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Sökning: WFRF:(Zou Ding 1970)

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1.
  • Basoglu, Ozen K, et al. (författare)
  • Change in weight and central obesity by positive airway pressure treatment in obstructive sleep apnea patients: longitudinal data from the ESADA cohort.
  • 2018
  • Ingår i: Journal of sleep research. - : Wiley. - 1365-2869 .- 0962-1105. ; 27:6
  • Tidskriftsartikel (refereegranskat)abstract
    • 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±6.4kg/m2 , apnea-hypopnea index 37±24n 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±1.0years and compliance 5.2±2.1hr per day). However, in non-obese (body mass index <30kg/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.
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2.
  • Dieltjens, Marijke, et al. (författare)
  • Use of the Clinical Global Impression scale in sleep apnea patients-Results from the ESADA database.
  • 2019
  • Ingår i: Sleep medicine. - : Elsevier BV. - 1878-5506 .- 1389-9457. ; 59, s. 56-65
  • Tidskriftsartikel (refereegranskat)abstract
    • The Clinical Global Impression scale (CGI) reflects the clinician's assessment of the disease impact on patient's global functioning. We assessed predictors of CGI scale rating in patients with obstructive sleep apnea (OSA).Consecutive patients with suspected OSA (n=7581) were identified in the European Sleep Apnea Database (ESADA). Anthropometrics, comorbidities, apnea severity obtained by polygraphy or polysomnography, and daytime sleepiness [Epworth Sleepiness Scale (ESS)] were assessed. The CGI 7-point scale was completed at the end of the diagnostic process (CGI-severity, ie, CGI-S) and, in a subpopulation, at treatment follow-up (CGI-Improvement).CGI-S was rated mild to moderate in 44% of patients. CGI rating at any given apnea intensity was worse in women than in men (p<0.01). Patients undergoing polygraphy (n=5075) were more frequently rated as severely ill compared to those studied with polysomnography (19.0% vs 13.0%, p<0.001). In patients aged ≤65 years, CGI scoring was generally better than in the elderly despite a similar degree of OSA (eg, 'normal, not ill' 24.2% vs 15.3%, p<0.01, respectively). Independent predictors of CGI rating included age, BMI, AHI, ESS, cardio-metabolic comorbidities, and diagnosis based on polygraphy. CGI-improvement rating (Beta=-0.406, p<0.01) was superior to sleep apnea severity or ESS-score (Beta=0.052 and-0.021, p=0.154 and 0.538 respectively) at baseline for prediction of good CPAP compliance at follow-up.CGI rating is confounded by gender, age class and the type of sleep diagnostic method. As OSA phenotypes differ, CGI may contribute as a clinical tool to reflect the significance of clinical disease.
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3.
  • Eder, Derek, 1959, et al. (författare)
  • Self-Reported Features of Sleep, Utilization of Medical Resources, and Socioeconomic Position: A Swedish Population Survey
  • 2011
  • Ingår i: Behavioral Sleep Medicine. - 1540-2002. ; 9:3, s. 162-172
  • Tidskriftsartikel (refereegranskat)abstract
    • This study examined aspects of self reported qualities of sleep and daytime functioning attributed to sleep, including the utilization of physician consultations and prescription medications, and their relationships with age, gender, and educational attainment in the Swedish population using telephone interviews of 1,000 random households. Women were twice as likely to use hypnotics and experienced more poor quality sleep and excessive daytime sleepiness (EDS). Lower educational attainment was associated with twofold increased hypnotic use, life impacts of sleep problems, and EDS, but not dimensions reflecting poor quality sleep. This study demonstrates that educational attainment, gender, and age combine to shape both the attributions of the effects of sleep on wakeful functioning and patterns of using medical resources.
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4.
  • Eskandari, Davoud, et al. (författare)
  • Acetazolamide Reduces Blood Pressure and Sleep-Disordered Breathing in Patients with Hypertension and Obstructive Sleep Apnea: A Randomized Controlled Trial
  • 2018
  • Ingår i: Journal of Clinical Sleep Medicine. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 14:3, s. 309-317
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Objectives: The carbonic anhydrase inhibitor acetazolamide (AZT) modulates blood pressure at high altitude and reduces sleep-disordered breathing in patients with obstructive sleep apnea (OSA). We aimed to investigate the treatment effect of AZT and in combination with continuous positive airway pressure (CPAP) on blood pressure in patients with hypertension and OSA. Methods: In a prospective, randomized, three-way crossover study, 13 male patients with hypertension and moderate to severe OSA (age 64 ± 7 years, body mass index 29±4 kg/m2, and mean apnea-hypopnea index 37±23 events/h) received AZT, CPAP, or AZT plus CPAP for 2-week periods. Antihypertensive medication was washed out. Office and 24-hour blood pressure, arterial stiffness, polygraphic sleep study data, and blood chemistry were compared. Results: AZT alone and AZT plus CPAP, but not CPAP alone, reduced office mean arterial pressure compared to baseline (-7 [95% CI-11 to-4],-7 [95% CI-11 to-4] and-1 [95% CI-5 to 4] mmHg, respectively; repeated-measures analysis of variance (RM-ANOVA; P = .015). Aortic systolic pressure and augmentation index, assessed by radial artery oscillatory tonometry, were unaffected by CPAP but decreased after AZT and AZT plus CPAP (RM-ANOVA P = .030 and .031, respectively). The apnea-hypopnea index was significantly reduced in all three treatment arms, most prominently by AZT plus CPAP (RM-ANOVA P = .003). The reduction of venous bicarbonate concentration following AZT was correlated with the change of apnea-hypopnea index (r = 0.66, P = .013). Conclusions: AZT reduced blood pressure, vascular stiffness, and sleep-disordered breathing in patients with OSA and comorbid hypertension. Carbonic anhydrase inhibition may constitute a potential target for drug therapy in patients with sleep apnea and comorbid hypertension.
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5.
  • Eskandari, Davoud, et al. (författare)
  • Independent associations between arterial bicarbonate, apnea severity and hypertension in obstructive sleep apnea
  • 2017
  • Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-993X. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Obstructive sleep apnea is characterized by intermittent hypoxia and hypercapnia. CO2 production, transport and elimination are influenced by the carbonic anhydrase enzyme. We hypothesized that elevated standard bicarbonate, a proxy for increased carbonic anhydrase activity, is associated with apnea severity and higher blood pressure in patients with obstructive sleep apnea. Methods: A retrospective analysis of a sleep apnea cohort (n = 830) studied by ambulatory polygraphy. Office systolic/diastolic blood pressure, lung function, and arterial blood gases were assessed during daytime. Results: Arterial standard bicarbonate was increased with apnea severity (mild/moderate/severe 24.1 +/- 1.8, 24.4 +/- 1.7 and 24.9 +/- 2.9 mmol/l, respectively, Kruskal-Wallis test p < 0.001). Standard bicarbonate was independently associated with apnea hypopnea index after adjustment for sex, age, body mass index, smoking, alcohol, hypertension, pO(2) and pCO(2) (standard bicarbonate quartile 1 vs. quartile 4, beta = 10.6, p < 0.001). Log-transformed standard bicarbonate was associated with a diagnosis of hypertension or diastolic blood pressure but not systolic blood pressure adjusting for cofounders (p = 0.007, 0.048 and 0.45, respectively). Conclusions: There was an independent association between sleep apnea severity and arterial standard bicarbonate. The link between high standard bicarbonate and daytime hypertension suggests that carbonic anhydrase activity may constitute a novel mechanism for blood pressure regulation in sleep apnea.
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6.
  • Eskandari, Davoud, et al. (författare)
  • Zonisamide reduces obstructive sleep apnoea: a randomised placebo-controlled study
  • 2014
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 44:1, s. 140-149
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbonic anhydrase inhibition reduces apnoeic events in sleep disordered breathing. Zonisamide inhibits carbonic anhydrase, and induces weight loss in obese patients. This study explored the relative influence of these two properties, which may both alleviate obstructive sleep apnoea (OSA). Continuous positive airway pressure (CPAP) was used as a standard care comparator. 47 patients with moderate-to-severe OSA and a body mass index of 27-35 kg.m(-2) were randomised to receive either zonisamide, placebo or CPAP for 4 weeks. The open extension phase (20 weeks) compared CPAP and zonisamide. Polysomnography, biochemistry and symptoms were evaluated. At 4 weeks, zonisamide reduced apnoea/hypopnoea index (AHI) by a mean +/- SD 33 +/- 39% and oxygen desaturation index by 28 +/- 31% (p=0.02 and 0.014, respectively; placebo adjusted). The mean compliance adjusted reduction of AHI after zonisamide and CPAP was 13 and 61%, respectively, (p=0.001) at 24 weeks. Body weight was marginally changed at 4 weeks, but reduced after zonisamide and increased after CPAP at 24 weeks (-2.7 +/- 3.0 kg versus 2.3 +/- 2.0 kg, p<0.001). Zonisamide decreased bicarbonate at 4 and 24 weeks. Side-effects were more common after zonisamide. Zonisamide reduced OSA independent of body weight potentially by mechanisms related to carbonic anhydrase inhibition. The effect was less pronounced than that obtained by CPAP.
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7.
  • Fridriksson, Benedikt, 1987, et al. (författare)
  • Beneficial Effects of Early Intervention Telemedicine-based Follow-Up in Sleep Apnea A Randomized Controlled Multicenter Trial
  • 2023
  • Ingår i: Annals of the American Thoracic Society. - 1546-3222. ; 20:10, s. 1499-1507
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Positive airway pressure (PAP) is standard treatment for obstructive sleep apnea. Telemedicine has been introduced for improved PAP follow-up. Objectives: Our study aim was to evaluate the clinical utility of and patient satisfaction with PAP follow-up with an early intervention telemedical protocol. Methods: A randomized controlled trial was conducted at four sleep clinics of the same county. Treatment-naive patients with obstructive sleep apnea were randomized to standard PAP follow-up (203 patients, fixed follow-up procedures) or early intervention telemedical follow-up (AirView, ResMed; 206 patients, continuous follow-up) for 3 months. Evaluated variables included PAP adherence at 3 months, patient-reported outcome measures (Epworth Sleepiness Scale, 36-item Short Form Health Survey, Insomnia Severity Index, Hospital Anxiety and Depression Scale), and staff time. Group differences were analyzed with linear mixed regression models adjusted for age, body mass index, apnea-hypopnea index, and study center. Results: The study groups were comparable at baseline (N= 409; mean age, 59 +/- 12 yr; body mass index, 31.9 +/- 6 kg/m(2), apnea-hypopnea index, 41.5 +/- 21 events/h). PAP adherence was higher in the proactive telemedicine group than in the control group (4.3 +/- 2.4 and 4.1 +/- 2.6 h/night; P = 0.01, respectively), and mean mask pressure at follow-up was significantly lower in the telemedicine group than in the control group (8.7 +/- 2.1 cm H2O vs. 9.2 +/- 2.5 cm H2O; P = 0.028). In post hoc analysis, the difference in PAP adherence between groups was most pronounced in patients with depression (4.8 +/- 2.6 h/night vs. 2.7 +/- 2.3 h/night; P = 0.03). Relevant mask leakage (>24 L/min) was lower in the telemedicine group (5.4% vs. 12.1%, P = 0.024). Improvement of patient-reported outcome measures and patient satisfaction was equivalent between groups. Conclusions: Proactive telemedical management of the initial follow-up of PAP treatment compared favorably with conventional follow-up in terms of adherence, pressure level, and mask leakage. Patients with depression may particularly benefit from telemedical follow-up. Specific clinical routines are required to establish this practice in sleep clinics.
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8.
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9.
  • Grote, Ludger, 1964, et al. (författare)
  • Oximeter-based autonomic state indicator algorithm for cardiovascular risk assessment.
  • 2011
  • Ingår i: Chest. - : Elsevier BV. - 1931-3543 .- 0012-3692. ; 139:2, s. 253-259
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cardiovascular (CV) risk assessment is important in clinical practice. An autonomic state indicator (ASI) algorithm based on pulse oximetry was developed and validated for CV risk assessment. Methods: One hundred forty-eight sleep clinic patients (98 men, mean age 50 ± 13 years) underwent an overnight study using a novel photoplethysmographic sensor. CV risk was classified according to the European Society of Hypertension/European Society of Cardiology (ESH/ESC) risk factor matrix. Five signal components reflecting cardiac and vascular activity (pulse wave attenuation, pulse rate acceleration, pulse propagation time, respiration-related pulse oscillation, and oxygen desaturation) extracted from 99 randomly selected subjects were used to train the classification algorithm. The capacity of the algorithm for CV risk prediction was validated in 49 additional patients. Results: Each signal component contributed independently to CV risk prediction. The sensitivity and specificity of the algorithm to distinguish high/low CV risk in the validation group were 80% and 77%, respectively. The area under the receiver operating characteristic curve for high CV risk classification was 0.84. β-Blocker treatment was identified as an important factor for classification that was not in line with the ESH/ESC reference matrix. Conclusions: Signals derived from overnight oximetry recording provide a novel potential tool for CV risk classification. Prospective studies are warranted to establish the value of the ASI algorithm for prediction of outcome in CV disease.
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10.
  • Grote, Ludger, 1964, et al. (författare)
  • Pulse Wave Analysis During Sleep
  • 2017
  • Ingår i: Principles and Practice of Sleep Medicine. Meir H. Kryger & Thomas Roth & William C. Dement (eds.). - : Elsevier. - 9780323242882
  • Bokkapitel (refereegranskat)
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11.
  • Gunduz, C., et al. (författare)
  • 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
  • Ingår i: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 75, s. 201-209
  • Tidskriftsartikel (refereegranskat)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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12.
  • Gündüz, Canan, et al. (författare)
  • Obstructive sleep apnoea independently predicts lipid levels: Data from the European Sleep Apnea Database.
  • 2018
  • Ingår i: Respirology (Carlton, Vic.). - : Wiley. - 1440-1843 .- 1323-7799. ; 23:12, s. 1180-1189
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.The cross-sectional analysis included 8592 patients without physician-diagnosed hyperlipidaemia or reported intake of a lipid-lowering drug (age 50.1±12.7years, 69.1% male, BMI: 30.8±6.6kg/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.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.OSA severity was independently associated with cholesterol and TG concentrations.
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13.
  • Hansson, D., et al. (författare)
  • Clinical impact of routine sleep assessment by peripheral arterial tonometry in patients with COPD
  • 2023
  • Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 9:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Coexisting obstructive sleep apnoea (OSA) in patients with COPD, defined as overlap syndrome (OVS), is prevalent and underdiagnosed. Routine assessment of OSA is not common practice in COPD care. Our study assessed the clinical impact of sleep assessment by peripheral arterial tonometry (PAT) in COPD patients. Methods 105 COPD patients (mean age 68.1 +/- 9 years, body mass index (BMI) 28.3 +/- 6.0 kg center dot m(-2), 44% males, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I to IV in 2%, 40%, 42% and 16%, respectively) underwent assessment at an outpatient COPD clinic including anthropometrics, arterial blood gas (ABG) and spirometry in this clinical cohort study. PAT-based sleep studies were performed. Predictors of OVS and ABG were determined. Rapid eye movement (REM) sleep-related OSA (REM-OSA) was analysed in OVS. Results 49 COPD patients (47%) suffered from moderate to severe OSA (OVS group, mean apnoea-hypopnoea index 30.8 +/- 18 events center dot h(-)1, REM-oxygen desaturation index (REM-ODI) 26.9 +/- 17 events center dot h(-)1). OVS was more prevalent in males compared to females (59% and 37%, p=0.029, respectively). Age (70.1 +/- 8 versus 66.3 +/- 10 years), BMI (30.0 +/- 6 versus 26.4 +/- 7 kg center dot m(-2)) and hypertension prevalence (71% versus 45%) were elevated (all p<0.03, respectively), while deep sleep (12.7 +/- 7% and 15.4 +/- 6%, p=0.029) and mean overnight oxygenation (90.6 +/- 3% and 92.3 +/- 2%, p=0.003) were lower in OVS compared to COPD alone. REM-ODI was independently associated with daytime arterial carbon dioxide tension (P-aCO2) (beta=0.022, p<0.001). REM-OSA was associated with an elevated prevalence of atrial fibrillation compared to no REM-OSA (25% and 3%, p=0.022). Conclusions OVS was highly prevalent, specifically in obese males. REM-related OSA showed strong association with elevated daytime P-aCO2 and prevalent cardiovascular disease. PAT was feasible for sleep assessment in COPD.
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14.
  • Hedner, Jan A, 1953, et al. (författare)
  • A novel adaptive wrist actigraphy algorithm for sleep-wake assessment in sleep apnea patients
  • 2004
  • Ingår i: Sleep. ; 27:8
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY OBJECTIVES: Current actigraphic algorithms are relatively less accurate in detecting sleep and wake in sleep apnea patients than in people without sleep apnea. In the current study, we attempted to validate a novel automatic algorithm, which was developed for actigraphic studies in normal subjects and patients with obstructive sleep apnea by comparing it on an epoch-by-epoch basis to standard polysomnography. DESIGN: Prospective cohort study. SETTING: Multicenter, university hospital, sleep laboratories. PARTICIPANTS: A total of 228 subjects from 3 different sleep centers (Skara, Boston, Haifa) participated. INTERVENTION AND MEASUREMENTS: Simultaneous recording of polysomnography and Watch_PAT100, an ambulatory device that contains a built-in actigraph. The automatic sleep/wake algorithm is based on both the quantification of motion (magnitude and duration) and the various periodic movement patterns, such as those occurring in patients with moderate to severe obstructive sleep apnea. RESULTS: The overall sensitivity and specificity to identify sleep was 89% and 69%, respectively. The agreement ranged from 86% in the normal subjects to 86%, 84%, and 80% in the patients with mild, moderate, and severe obstructive sleep apnea, respectively. There was a tight agreement between actigraphy and polysomnography in determining sleep efficiency (78.4 +/- 9.9 vs 78.8 +/- 13.4%), total sleep time (690 +/- 152 vs 690 +/- 154 epochs), and sleep latency (56.8 +/- 31.4 vs 43.3 +/- 45.4 epochs). While for most individuals the difference between the polysomnography and actigraphy was relatively small, for some there was a substantial disagreement. CONCLUSIONS: We conclude that this actigraphy algorithm provides a reasonably accurate estimation of sleep and wakefulness in normal subjects and patients with obstructive sleep apnea on an epoch-by-epoch basis. This simple method for assessment of total sleep time may provide a useful tool for the accurate quantification of obstructive sleep apnea in the home environment.
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15.
  • Hedner, Jan A, 1953, et al. (författare)
  • A Randomized Controlled Clinical Trial Exploring Safety and Tolerability of Sulthiame in Sleep Apnea
  • 2022
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 205:12, s. 1461-1469
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Current therapies for obstructive sleep apnea (OSA) are limited by insufficient efficacy, compliance, or tolerability. An effective pharmacological treatment for OSA is warranted. Carbonic anhydrase inhibition has been shown to ameliorate OSA. Objectives: To explore safety and tolerability of the carbonic anhydrase inhibitor sulthiame (STM) in OSA. Methods: A 4-week double-blind, randomized, placebo-controlled dose-guiding trial was conducted in patients with moderate and/or severe OSA not tolerating positive airway pressure treatment. Measurements and Main Results: Intermittent paresthesia was reported by 79%, 67%, and 18% of patients receiving 400 mg STM (n = 34), 200 mg STM (n =12), and placebo (n = 22), respectively. Dyspnea was reported after 400 mg STM (18%). Six patients in the higher dose group withdrew because of adverse events. There were no serious adverse events. STM reduced the apnea-hypopnea index from 55.2 to 33.0 events/h (-41.0%) in the 400-mg group and from 61.1 to 40.6 events/h (-32.1%) after 200 mg (P < 0.001 for both). Corresponding placebo values were 53.9 and 50.9 events/h (-5.4%). The apnea-hypopnea index reduction threshold of >= 50% was reached in 40% of patients after 400 mg, 25% after 200 mg, and 5% after placebo. Mean overnight oxygen saturation improved by 1.1% after 400 and 200 mg (P < 0.001 and P = 0.034, respectively). Patient-related outcomes were unchanged. Conclusions: STM showed a satisfactory safety profile in moderate and/or severe OSA. STM reduced OSA, on average, by more than 20 events/h, one of the strongest reductions reported in a drug trial in OSA. Larger scale clinical studies of STM in OSA are justified.
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16.
  • Hedner, Jan A, 1953, et al. (författare)
  • Drug Therapy in Obstructive Sleep Apnea
  • 2018
  • Ingår i: Sleep Medicine Clinics. - : Elsevier BV. - 1556-407X. ; 13:2, s. 203-17
  • Forskningsöversikt (refereegranskat)abstract
    • There are several reasons to develop a pharmacologic remedy in obstructive sleep apnea (OSA); but so far, there is no generally effective drug available. Previous attempts to find a drug in OSA therapy were serendipity driven in small pilot trials. There is a growing literature on phenotyping pathophysiologic mechanisms of OSA that may be exploited in strategic drug development programs. This article addresses potential pitfalls encountered in previous studies and highlights several drug candidates under development in the field.
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17.
  • Hedner, Jan A, 1953, et al. (författare)
  • New pharmacologic agents for obstructive sleep apnoea: what do we know and what can we expect?
  • 2022
  • Ingår i: Current Opinion in Pulmonary Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 1070-5287 .- 1531-6971. ; 28:6, s. 522-528
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose of review This review provides a condensed description of pharmacological remedies explored in patients with obstructive sleep apnoea (OSA) as well as projections of what we might expect in terms of clinical performance of these drugs. Recent findings Conventional drug therapies explored in OSA have generally produced disappointing results and there is a shortage of pharmacological treatment alternatives in this disorder. Recent insights into pathophysiological mechanisms potentially involved in OSA suggest that the condition may be divided into distinct subgroups based on clusters or defined by means of unique functional endotypic criteria. In fact, positive outcomes in clinical trials have now resulted in several drug candidates that show a convincing reduction of sleep disordered breathing in both short and intermediate term. Such drugs may be particularly useful in certain variants of OSA but not in others. These insights have also raised the ambition to create personalized therapies in OSA. Another recent development is the insight that OSA-linked conditions such as obesity, daytime somnolence and various forms of cardiovascular/metabolic disease may provide drug-based targets. For instance, pharmacological obesity therapy may provide not only positive metabolic effects but may also be a way to eliminate the anatomic component in obese OSA patients. Summary Recent insights into the pathophysiology of OSA have opened possibilities to develop personalized therapy. Drugs addressing fundamental aspects of the sleep and breathing disorder provide a particularly promising avenue for development of novel forms of treatment in OSA.
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18.
  • Hedner, Jan A, 1953, et al. (författare)
  • Overview and pathophysiology
  • 2021
  • Ingår i: Section J. Sleep and Pulmonology. Editor Bassetti C, McNicholas W and Paunio T. European Sleep Medicine Textbook, 2nd ed.. - : European Sleep Research Society. - 111978901X ; , s. 717-724
  • Bokkapitel (refereegranskat)
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19.
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20.
  • Hedner, Jan A, 1953, et al. (författare)
  • Pharmacological management of sleep-disordered breathing
  • 2010
  • Ingår i: European Respiratory Monograph: Sleep Apnoea. - ENGLAND : EUROPEAN RESPIRATORY SOCIETY. - 9781849840071 ; , s. 321-339
  • Bokkapitel (refereegranskat)abstract
    • Several attempts have been made to identify a uniformly effective pharmacological remedy in obstructive sleep apnoea (OSA). However, no currently described drug has consistently reduced the severity of the condition by more than 50% in controlled trials. Most of the data is based on testing of compounds used in other therapeutic areas and there are few examples of rational strategic drug development. OSA is frequently associated with considerable comorbidities, including: hypertension, obesity, metabolic derangement and hormonal dysfunction, beside the more or less consistent symptoms of daytime sleepiness and cognitive dysfunction. Hence, specific considerations, such as classification of phenotype, existing comorbidity etc., should be taken into account when explorative clinical trials are designed in patients with OSA. The clinician should be made aware that there is no systematically documented drug yet available for the treatment of sleep apnoea. Future drug development is likely to incorporate a more global approach to comorbid conditions and risk modification in OSA.
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21.
  • Hedner, Jan A, 1953, et al. (författare)
  • Pharmacological treatment of sleep apnea: Current situation and future strategies.
  • 2008
  • Ingår i: Sleep medicine reviews. - : Elsevier BV. - 1087-0792. ; 12:1, s. 33-47
  • Forskningsöversikt (refereegranskat)abstract
    • Current forms of mechanical treatment in obstructive sleep apnea (OSA) are generally effective in eliminating sleep and breathing disorders. However, they do have drawbacks, such as incomplete tolerability and non-compliance. Several attempts have been made to identify pharmacological treatments for OSA, but no drug has consistently reduced the severity of the condition by more than 50%. OSA, in most cases, is a condition characterized by considerable comorbidity, including hypertension, obesity, metabolic derangement and hormonal dysfunction. Daytime sleepiness and cognitive dysfunction represent common, but not consistent, findings in people with this nocturnal sleep and breathing disorder. Hence, future pharmacological treatments for OSA may need to take aspects other than the nocturnal breathing events alone into consideration. Drug research into OSA has been hampered by the lack of useful experimental systems and animal models for drug screening. In addition, the phenotypic characterization of OSA seems to be incomplete, and this limits the possibility of using stringent criteria for patient selection in drug studies. Finally, the criteria for defining the severity of OSA and disease impact seem to be insufficient for adequate definition of efficacy end points in clinical trials. This review will list some potential shortcomings and possibilities of pharmacological treatment in OSA, and discuss some of the already attempted modes of treatment.
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22.
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23.
  • Hedner, Jan A, 1953, et al. (författare)
  • Sleep staging based on autonomic signals: a multi-center validation study.
  • 2011
  • Ingår i: Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. - 1550-9397. ; 7:3, s. 301-6
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the most important caveats of ambulatory devices is the inability to record and stage sleep. We assessed an algorithm determining 4 different stages: wake, light sleep, deep sleep, and REM sleep using signals derived from the portable monitor Watch-PAT100 (PAT recorder).
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24.
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25.
  • Hoff, Erik, et al. (författare)
  • Carbonic anhydrase, obstructive sleep apnea and hypertension: Effects of intervention
  • 2020
  • Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 29:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Whole blood carbonic anhydrase activity (CAa) is increased in patients with obstructive sleep apnea (OSA). Our study investigated the influence of positive airway pressure (PAP) or CA inhibitor acetazolamide (ACT) therapy on CAa, OSA and blood pressure. Thirty‐three OSA patients (21 hypertensive, body mass index (BMI) 37 ± 7 kg/m2 and apnea–hypopnea index (AHI) of 47 ± 31 events/hr) were followed‐up after PAP treatment (compliance, 4.7 ± 1.5 hr/day; duration, median 6 [IQR 6,6] months) (Cohort A). A second OSA Cohort (B) contained nine hypertensive patients (BMI, 29 ± 4 kg/m2; AHI, 39 ± 20 events/hr) with 2‐week treatment of ACT, PAP or ACT + PAP in an open crossover study. CAa was assessed at baseline and at the end of each treatment period. In Cohort A, baseline CAa was higher in hypertensive, compared with normotensive, patients (1,033 ± 204 versus 861 ± 201 units, p = .028). PAP treatment reduced systolic/diastolic blood pressure but not CAa (−9 ± 11/−5 ± 7 mmHg and −20 ± 289 units, p < .001, <.001 and .70). In Cohort B, blood pressure was reduced in both ACT‐treated groups (−10 ± 10/−5 ± 7 mmHg, p = .043 and .019; and −5 ± 5/−13 ± 13 mmHg, p < .001 and .009). AHI was reduced in both groups: ACT only, −17 ± 9 events/hr p = .001; and ACT + PAP, −39 ± 19 events/hr, p < .001. PAP did not change CAa (p = .98) but activity tended to decrease after ACT with or without PAP (p = .081 and .056). CAa is elevated in hypertensive OSA patients. Long‐term PAP reduced blood pressure without affecting CAa. ACT reduced blood pressure and CAa. Increased CAa may constitute a physiological characteristic in OSA, contributing to comorbid hypertension.
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26.
  • Hoff, Erik, et al. (författare)
  • Modification of Endotypic Traits in OSA by the Carbonic Anhydrase Inhibitor Sulthiame
  • 2024
  • Ingår i: CHEST. - 0012-3692 .- 1931-3543. ; 165:3, s. 704-715
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The carbonic anhydrase inhibitor sulthiame reduces OSA severity, increases overnight oxygenation, and improves sleep quality. Insights into how sulthiame modulates OSA pathophysiologic features (endotypic traits) adds to our understanding of the breathing disorder itself, as well as the effects of carbonic anhydrases in respiratory regulation. RESEARCH QUESTION: How does sulthiame treatment modify endotypic traits in OSA? STUDY DESIGN AND METHODS: Per -protocol tertiary analysis of a randomized controlled trial with the inclusion criteria as follow:BMI, >= 20 to # 35 kg/m(2) ; age, 18-75 years; apneahypopnea index (AHI) >= 15 events/h; Epworth sleepiness scale score, >= 6; as well as nonacceptance or nontolerance of positive airway pressure treatment. Patients were randomized to receive placebo (n = 22), sulthiame 200 mg (n = 12), or sulthiame 400 mg (n = 24) during 4 weeks of treatment. Polysomnography was applied twice at baseline and follow-up. Endotypic traits were determined from polysomnography tracings (PUPBeta). Sulthiame plasma concentration was analyzed. Differences from baseline to follow-up ( A s) were analyzed with the analysis of covariance or Kruskal-Wallis H test and Pearson ( r ) or Spearman correlations (r(s)). RESULTS: Sulthiame (200 -mg and 400 -mg groups) consistently reduced loop gain (response to a 1-cycle/min disturbance, Delta G(1) ; mean, - 0.16 [95% CI, - 0.18 to - 0.13]; P < .05) in addition to increased ventilation at lowest decile of ventilatory drive (V (min) ; median, + 12 [95% CI, 420]; P < .05) and median ventilation at eupneic ventilatory drive (V- passive ; median, + 4 [95% CI, 0-5]; P < .05). A Delta G(1 )correlated with A AHI percentage (200 mg: r = 0.65; P < .05). V (min )and V- passive correlated with A AHI (all sulthiame: r(s)= - 0.59 and r(s) = - 0.65; P < .05 for all). The reduction of Delta G(1) was seen already in the lower sulthiame concentration range, whereas changes in V (min) peaked in the higher range. INTERPRETATION: The effect of sulthiame in OSA may be explained by a reduction of ventilatory instability (Delta G(1)) as well as upper airway collapsibility (V (min) and V- passive ).
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27.
  • Hoff, Erik, et al. (författare)
  • The placebo effect in pharmacological treatment of obstructive sleep apnea, a systematic review and meta-analysis
  • 2023
  • Ingår i: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 106, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: New drug treatments are under development in obstructive sleep apnea (OSA). The placebo effect is well recognized in various conditions, but its relevance in OSA is debated. In the current study we determined the influence of a placebo effect in studies of drug therapy in OSA.Methods: A systematic review and meta-analysis (PROSPERO CRD42021229410) with searches in MEDLINE, Scopus, Web of Science and Cochrane CENTRAL from inception to 2021-01-19. Inclusion criteria were (i) RCTs of adults with OSA, (ii) drug intervention with placebo baseline and follow-up sleep study (iii) outcomes: apnea hypopnea index (AHI), mean oxygen saturation (mSaO2), oxygen desatura-tion index (ODI) and/or Epworth Sleepiness Scale (ESS). Risk-of-bias was assessed with Cochrane RoB 2.Results: 7436 articles were identified and 29 studies included (n = 413). Studies were generally small (median n = 14), with 78% men, baseline AHI range 9-74 events/h and treatment duration range 1-120 days. Meta-analyses were conducted for main outcomes. Mean change of the primary outcome, AHI, was-0.84 (95% CI-2.98 to 1.30); mSaO2 and ODI estimations were also non-significant. ESS showed a trend towards a reduction of-1 unit. Subgroup analysis did not show significant differences. Risk-of-bias assessment indicated mostly low risk but studies were small with wide confidence intervals. Conclusions: In this meta-analysis we did not identify systematic placebo effects on the AHI, ODI or mSaO2 while ESS score showed a trend for a small reduction. These results have an impact on the design and interpretation of drug trials in OSA.(c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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28.
  • Hrubos-Strom, H., et al. (författare)
  • Longitudinal Management and a Decision-Aid Tool in Treatment-Resistant Sleep Apnea
  • 2023
  • Ingår i: Current Sleep Medicine Reports. - 2198-6401. ; 9:3, s. 133-139
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose of ReviewWe expect an increased pressure of treating residual sleepiness in parallel with the introduction of novel wakefulness-promoting drugs to the European market. Our purpose is to review the literature on longitudinal management of treatment-resistant obstructive sleep apnea (OSA) and on this background to propose a management plan for this patient group focusing on both reduction of cardiovascular risk and relief of symptoms.Recent FindingsMost OSA literature focuses on primary diagnostics and primary or secondary treatment options in unstratified clinical populations. In this review, we focus on longitudinal management of treatment-resistant OSA described in recent, key publications. Moreover, we identified future diagnostic trends that also may be of clinical importance in this patient group. Finally, based on this background, we propose a standardized approach to secondary diagnostics and treatment decisions in treatment-resistant OSA based on a novel decision-aid tool.Limited literature was found on the longitudinal aspects of OSA treatment. Based on this background, a standardized management plan for treatment-resistant OSA and a shared decision-aid tool is proposed. The management plan focuses on both stabilization of the upper airway and relief of symptoms.
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29.
  • Huang, X, et al. (författare)
  • [Auto CPAP Set system for diagnosis and therapy of sleep breathing disorders].
  • 1998
  • Ingår i: Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases. - 1001-0939. ; 21:8, s. 468-70
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To compare the Auto CPAP Set system with standard polysomnography (PSG) in diagnosis and therapy of sleep breathing disorders. METHOD: Two studies were completed. The Auto CPAP Set system was compared with a simultaneously obtained PSG in eleven patients with sleep breathing disorders. Twenty-three additional patients with obstructive sleep apnea syndrome (OSAS) were treated by Auto CPAP Set. Student's t test was employed to evaluate statistical significance. RESULT: No differences were found between these two systems in AHI, SaO2 and the longest apnea duration (P > 0.05), and the Auto CPAP Set system had a sensitivity of 70% and a specificity 100% for diagnosis of OSAS. AHI decreased and SaO2 increased significantly in OSAS patients after treatment. CONCLUSION: The Auto CPAP Set system provides an accurate and simple method for diagnosis and therapy of sleep breathing disorders, and the time required for analysis of test results was shorter as compared with PSG.
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30.
  • Karimi, Mahssa, et al. (författare)
  • Attention deficits detected in cognitive tests differentiate between sleep apnea patients with or without a motor vehicle accident
  • 2015
  • Ingår i: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 16:4, s. 528-533
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Obstructive sleep apnea (OSA) is associated with an increased motor vehicle accident (MVA) risk. Conventional measures of OSA severity do not predict individual risk. Cognitive function tests have failed to incorporate outcomes in risk prediction. We aimed to identify markers of cognitive function for MVA risk prediction in OSA. Methods: OSA patients [n = 114, 75% male, median age 51 (43-61) years, body mass index (BMI) 30 (27-33) kg/m(2), apnea-hypopnea index 25 (6-49) n/h, and Epworth Sleepiness (ESS) score 11 (8-16)] were recruited from a sleep laboratory. Two cognitive function tests, the Attention Network Test (ANT) and a modified Oxford Sleep Resistance Test (OSLER) test (GOSLING), were assessed. Results: OSA patients with (n = 11) or without (n = 103) a MVA record in the Swedish traffic accident registry were identified. In patients with a MVA, 64% were commercial drivers. In patients with a MVA history, more lapses [42 (5-121) vs. 5 (1-25), P = 0.02] and fewer responses [238 (158-272) vs. 271 (256-277), P = 0.03] to stimuli in the ANT were found. In the GOSLING, the number of lapses was higher (29 (10-97) vs. 7 (2-19), P = 0.01) and the reaction time was longer [462 (393-551) vs. 407 (361-449) ms, P = 0.05]. OSA severity and ESS score poorly predicted MVAs (P > 0.2). Conclusions: We have demonstrated that deficit in sustained attention, assessed by daytime neurocognitive function tests, was associated with MVA risk in OSA patients. We were unable to detect an association between MVA history and severity of OSA or the ESS score. The findings provide a rationale for further development of objective MVA risk assessment tools in OSA. (C) 2014 Elsevier B.V. All rights reserved.
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31.
  • Karimi, Mahssa, et al. (författare)
  • Impaired vigilance and increased accident rate in public transport operators is associated with sleep disorders.
  • 2013
  • Ingår i: Accident Analysis and Prevention. - : Elsevier BV. - 0001-4575. ; 51, s. 208-214
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Sleep disturbances can impair alertness and neurocognitive performance and increase the risk of falling asleep at the wheel. We investigated the prevalence of sleep disorders among public transport operators (PTOs) and assessed the interventional effects on hypersomnolence and neurocognitive function in those diagnosed with obstructive sleep apnea (OSA). METHODS: Overnight polygraphy and questionnaire data from 101 volunteers (72 males, median age 48 range [22-64] years, 87 PTOs) employed at the Gothenburg Public Transportation Company were assessed. Treatment was offered in cases with newly detected OSA. Daytime sleep episodes and neurocognitive function were assessed before and after intervention. RESULTS: At baseline, symptoms of daytime hypersomnolence, insomnia, restless legs syndrome as well as objectively assessed OSA (apnea hypopnea index (AHI, determined by polygraphic recording)=17[5-46]n/h) were highly present in 26, 24, 10 and 22%, respectively. A history of work related traffic accident was more prevalent in patients with OSA (59%) compared to those without (37%, p<0.08). In the intervention group (n=12) OSA treatment reduced AHI by -23 [-81 to -5]n/h (p=0.002), determined by polysomnography. Reduction of OSA was associated with a significant reduction of subjective sleepiness and blood pressure. Measures of daytime sleep propensity (microsleep episodes from 9 [0-20.5] to 0 [0-12.5], p<0.01) and missed responses during performance tests were greatly reduced, indices of sustained attention improved. CONCLUSIONS: PTOs had a high prevalence of sleep disorders, particularly OSA, which demonstrated a higher prevalence of work related accidents. Elimination of OSA led to significant subjective and objective improvements in daytime function. Our findings argue for greater awareness of sleep disorders and associated impacts on daytime function in public transport drivers.
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32.
  • Kobayashi Frisk, Mio, et al. (författare)
  • Eveningness is associated with coronary artery calcification in a middle-aged Swedish population
  • 2024
  • Ingår i: Sleep Medicine. - : Elsevier. - 1389-9457 .- 1878-5506. ; 113, s. 370-377
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronary artery calcification (CAC) is an established imaging biomarker of subclinical atherosclerosis, but its relationship to diurnal preference is not well studied. We investigated the association between chronotype and CAC in the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort. Participants aged 50–64 years were randomly recruited and underwent extensive examination including imaging and accelerometry-assessed physical activity. 771 participants (47.3 % male, 57.6 ± 4.4 years) were included in this cross-sectional analysis. CAC was assessed by non-contrast computed tomography, and a CAC score > 10 was considered significant calcification. Self-assessed chronotype was classified as extreme morning, moderate morning, intermediate, moderate evening, or extreme evening. 10-year risk of first-onset cardiovascular disease was estimated by the Systemic Coronary Risk Evaluation 2 (SCORE2). Significant CAC was present in 29 % of the cohort. CAC prevalence increased from extreme morning to extreme evening type (22 %, 28 %, 29 %, 27 %, 41 % respectively, p = 0.018). In a multivariate logistic regression model controlling for confounders, extreme evening chronotype was independently associated with increased CAC prevalence compared to extreme morning type (OR 1.90, [95%CI 1.04–3.46], p = 0.037). When stratified by SCORE2 risk category (low: <5 %; moderate: 5 to <10 %; high: ≥10 %), significant CAC was most prevalent among extreme evening chronotypes in the low and moderate-risk groups, while chronotype seemed less important in the high-risk group (p = 0.011, p = 0.023, p = 0.86, respectively). Our findings suggest circadian factors may play an important role in atherosclerosis and should be considered in early cardiovascular prevention.
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33.
  • Kobayashi Frisk, Mio, et al. (författare)
  • Eveningness is associated with sedentary behavior and increased 10-year risk of cardiovascular disease: the SCAPIS pilot cohort
  • 2022
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronotype reflects individual preferences for timing activities throughout the day, determined by the circadian system, environment and behavior. The relationship between chronotype, physical activity, and cardiovascular health has not been established. We studied the association between chronotype, physical activity patterns, and an estimated 10-year risk of first-onset cardiovascular disease (CVD) in the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort. A cross-sectional analysis was performed in a middle-aged population (n = 812, 48% male). Self-assessed chronotype was classified as extreme morning, moderate morning, intermediate, moderate evening, or extreme evening. Time spent sedentary (SED) and in moderate to vigorous physical activity (MVPA) were derived from hip accelerometer. The newly introduced Systematic COronary Risk Evaluation 2 (SCORE2) model was used to estimate CVD risk based on gender, age, smoking status, systolic blood pressure, and non-HDL cholesterol. Extreme evening chronotypes exhibited the most sedentary lifestyle and least MVPA (55.3 +/- 10.2 and 5.3 +/- 2.9% of wear-time, respectively), with a dose-dependent relationship between chronotype and SED/MVPA (p < 0.001 and p = 0.001, respectively). In a multivariate generalized linear regression model, extreme evening chronotype was associated with increased SCORE2 risk compared to extreme morning type independent of confounders (beta = 0.45, SE = 0.21, p = 0.031). Mediation analysis indicated SED was a significant mediator of the relationship between chronotype and SCORE2. Evening chronotype is associated with unhealthier physical activity patterns and poorer cardiovascular health compared to morning chronotype. Chronotype should be considered in lifestyle counseling and primary prevention programs as a potential modifiable risk factor.
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34.
  • Laharnar, N., et al. (författare)
  • Overnight pulse wave analysis to assess autonomic changes during sleep in insomnia patients and healthy sleepers
  • 2020
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Insomnia has been associated with increased cardiovascular (CV) risk, which may be linked to sympathetic activation. Non-invasive overnight pulse wave analysis may be a useful tool to detect early signs of autonomic changes during sleep in insomniacs. Fifty-two participants (26 men, 37±13 years, BMI: 24±5 kg/m2, 26 insomniacs/ 26 controls) underwent overnight polysomnography with pulse oximetry and pulse wave analysis including pulse rate, vascular stiffness (pulse propagation time, PPT), and a composite cardiac risk index based on autonomic function and overnight hypoxia. We identified two subgroups of insomniacs, with and without objectively disturbed sleep (sleep efficiency SE≤80%, n = 14 vs. SE>80%, n = 12), and observed increased pulse rate and vascular stiffness in insomnia cases when diagnosis was based on both, subjective and objective criteria. Both insomnia groups were associated with higher overnight pulse rate than controls (median/ IQR: low-SE (low sleep efficiency): 67/ 58-70bpm; high-SE: 66/ 63-69bpm; controls: 58/ 52-63bpm; p = 0.01). Vascular stiffness was higher (reduction of PPT) in low-SE insomniacs compared with high-SE insomniacs and controls (169/ 147-232ms; 237/ 215-254ms; 244/ 180-284ms; p = 0.01). The cardiac risk index was increased in low-SE insomniacs (0.2/ 0.0–0.7; 0.0/ 0.0–0.4; 0.0/ 0.0–0.3; p = 0.05). Our results suggest a hyperarousal state in young and otherwise healthy insomniacs during sleep. The increased pulse rate and vascular stiffness in insomniacs with low SE suggest early signs of rigid vessels and potentially, an elevated CV risk. Overnight pulse wave analysis may be feasible for CV risk assessment in insomniacs and may provide a useful tool for phenotyping insomnia in order to provide individualized therapy. © 2020 Laharnar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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35.
  • Lisik, Daniil, et al. (författare)
  • Perspective: Systematic review and meta-analysis in obstructive sleep apnea - What is lacking?
  • 2023
  • Ingår i: SLEEP MEDICINE. - 1389-9457 .- 1878-5506. ; 111, s. 54-61
  • Forskningsöversikt (refereegranskat)abstract
    • Obstructive sleep apnea (OSA) affects nearly one billion of the global adult population. It is associated with substantial burden in terms of quality of life, cognitive function, and cardiovascular health. Positive airway pressure (PAP) therapy, commonly considered the first-line treatment, is limited by low compliance and lacking efficacy on long-term cardiovascular outcomes. A substantial body of research has been produced investigating (novel) non-PAP treatments. With increased understanding of OSA pathogenesis, promising therapeutic approaches are emerging. There is an imperative need of high-quality synthesis of evidence; however, current systematic reviews and meta-analyses (SR/MA) on the topic demonstrate important methodological limitations and are seldom based on research questions that fully reflect the complex intricacies of OSA management. Here, we discuss the current challenges in management of OSA, the need of treatable traits based OSA treatment, the methodological limitations of existing SR/MA in the field, potential remedies, as well as future perspectives.
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36.
  • Randerath, WJ, et al. (författare)
  • Parameters of Overnight Pulse Wave under Treatment in Obstructive Sleep Apnea.
  • 2016
  • Ingår i: Respiration. - : S. Karger AG. - 0025-7931 .- 1423-0356. ; 92:3, s. 136-43
  • Tidskriftsartikel (refereegranskat)abstract
    • Sleep-related breathing disorders may promote cardiovascular (CV) diseases. A novel and differentiated approach to overnight photoplethysmographic pulse wave analysis, which includes risk assessment and measurement of various pulse wave characteristics, has been evaluated in obstructive sleep apnea (OSA).The purpose of this study was to assess if and which of the differentiated pulse wave characteristics might be influenced by OSA treatment with positive airway pressure (PAP).The study included two protocols. In the case-control study (group A), pulse wave-derived CV risk indices recorded during PAP therapy were compared with those obtained in age, body mass index, and CV risk class-matched patients with untreated OSA (n = 67/67). In the prospective PAP treatment study (group B), 17 unselected patients undergoing a full-night sleep test at baseline and after 23 ± 19 weeks of treatment were analyzed.In untreated OSA patients (group A), the overnight hypoxic load was increased (SpO2 index 38.7 ± 17.5 vs. 24.0 ± 11.1, p < 0.001) and the pulse wave attenuation index (PWA-I) was lower (29.4 ± 9.2 vs. 33.5 ± 11.8, p = 0.022) than in treated patients. In group B, PAP therapy reduced the hypoxic load and increased the PWA-I significantly. The composite CV risk index was slightly but not significantly reduced.PAP therapy modified the hypoxic load and pulse wave-derived markers. The PWA-I - associated with sympathetic vascular tone - was most prominently modified by PAP. This novel approach to markers of CV function should be further evaluated in prospective studies.
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37.
  • RODENSTEIN, DANIEL, et al. (författare)
  • Driving in Europe: the need of a common policy for drivers with obstructive sleep apnoea syndrome
  • 2008
  • Ingår i: Journal of sleep research. - : Wiley. - 1365-2869 .- 0962-1105. ; 17:3, s. 281-284
  • Tidskriftsartikel (refereegranskat)abstract
    • Obstructive sleep apnoea syndrome (OSA) increases the risk of motor vehicle crashes, and of all medical disorders, has greatest risk in this respect. There is no consistency in the way OSA is considered by the national 'Physical Fitness to Drive' legislations within the 27 member countries of the European Union (EU), and most ignore OSA. This is further reflected by the absence of any reference to OSA in Annex III of the Directive 91/439/EEC, harmonizing Driving License regulations in the EU. A recent meeting brought together experts from several European and other countries, together with a representative of the European Commission. They discussed the best way to design and implement a uniform policy within Europe, for OSA and driving. It was agreed that: (i) other forms of pathological sleepiness be included, (ii) it covers both private and professional drivers, (iii) police accident report forms should explicitly consider sleepiness as a potential cause, (iv) sleep-wake education should be incorporated into the mandatory program of continuous education for professional drivers, ideally from 2010, (v) driver screening methods should contain questions on sleepiness at the wheel, habitual snoring and witnessed apneas during sleep, as well as the Epworth Sleepiness Score and Body Mass Index and (vi) following effective and efficient treatment, patients should be permitted to drive. In the light of medical, scientific and technical progress, EU procedures exist to enable the rapid modification of existing legislation. If such a procedure could be enacted for these aspects of driver sleepiness, then roads would be safer for 400 million people.
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38.
  • Sommermeyer, Dirk, 1975, et al. (författare)
  • Detection of cardiovascular risk from a photoplethysmographic signal using a matching pursuit algorithm.
  • 2016
  • Ingår i: Medical & biological engineering & computing. - : Springer Science and Business Media LLC. - 1741-0444 .- 0140-0118. ; 54:7, s. 1111-1121
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiovascular disease is the main cause of death in Europe, and early detection of increased cardiovascular risk (CR) is of clinical importance. Pulse wave analysis based on pulse oximetry has proven useful for the recognition of increased CR. The current study provides a detailed description of the pulse wave analysis technology and its clinical application. A novel matching pursuit-based feature extraction algorithm was applied for signal decomposition of the overnight photoplethysmographic pulse wave signals obtained by a single-pulse oximeter sensor. The algorithm computes nine parameters (pulse index, SpO2 index, pulse wave amplitude index, respiratory-related pulse oscillations, pulse propagation time, periodic and symmetric desaturations, time under 90% SpO2, difference between pulse and SpO2 index, and arrhythmia). The technology was applied in 631 patients referred for a sleep study with suspected sleep apnea. The technical failure rate was 1.4%. Anthropometric data like age and BMI correlated significantly with measures of vascular stiffness and pulse rate variability (PPT and age r=-0.54, p<0.001, PR and age r=-0.36, p<0.01). The composite biosignal risk score showed a dose-response relationship with the number of CR factors (p<0.001) and was further elevated in patients with sleep apnea (AHI≥15n/h; p<0.001). The developed algorithm extracts meaningful parameters indicative of cardiorespiratory and autonomic nervous system function and dysfunction in patients suspected of SDB.
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39.
  • Sommermeyer, Dirk, 1975, et al. (författare)
  • Detection of Sleep Disordered Breathing and Its Central/Obstructive Character Using Nasal Cannula and Finger Pulse Oximeter
  • 2012
  • Ingår i: Journal of Clinical Sleep Medicine. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 8:5, s. 527-533
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Objective: To assess the accuracy of novel algorithms using an oximeter-based finger plethysmographic signal in combination with a nasal cannula for the detection and differentiation of central and obstructive apneas. The validity of single pulse oximetry to detect respiratory disturbance events was also studied. Methods: Patients recruited from four sleep laboratories underwent an ambulatory overnight cardiorespiratory polygraphy recording. The nasal flow and photoplethysmographic signals of the recording were analyzed by automated algorithms. The apnea hypopnea index (AHI(auto)) was calculated using both signals, and a respiratory disturbance index (RDIauto) was calculated from photoplethysmography alone. Apnea events were classified into obstructive and central types using the oximeter derived pulse wave signal and compared with manual scoring. Results: Sixty-six subjects (42 males, age 54 +/- 14 yrs, body mass index 28.5 +/- 5.9 kg/m(2)) were included in the analysis. AHI(manual) (19.4 +/- 18.5 events/h) correlated highly significantly with AHI(auto) (19.9 +/- 16.5 events/h) and RDIauto (20.4 +/- 17.2 events/h); the correlation coefficients were r = 0.94 and 0.95, respectively (p < 0.001) with a mean difference of -0.5 +/- 6.6 and -1.0 +/- 6.1 events/h. The automatic analysis of AHI(auto) and RDIauto detected sleep apnea (cutoff AHI(manual) >= 15 events/h) with a sensitivity/specificity of 0.90/0.97 and 0.86/0.94, respectively. The automated obstructive/central apnea indices correlated closely with manually scoring (r = 0.87 and 0.95, p < 0.001) with mean difference of -4.3 +/- 7.9 and 0.3 +/- 1.5 events/h, respectively. Conclusions: Automatic analysis based on routine pulse oximetry alone may be used to detect sleep disordered breathing with accuracy. In addition, the combination of photoplethysmographic signals with a nasal flow signal provides an accurate distinction between obstructive and central apneic events during sleep.
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40.
  • Stehlik, Romana, et al. (författare)
  • Morning cortisol and fasting glucose are elevated in women with chronic widespread pain independent of comorbid restless legs syndrome
  • 2018
  • Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter GmbH. - 1877-8860 .- 1877-8879. ; 18:2, s. 187-194
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Chronic widespread pain (CWP) is associated with poor quality of sleep, but the detailed underlying mechanisms are still not fully understood. In this study we investigated the influence of CWP on morning cortisol and fasting glucose concentrations as well as sleep disordered breathing.Methods: In this case-control study, subjects with CWP (n=31) and a control group without CWP (n=23) were randomly selected from a population-based cohort of women. Current pain intensity, sleep quality, excessive daytime sleepiness [Epworth sleepiness scale (ESS)], psychiatric comorbidity and occurrence of restless legs syndrome (RLS) were assessed. Overnight polygraphy was applied to quantify sleep apnoea, airflow limitation and attenuations of finger pulse wave amplitude (>50%) as a surrogate marker for increased skin sympathetic activity. Morning cortisol and fasting glucose concentrations were determined. Generalised linear models were used for multivariate analyses.Results: CWP was associated with higher cortisol (464±141 vs. 366±111 nmol/L, p=0.011) and fasting glucose (6.0±0.8 vs. 5.4±0.7 mmol/L, p=0.007) compared with controls. The significance remained after adjustment for age, body mass index, RLS and anxiety status (β=122±47 nmol/L and 0.89±0.28 mmol/L, p=0.009 and 0.001, respectively). The duration of flow limitation in sleep was longer (35±22 vs. 21±34 min, p=0.022), and pulse wave attenuation was more frequent (11±8 vs. 6±2 events/h, p=0.048) in CWP subjects compared with controls. RLS was associated with higher ESS independent of CWP (β=3.1±1.3, p=0.018).Conclusions: Elevated morning cortisol, impaired fasting glucose concentration and increased skin sympathetic activity during sleep suggested an activated adrenal medullary system in subjects with CWP, which was not influenced by comorbid RLS.Implications: CWP is associated with activated stress markers that may deteriorate sleep.
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41.
  • Stehlik, Romana, et al. (författare)
  • Perceived sleep deficit is a strong predictor of RLS in multisite pain - A population based study in middle aged females
  • 2017
  • Ingår i: Scandinavian Journal of Pain. - : WALTER DE GRUYTER GMBH. - 1877-8860 .- 1877-8879. ; 17:1, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Chronic pain conditions as well as Restless Legs Syndrome (RLS) are known to be associated with subjectively and objectively disturbed sleep. RLS has been recently described as highly prevalent in multisite pain and the role of sleep as a modifying factor in this RLS phenotype is unknown. This study aimed to investigate if perceived sleep deficit and other sleep related parameters predict RLS in subjects with multisite pain.Current knowledge/study rationale: We have recently demonstrated a strong association between Restless Legs Syndrome (RLS) and number of pain locations. In the current analysis we hypothesized that impaired sleep predicts RLS in subjects with multisite pain.Method: Questionnaire-based data from 2727 randomly selected women aged 18-64 years were used to analyze RLS symptoms, self-reported sleep quality, and the degree of daytime sleepiness (Epworth Sleepiness Scale (ESS)) in relation to type, degree and localization of body pain. Potential confounders including anthropometrics, pain localization, co-morbidities, and medication were adjusted for in the Generalized Linear Models (GLM).Results: Perceived sleep deficit >= 90 min (OR 2.4 (1.5-3.8), p < 0.001) and frequent nocturnal awakenings (OR 2.3 (1.4-3.6), p < 0.001) were the strongest sleep related predictors for RLS in subjects with multisite pain. Additional factors include prolonged sleep latency (>= 30 min, OR 1.8 (1.1-2.8), p = 0.01) and daytime symptoms like elevated daytime sleepiness (ESS score = 9, OR 1.8 (1.2-2.7), p = 0.005). Accordingly, RLS diagnosis was associated with impaired sleep quality (TST (Total Sleep Time) -8.2 min, sleep latency + 8.0 min, and number of awakenings from sleep + 0.4, p < 0.01). ESS score increased with RLS diagnosis (+0.74, p < 0.01) and number of pain locations (0.5, 1.7, and 1.8 for 1, 3, and 5 pain areas, p < 0.001). In addition, confounders like pain severity, the history of psychiatric disease, and current smoking were associated with impaired sleep quality in this group of females. Conclusions: Perceived sleep deficit and sleep fragmentation are the strongest sleep related predictors of RLS in multisite pain. Potential implication of our results are that clinical management programmes of RLS in subjects with multisite pain need to consider both sleep quality and sleep quantity for individually tailored treatment regimes. Study impact: RLS, pain, and sleep disorders are highly interrelated. Our study strongly suggests that clinical management of RLS in patients with multisite pain needs to consider sleep quality as an independent risk factor.
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42.
  • Strassberger, Christian, et al. (författare)
  • Beyond the AHI-pulse wave analysis during sleep for recognition of cardiovascular risk in sleep apnea patients
  • 2021
  • Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 30:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent evidence supports the use of pulse wave analysis during sleep for assessing functional aspects of the cardiovascular system. The current study compared the influence of pulse wave and sleep study-derived parameters on cardiovascular risk assessment. In a multi-centric study design, 358 sleep apnea patients (age 55 +/- 13 years, 64% male, body mass index 30 +/- 6 kg m(-2), apnea-hypopnea index 13 [5-26] events per hr) underwent a standard overnight sleep recording. A novel cardiac risk index was computed based on pulse wave signals derived from pulse oximetry, reflecting vascular stiffness, cardiac variability, vascular autonomic tone and nocturnal hypoxia. Cardiovascular risk was determined using the ESC/ESH cardiovascular risk matrix, and categorized to high/low added cardiovascular risk. Comparisons between cardiac risk index and sleep parameters were performed for cardiovascular risk prediction. Apnea-hypopnea index, oxygen desaturation index and cardiac risk index were associated with high cardiovascular risk after adjustment for confounders (p = .002, .001, < .001, respectively). In a nested reference model consisting of age, gender and body mass index, adding cardiac risk index but not apnea-hypopnea index or oxygen desaturation index significantly increased the area under the receiver operating characteristic curve (p = .012, .22 and .16, respectively). In a direct comparison of oxygen desaturation index and cardiac risk index, only the novel risk index had an independent effect on cardiovascular risk prediction (p(CRI) < .001, p(ODI) = .71). These results emphasize the association between nocturnal pulse wave and overall cardiovascular risk determined by an established risk matrix. Thus, pulse wave analysis during sleep provides a powerful approach for cardiovascular risk assessment in addition to conventional sleep study parameters.
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43.
  • Strassberger, C., et al. (författare)
  • Night-to-Night Variability of Polysomnography-Derived Physiologic Endotypic Traits in Patients With Moderate to Severe OSA
  • 2023
  • Ingår i: Chest. - : Elsevier BV. - 0012-3692. ; 163:5, s. 1266-1278
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Emerging data suggest that determination of physiologic endotypic traits (eg, loop gain) may enable precision medicine in OSA.RESEARCH QUESTION: Does a single-night assessment of polysomnography-derived endotypic traits provide reliable estimates in moderate to severe OSA?STUDY DESIGN AND METHODS: Two consecutive in-lab polysomnography tests from a clinical trial (n = 67; male, 69%; mean +/- SD age, 61 +/- 10 years; apnea-hypopnea index [AHI] 53 +/- 22 events/h) were used for the reliability analysis. Endotypic traits, reflecting upper airway collapsibility (ventilation at eupneic drive [Vpassive]), upper airway dilator muscle tone (ventilation at the arousal threshold [Vactive]), loop gain (stability of ventilatory control, LG1), and arousal threshold (ArTh) were determined. Reliability was expressed as an intraclass correlation coefficient (ICC). Minimal detectable differences (MDDs) were computed to pro-vide an estimate of maximum spontaneous variability. Further assessment across four repeated polysomnography tests was performed in a subcohort (n = 22). RESULTS: Reliability of endotypic traits between the two consecutive nights was moderate to good (ICC: Vpassive = 0.82, Vactive = 0.76, LG1 = 0.72, ArTh = 0.83). Variability in AHI, but not in body position or in sleep stages, was associated with fluctuations in Vpassive and Vactive (r = -0.49 and r = -0.41, respectively; P < .001 for both). MDDs for single-night assessments were: Vpassive = 22, Vactive = 34, LG1 = 0.17, and ArTh = 21. Multiple assessments (mean of two nights, n = 22) further reduced MDDs by approximately 20% to 30%. INTERPRETATION: Endotypic trait analysis using a single standard polysomnography shows acceptable reliability and reproducibility in patients with moderate to severe OSA. The re-ported MDDs of endotypic traits may facilitate the quantification of relevant changes and may guide future evaluation of interventions in OSA. CHEST 2023; 163(5):1266-1278
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44.
  • Svedmyr, Sven, 1976, et al. (författare)
  • Blood pressure control in hypertensive sleep apnoea patients of the European Sleep Apnea Database cohort - effects of positive airway pressure and antihypertensive medication
  • 2023
  • Ingår i: European Heart Journal Open. - 2752-4191. ; 3:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: We analysed longitudinal blood pressure (BP) data from hypertensive obstructive sleep apnoea (OSA) patients in the European Sleep Apnea Database cohort. The study investigated the interaction between positive airway pressure (PAP)-induced BP change and antihypertensive treatment (AHT). Methods and results: Hypertensive patients with AHT [monotherapy/dual therapy n = 1283/652, mean age 59.6 ± 10.7/60.6 ± 10.3 years, body mass index (BMI) 34.2 ± 6.5/34.8 ± 7.0 kg/m2, apnoea-hypopnoea index 46 ± 25/46 ± 24 n/h, proportion female 29/26%, respectively] started PAP treatment. Office BP at baseline and 2- to 36-month follow-up were assessed. The interaction between AHT drug classes and PAP on BP was quantified and the influences of age, gender, BMI, co-morbidities, BP at baseline, and study site were evaluated. Following PAP treatment (daily usage, 5.6 ± 1.6/5.7 ± 1.9 h/day), systolic BP was reduced by -3.9 ± 15.5/-2.8 ± 17.7 mmHg in mono/dual AHT and diastolic BP by -3.0 ± 9.8/-2.7 ± 10.8 mmHg, respectively, all P < 0.0001. Systolic and diastolic BP control was improved following PAP treatment (38/35% to 54/46% and 67/67% to 79/74%, mono/dual AHT, respectively). PAP treatment duration predicted a larger BP improvement in the monotherapy group. Intake of renin-angiotensin blockers [angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)] alone or in any AHT combination was associated with better BP control. The AHT-dependent BP improvement was independent of confounders. Conclusion: In this pan-European OSA patient cohort, BP control improved following initiation of PAP. Longer PAP treatment duration, was associated with a favourable effect on BP. Our study suggests that ACEI/ARB, alone or in combination with other drug classes, provides a particularly strong reduction of BP and better BP control when combined with PAP in OSA.
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45.
  • Svedmyr, Sven, 1976, et al. (författare)
  • Hypertension treatment in patients with sleep apnea from the European Sleep Apnea Database (ESADA) cohort - towards precision medicine
  • 2022
  • Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 32:4
  • Tidskriftsartikel (refereegranskat)abstract
    • We recruited 5,970 patients with hypertension with obstructive sleep apnea (OSA) on current antihypertensive treatment from the European Sleep Apnea Database (ESADA) cohort. The group was subdivided into those receiving monotherapy (n = 3,594) and those receiving dual combined therapy (n = 2,376). We studied how major OSA confounders like age, gender, and body mass index as well as the degree of sleep apnea modified office systolic and diastolic blood pressure. Beta-blockers alone or in combination with a diuretic were compared with other antihypertensive drug classes. Monotherapy with beta-blocker was associated with lower systolic blood pressure, particularly in non-obese middle-aged males with hypertension. Conversely, the combination of a beta-blocker and a diuretic was associated with lower systolic and diastolic blood pressure in patients with hypertension with moderate-severe OSA. Systolic blood pressure was better controlled in female patients using this combined treatment. Our cross-sectional data suggest that specific clinical characteristics and type of antihypertensive medication influence the degree of blood pressure control in patients with hypertension with OSA. Controlled trials are warranted.
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46.
  • Svedmyr, Sven, 1976, et al. (författare)
  • Superior hypertension control with betablockade in the European Sleep Apnea Database
  • 2021
  • Ingår i: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352 .- 1473-5598. ; 39:2, s. 292-301
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Arterial hypertension is highly prevalent and difficult to control in patients with obstructive sleep apnea (OSA). High sympathoadrenergic activity is a hallmark physiological phenomenon in OSA. We hypothesized that an antihypertensive drug with inhibitory properties on this activity, such as beta blockers (BBs), may be particularly efficacious in OSA patients. Methods: Hypertensive OSA patients receiving blood pressure-lowing treatment in the European Sleep A pnea Database (ESADA) (n =5818, 69% men, age 58 +/- 11 years, body mass index 33 +/- 7 kg/m(2), apnea hypopnea index 34 +/- 26 events/h) were analyzed. Reported medications [BB, diuretic, renin-angiotensin blocker (RAB), calcium channel blocker (CCB), and centrally acting antihypertensive (CAH)] were classified according to ATC code. Office blood pressure was compared in patients with monotherapy or combination therapy controlling for confounders. Results: Poorly controlled SBP according to the ESC/ESH guidelines was found in 66% of patients. Patients receiving monotherapy with RAB, CCB or CAH had 2.2 (95% CI 1.4-3.0), 3.0 (1.9-4.1) and 3.0 (1.7-4.7) mmHg higher SBP compared with those on BB (adjusted model, P=0.007, 0.008 and 0.017, respectively). In those with a combination of two antihypertensive drugs, SBP was 5.5 (4.0-7.1), 5.1 (3.7-6.6), 4.3 (2.5-6.1) and 3.1 (1.6-4.6) mmHg higher in those on CCB/RAB, BB/RAB, BB/CCB or diuretic/RAB compared with those on BB/diuretic (adjusted model, P< 0.001, <0.001, 0.018 and 0.036, respectively). Conclusion: Poorly controlled blood pressure was common in OSA patients with antihypertensive medication. Treatment with BB alone or BB in combination with a diuretic was associated with the lowest systolic pressure in this large clinical cohort.
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47.
  • Svedmyr, S., et al. (författare)
  • Vascular stiffness determined from a nocturnal digital pulse wave signal: association with sleep, sleep-disordered breathing, and hypertension
  • 2016
  • Ingår i: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352. ; 34:12, s. 2427-2433
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Reflection of the finger pulse wave form is a valid measure of arterial stiffness, which may be continuously assessed during sleep. We investigated the relationships between sleep, sleep-disordered breathing, hypertension, and pulse propagation time (PPT) in patients with suspected sleep apnea. Methods: The digital photoplethysmographic signal derived from finger pulse oximetry was recorded during overnight sleep studies in 440 patients (64% men, age 55 +/- 12 years, BMI 30 +/- 6 kg/m(2), apnea-hypopnea index 19 +/- 19 n/h). PPT, defined as the time interval between the systolic and diastolic peak of the finger pulse wave, was calculated. The influence of sleep stages on PPT were assessed in patients undergoing polysomnography. Generalized linear models were used to study predictors of PPT and hypertension. Results: Mean overnight PPT was independently associated with age (beta = 1.34, P < 0.001), height (beta = 0.47, P = 0.047), history of smoking (beta = -9.44, P = 0.005), and apnea-hypopnea index (beta = -0.18, P = 0.043). PPT was shorter in hypertensive patients compared with normotensive patients (160 +/- 33 vs. 177 +/- 47 ms, P < 0.001) and independently associated with a diagnosis of hypertension (P = 0.043). PPT was influenced by sleep stage (highest PPT during slow wave sleep compared with wake and all other sleep stages, all P < 0.001) and varied across sleep apnea severity groups in normotensive but not in hypertensive patients (P = 0.028 and 0.64, respectively). Conclusion: Overnight PPT by oximetry was strongly associated with factors known to determine daytime vascular stiffness. In addition, PTT provides information on functional and structural vascular properties during sleep. This novel technique offers new opportunities to noninvasively monitor vascular function during the sleeping period.
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48.
  • Wang, Tengyu, et al. (författare)
  • Increased Carbonic Anhydrase Activity is Associated with Sleep Apnea Severity and Related Hypoxemia
  • 2015
  • Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 38:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Objectives: The catalytic function of the enzyme carbonic anhydrase (CA) plays a fundamental role in carbon dioxide (CO2), proton (H+), and bicarbonate (HCO3-) homeostasis. Hypoxia and tissue acidosis have been proposed to increase physiological CA activity in various compartments of the body. We hypothesized that CA activity in blood is upregulated in patients with obstructive sleep apnea (OSA). Participants: Seventy referred patients with suspected OSA (48 males, age 54 +/- 13 y, apnea-hypopnea index (AHI) median [interquartile range] 21 [8-41] n/h). Measurements and Results: In-laboratory cardiorespiratory polygraphy was used to assess OSA. CA activity was determined by an in vitro assay that quantifies the pH change reflecting the conversion of CO2 and H2O to HCO3- and H+. CA activity was positively associated with AHI and 4% oxygen desaturation index (ODI4) (Spearman correlation r = 0.44 and 0.47, both P < 0.001). The associations (CA activity versus logAHI and CA versus logODI4) were independent of sex, age, body mass index, presleep oxygen saturation, nocturnal oxygen saturation, hypertension status, and use of diuretic medication in two generalized linear models (P = 0.007 and 0.011, respectively). Sitting diastolic blood pressure was associated with CA activity after adjustment of sex, age, body mass index, mean oxygen saturation, and AHI (P = 0.046). Conclusions: Carbonic anhydrase (CA) activity increased with apnea-hypopnea index and related nocturnal hypoxemia measures in patients with obstructive sleep apnea (OSA). Altered CA activity may constitute a component that modulates respiratory control and hemodynamic regulation in patients with OSA.
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49.
  • Yassen, A., et al. (författare)
  • Baseline clusters and the response to positive airway pressure treatment in obstructive sleep apnoea patients: longitudinal data from the European Sleep Apnea Database cohort
  • 2022
  • Ingår i: European Respiratory Journal Open Research (ERJ Open Research). - : European Respiratory Society (ERS). - 2312-0541. ; 8:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction The European Sleep Apnea Database was used to identify distinguishable obstructive sleep apnoea (OSA) phenotypes and to investigate the clinical outcome during positive airway pressure (PAP) treatment. Method Prospective OSA patient data were recruited from 35 sleep clinics in 21 European countries. Unsupervised cluster analysis (anthropometrics, clinical variables) was performed in a random sample (n=5000). Subsequently, all patients were assigned to the clusters using a conditional inference tree classifier. Responses to PAP treatment change in apnoea severity and Epworth sleepiness scale (ESS) were assessed in relation to baseline patient clusters and at short- and long-term follow-up. Results At baseline, 20 164 patients were assigned (mean age 54.1 +/- 12.2 years, 73% male, median apnoea-hypopnoea index (AHI) 27.3 (interquartile range (IQR) 14.1-49.3) events.h(-1), and ESS 9.8 +/- 5.3) to seven distinct clusters based on anthropometrics, comorbidities and symptoms. At PAP follow-up (median 210 [IQR 134-465] days), the observed AHI reduction (n=1075) was similar, whereas the ESS response (n=3938) varied: largest reduction in cluster 3 (young healthy symptomatic males) and 6 (symptomatic males with psychiatric disorders, -5.0 and -5.1 units, respectively (all p<0.01), limited reduction in clusters 2 (obese males with systemic hypertension) and 5 (elderly multimorbid obese males, -4.2 (p<0.05) and -3.7 (p<0.001), respectively). Residual sleepiness in cluster 5 was particularly evident at long-term follow-up (p<0.05). Conclusion OSA patients can be classified into clusters based on clinically identifiable features. Importantly, these clusters may be useful for prediction of both short- and long-term responses to PAP intervention.
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50.
  • Zou, Ding, 1970, et al. (författare)
  • A double-blind, crossover study of Doxazosin and Enalapril on peripheral vascular tone and nocturnal blood pressure in sleep apnea patients.
  • 2010
  • Ingår i: Sleep medicine. - : Elsevier BV. - 1878-5506 .- 1389-9457. ; 11:3, s. 325-8
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Pulse wave attenuation, which occurs in association with obstructive sleep apnea (OSA), is sympathetically mediated. We compared the effect of Doxazosin (DO, a peripheral alpha-receptor inhibitor) and Enalapril (EN, an ACE inhibitor) on digital vasoconstriction and nocturnal blood pressure (BP) in hypertensive OSA patients. METHODS: A double-blind, crossover study comparing equipotent dosages of DO (4 mg/day for 2 weeks with 8 mg/day for an additional 2 weeks) and EN (10mg/day and 20mg/day, respectively) was undertaken in 16 male OSA patients (age 55+/-7 years, body mass index 30.1+/-3.8 kg/m(2)) with hypertension. Assessments including ambulatory 24-h BP, full-night polysomnography with simultaneous peripheral arterial tone (PAT) and beat-to-beat finger BP monitoring (Finapres) were made at the end of each treatment period. Nighttime BP and digital vasoconstrictions associated with apneic events (measured as the ratio of PAT amplitudes during and after apneas) were analyzed. RESULTS: There were no differences between the two treatments in the 24-h BP profile and OSA severity. But the nighttime average beat-to-beat finger BP was significantly higher under DO treatment (systolic BP 129+/-13 vs. 119+/-23 mm Hg, P=0.02; diastolic BP 81+/-12 vs. 74+/-14 mm Hg, P=0.04, DO and EN respectively). In a linear mixed effects regression model, the PAT ratio during apnea increased 5.3% under DO compared with EN (P<0.0001). Each percentage decrease of apneic related oxygen desaturation was associated with 0.9% decrease in the PAT ratio (P<0.0001). REM sleep was associated with 2.2% decrease of PAT ratio compared to NREM sleep (P=0.002). CONCLUSION: Digital vasoconstrictions associated with apneic events are alpha-receptor mediated. DO compared to EN has a proportionally poor effect on nocturnal BP control in OSA patients, which may be due to the enhanced sympathetic nervous system activity characteristic of this condition.
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