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1.
  • Gunduz, C., et al. (author)
  • Hyperlipidaemia prevalence and cholesterol control in obstructive sleep apnoea: Data from the European sleep apnea database (ESADA)
  • 2019
  • In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 676-688
  • Journal article (peer-reviewed)abstract
    • 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/m(2), 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.
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  • Fietze, I, et al. (author)
  • Management of obstructive sleep apnea in Europe
  • 2011
  • In: Sleep Medicine. - : Elsevier. - 1389-9457 .- 1878-5506. ; 12:2, s. 190-197
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Gunduz, C., et al. (author)
  • Long-term positive airway pressure therapy is associated with reduced total cholesterol levels in patients with obstructive sleep apnea: data from the European Sleep Apnea Database (ESADA)
  • 2020
  • In: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 75, s. 201-209
  • Journal article (peer-reviewed)abstract
    • Background and aim: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). Methods: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). Results: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). Conclusion: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies. © 2020 Elsevier B.V.
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  • Lombardi, C., et al. (author)
  • Periodic limb movements during sleep and blood pressure changes in sleep apnoea: Data from the European Sleep Apnoea Database
  • 2020
  • In: Respirology. - : Wiley. - 1323-7799 .- 1440-1843. ; 25:8, s. 872-879
  • Journal article (peer-reviewed)abstract
    • Background and objective OSA and PLMS are known to induce acute BP swings during sleep. Our current study aimed to address the independent effect of PLMS on BP in an unselected OSA patient cohort. Methods This cross‐sectional analysis included 1487 patients (1110 males, no previous hypertension diagnosis or treatment, mean age: 52.5years, mean BMI: 30.5kg/m2) with significant OSA (defined as AHI≥10) recruited from the European Sleep Apnoea Cohort. Patients underwent overnight PSG. Patients were stratified into two groups: patients with significant PLMS (PLMSI>25 events/hour of sleep) and patients without significant PLMS (PLMSI<25 events/hour of sleep). SBP, DBP and PP were the variables of interest. For each of these, a multivariate regression linear model was fitted to evaluate the relationship between PLMS and outcome adjusting for sociodemographic and clinical covariates (gender, age, BMI, AHI, ESS, diabetes, smoking and sleep efficiency). Results The univariate analysis of SBP showed an increment of BP equal to 4.70mm Hg (P<0.001) in patients with significant PLMS compared to patients without significant PLMS. This increment remained significant after implementing a multivariate regression model (2.64mm Hg, P = 0.044). No significant increment of BP was observed for DBP and PP. Conclusion PLMS is associated with a rise in SBP regardless of AHI, independent of clinical and sociodemographic confounders. A PLMS phenotype may carry an increased risk for cardiovascular disease in OSA patients.
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  • Saaresranta, T., et al. (author)
  • Clinical Phenotypes and Comorbidity in European Sleep Apnoea Patients
  • 2016
  • In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:10
  • Journal article (peer-reviewed)abstract
    • 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. 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/noninsomnia (daytime-/nighttime-), 4) and insomnia (daytime-/nighttime+) phenotype. 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. 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.
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7.
  • Arnardottir, E. S., et al. (author)
  • The Sleep Revolution project: the concept and objectives
  • 2022
  • In: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 31:4
  • Journal article (peer-reviewed)abstract
    • Obstructive sleep apnea is linked to severe health consequences such as hypertension, daytime sleepiness, and cardiovascular disease. Nearly a billion people are estimated to have obstructive sleep apnea with a substantial economic burden. However, the current diagnostic parameter of obstructive sleep apnea, the apnea-hypopnea index, correlates poorly with related comorbidities and symptoms. Obstructive sleep apnea severity is measured by counting respiratory events, while other physiologically relevant consequences are ignored. Furthermore, as the clinical methods for analysing polysomnographic signals are outdated, laborious, and expensive, most patients with obstructive sleep apnea remain undiagnosed. Therefore, more personalised diagnostic approaches are urgently needed. The Sleep Revolution, funded by the European Union's Horizon 2020 Research and Innovation Programme, aims to tackle these shortcomings by developing machine learning tools to better estimate obstructive sleep apnea severity and phenotypes. This allows for improved personalised treatment options, including increased patient participation. Also, implementing these tools will alleviate the costs and increase the availability of sleep studies by decreasing manual scoring labour. Finally, the project aims to design a digital platform that functions as a bridge between researchers, patients, and clinicians, with an electronic sleep diary, objective cognitive tests, and questionnaires in a mobile application. These ambitious goals will be achieved through extensive collaboration between 39 centres, including expertise from sleep medicine, computer science, and industry and by utilising tens of thousands of retrospectively and prospectively collected sleep recordings. With the commitment of the European Sleep Research Society and Assembly of National Sleep Societies, the Sleep Revolution has the unique possibility to create new standardised guidelines for sleep medicine.
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  • Eliasson, T, et al. (author)
  • Myocardial turnover of endogenous opioids and calcitonin-gene-related peptide in the human heart and the effects of spinal cord stimulation on pacing-induced angina pectoris.
  • 1998
  • In: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 89:3, s. 170-7
  • Journal article (peer-reviewed)abstract
    • Earlier studies have shown that spinal cord stimulation (SCS) has antianginal and anti-ischemic effects in severe coronary artery disease. In the present study, 14 patients were subjected to right-sided atrial catheterization and atrial pacing. The patients were paced to angina during a control session and during spinal cord stimulation. Myocardial extraction of beta-endorphin (BE) during control pacing (8 +/- 22%) changed to release at the maximum pacing rate during treatment (-21 +/- 47%, a negative value representing release). Furthermore, the results indicate local myocardial turnover of leuenkephalin, BE and calcitonin-gene-related peptide. In addition, it is implied that SCS may induce myocardial release of BE which could explain the beneficial effects in myocardial ischemia.
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  • Hirsch, Jan M, et al. (author)
  • Hemodynamic effects of the use of oral snuff
  • 1992
  • In: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 52:4, s. 394-401
  • Journal article (peer-reviewed)abstract
    • The hemodynamic effects during rest and exercise of oral snuff were investigated in an open, placebo-controlled study of nine habitual users of oral snuff. Blood pressure, heart rate, and central hemodynamics were measured noninvasively. Plasma concentrations of nicotine, cotinine, norepinephrine, and epinephrine, as well as neuropeptide Y-like immunoreactivity were measured before and after snuff intake during rest and exercise. Snuff intake induced a significant increase in heart rate and blood pressure and a decrease in stroke volume during rest. Hemodynamic changes were unrelated to nicotine or cotinine concentrations. Resting levels of norepinephrine and neuropeptide Y-like immunoreactivity were similar with or without snuff, whereas epinephrine was slightly increased 30 minutes after snuff intake. The exercise-induced increase in norepinephrine and neuropeptide Y-like immunoreactivity did not differ between the days subjects received snuff and the days they received placebo. In contrast, maximum work load was associated with a slight increase in circulating epinephrine after snuff intake. The findings suggest that snuff intake is associated with significant hemodynamic effects during rest but not during exercise. These effects could not be readily explained by activation of the sympathetic nervous system.
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  • Marrone, O., et al. (author)
  • Fixed But Not Autoadjusting Positive Airway Pressure Attenuates the Time-dependent Decline in Glomerular Filtration Rate in Patients With OSA
  • 2018
  • In: Chest. - : Elsevier BV. - 0012-3692. ; 154:2, s. 326-334
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The impact of treating OSA on renal function decline is controversial. Previous studies usually included small samples and did not consider specific effects of different CPAP modalities. The aim of this study was to evaluate the respective influence of fixed and autoadjusting CPAP modes on estimated glomerular filtration rate (eGFR) in a large sample of patients derived from the prospective European Sleep Apnea Database cohort. METHODS: In patients of the European Sleep Apnea Database, eGFR prior to and after follow-up was calculated by using the Chronic Kidney Disease-Epidemiology Collaboration equation. Three study groups were investigated: untreated patients (n = 144), patients receiving fixed CPAP (fCPAP) (n = 1,178), and patients on autoadjusting CPAP (APAP) (n = 485). RESULTS: In the whole sample, eGFR decreased over time. The rate of eGFR decline was significantly higher in the subgroup with eGFR above median (91.42 mL/min/1.73 m(2)) at baseline (P < .0001 for effect of baseline eGFR). This decline was attenuated or absent (P < .0001 for effect of treatment) in the subgroup of patients with OSA treated by using fCPAP. A follow-up duration exceeding the median (541 days) was associated with eGFR decline in the untreated and APAP groups but not in the fCPAP group (P < .0001 by two-way ANOVA for interaction between treatment and follow-up length). In multiple regression analysis, eGFR decline was accentuated by advanced age, female sex, cardiac failure, higher baseline eGFR, and longer follow-up duration, whereas there was a protective effect of fCPAP. CONCLUSIONS: fCPAP but not APAP may prevent eGFR decline in OSA.
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  • Tasbakan, M. S., et al. (author)
  • Positive airway pressure (PAP) treatment reduces glycated hemoglobin (HbA1c) levels in obstructive sleep apnea patients with concomitant weight loss: Longitudinal data from the ESADA
  • 2021
  • In: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 30:5
  • Journal article (peer-reviewed)abstract
    • 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. © 2021 European Sleep Research Society
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  • Alonderis, A, et al. (author)
  • Medico-legal implications of sleep apnoea syndrome: Driving license regulations in Europe.
  • 2008
  • In: Sleep medicine. - : Elsevier BV. - 1389-9457 .- 1878-5506. ; 9:4, s. 362-75
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Andersson, Bert, 1952, et al. (author)
  • Exercise hemodynamics and myocardial metabolism during long-term beta-adrenergic blockade in severe heart failure.
  • 1991
  • In: Journal of the American College of Cardiology. - 0735-1097 .- 1558-3597. ; 18:4, s. 1059-66
  • Journal article (peer-reviewed)abstract
    • Hemodynamics and myocardial metabolism at rest and during exercise were investigated in 21 patients with heart failure. The patients were evaluated before and after long-term treatment (14 +/- 7 months) with the beta-adrenergic blocking agent metoprolol. Clinical improvement with increased functional capacity occurred during treatment. Maximal work load increased by 25% (104 to 130 W; p less than 0.001). Hemodynamic data showed an increased cardiac index (3.8 to 4.6 liters/min per m2; p less than 0.02) during exercise. Pulmonary capillary wedge pressure decreased at rest (20 to 13 mm Hg; p less than 0.01) and during exercise (32 to 28 mm Hg; p = NS). Stroke volume index (30 to 39 g.m/m2; p less than 0.006) and stroke work index (28 to 46 g.m/m2; p less than 0.006) increased during exercise and long-term metoprolol treatment. The arterial norepinephrine concentration decreased at rest (3.72 to 2.19 nmol/liter; p less than 0.02) but not during exercise (13.2 to 11.1 nmol/liter; p = NS). The arterial-coronary sinus norepinephrine difference suggested a decrease in myocardial spillover during metoprolol treatment (-0.28 to -0.13 nmol/liter; p = NS at rest and -1.13 to -0.27 nmol/liter; p less than 0.05 during exercise). Coronary sinus blood flow was unchanged during treatment. Four patients produced myocardial lactate before the study, but none produced lactate after beta-blockade (p less than 0.05). There was no obvious improvement in a subgroup of patients with ischemic cardiomyopathy. In summary, there were signs of increased myocardial work load without higher metabolic costs after treatment with metoprolol.
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  • Bailly, S., et al. (author)
  • Clusters of sleep apnoea phenotypes: A large pan-European study from the European Sleep Apnoea Database (ESADA)
  • 2021
  • In: Respirology. - : Wiley. - 1323-7799 .- 1440-1843. ; 26:4, s. 378-387
  • Journal article (peer-reviewed)abstract
    • 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. © 2020 Asian Pacific Society of Respirology
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  • Bonsignore, M. R., et al. (author)
  • Clinical presentation of patients with suspected obstructive sleep apnea and self-reported physician-diagnosed asthma in the ESADA cohort
  • 2018
  • In: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 27:6
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Bouloukaki, I., et al. (author)
  • Mild obstructive sleep apnea increases hypertension risk, challenging traditional severity classification
  • 2020
  • In: Journal of Clinical Sleep Medicine. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 16:6, s. 889-898
  • Journal article (peer-reviewed)abstract
    • Study Objectives: The association of mild obstructive sleep apnea (OSA) with important clinical outcomes remains unclear. We aimed to investigate the association between mild OSA and systemic arterial hypertension (SAH) in the European Sleep Apnea Database cohort. Methods: In a multicenter sample of 4,732 participants, we analyzed the risk of mild OSA (subclassified into 2 groups: mild(AHI) (5-<)(11)(/h) (apnea-hypopnea index [AHI], 5 to <11 events/h) and mild(AHI) (1)(1-<15/h) (AHI, >= 11 to <15 events/h) compared with nonapneic snorers for prevalent SAH after adjustment for relevant confounding factors including sex, age, smoking, obesity, daytime sleepiness, dyslipidemia, chronic obstructive pulmonary disease, type 2 diabetes, and sleep test methodology (polygraphy or polysomnography). Results: SAH prevalence was higher in the mild(AHI) (11-<15/h) OSA group compared with the mild(AHI 5-<11/h) group and nonapneic snorers (52% vs 45% vs 30%; P < .001). Corresponding adjusted odds ratios for SAH were 1.789 (mild(AHI) (11-<15/h); 95% confidence interval [CI], 1.49-2.15) and 1.558 (mild 1.34-1.82), respectively (P < .001). In sensitivity analysis, mild(AHI) (11-<15/h) OSA remained a significant predictor for SAH both in the polygraphy (odds ratio, 1.779; 95% CI, 1.403-2.256; P < .001) and polysomnography groups (odds ratio, 1.424; 95% CI, 1.047-1.939; P = .025). Conclusions: Our data suggest a dose-response relationship between mild OSA and SAH risk, starting from 5 events/h in polygraphy recordings and continuing with a further risk increase in the 11- to <150-events/h range. These findings potentially introduce a challenge to traditional thresholds of OSA severity and may help to stratify participants with OSA according to cardiovascular risk.
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  • Clark, C A, et al. (author)
  • Endothelial cell protein C receptor-mediated redistribution and tissue-level accumulation of factor VIIa.
  • 2012
  • In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 10:11, s. 2383-2391
  • Journal article (peer-reviewed)abstract
    • Background: Recent studies show that FVIIa binds to endothelial cell protein C receptor (EPCR) on vascular endothelium; however, the importance of this interaction in hemostasis or pathophysiology is unknown. Objective, The aim of the present study is to investigate the role of FVIIa interaction with EPCR on the endothelium in mediating FVIIa transport from the circulation to extravascular tissues. Methods: Wild-type, EPCR-deficient or ECPR-over expressing mice were injected with human rFVIIa (120 μg/kg b.w.) via tail vein. At varying time intervals following rFVIIa administration, blood and various tissues were collected to measure FVIIa antigen and activity levels. Tissue sections were analyzed by immunohistochemistry for FVIIa and EPCR. Results: The data reveal that, following intravenous injection, rFVIIa rapidly disappears from blood and associates with the endothelium in an EPCR-dependent manner. Immunohistochemical analyses revealed that association of FVIIa with the endothelium was maximal at 30 min and thereafter progressively declined. FVIIa association with the endothelium was undetectable at time points exceeding 24 h post FVIIa administration. The levels of rFVIIa accumulated in tissue correlates with expression levels of EPCR in mice and FVIIa associated with tissues remained functionally active for periods of at least 7 days. Conclusions: The observation that EPCR-dependent association of FVIIa with the endothelium is most pronounced soon after rFVIIa administration and subsequently declines temporally, combined with the retention of functionally-active FVIIa in tissue homogenates for extended periods, indicates that FVIIa binding to EPCR on the endothelium facilitates the transport of FVIIa from circulation to extravascular tissues where TF resides. © 2012 International Society on Thrombosis and Haemostasis.
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