European Sleep Apnea Database Cohort Research Articles

Blood pressure control in hypertensive sleep apnoea patients of the European Sleep Apnea Database cohort - effects of positive airway pressure and antihypertensive medication.

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). 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. 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.

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

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

Baseline clusters and the response to positive airway pressure treatment in obstructive sleep apnoea patients: longitudinal data from the European Sleep Apnea Database cohort.

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. 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. 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). 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.

Impact of Sleep Apnea on Cardioembolic Risk in Patients With Atrial Fibrillation: Data From the ESADA Cohort.

An accurate determination of the cardioembolic risk in patients with atrial fibrillation (AF) is crucial to prevent consequences like stroke. Obstructive sleep apnea (OSA) is a known risk factor for both AF and stroke. We aim to explore a possible association between OSA and an increased cardioembolic risk in patients with AF. We assessed data from the ESADA (European Sleep Apnea Database) cohort where patients with known AF and OSA were included. Parameters of OSA severity and related hypoxia like lowest Spo2 and 4% oxygen desaturation index were analyzed. Patients were stratified according to their cardioembolic risk estimated with the CHA2DS2-VASc score. From the initial cohort of 14 646 patients, a final set of 363 patients were included in the analysis. Indices of hypoxia during sleep were associated with increased CHA2DS2-VASc score (4% oxygen desaturation index 17.9 versus 29.6 versus 30.5 events/hour and the lowest Spo2 81.2 versus 77.8 versus 77.5% for low, moderate, and high cardioembolic risk, respectively, P<0.05). These results support the potential role of OSA-related hypoxia in the risk for cardioembolic complications such as stroke in patients with AF.

Effects of sleep apnea and kidney dysfunction on objective sleep quality in nondialyzed patients with chronic kidney disease: an ESADA study.

Patients with chronic kidney disease (CKD) often report poor sleep quality, but they commonly exhibit OSA. The aim of this study was to evaluate the influence of OSA severity and of estimated glomerular filtration rate impairment on objective sleep quality in nondialyzed patients with CKD, defined as an estimated glomerular filtration rate <60 mL/min/1.73m². Polysomnographic sleep characteristics were compared between patients with (n = 430) and without CKD (n = 6,639) in the European Sleep Apnea Database cohort. Comparisons were repeated in 375 patients with CKD and 375 control patients without CKD matched for sleep center, age, sex, and AHI, and in 310 matched CKD and non-CKD patients without psychiatric disturbances. Among all patients with and without CKD, total sleep time was similar but sleep stage N1 (median 8.7% [IQR 4.8-18.0] vs 6.7% [3.6-12.7], respectively) and sleep stage R (12.6% [6.8-17.7] vs 14.2% [8.8-19.8], respectively) significantly differed (P < .0001). No difference in sleep characteristics was observed between matched patients either with or without psychiatric disturbances. After subdividing the matched patients according to AHI tertile (<25, ≥25 to <49, and ≥49 events/h) and estimated glomerular filtration rate (≥60, 45 to <60, <45 mL/min/1.73m²), we found a significant effect of AHI on sleep stages N2, N3, and R (P < .001), but there was no effect of CKD. In nondialyzed patients with CKD, objective sleep quality is influenced similarly by AHI as in patients without CKD but is not affected by CKD severity. Previously reported poor sleep quality in CKD may partly result from the high prevalence of OSA in CKD.

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

The effect of positive airway pressure treatment on weight and markers of central obesity in patients with obstructive sleep apnea remains unclear. We studied the change in body weight and anthropometric measures following positive airway pressure treatment in a large clinical cohort. Patients with obstructive sleep apnea with positive airway pressure treatment from the European Sleep Apnea Database registry (n=1,415, 77% male, age 54±11 [mean±SD] years, body mass index 31.7±6.4kg/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.

Fixed But Not Autoadjusting Positive Airway Pressure Attenuates the Time-dependent Decline in Glomerular Filtration Rate in Patients With OSA

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. 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). In the whole sample, eGFR decreased over time. The rate of eGFR decline was significantly higher in the subgroup with eGFR above median (91.42mL/min/1.73 m2) 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 (541days) 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. fCPAP but not APAP may prevent eGFR decline in OSA.