Management of obstructive sleep apnea in Europe - A 10-year follow-up.

OBJECTIVE: In 2010, a questionnaire-based study on obstructive sleep apnea (OSA) management in Europe identified differences regarding reimbursement, sleep specialist qualification, and titration procedures. Now, 10 years later, a follow-up study was conducted as part of the ESADA (European Sleep Apnea Database) network to explore the development of OSA management over time. METHODS: The 2010 questionnaire including questions on sleep diagnostic, reimbursement, treatment, and certification was updated with questions on telemedicine and distributed to European Sleep Centers to reflect European OSA management practice. RESULTS: 26 countries (36 sleep centers) participated, representing 20 ESADA and 6 non-ESADA countries. All 21 countries from the 2010 survey participated. In 2010, OSA diagnostic procedures were performed mainly by specialized physicians (86%), whereas now mainly by certified sleep specialists and specialized physicians (69%). Treatment and titration procedures are currently quite homogenous, with a strong trend towards more Autotitrating Positive Airway Pressure treatment (in hospital 73%, at home 62%). From 2010 to 2020, home sleep apnea testing use increased (76%-89%) and polysomnography as sole diagnostic procedure decreased (24%-12%). Availability of a sleep specialist qualification increased (52%-65%) as well as the number of certified polysomnography scorers (certified physicians: 36%-79%; certified technicians: 20%-62%). Telemedicine, not surveyed in 2010, is now in 2020 used in diagnostics (8%), treatment (50%), and follow-up (73%). CONCLUSION: In the past decade, formal qualification of sleep center personnel increased, OSA diagnostic and treatment procedures shifted towards a more automatic approach, and telemedicine became more prominent.

Epileptic spasms with terror during sleep in CDKL5 encephalopathy.

Study Objectives: To describe early diagnostic clues in Cyclin-Dependent Kinase-Like 5 (CDKL5) refractory encephalopathy, to improve treatment strategies. Methods: We retrospectively studied 35 patients (25 females, 10 males) with CDKL5 gene mutations or deletion, focusing on their early seizure semiology, the electroencephalogram (EEG) pattern, the effect of treatment, and developmental outcome. Results: The first seizures were recognizable and consisted of tonic, then clonic, and spasms phases, occurring in sleep at a median age of 6 weeks. Clusters of spasms were observed in quiet sleep or slow-wave sleep (SWS), with screaming, staring, and arms' extension that mimicked sleep terror in 28 of 35 patients (80%). Programmed awakening prevented these spasms in 9 of 16 patients and small doses of clonazepam given at night improved epilepsy in 14 of 23 patients. Conclusions: Peculiar seizures with spasms starting in SWS are an early diagnostic clue in infants with CDKL5 encephalopathy. Sleep video-EEG polygraphy is an easy tool to disclose these early seizures and epileptic spasms in infants during the first months of life while polysomnography is unlikely to give a contribution at that early age. While conventional antiepileptic treatment and corticosteroids are poorly, transiently, or not efficient, therapeutic strategy used for sleep terror could help, although the mechanism of spasms generation in SWS needs to be elucidated.

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

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

Orofacial Myofunctional Therapy in Obstructive Sleep Apnea Syndrome: A Pathophysiological Perspective.

Obstructive sleep apnea (OSA) syndrome is a multi-factorial disorder. Recently identified pathophysiological contributing factors include airway collapsibility, poor pharyngeal muscle responsiveness, a low arousal threshold, and a high loop gain. Understanding the pathophysiology is of pivotal importance to select the most effective treatment option. It is well documented that conventional treatments (continuous positive airway pressure (CPAP), upper airway surgery, and dental appliance) may not always be successful in the presence of non-anatomical traits, especially in mild to moderate OSA. Orofacial myofunctional therapy (OMT) consists of isotonic and isometric exercises targeted to oral and oropharyngeal structures, with the aim of increasing muscle tone, endurance, and coordinated movements of pharyngeal and peripharyngeal muscles. Recent studies have demonstrated the efficacy of OMT in reducing snoring, apnea-hypopnea index, and daytime sleepiness, and improving oxygen saturations and sleep quality. Myofunctional therapy helps to reposition the tongue, improve nasal breathing, and increase muscle tone in pediatric and adult OSA patients. Studies have shown that OMT prevents residual OSA in children after adenotonsillectomy and helps adherence in CPAP-treated OSA patients. Randomized multi-institutional studies will be necessary in the future to determine the effectiveness of OMT in a single or combined modality targeted approach in the treatment of OSA. In this narrative review, we present up-to-date literature data, focusing on the role of OSA pathophysiology concepts concerning pharyngeal anatomical collapsibility and muscle responsiveness, underlying the response to OMT in OSA patients.

Validation of the Withings Sleep Analyzer, an under-the-mattress device for the detection of moderate-severe sleep apnea syndrome.

STUDY OBJECTIVES: To assess the diagnostic performance of a nonintrusive device placed under the mattress to detect sleep apnea syndrome. METHODS: One hundred eighteen patients suspected to have obstructive sleep apnea syndrome completed a night at a sleep clinic with a simultaneous polysomnography (PSG) and recording with the Withings Sleep Analyzers. PSG nights were scored twice: first as simple polygraphy, then as PSG. RESULTS: Average (standard deviation) apnea-hypopnea index from PSG was 31.2 events/h (25.0) and 32.8 events/h (29.9) according to the Withings Sleep Analyzers. The mean absolute error was 9.5 events/h. The sensitivity, specificity, and area under the receiver operating characteristic curve at thresholds of apnea-hypopnea index ≥ 15 events/h were, respectively, sensitivity (Se)15 = 88.0%, specificity (Sp)15 = 88.6%, and area under the receiver operating characteristic curve (AUROC) 15 = 0.926. At the threshold of apnea-hypopnea index ≥ 30 events/h, results included Se30 = 86.0%, Sp30 = 91.2%, AUROC30 = 0.954. The average total sleep time from PSG and the Withings Sleep Analyzers was 366.6 (61.2) and 392.4 (67.2) minutes, sleep efficiency was 82.5% (11.6) and 82.6% (11.6), and wake after sleep onset was 62.7 (48.0) and 45.2 (37.3) minutes, respectively. CONCLUSIONS: Withings Sleep Analyzers accurately detect moderate-severe sleep apnea syndrome in patients suspected of sleep apnea syndrome. This simple and automated approach could be of great clinical value given the high prevalence of sleep apnea syndrome in the general population. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Validation of Withings Sleep for the Detection of Sleep Apnea Syndrome; URL: https://clinicaltrials.gov/ct2/show/NCT04234828; Identifier: NCT04234828.

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

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

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).

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.

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

STUDY OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Periodic limb movements during sleep and blood pressure changes in sleep apnoea: Data from the European Sleep Apnoea Database.

BACKGROUND AND OBJECTIVE: OSA and PLMS are known to induce acute BP swings during sleep. Our current study aimed to address the independent effect of PLMS on BP in an unselected OSA patient cohort. METHODS: This cross-sectional analysis included 1487 patients (1110 males, no previous hypertension diagnosis or treatment, mean age: 52.5 years, mean BMI: 30.5 kg/m2 ) with significant OSA (defined as AHI ≥ 10) recruited from the European Sleep Apnoea Cohort. Patients underwent overnight PSG. Patients were stratified into two groups: patients with significant PLMS (PLMSI > 25 events/hour of sleep) and patients without significant PLMS (PLMSI < 25 events/hour of sleep). SBP, DBP and PP were the variables of interest. For each of these, a multivariate regression linear model was fitted to evaluate the relationship between PLMS and outcome adjusting for sociodemographic and clinical covariates (gender, age, BMI, AHI, ESS, diabetes, smoking and sleep efficiency). RESULTS: The univariate analysis of SBP showed an increment of BP equal to 4.70 mm Hg (P < 0.001) in patients with significant PLMS compared to patients without significant PLMS. This increment remained significant after implementing a multivariate regression model (2.64 mm Hg, P = 0.044). No significant increment of BP was observed for DBP and PP. CONCLUSION: PLMS is associated with a rise in SBP regardless of AHI, independent of clinical and sociodemographic confounders. A PLMS phenotype may carry an increased risk for cardiovascular disease in OSA patients.

New physiological bench test reproducing nocturnal breathing pattern of patients with sleep disordered breathing.

Previous studies have shown that Automatic Positive Airway Pressure devices display different behaviors when connected to a bench using theoretical respiratory cycle scripts. However, these scripts are limited and do not simulate physiological behavior during the night. Our aim was to develop a physiological bench that is able to simulate patient breathing airflow by integrating polygraph data. We developed an algorithm analyzing polygraph data and transformed this information into digital inputs required by the bench hardware to reproduce a patient breathing profile on bench. The inputs are respectively the simulated respiratory muscular effort pressure input for an artificial lung and the sealed chamber pressure to regulate the Starling resistor. We did simulations on our bench for a total of 8 hours and 59 minutes for a breathing profile from the demonstration recording of a Nox T3 Sleep Monitor. The simulation performance results showed that in terms of relative peak-valley amplitude of each breathing cycle, simulated bench airflow was biased by only 1.48% ± 6.80% compared to estimated polygraph nasal airflow for a total of 6,479 breathing cycles. For total respiratory cycle time, the average bias ± one standard deviation was 0.000 ± 0.288 seconds. For patient apnea events, our bench simulation had a sensitivity of 84.7% and a positive predictive value equal to 90.3%, considering 149 apneas detected both in polygraph nasal simulated bench airflows. Our new physiological bench would allow personalizing APAP device selection to each patient by taking into account individual characteristics of a sleep breathing profile.

Combined effects of leaks, respiratory system properties and upper airway patency on the performance of home ventilators: a bench study.

BACKGROUND: Combined effects of leaks, mechanical property of respiratory system and upper airway (UA) patency on patient-ventilator synchrony (PVA) and the level of clinically "tolerable" leaks are not well established in home ventilators. METHODS: We comparatively assessed on a bench model, the highest leak level tolerated without inducing significant asynchrony ("critical leak") in three home ventilators (Astral 150, Trilogy 100 and Vivo 60; noted as A150, T100 and V60 respectively) subjected to three simulated diseased respiratory conditions: chronic obstructive pulmonary disease (COPD), obesity hypoventilation (OHS) and neuromuscular disorders (NMD), with both open and closed UA. Also, total leak values in the device reports were compared to the bench-measured values. RESULTS: With open UA, all ventilators were able to avoid asynchrony up to a 30 L/min leak and even to 55 L/min in some cases. UA closure and respiratory diseases especially OHS influenced PVA. With closed UA, the critical leak of A150 and T100 remained higher than 55 L/min in COPD and OHS, while for V60 decreased to 41 and 33 L/min respectively. In NMD with closed UA, only T100 reached a high critical leak of 69 L/min. Besides, inspiratory trigger sensitivity change was often necessary to avoid PVA. CONCLUSIONS: Home ventilators were able to avoid PVA in high-level leak conditions. However, asynchrony appeared in cases of abnormal mechanical properties of respiratory system or closed UA. In case of closed UA, the EPAP should be adjusted prior to the inspiratory trigger. TRIAL REGISTRATION: Not applicable.

Pressure-Relief Features of Fixed and Autotitrating Continuous Positive Airway Pressure May Impair Their Efficacy: Evaluation with a Respiratory Bench Model.

STUDY OBJECTIVES: Pressure-relief features are aimed at improving the patient's comfort during continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea. The objective of this study was to determine the effect of these therapy features on fixed CPAP and autotitrating CPAP (APAP) treatment efficacy. METHODS: Seven pressure-relief features applied by three CPAP devices were included in our study (Remstar Auto: C-Flex 3, C-Flex+ 3, A-Flex 3, P-Flex; AirSense 10: EPR 3; Prisma 20A: SoftPAP 2 and 3). In fixed CPAP, the devices were subjected to a 10-min bench-simulated obstructive apnea sequence (initial apnea-hypopnea index, AHI = 60/h) with and without pressure-relief features. In APAP, the sequence was lengthened to 4.2 h (initial AHI = 58.6/h). The residual AHI and mean/median pressure were compared with and without pressure-relief features. RESULTS: Compared to conventional CPAP, where pressure was adjusted to be just sufficient to control the simulated obstructive events, C-Flex+ 3, P-Flex, and EPR 3 failed to normalize the breathing flow and did not reduce the AHI. The mean pressures with the three features, respectively, were 1.8, 2.6, and 2.6 cmH2O lower than the conventional CPAP. Compared to conventional APAP, similar levels of control were observed with pressure-relief features, apart from P-Flex where the delivered mean pressure was lower and residual AHI greater. The device-reported mean/median pressures in APAP with A-Flex 3, P-Flex, EPR 3, and SoftPAP 3 were higher than that measured on the bench. CONCLUSIONS: Pressure-relief features may attenuate CPAP efficacy if not adjusted for at the time of their introduction. In clinical practice, efficacy can be ensured by increasing the therapeutic pressure delivered by fixed CPAP or by enabling the pressure-relief features prior to initial pressure titration. Device-reported pressures in APAP devices with pressure relief activated may overstate delivered pressures.

All APAPs Are Not Equivalent for the Treatment of Sleep Disordered Breathing: A Bench Evaluation of Eleven Commercially Available Devices.

STUDY OBJECTIVES: This study challenged on a bench-test the efficacy of auto-titrating positive airway pressure (APAP) devices for obstructive sleep disordered breathing treatment and evaluated the accuracy of the device reports. METHODS: Our bench consisted of an active lung simulator and a Starling resistor. Eleven commercially available APAP devices were evaluated on their reactions to single-type SDB sequences (obstructive apnea and hypopnea, central apnea, and snoring), and to a long general breathing scenario (5.75 h) simulating various SDB during four sleep cycles and to a short scenario (95 min) simulating one sleep cycle. RESULTS: In the single-type sequence of 30-minute repetitive obstructive apneas, only 5 devices normalized the airflow (> 70% of baseline breathing amplitude). Similarly, normalized breathing was recorded with 8 devices only for a 20-min obstructive hypopnea sequence. Five devices increased the pressure in response to snoring. Only 4 devices maintained a constant minimum pressure when subjected to repeated central apneas with an open upper airway. In the long general breathing scenario, the pressure responses and the treatment efficacy differed among devices: only 5 devices obtained a residual obstructive AHI < 5/h. During the short general breathing scenario, only 2 devices reached the same treatment efficacy (p < 0.001), and 3 devices underestimated the AHI by > 10% (p < 0.001). The long scenario led to more consistent device reports. CONCLUSION: Large differences between APAP devices in the treatment efficacy and the accuracy of report were evidenced in the current study.

High occurrence of hypoxemic sleep respiratory disorders in precapillary pulmonary hypertension and mechanisms.

BACKGROUND: The occurrence and mechanisms of nocturnal hypoxemia in precapillary pulmonary hypertension (PH) are not clearly defined. METHODS: In an observational, prospective, and transversal design, we studied 46 clinically stable patients with PH and a BMI < 35 kg/m(2), an FEV(1) > 60% predicted, and idiopathic pulmonary arterial hypertension (n = 29) or chronic thromboembolic pulmonary hypertension (n = 17). They underwent nocturnal polysomnography with transcutaneous capnography. RESULTS: Most patients (69.6%) had New York Heart Association functional class II disease. Mean pulmonary artery pressure was 44 ± 13 mm Hg, and the cardiac index was 3.2 ± 0.6 L/min/m(2). Duration of sleep time spent with oxygen saturation as measured by pulse oximetry <90% was 48.9% ± 35.9%, and 38 of 46 patients (82.6%) had nocturnal hypoxemia. Mean apnea-hypopnea index was 24.9 ± 22.1/h, and 41 patients (89%) had sleep apnea. The major mechanism of nocturnal hypoxemia was a ventilation/perfusion mismatch alone or associated with obstructive apneic events. Multivariate logistic regression identified both FEV(25%-75%) (OR, 0.9519; 95% CI, 0.9089-0.9968; P = .036) and mean pulmonary artery pressure (OR, 1.1068; 95% CI, 1.0062-1.2175; P = .037) as significant predictors of nocturnal hypoxemia. Clinical symptoms were not predictive of nocturnal hypoxemia. CONCLUSIONS: The occurrence of nocturnal hypoxemia is high in PH and should be screened for systematically. Further studies are needed to determine the impact of nocturnal hypoxemia on the outcome of patients with PH. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01371669; URL: www.clinicaltrials.gov

A mandibular advancement device for the treatment of obstructive sleep apnea: long-term use and tolerance.

Long-term efficacy and compliance with mandibular advancement devices (MAD) in the treatment of obstructive sleep apnea syndrome (OSAS) are under-studied. Our objective was to conduct a long-term assessment of the OPM4J device, measuring symptoms, compliance rate, and adverse effects in a cohort of consecutive patients treated with OPM4J for an average period of nearly three years. Out of 140 patients aged 62 ± 10 years with body mass index (BMI) 27 ± 4 kg/m(2) and initial apnea-hypopnea index (AHI) 27 ± 16, complete reversal of OSAS was achieved in 65%. A total of 76% reported regular MAD use, with 24% stopping treatment and half of those 24% falling back on continuous positive airway pressure (CPAP). Patients with lower residual AHI or residual Epworth scores at month 3 were more likely to continue treatment (P < 0.007 and P < 0.02). Reasons for discontinuing treatment included tooth pain, persistent snoring or fatigue, loss or breakage of the device, and the cost of replacing it. OPM4J reduced OSAS symptoms in the long-term. Regular use was reported in 76% of patients. Adverse effects were common but minor. Half of non-users were lost to follow-up and probably remain without treatment.

Overnight heart rate variability in patients with obstructive sleep apnoea: a time and frequency domain study.

Heightened sympathetic activity plays a role in the cardiovascular sequelae of obstructive sleep apnoea (OSA). Cardiac autonomic function may be assessed non-invasively by studying heart rate variability (HRV). The aim of the present study was to compare overnight HRV between a control group and a group of subjects with severe OSA. The potential confounding effects of age, sex, baseline autonomic status and sleep stage distribution were taken into account. Our prospective Holter study compared overnight (0030-0530 hours) HRV in 23 controls (apnoea hypopnoea index (AHI) = 5 ± 3 /h) and 23 subjects with severe OSA (AHI = 65 ± 23 /h), matched for age and sex and with a similar percentage of rapid eye movement sleep. The mean normal-to-normal RR interval (NN) was shorter in the OSA compared with control group (903 vs 1039 ms, respectively), whereas the other time-domain indices of HRV, as well as the classic frequency-domain indices, were similar. Essentially similar results were obtained hourly and when only subjects with high mean values of the standard deviation of all NN (≥ 90 ms) were evaluated. In the 0.01-0.06 Hz range corresponding to the typical OSA pattern of bradycardia-tachycardia termed cyclic variation of heart rate (CVHR), higher power was documented hourly in OSA, with a significant correlation between overnight power and both AHI and mean oxyhaemoglobin saturation. The percentage of NN > x ms different from the previous one (pNNx family) had no diagnostic value. The results of the present study suggest that NN may be the best index to quantify the overnight sympathovagal balance in OSA and that a spectral band overlapping the apnoea-related pattern of CVHR slightly improved the characterization of the apnoea-related HRV patterns.