnea phenotype without established obesity. Lifestyle intervention needs to be considered in both lean and obese patients with obstructive sleep apnea receiving positive airway pressure treatment.

Clinical presentation of patients with suspected obstructive sleep apnea and self-reported physician-diagnosed asthma in the ESADA cohort.

Obstructive sleep apnea (OSA) and asthma are often associated and several studies suggest a bidirectional relationship between asthma and OSA. This study analyzed the characteristics of patients with suspected OSA from the European Sleep Apnea Database according to presence/absence of physician-diagnosed asthma. Cross-sectional data in 16,236 patients (29.1% female) referred for suspected OSA were analyzed according to occurrence of physician-diagnosed asthma for anthropometrics, OSA severity and sleepiness. Sleep structure was assessed in patients studied by polysomnography (i.e. 48% of the sample). The prevalence of physician-diagnosed asthma in the entire cohort was 4.8% (7.9% in women, 3.7% in men, p < 0.0001), and decreased from subjects without OSA to patients with mild-moderate and severe OSA (p = 0.02). Obesity was highly prevalent in asthmatic women, whereas BMI distribution was similar in men with and without physician-diagnosed asthma. Distribution of OSA severity was similar in patients with and without physician-diagnosed asthma, and unaffected by treatment for asthma or gastroesophageal reflux. Asthma was associated with poor sleep quality and sleepiness. Physician-diagnosed asthma was less common in a sleep clinic population than expected from the results of studies in the general population. Obesity appears as the major factor raising suspicion of OSA in asthmatic women, whereas complaints of poor sleep quality were the likely reason for referral in asthmatic men.

Obstructive sleep apnoea independently predicts lipid levels: Data from the European Sleep Apnea Database.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) and dyslipidaemia are independent risk factors for cardiovascular disease. This study investigates the association between OSA and plasma lipid concentrations in patients enrolled in the European Sleep Apnea Database (ESADA) cohort. METHODS: The cross-sectional analysis included 8592 patients without physician-diagnosed hyperlipidaemia or reported intake of a lipid-lowering drug (age 50.1 ± 12.7 years, 69.1% male, BMI: 30.8 ± 6.6 kg/m2 , mean apnoea-hypopnoea index (AHI): 25.7 ± 25.9 events/h). The independent relationship between measures of OSA (AHI, oxygen desaturation index (ODI), mean and lowest oxygen saturation) and lipid profile (total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and fasting triglycerides (TG)) was determined by means of general linear model analysis. RESULTS: There was a dose response relationship between TC and ODI (mean ± SE (mg/dL): 180.33 ± 2.46, 184.59 ± 2.42, 185.44 ± 2.42 and 185.73 ± 2.44; P < 0.001 across ODI quartiles I-IV). TG and LDL concentrations were better predicted by AHI than by ODI. HDL-C was significantly reduced in the highest AHI quartile (mean ± SE (mg/dL): 48.8 ± 1.49 vs 46.50 ± 1.48; P = 0.002, AHI quartile I vs IV). Morbid obesity was associated with lower TC and higher HDL-C values. Lipid status was influenced by geographical location with the highest TC concentration recorded in Northern Europe. CONCLUSION: OSA severity was independently associated with cholesterol and TG concentrations.

Gender differences in clinical and polysomnographic features of obstructive sleep apnea: a clinical study of 2827 patients.

PURPOSE: Obstructive sleep apnea (OSA) is underdiagnosed in females due to different clinical presentation. We aimed to determine the effect of gender on clinical and polysomnographic features and identify predictors of OSA in women. METHODS: Differences in demographic, clinical, and polysomnographic parameters between 2052 male and 775 female OSA patients were compared. RESULTS: In female OSA patients, age (56.1 ± 9.7 vs. 50.4 ± 11.6 years, p < 0.0001) and body mass index (36.3 ± 8.6 vs. 31.8 ± 5.9 kg/m2, p < 0.0001) were increased, whereas men had higher waist-to-hip ratio and neck circumference (p < 0.0001). Hypertension, diabetes mellitus, thyroid disease, and asthma were more common in females (p < 0.0001). Men reported more witnessed apnea (p < 0.0001), but nocturnal choking, morning headache, fatigue, insomnia symptoms, impaired memory, mood disturbance, reflux, nocturia, and enuresis were more frequent in women (p < 0.0001). The indicators of OSA severity including apnea-hypopnea index (AHI) (p < 0.0001) and oxygen desaturation index (p = 0.007) were lower in women. REM AHI (p < 0.0001) was higher, and supine AHI (p < 0.0001) was lower in females. Besides, women had decreased total sleep time (p = 0.028) and sleep efficiency (p = 0.003) and increased sleep latency (p < 0.0001). In multivariate logistic regression analysis, increased REM AHI, N3 sleep, obesity, age, morning headache, and lower supine AHI were independently associated with female gender. CONCLUSIONS: These data suggest that frequency and severity of sleep apnea is lower in female OSA patients, and they are presenting with female-specific symptoms and increased medical comorbidities. Therefore, female-specific questionnaires should be developed and used for preventing underdiagnosis of OSA.

Quality of life in obstructive sleep apnea is related to female gender and comorbid insomnia.

PURPOSE: Obstructive sleep apnea (OSA) is a common sleep disorder affecting health-related quality of life (QoL), and OSA severity is not a reliable indicator for QoL. The aim of this study was (1) to evaluate the impact of gender on QoL and (2) to identify the predictors of QoL in OSA patients. METHODS: World Health Organization Quality of Life Scale short form (WHOQOL-Bref) was used for evaluating QoL in OSA patients undergoing polysomnography in sleep laboratory of a university hospital. RESULTS: Out of 197 patients (age 50.4 ± 12.1 years, AHI 38.5 ± 28.4/h), 139 (70.6%) were men and 79.2% had moderate-to-severe OSA. Female gender, increased BMI, higher Epworth sleepiness score (ESS), and lower oxygen saturations were associated significantly with poor QoL in terms of all domains (physical, psychological, social relationship, and environmental) of WHOQOL-Bref questionnaire. The indicators of OSA severity (AHI and ODI) correlated negatively only with the physical domain. The subjects with comorbid insomnia and OSA had lower physical and social scores than subjects with no insomnia, and women with insomnia had significantly worse QoL scores in all domains than the others. In the multivariate linear regression analysis, female gender, comorbid insomnia, increased sleepiness, and higher BMI were significantly associated with poor QoL. CONCLUSIONS: Female gender, comorbid insomnia, and daytime sleepiness were the outstanding factors affecting health-related QoL negatively in OSA. Besides, the impact of OSA on QoL may be explained by the presence of daytime sleepiness rather than OSA severity.

Contrasting effects of ATP and adenosine on capsaicin challenge in asthmatic patients.

BACKGROUND: Adenosine 5'-triphosphate (ATP) stimulates pulmonary vagal slow conducting C-fibres and fast conducting Aδ-fibres with rapidly adapting receptors (RARs). Pulmonary C-fibres but not RARs are also sensitive to capsaicin, a potent tussigenic agent in humans. Thus, the aim of this study was to determine the effects of ATP and its metabolite adenosine (given as adenosine 5'-monophosphate, AMP) on capsaicin challenge in asthmatic patients. METHODS: Cough (quantified as visual analogue scale, VAS), dyspnoea (quantified as Borg score), and FEV1 were quantified following bronchoprovocation using capsaicin, adenosine and ATP in healthy non-smokers (age 40±4y, 6 males), smokers (45±4y, 5 males) and asthmatic patients (37±3y, 5 males); n = 10 in each group. RESULTS: None of the healthy non-smokers responded to either AMP or ATP. AMP induced bronchoconstriction in one smoker and eight asthmatics, and ATP in two smokers and all ten asthmatics. The geometric mean of capsaicin causing ≥5 coughs (C5) increased from 134 to 203 µM in non-smokers and from 117 to 287 µM in asthmatics after AMP, whereas it decreased from 203 to 165 µM and 125 to 88 µM, respectively after ATP. AMP decreased C5 from 58 to 29 µM and ATP increased from 33 to 47 µM in smokers. However, due to intergroup variability, these effects of ATP and AMP were not statistically significant (0.125 ≤ p ≤ 0.998). That notwithstanding, in healthy and asthmatic subjects the effects of the ATP showed a tendency to be greater than those of AMP (p < 0.053). Dyspnea, assessed by Borg score, increased after ATP (p < 0.001) and AMP (p < 0.001) only in asthmatic patients. Intensity of cough assessed by VAS increased (p < 0.05) after second capsaicin challenges performed after AMP in all groups, but not after ATP. CONCLUSIONS: Asthmatic patients exhibit hypersensitivity to aerosolized AMP and ATP, but aerosolized AMP does not mimic the effects of ATP and the effects of ATP are not mediated by adenosine.

Chronic kidney disease in European patients with obstructive sleep apnea: the ESADA cohort study.

The cross-sectional relationship of obstructive sleep apnea with moderate to severe chronic kidney disease, defined as an estimated glomerular filtration rate <60 mL min-1 ∙1.73 m-2 , was investigated in a large cohort of patients with suspected obstructive sleep apnea studied by nocturnal polysomnography or cardiorespiratory polygraphy. Data were obtained from the European Sleep Apnea Database, where information from unselected adult patients with suspected obstructive sleep apnea afferent to 26 European sleep centres had been prospectively collected. Both the Modification of Diet in Renal Disease and the Chronic Kidney Disease-Epidemiology Collaboration equations were used for the assessment of estimated glomerular filtration rate. The analysed sample included 7700 subjects, 71% male, aged 51.9 ± 12.5 years. Severe obstructive sleep apnea (apnea-hypopnea index ≥30) was found in 34% of subjects. The lowest nocturnal oxygen saturation was 81 ± 10.2%. Chronic kidney disease prevalence in the whole sample was 8.7% or 6.1%, according to the Modification of Diet in Renal Disease or the Chronic Kidney Disease-Epidemiology Collaboration equations, respectively. Subjects with lower estimated glomerular filtration rate were older, more obese, more often female, had worse obstructive sleep apnea and more co-morbidities (P < 0.001, each). With both equations, independent predictors of estimated glomerular filtration rate <60 were: chronic heart failure; female gender; systemic hypertension; older age; higher body mass index; and worse lowest nocturnal oxygen saturation. It was concluded that in obstructive sleep apnea, chronic kidney disease is largely predicted by co-morbidities and anthropometric characteristics. In addition, severe nocturnal hypoxaemia, even for only a small part of the night, may play an important role as a risk factor for kidney dysfunction.

Effect of Semirecumbent Sleep Position on Severity of Obstructive Sleep Apnea in Patients With Heart Failure.

BACKGROUND: Overnight rostral leg fluid displacement in heart failure (HF) patients is related to the high prevalence and severity of obstructive sleep apnea syndrome (OSAS). We hypothesized that rostral fluid shift would decrease in a semirecumbent (45-degree elevated) position, and evaluated the effect of semirecumbent sleeping on severity of sleep apnea in HF patients with OSAS. METHODS AND RESULTS: Demographic, anthropometric characteristics, and medical history of 30 consecutive patients with HF and OSAS were recorded. The patients underwent 2 polysomnographic procedures within 1 week: 1 while lying flat and the other in a semirecumbent position. Out of 30 patients (mean age 54.7 ± 10.2, 26 men), 16 (53.3%) were obese and 29 (96.7%) had comorbidities other than HF. Mean apnea-hypopnea index was 30.8 ± 20.7 events/h while lying flat which decreased to 17.8 ± 12.1 events/h in semirecumbent position (P < .0001). Similarly, oxygen desaturation index decreased from 22.3 ± 19.8 to 12.7 ± 11.5 events/h (P < .0001), and the percentage of sleep time with oxygen saturation (SpO2) <90% (P = .036) and lowest SpO2 (P = .004) were improved in the semirecumbent position. Furthermore, the percentage of stage N2 sleep decreased from 47.0% while lying flat to 39.6% (P = .014). CONCLUSIONS: The present findings support that the severity of OSAS decreased significantly in a semirecumbent sleep position in patients with HF. Therefore, semirecumbent sleeping may be a promising therapeutic option in the management of HF-related sleep apnea.

Obstructive sleep apnea syndrome and gastroesophageal reflux disease: the importance of obesity and gender.

BACKGROUND: It is claimed that gastroesophageal reflux disease (GERD) increases in patients with obstructive sleep apnea syndrome (OSAS). We aimed to evaluate the prevalence of GERD in patients with OSAS and primary snoring and identify OSAS-related risk factors associated with GERD. METHODS: In this prospective, cross-sectional, multicenter study, in total 1,104 patients were recruited for polysomnography: 147 subjects were in non-OSAS (primary snoring) and 957 patients were in OSAS group. All patients completed a validated GERD questionnaire. Demographic, anthropometric characteristics, and medical history were recorded. RESULTS: The prevalence of GERD was similar in OSAS (38.9%) and non-OSAS (32.0%) groups (p = 0.064). There was no difference in terms of major gastroesophageal reflux (GER) symptoms (heartburn/acid regurgitation) between non-OSAS and mild, moderate, and severe OSAS groups. The prevalence of GERD was increased in female OSAS patients (46.6%) compared to males (35.7%) (p = 0.002). In OSAS patients with GERD, body mass index was greater (34.0 ± 7.0 vs. 33.1 ± 6.8, p = 0.049), waist (115.5 ± 13.9 vs. 113.1 ± 13.4, p = 0.007) and hip (117.9 ± 13.7 vs. 114.2 ± 12.8, p < 0.0001) circumferences were larger, and Epworth sleepiness scores were higher (10.3 ± 6.0 vs. 8.8 ± 5.6, p < 0.0001) than OSAS patients without GERD. Multivariate analysis showed that GERD was significantly associated with female gender, hip circumference, and daytime sleepiness. CONCLUSIONS: In this large cohort, the prevalence of GERD was significantly increased in those with primary snoring and OSAS compared to the general population, but severity of OSAS did not influence GERD prevalence. The present results suggest that OSAS was not likely a causative factor but female gender, obesity, and sleepiness were related with prevalence of GERD in OSAS patients.

Dyslipidemia prevalence in nonobese, nondiabetic patients with obstructive sleep apnea: does sex matter?

STUDY OBJECTIVES: Dyslipidemia in obstructive sleep apnea (OSA) has been attributed to confounding obesity and/or diabetes. This study aimed to examine lipid profiles in nondiabetic, nonobese patients with OSA and identify the possible effects of age and sex. METHODS: We retrospectively evaluated the lipid parameters of 3,050 adults who underwent polysomnography. A total of 2,168 patients were excluded due to obesity (body mass index ≥ 30 kg/m2), diabetes, alcoholism, untreated hypothyroidism, lipid-lowering drug use, missing sleep data, or treatment for suspected OSA. RESULTS: Of 882 patients (75% males, aged 46.8 ± 12.2 years) included in the study, 88.4% had OSA. Levels of total cholesterol (P = .003), low-density-lipoprotein (LDL) cholesterol (P = .005), non-high-density-lipoprotein (non-HDL) cholesterol (P = .001), and triglycerides (P = .007) were significantly higher in patients with OSA than in those without, whereas HDL-cholesterol levels did not differ. The proportion of patients with hypercholesterolemia and/or elevated non-HDL cholesterol (> 160 mg/dL) was significantly higher in OSA than in non-OSA. Correlation analyses by sex revealed stronger and more significant relationships between lipid parameters and apnea-hypopnea index in women than in men (r = .135, P < .001, vs r = .080, P = .043 for total cholesterol; r = .111, P < .001, vs r = .080, P = .046 for non-HDL cholesterol; r = .122, P < .001, vs r = .061, P = .107 for LDL cholesterol, respectively). In regression analysis, the rate of hypercholesterolemia increased with age (P < .001 for women and P = .031 for men); non-HDL- and LDL-cholesterol levels significantly increased with OSA severity (P = .035 and P = .023, respectively) and age (P = .004 and P = .001, respectively) in women. CONCLUSIONS: After excluding confounding obesity and diabetes, patients with OSA have an impaired lipid profile including total cholesterol, LDL cholesterol, non-HDL cholesterol, and triglycerides. A significant association between dyslipidemia and OSA severity was observed in women but not in men. CITATION: Basoglu OK, Tasbakan MS, Kayikcioglu M. Dyslipidemia prevalence in nonobese, nondiabetic patients with obstructive sleep apnea: does sex matter? J Clin Sleep Med. 2023;19(5):889-898.

Sleep and cardiometabolic comorbidities in the obstructive sleep apnoea-COPD overlap syndrome: data from the European Sleep Apnoea Database.

Aim: The impact of obstructive sleep apnoea (OSA)-COPD overlap syndrome (OVS) on sleep quality and cardiovascular outcomes has not been fully explored. We aimed to compare clinical and polysomnographic characteristics of patients with OVS versus patients with OSA, and to explore pathophysiological links between OVS and comorbidities. Study design and methods: This cross-sectional analysis initially included data from 5600 patients with OSA and lung function in the European Sleep Apnoea Database. Two subgroups of patients with OSA (n=1018) or OVS (n=509) were matched (2:1) based on sex, age, body mass index and apnoea-hypopnea index at baseline. Results: After matching, patients with OVS had more severe hypoxia, lower sleep efficiency and presented with higher prevalences of arterial hypertension, ischaemic heart disease and heart failure compared with patients with OSA. OVS was associated with a significant decrease in sleep efficiency (mean difference (ß) -3.0%, 95% CI -4.7 to -1.3) and in nocturnal mean peripheral oxyhaemoglobin saturation (SpO2) (ß -1.1%, 95% CI -1.5 to -0.7). Further analysis revealed that a decrease in forced expiratory volume in 1 s and arterial oxygen tension was related to a decrease in sleep efficiency and in mean nocturnal SpO2. A COPD diagnosis increased the odds of having heart failure by 1.75 (95% CI 1.15-2.67) and systemic hypertension by 1.36 (95% CI 1.07-1.73). Nocturnal hypoxia was strongly associated with comorbidities; the mean nocturnal SpO2 and T90 (increase in time below SpO2 of 90%) were associated with increased odds of systemic hypertension, diabetes and heart failure but the oxygen desaturation index was only related to hypertension and diabetes. Conclusion: Patients with OVS presented with more sleep-related hypoxia, a reduced sleep quality and a higher risk for heart failure and hypertension.

Arterial bicarbonate is associated with hypoxic burden and uncontrolled hypertension in obstructive sleep apnea - The ESADA cohort.

OBJECTIVE: Blood bicarbonate concentration plays an important role for obstructive sleep apnea (OSA) patients to maintain acid-base balance. We investigated the association between arterial standard bicarbonate ([HCO3-]) and nocturnal hypoxia as well as comorbid hypertension in OSA. METHODS: A cross-sectional analysis of 3329 patients in the European Sleep Apnea Database (ESADA) was performed. Arterial blood gas analysis and lung function test were performed in conjunction with polysomnographic sleep studies. The 4% oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO2), and percentage of time with SpO2 below 90% (T90%) were used to reflect nocturnal hypoxic burden. Arterial hypertension was defined as a physician diagnosis of hypertension with ongoing antihypertensive medication. Hypertensive patients with SBP/DBP below or above 140/90 mmHg were classified as controlled-, uncontrolled hypertension, respectively. RESULTS: The [HCO3-] level was normal in most patients (average 24.0 ± 2.5 mmol/L). ODI, T90% increased whereas mean and minimum SpO2 decreased across [HCO3-] tertiles (ANOVA, p = 0.030, <0.001, <0.001, and <0.001, respectively). [HCO3-] was independently associated with ODI, mean SpO2, minimum SpO2, and T90% after adjusting for confounders (ß value [95%CI]: 1.21 [0.88-1.54], -0.16 [-0.20 to -0.11], -0.51 [-0.64 to -0.37], 1.76 [1.48-2.04], respectively, all p < 0.001). 1 mmol/L elevation of [HCO3-] was associated with a 4% increased odds of uncontrolled hypertension (OR: 1.04 [1.01-1.08], p = 0.013). CONCLUSION: We first demonstrated an independent association between [HCO3-] and nocturnal hypoxic burden as well as uncontrolled hypertension in OSA patients. Bicarbonate levels as an adjunctive measure provide insight into the pathophysiology of hypertension in OSA.