Nigel McArdle

CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea

BACKGROUND Obstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain. METHODS After a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood. RESULTS Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P=0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood. CONCLUSIONS Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease. (Funded by the National Health and Medical Research Council of Australia and others; SAVE ClinicalTrials.gov number, NCT00738179 ; Australian New Zealand Clinical Trials Registry number, ACTRN12608000409370 .).

Tumour necrosis factor-α (−308) gene polymorphism in obstructive sleep apnoea–hypopnoea syndrome

Patients with obstructive sleep apnoea–hypopnoea syndrome (OSAHS) have elevated circulating levels of tumour necrosis factor (TNF)-α. The hypothesis in this study was that OSAHS might be associated with the TNF-α (−308A) gene polymorphism, which results in increased TNF-α production. This hypothesis was examined in OSAHS patients, their siblings and population controls. A total of 206 subjects were recruited. All underwent sleep studies and clinical review, and were subsequently classified as having OSAHS or not depending on apnoea–hypopnoea frequency, sex, age and symptoms. All subjects had blood collected and genotyping was performed on DNA extracted from peripheral leukocytes. Some 192 random UK blood donors were used as population controls. The results demonstrated a significant association for TNF-α (−308A) allele carriage with OSAHS (OR = 1.8; 95% Confidence interval: 1.18–2.75) when compared with population controls. Siblings with OSAHS were significantly more likely to carry the TNF-α (−308A) allele. In addition, 21 pairs of male siblings discordant for carriage of the −308A allele showed a significant level of discordance for the OSAHS phenotype. In conclusion, this study demonstrates an association of tumour necrosis factor-α (−308A) carriage with obstructive sleep apnoea–hypopnoea syndrome, suggesting that inflammation may be implicated in the pathogenesis of this condition.

Sleep-Disordered Breathing as a Risk Factor for Cerebrovascular Disease A Case-Control Study in Patients With Transient Ischemic Attacks

Background and Purpose— The evidence that obstructive sleep apnea/hypopnea (OSAH) is a risk factor for ischemic cerebrovascular disease is inconclusive. We explored this relationship in transient ischemic attack (TIA) patients because they are less likely than stroke patients to have OSAH as a consequence of cerebrovascular disease. Methods— We performed a case-control study among 86 patients with TIA from a hospital neurovascular clinic, matched for age (±5 years) and sex with controls from the referring local family practice registers. Results— Forty-nine of the 86 matched pairs were male and the body mass index was similar among cases and controls. The primary outcome measure, the apnea/hypopnea index [AHI=number of (apneas+hypopneas)/h slept, measured during overnight polysomnography and scored blind to case-control status], was the same for cases and controls (21/hour). However, the median number of 4% desaturations during sleep was slightly greater in the cases (12/hour) than controls (6/hour, P =0.04). There were the expected associations between TIA and higher fibrinogen levels (TIA 3.3, control 3.0 g/L, P =0.01), previous myocardial infarction (TIA 22, control 6%, P =0.007), a history of ever smoking (TIA 71, control 54%, P =0.01), hypertension (TIA 51, control 21%, P =0.001), and raised cholesterol (TIA 27, control 10%, P =0.01), with a weak trend for diabetes mellitus (TIA 10, control 6%, P =0.4). Conclusion— OSAH does not appear to be strongly associated with TIAs.

Home mechanical ventilation in australia and new zealand

This study aims to describe the pattern of home mechanical ventilation (HMV) usage in Australia and New Zealand. 34 centres providing HMV in the region were identified and asked to complete a questionnaire regarding centre demographics, patient diagnoses, HMV equipment and settings, staffing levels and methods employed to implement and follow-up therapy. 28 (82%) centres responded, providing data on 2,725 patients. The minimum prevalence of HMV usage was 9.9 patients per 100,000 population in Australia and 12.0 patients per 100,000 population in New Zealand. Variation existed across Australian states (range 4–13 patients per 100,000 population) correlating with population density (r=0.82; p<0.05). The commonest indications for treatment were obesity hypoventilation syndrome (OHS) (31%) and neuromuscular disease (NMD) (30%). OHS was more likely to be treated in New Zealand, in smaller, newer centres, whilst NMD was more likely to be treated in Australia, in larger, older centres. Chronic obstructive pulmonary disease was an uncommon indication (8.0%). No consensus on indications for commencing treatment was found. In conclusion, the prevalence of HMV usage varies across Australia and New Zealand according to centre location, size and experience. These findings can assist HMV service planning locally and highlight trends in usage that may be relevant in other countries.

Severity of OSA Is an Independent Predictor of Incident Atrial Fibrillation Hospitalization in a Large Sleep-Clinic Cohort

BACKGROUND OSA is a common condition that has been associated with atrial fibrillation (AF), but there is a paucity of data from large longitudinal cohorts to establish whether OSA is a risk factor for AF independent of obesity and other established risk factors. METHODS We studied patients attending a sleep clinic referred for in-laboratory polysomnography for possible OSA between 1989 and 2001. Whole-population hospital data in Western Australia for 1970 to 2009 were linked to sleep study cases to determine incident AF hospitalization to 2009. Cox regression analyses were used to assess the independent association of OSA with incident AF. RESULTS Study case subjects (6,841) were predominantly middle aged (48.3 ± 12.5 years old) and men (77%), and 455 developed AF during a median 11.9 years of follow-up. Univariate predictors of AF included age, BMI, hypertension, diabetes, valvular heart disease, coronary or peripheral artery disease, heart failure, and COPD (all P < .001). After multivariable adjustment, independent predictors of incident AF were an apnea/hypopnea index (AHI) > 5/h (hazard ratio [HR], 1.55; 95% CI, 1.21-2.00), log (AHI + 1) (HR, 1.15; 95% CI, 1.06-1.26), and log (time with oxygen saturation < 90% + 1) (HR, 1.12; 95% CI, 1.06-1.19). There were no interactions between age, sex, or BMI and AHI for AF development. CONCLUSIONS OSA diagnosis and severity are independently associated with incident AF. Clinical trials are required to determine if treatment of OSA will reduce the burden of AF.

Continuous positive airway pressure titration for obstructive sleep apnoea: automatic versus manual titration

Background and aims Manual laboratory continuous positive airway pressure (CPAP) titration for obstructive sleep apnoea (OSA) is costly, time intensive and delays access to treatment. Automatic positive airway pressure (APAP) titration has the potential to reduce cost and improve access to treatment. The aim of this study was to assess the clinical efficacy and costs of APAP titration compared with manual titration in moderate–severe OSA. Methods Patients with moderate–severe OSA (apnoea/hypopnoea index >15 and Epworth Sleepiness Score ≥8) who were free of co-morbidities that could impair APAP titration were eligible. 249 participants were randomised to manual titration, home APAP or laboratory APAP titration to determine a fixed pressure for CPAP. Clinical and direct cost outcomes were assessed after 4 weeks of treatment. Results Average nightly CPAP use, subjective sleepiness, SF36 quality of life, Trails A and B cognitive function and polysomnographic outcomes were similar among the per-protocol groups. Non-hypertensive patients had a lower resting heart rate (and greater reduction in heart rate) at 4 weeks after laboratory APAP titration compared with home APAP titration. Costs per patient were highest in manual (AU

Relationships between ventilatory impairment, sleep hypoventilation and type 2 respiratory failure

817.84), followed by laboratory (AU

Study of a Novel APAP Algorithm for the Treatment of Obstructive Sleep Apnea in Women

647.56) and home (AU

Physical inactivity is associated with moderate-severe obstructive sleep apnea

132.09) APAP titration. An intention-to-treat analysis confirmed the effectiveness of APAP titration compared with manual titration in the standard clinical setting. Conclusions Among patients with moderate–severe OSA without serious co-morbidities, outcomes at 1 month indicate that APAP titration is more cost-effective than manual laboratory titration to determine an appropriate pressure for CPAP for long-term use; with the largest savings occurring in the home APAP patients. Australian New Zealand Clinical Trials Registry Number ACTRN12608000054314.

Control of OSA during automatic positive airway pressure titration in a clinical case series: predictors and accuracy of device download data.

Conditions that increase load on respiratory muscles and/or reduce their capacity to cope with this load predispose to type 2 (hypercapnic) respiratory failure. In its milder forms, this imbalance between load and capacity may primarily manifest as sleep hypoventilation which, if untreated, can increase the likelihood of wakeful respiratory failure. Such problems are commonly seen in progressive respiratory neuromuscular disorders, morbid obesity and chronic obstructive pulmonary disease, either separately or together. Identifying patients at risk can be important in determining whether and when to intervene with treatments such as non‐invasive ventilatory assistance. Measurements of wakeful respiratory function are fundamental to this risk assessment. These issues are reviewed in this paper.