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Background: A post hoc analysis of the MERGE trial was conducted, to investigate whether sex differences are evident at the mildest end of the disease spectrum, for symptoms associated with obstructive sleep apnoea (OSA) and the response to continuous positive airway pressure (CPAP) treatment. Methods: MERGE participants with mild OSA (apnoea-hypopnoea index 5-15â events·h-1; American Academy of Sleep Medicine 2012 criteria) were randomised to either CPAP plus standard care (sleep hygiene counselling) or standard care alone for 3â months. Quality of life (QoL) was measured by questionnaires completed before and after the 3â months. This post hoc analysis of participants of the MERGE trial compared the symptom presentation, and response to CPAP, between the sexes. Results: 233 patients were included; 71 (30%) were female. Females were more symptomatic at baseline in all QoL questionnaires. Specifically, females had lower 36-item Short-Form Health Survey (SF-36) Vitality scores (mean±sd 39.1±10.1 versus 44.8±10.3) and higher Epworth Sleepiness Scale (ESS) scores (mean±sd 11.0±4.2 versus 9.5±4.4). Both sexes experienced snoring, but more females reported fatigue and more males reported witnessed apnoeas. All symptoms improved with CPAP for both sexes; however, females had larger improvements in SF-36 Vitality scores, which was the primary outcome of the MERGE trial (mean change 9.4 (95% CI 6.8-12.0) versus 6.0 (95% CI 4.3-7.7); p=0.034), and ESS (mean change -4.1 (95% CI -5.1- -3.0) versus -2.5 (95% CI -3.1- -1.8); p=0.015), after adjustment for baseline scores and CPAP usage. Conclusions: Sex differences are apparent in patients with mild OSA. Females experience worse QoL symptoms than males at presentation to the sleep clinic; however, these improve significantly with CPAP treatment.
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Obstructive sleep apnoea (OSA) was traditionally thought to be mainly caused by obesity and upper airway crowding, and hence OSA management was not personalised according to particular characteristics, with most symptomatic patients receiving continuous positive airway pressure therapy. Recent advances in our understanding have identified additional potential and distinct causes of OSA (endotypes), and subgroups of patients (phenotypes) with increased risk of cardiovascular complications. In this review, we discuss the evidence to date as to whether there are distinct clinically useful endotypes and phenotypes of OSA, and the challenges to the field in moving towards delivering personalised therapy in OSA.
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Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/terapia , Presión de las Vías Aéreas Positiva Contínua , ObesidadRESUMEN
Excessive daytime sleepiness in obstructive sleep apnoea (OSA) is often measured differently by patients and their partners. This study investigated the association between patient- and partner-completed Epworth Sleepiness Scale (ESS) scores and a potential correlation with OSA severity. One hundred two participants, 51 patients and 51 partners, completed the ESS before and three months after initiating CPAP treatment. There was no significant difference when comparing patients' and partners' ESS scores at baseline (10.75 ± 5.29 vs. 11.47 ± 4.96, respectively) and at follow-up (6.04 ± 4.49 vs. 6.41 ± 4.60, respectively). There was a strong correlation between patients' and partners' ESS scores on both (baseline and follow-up) assessments (p < 0.001). There was significant improvement in patients' and partners' ESS scores after CPAP therapy (p < 0.001). There was no significant difference in patients' or partners' ESS scores between patients with mild, moderate or severe OSA. There was no significant correlation between oxygen desaturation index (ODI) and ESS score reported either by patient or by partner. In conclusion, our study revealed a strong correlation between patient- and partner-reported ESS scores. However, neither patient- nor partner-completed ESS scores were associated with OSA severity.
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The role of nasal symptoms in continuous positive airway pressure (CPAP) tolerance is not completely clear. This study aimed to investigate the association between CPAP usage and nasal symptoms, either prior to, or developing during, CPAP use in patients with obstructive sleep apnoea (OSA). Two hundred thirty patients were studied and divided into high-, low-, and non-CPAP users. Nasal symptoms and related quality of life parameters were evaluated prior to CPAP initiation and after three months. We also investigated predictive factors for CPAP usage. Non-CPAP users had significantly worse baseline scores for runny nose compared with high and low users (1.34 vs. 0.68 and 0.75, respectively, p = 0.006). There were no other significant differences between the groups. Runny nose was an independent predictive factor for lower CPAP usage (p = 0.036). An evaluation after three months showed worsening in runny nose score in high-CPAP users (p = 0.025) but not in low- and non-users. There were no significant changes in other nasal symptoms. Our study demonstrates that nasal symptoms were very common in this population but rhinorrhoea was the only symptom associated with poorer CPAP adherence. Moreover, rhinorrhoea worsened after a three-month trial of high-CPAP usage.
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PURPOSE: Retinal microvascular endothelial dysfunction is thought to be of importance in the development of ocular vascular diseases. Obstructive sleep apnoea (OSA) causes macrovascular endothelial dysfunction, but the effect of OSA on retinal microvascular endothelial function is not known. We aimed to determine the effect of OSA on retinal microvascular function. METHODS: We conducted a multi-centre, double-blind, randomised, parallel, controlled trial in patients with known moderate-to-severe OSA, established on continuous positive airway pressure (CPAP). Participants were randomised to 14 nights of either continued CPAP or sham CPAP to generate a return of OSA. Retinal vascular responses to flickering light were measured using dynamic vessel analysis both at baseline and after 14 nights of intervention. The primary outcome was the change from baseline to follow-up in the area under the curve of the arteriolar response to flickering light, sham CPAP versus continued CPAP. RESULTS: Nineteen patients were randomised to sham CPAP, and 18 patients were randomised to continued CPAP. There was no significant effect of CPAP withdrawal and return of OSA on retinal responses, with a change in the area under the curve of the arteriole response to flickering light of + 3.8 arbitrary units (95% CI - 10.6 to + 18.2, p = 0.59), sham CPAP versus continued CPAP. CONCLUSIONS: CPAP withdrawal and a return of OSA had no significant effect on retinal microvascular responses. This contrasts with the effect of CPAP withdrawal on macrovascular endothelial function and suggests that OSA has different effects on macrovascular and microvascular endothelial function. ISRCTN 78082983, 23/10/2014, Prospectively registered.
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Apnea Obstructiva del Sueño , Presión de las Vías Aéreas Positiva Contínua , Método Doble Ciego , Humanos , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/terapiaRESUMEN
INTRODUCTION: The severity of obstructive sleep apnoea (OSA) is highly variable on a night-to-night basis. Patients are commonly categorised based on the severity of their OSA, and this is then used to influence management and reimbursement, including continuous positive airway pressure (CPAP). We aimed to establish to what extent the OSA severity category changes during two periods of OSA, based on mean and maximum oxygen desaturation index (ODI). METHODS: Patients with a diagnosis of moderate to severe OSA who had been on CPAP for greater than 1 year were included in this study. Subjects underwent two periods of CPAP withdrawal for four nights each. RESULTS: Twenty-five patients completed the study. Based on the mean ODI of the four nights, 14 (56%) patients changed OSA severity categorisation, with three (12%) changing category to mild. Based on the maximum ODI of the four nights, nine (36%) patients changed OSA severity categorisation, with one (4%) changing category to mild. One third to a half of patients' OSA severity category changed between the two periods of four night's CPAP withdrawal. CONCLUSIONS: OSA is highly variable on a period-to-period basis as well as on a night-to-night basis. We believe the concept of patients having a definable and 'real' level of OSA severity is therefore flawed. OSA severity should be based mainly on symptoms, as these are the dominant reasons for treatment, and the sleep study should be used qualitatively to ascertain whether respiratory events are the likely cause of the symptoms. TRIAL REGISTRATION: ISRCTN17987510.
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It has been suggested that metabolic dysfunction in obesity is at least in part driven by adipose tissue (AT) hypoxia. However, studies on AT hypoxia in humans have shown conflicting data. Therefore we aimed to investigate if markers of AT hypoxia were present in the subcutaneous AT of severly obese individuals (class III obesity) with and without hypoventilation syndrome (OHS) in comparison to moderately obese (class I obesity) and lean controls. To provide a proof-of-concept study, we quantified AT hypoxia by hypoxia inducible factor 1 A (HIF1A) protein abundance in human participants ranging from lean to severly obese (class III obesity). On top of that nightly arterial O2 saturation in individuals with obesity OHS was assessed. Subjects with class III obesity (BMI > 40 kg/m2) and OHS exhibited significantly higher adipose HIF1A protein levels versus those with class I obesity (BMI 30-34.9 kg/m2) and lean controls whereas those with class III obesity without OHS showed an intermediate response. HIF1A gene expression was not well correlated with protein abundance. Although these data demonstrate genuine AT hypoxia in the expected pathophysiological context of OHS, we did not observe a hypoxia signal in lesser degrees of obesity suggesting that adipose dysfunction may not be driven by hypoxia in moderate obesity.
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Tejido Adiposo/metabolismo , Hipoxia de la Célula/genética , Síndrome de Hipoventilación por Obesidad/metabolismo , Obesidad Mórbida/metabolismo , Grasa Subcutánea/metabolismo , Humanos , Transcriptoma/genéticaRESUMEN
BACKGROUND: Obstructive sleep apnoea (OSA) is associated with an increased prevalence of aortic aneurysms and it has also been suggested that severe OSA furthers aneurysm expansion in the abdomen. We evaluated whether OSA is a risk factor for the progression of ascending thoracic aortic aneurysm (TAA). METHODS: Patients with TAA underwent yearly standardised echocardiographic measurements of the ascending aorta over 3â years and two level III sleep studies. The primary outcome was the expansion rate of TAA in relation to the apnoea-hypopnoea index (AHI). Secondary outcomes included surveillance for aortic events (composite end-points of rupture/dissection, elective surgery or death). RESULTS: Between July 2014 and March 2020, 230 patients (median age 70â years, 83.5% male) participated in the cohort. At baseline, 34.8% of patients had AHI ≥15â events·h-1. There was no association between TAA diameter and AHI at baseline. After 3â years, mean±sd expansion rates were 0.55±1.25â mm at the aortic sinus and 0.60±1.12â mm at the ascending aorta. In the regression analysis, after controlling for baseline diameter and cardiovascular risk factors, there was strong evidence for a positive association of TAA expansion with AHI (aortic sinus estimate 0.025â mm, 95% CI 0.009-0.040â mm; p<0.001 and ascending aorta estimate 0.026â mm, 95% CI 0.011-0.041â mm; p=0.001). 20 participants (8%) experienced an aortic event; however, there was no association with OSA severity. CONCLUSION: OSA may be a modest but independent risk factor for faster TAA expansion and thus potentially contributes to life-threatening complications in aortic disease.
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Aneurisma de la Aorta Torácica , Apnea Obstructiva del Sueño , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Polisomnografía , Estudios Prospectivos , Factores de RiesgoRESUMEN
The effect of continuous positive airway pressure (CPAP) on cardiovascular events is uncertain in minimally symptomatic obstructive sleep apnoea. Previous 2-year follow-up data from the Multicentre Obstructive Sleep Apnoea Intervention Cardiovascular (MOSAIC) trial showed a marginal reduction in cardiovascular events with CPAP therapy. We now present long-term MOSAIC study follow-up data. Median (first quartile, third quartile) follow-up was 5.0 (2.2, 5.0) and 3.7 (1.5, 5.0) years for CPAP and standard care, respectively. Compared to standard care, CPAP had no statistically significant effect on the risk of cardiovascular events (HR=0.83, p=0.54, 95% CI 0.46-1.51).
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Enfermedades Cardiovasculares/epidemiología , Presión de las Vías Aéreas Positiva Contínua/métodos , Apnea Obstructiva del Sueño/terapia , Anciano , Enfermedades Cardiovasculares/etiología , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Apnea Obstructiva del Sueño/complicaciones , Resultado del TratamientoRESUMEN
BACKGROUND: The evidence base for the treatment of mild obstructive sleep apnoea is limited and definitions of disease severity vary. The MERGE trial investigated the clinical effectiveness of continuous positive airway pressure in patients with mild obstructive sleep apnoea. METHODS: MERGE, a multicentre, parallel, randomised controlled trial enrolled patients (≥18 years to ≤80 years) with mild obstructive sleep apnoea (apnoea-hypopnoea index [AHI] ≥5 to ≤15 events per h using either AASM 2007 or AASM 2012 scoring criteria) from 11 UK sleep centres. Participants were assigned (1:1) to either 3 months of continuous positive airway pressure plus standard care (sleep counselling), or standard care alone, by computer-generated randomisation; neither participants nor researchers were blinded. The primary outcome was a change in the score on the Short Form-36 questionnaire vitality scale in the intention-to-treat population of patients with mild obstructive sleep apnoea diagnosed using the American Academy of Sleep Medicine 2012 scoring criteria. The study is registered with ClinicalTrials.gov, NCT02699463. FINDINGS: Between Nov 28, 2016 and Feb 12, 2019, 301 patients were recruited and randomised. 233 had mild obstructive sleep apnoea using AASM 2012 criteria and were included in the intention-to-treat analysis: 115 were allocated to receive continuous positive airway pressure and 118 to receive standard care. 209 (90%) of these participants completed the trial. The vitality score significantly increased with a treatment effect of a mean of 10·0 points (95% CI 7·2-12·8; p<0·0001) after 3 months of continuous positive airway pressure, compared with standard care alone (9·2 points [6·8 to 11·6] vs -0·8 points [-3·2 to 1·5]). Using the ANCOVA last-observation-carried-forward analysis, a more conservative estimate, the vitality score also significantly increased with a treatment effect of a mean of 7·5 points (95% CI 5·3 to 9·6; p<0·0001) after 3 months of continuous positive airway pressure, compared with standard care alone (7·5 points [6·0 to 9·0] vs 0·0 points [-1·5 to 1·5]). Three serious adverse events occurred (one allocated to the continuous positive airway pressure group) and all were unrelated to the intervention. INTERPRETATION: 3 months of treatment with continuous positive airway pressure improved the quality of life in patients with mild obstructive sleep apnoea. These results highlight the need for health-care professionals and providers to consider treatment for patients with mild obstructive sleep apnoea. FUNDING: ResMed Ltd.
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Presión de las Vías Aéreas Positiva Contínua/métodos , Consejo/métodos , Apnea Obstructiva del Sueño/terapia , Nivel de Atención , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Sueño , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Continuous positive airway pressure (CPAP) is currently the treatment of choice for sleepiness in patients with obstructive sleep apnoea (OSA); however, adherence is often thought to be suboptimal. We investigated the effects of suboptimal CPAP usage on objective and subjective sleepiness parameters in patients with OSA. MATERIAL AND METHODS: In this 2-week, parallel, double-blind, randomised controlled trial we enrolled moderate-to-severe OSA patients with excessive pre-treatment daytime sleepiness (Epworth sleepiness scale (ESS) score >10â points) who had suboptimal CPAP adherence over ≥12â months (mean nightly usage time 3-4â h). Patients were allocated through minimisation to either subtherapeutic CPAP ("sham CPAP") or continuation of CPAP ("therapeutic CPAP"). A Bayesian analysis with historical priors calculated the posterior probability of superiority. RESULTS: Between May, 2016 and November, 2018, 57 patients (aged 60±8â years, 79% male, 93% Caucasian) were allocated in total, and 52 who completed the study (50% in each arm) were included in the final analysis. The unadjusted ESS score increase was 2.4â points (95% CI 0.6-4.2, p=0.01) in the sham-CPAP group when compared to continuing therapeutic CPAP. The probability of superiority of therapeutic CPAP over sham CPAP was 90.4% for ESS, 90.1% for systolic blood pressure and 80.3% for diastolic blood pressure. CONCLUSIONS: Patients with moderate-to-severe OSA and daytime sleepiness are still getting a substantial benefit from suboptimal CPAP adherence, albeit not as much as they might get if they adhered more. Whether a similar statement can be made for even lower adherence levels remains to be established in future trials.
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Trastornos de Somnolencia Excesiva , Apnea Obstructiva del Sueño , Teorema de Bayes , Presión de las Vías Aéreas Positiva Contínua , Femenino , Humanos , Masculino , Apnea Obstructiva del Sueño/terapia , VigiliaRESUMEN
Impaired cerebral vascular reactivity (CVR) increases long-term stroke risk. Obstructive sleep apnoea (OSA) is associated with peripheral vascular dysfunction and vascular events. The aim of this trial was to evaluate the effect of continuous positive airway pressure (CPAP) withdrawal on CVR.41 OSA patients (88% male, mean age 57±10â years) were randomised to either subtherapeutic or continuation of therapeutic CPAP. At baseline and after 2â weeks, patients underwent a sleep study and magnetic resonance imaging (MRI). CVR was estimated by quantifying the blood oxygen level-dependent (BOLD) MRI response to breathing stimuli.OSA did recur in the subtherapeutic CPAP group (mean treatment effect apnoea-hypopnoea index +38.0â events·h-1, 95% CI 24.2-52.0; p<0.001) but remained controlled in the therapeutic group. Although there was a significant increase in blood pressure upon CPAP withdrawal (mean treatment effect +9.37â mmHg, 95% CI 1.36-17.39; p=0.023), there was no significant effect of CPAP withdrawal on CVR assessed via BOLD MRI under either hyperoxic or hypercapnic conditions.Short-term CPAP withdrawal did not result in statistically significant changes in CVR as assessed by functional MRI, despite the recurrence of OSA. We thus conclude that, unlike peripheral endothelial function, CVR is not affected by short-term CPAP withdrawal.
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Presión de las Vías Aéreas Positiva Contínua , Oxígeno/sangre , Polisomnografía , Apnea Obstructiva del Sueño/terapia , Adulto , Anciano , Presión Sanguínea , Encéfalo/diagnóstico por imagen , Circulación Cerebrovascular , Método Doble Ciego , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Perfusión , Recurrencia , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento , Adulto JovenRESUMEN
RATIONALE: Obstructive sleep apnea (OSA) is associated with systemic hypertension. Either overnight intermittent hypoxia, or the recurrent arousals that occur in OSA, could cause the daytime increases in blood pressure (BP). OBJECTIVES: To establish the role of intermittent hypoxia in the increased morning BP in patients with OSA. METHODS: Randomized, double-blinded, crossover trial assessing the effects of overnight supplemental oxygen versus air (sham) on morning BP, after continuous positive airway pressure (CPAP) withdrawal in patients with moderate to severe OSA. The primary outcome was the change in home morning BP after CPAP withdrawal for 14 nights, oxygen versus air. Secondary outcomes included oxygen desaturation index (ODI), apnea-hypopnea index (AHI), subjective sleepiness (Epworth Sleepiness Scale score), and objective sleepiness (Oxford Sleep Resistance Test). MEASUREMENTS AND MAIN RESULTS: Supplemental oxygen virtually abolished the BP rise after CPAP withdrawal and, compared with air, significantly reduced the rise in mean systolic BP (-6.6 mm Hg; 95% confidence interval [CI], -11.3 to -1.9; P = 0.008), mean diastolic BP (-4.6 mm Hg; 95% CI, -7.8 to -1.5; P = 0.006), and median ODI (-23.8/h; interquartile range, -31.0 to -16.3; P < 0.001) after CPAP withdrawal. There was no significant difference, oxygen versus air, in AHI, subjective sleepiness, or objective sleepiness. CONCLUSIONS: Supplemental oxygen virtually abolished the rise in morning BP during CPAP withdrawal. Supplemental oxygen substantially reduced intermittent hypoxia, but had a minimal effect on markers of arousal (including AHI), subjective sleepiness, or objective sleepiness. Therefore intermittent hypoxia, and not recurrent arousals, appears to be the dominant cause of daytime increases in BP in OSA.
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Presión de las Vías Aéreas Positiva Contínua , Hipertensión/prevención & control , Terapia por Inhalación de Oxígeno/métodos , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/terapia , Anciano , Presión Sanguínea , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Hipoxia/complicaciones , Hipoxia/fisiopatología , Hipoxia/terapia , Masculino , Persona de Mediana Edad , Oxígeno , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/complicacionesRESUMEN
BACKGROUND: The Epworth Sleepiness Scale (ESS) is a widely used tool for assessing sleepiness in patients with obstructive sleep apnoea (OSA). We aimed to estimate the minimal important difference (MID) in patients with OSA. METHODS: We used individual data from three randomised controlled trials (RCTs) in patients with OSA where the preintervention to postintervention change in ESS was used as a primary outcome. We used anchor-based linear regression and responder analysis approaches to estimate the MID. For anchors, we used the change in domains of the Functional Outcomes of Sleep Questionnaire and 36-Item Short Form Health Survey. We also used the distribution-based approaches Cohen's effect size, SE of measurement and empirical rule effect size to support the anchor-based estimates. The final MID was determined by triangulating all estimates to a single MID. FINDINGS: A total of 639 patients with OSA were included in our analyses across the three RCTs with a median (IQR) baseline ESS score of 10 (6-13). The median (IQR) ESS change score overall was -2 (-5 to 1). The anchor-based estimates of the MID were between -1.74 and -4.21 points and estimates from the responder analysis were between -1 and -3 points. Distribution-based estimates were smaller, ranging from -1.46 to -2.36. INTERPRETATION: We propose an MID for the ESS of 2 points in patients with OSA with a disease severity from mild to severe. This estimate provides the means to plan trials and interpret the clinical relevance of changes in ESS. TRIAL REGISTRATION NUMBER: Provent, NCT01332175; autoCPAP trial, NCT00280800; MOSAIC,ISRCTN (3416388).
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Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/complicaciones , Somnolencia , Presión de las Vías Aéreas Positiva Contínua , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Autoinforme , Apnea Obstructiva del Sueño/terapia , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
We sought to establish whether continuous positive airway pressure (CPAP) for obstructive sleep apnoea (OSA) in people with type 2 diabetes and diabetic macular oedema (DMO) improved visual acuity.We randomly assigned 131 eligible patients aged 30-85â years from 23 UK centres with significant DMO causing visual impairment (LogMAR letters identified ≥39 and ≤78, score 0.92-0.14) plus severe OSA on screening to either usual ophthalmology care (n=67) or usual ophthalmology care plus CPAP (n=64) for 12â months.Mean age of participants was 64â years, 73% male, mean body mass index 35.0â kg·m- 2 Mean 4% oxygen desaturation index was 36â events·h-1 There was no significant difference in the visual acuity at 12â months between the CPAP group and the control group (mean LogMAR 0.33 (95% CI 0.29-0.37) versus 0.31 (95% CI 0.27-0.35); p=0.39), and no significant correlation between change in LogMAR and average CPAP use. The median±sd (range) daily CPAP use was 3.33±2.25 (0-7.93)â h at 3â months, 3.19±2.54 (0-8.07)â h at 6â months and 3.21±2.70 (0-7.98)â h at 12â months.CPAP therapy for OSA did not improve visual acuity in people with type 2 diabetes and DMO compared with usual care alone over 12â months.
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Presión de las Vías Aéreas Positiva Contínua , Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/terapia , Edema Macular/terapia , Apnea Obstructiva del Sueño/terapia , Agudeza Visual , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Retina/patología , Apnea Obstructiva del Sueño/complicaciones , Resultado del Tratamiento , Reino UnidoRESUMEN
BACKGROUND: Obstructive sleep apnoea (OSA) has been proposed as an independent risk factor for sudden cardiac death (SCD). This study takes advantage of a previous randomized trial and seeks to evaluate circadian patterns of the QTc-interval, a marker of cardiac repolarization and biomarker for SCD, in patients with OSA. We hypothesized that patients with OSA would exhibit longest QTc during the night-time and that continuous positive airway pressure (CPAP) therapy would reverse this. METHODS: One hundred eighteen patients diagnosed with moderate-to-severe OSA were randomized to receive therapeutic or subtherapeutic CPAP for 4 weeks. Of these, 84 had full 24 h-Holter monitoring data at baseline and follow-up. Weighted means of all QTc-intervals were analysed over 24 h, during four time-periods (12 pm-6 am, 6 am-12 am, 12 am-6 pm, 6 pm-12 pm) as well as during each individual hour. A two-sided P value <0.05 was considered to be of statistical significance. RESULTS: QTc-intervals at baseline [mean (SD) over 24 h: 407.8 ms (36.6)] were highest from 6 pm-12 pm [411.7 ms (42.0)] and shortest from 6 am-12 am [405.4 ms (39.5)]. Overall 24 h CPAP treatment effect on QTc was -11.3 ms [95% confidence interval (CI), -22.1 to -0.6; P=0.039] and was estimated to be greater from 6 pm-12 pm than from 12 pm-6 am (P=0.068). The CPAP treatment effect on QTc was driven by those patients in the highest QTc decile at baseline (all >430 ms). In these patients, CPAP led to reductions in QTc, allowing reclassification into lower risk-associated values of QTc (<430 ms). CONCLUSIONS: In this exploratory study, CPAP treatment led to an overall reduction in the QTc-interval compared with subtherapeutic CPAP. This reduction seems more pronounced during evening hours and in patients with a QTc above 430 ms.