High prevalence of undiagnosed obstructive sleep apnoea in the general population and methods for screening for representative controls.

PURPOSE: Undiagnosed obstructive sleep apnoea (OSA) in the community makes comparisons of OSA subjects with control samples from the general population problematic. This study aims to estimate undiagnosed moderate to severe OSA in a general population sample and to determine the capacity of questions from the Berlin questionnaire (BQ) to identify subjects without diagnosed OSA of this severity. METHODS: Using a general population sample (n = 793) with no history of OSA, case and control status for moderate-severe OSA was determined by home-based nasal flow and oximetry-derived apnoea-hypopnoea index using a cut-off value of ≥ 15 events/h to define cases. The diagnostic accuracy of the complete BQ and its component questions in identifying cases was assessed by calculating sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and post-test probabilities. RESULTS: The age-standardised prevalence estimate of moderate-severe OSA was 9.1 % (12.4 % in men, 5.7 % in women). Sensitivity of the BQ in this population was 54 %, and specificity, 70 %. A combination of questions regarding snoring frequency and hypertension provided maximal post-test probability of OSA and greatest post-screen sample size. CONCLUSIONS: Undiagnosed OSA is highly prevalent in the Western Australian general population. While the complete BQ is a sub-optimal screening instrument for the general population, snoring frequency or hypertension can be used to screen out moderate-severe OSA from general population samples with limited reduction in sample size. As there are few general population samples available for epidemiological or genetic studies of OSA and its associated phenotypes, these results may usefully inform future case-control studies.

Cohort profile: the Western Australian Sleep Health Study.

BACKGROUND: Epidemiologic and genetic studies of obstructive sleep apnoea (OSA) are limited by a lack of large-scale, well-characterized OSA cohorts. These studies require large sample size to provide adequate power to detect differences between groups. This study describes the development of such a cohort (The Western Australian Sleep Health Study) in OSA patients of Caucasian-European origin attending the only public sleep clinic in Western Australia (WA). AIMS: The main aim of the study is to phenotype 4,000 OSA patients in order to define the genetics of OSA and its co-morbidities. METHODS: Almost all underwent laboratory-based attended polysomnography (PSG). RESULTS: Currently complete data (questionnaire, biochemistry, DNA, and PSG) has been obtained on over 3,000 individuals and will reach the target of 4,000 individuals by the end of 2010. In a separate but related study, we have developed a sleep study database containing data from all patients who have undergone PSG at the sleep laboratory since its inception in 1988 until the present day (over 30,000 PSG studies representing data from approximately 20,000 individuals). In addition, data from both cohorts have been linked prospectively to statutory health data collected by the WA Department of Health. CONCLUSION: This study will be the largest sleep clinic cohort database internationally with access to genetic and epidemiological data. It is unique among sleep clinic cohorts because of its size, the breadth of data collected and the ability to link prospectively to statutory health data. It will be a major tool to comprehensively assess genetic and epidemiologic factors determining OSA and its co-morbidities.

Sex differences in the association of regional fat distribution with the severity of obstructive sleep apnea.

STUDY OBJECTIVES: To describe sex differences in the associations between severity of obstructive sleep apnea (OSA) and measures of obesity in body regions defined using both dual-energy absorptiometry and traditional anthropometric measures in a sleep-clinic sample. DESIGN: A prospective case-series observational study. SETTING: The Western Australian Sleep Health Study operating out of the Sir Charles Gairdner Hospital Sleep Clinic, Perth, Western Australia. PARTICIPANTS: Newly referred clinic patients (60 men, 36 women) suspected of having OSA. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Obstructive sleep apnea severity was defined by apnea-hypopnoea index from laboratory-based overnight polysomnography. Body mass index, neck, waist and hip circumference, neck-to-waist ratio, and waist-to-hip ratio were measured. Dual energy absorptiometry measurements included percentage fat and lean tissue. Multivariate regression models for each sex were developed. In women, percentage of fat in the neck region and body mass index together explained 33% of the variance in apnea-hypopnea index. In men, percentage of fat in the abdominal region and neck-to-waist ratio together accounted for 37% of the variance in apnea-hypopnea index. CONCLUSIONS: Regional obesity is associated with obstructive sleep apnea severity, although differently in men and women. In women, a direct influence of neck fat on the upper airway patency is implicated. In men, abdominal obesity appears to be the predominant influence. The apnea-hypopnea index was best predicted by a combination of Dual Energy Absorptiometry-measured mass and traditional anthropometric measurements.

Depressive Symptoms before and after Treatment of Obstructive Sleep Apnea in Men and Women.

STUDY OBJECTIVES: To determine prevalence of depressive symptoms in obstructive sleep apnea (OSA) and the impact of OSA treatment on depression scores. METHODS: Consecutive new patients referred for investigation of suspected OSA were approached. Consenting patients completed a patient health questionnaire (PHQ-9) for depressive symptoms when attending for laboratory polysomnography. Those with moderate/severe (apneahypopnea index [AHI] ≥ 15 events/h) and/or symptomatic mild OSA (AHI 5-14.99 events/h) were offered continuous positive airway pressure (CPAP) therapy. PHQ-9 was repeated after 3 months of CPAP with compliance recorded. Of a maximum PHQ-9 score of 27, a cut point ≥ 10 (PHQ-9 ≥ 10) was used to indicate presence of clinically significant depressive symptoms. RESULTS: A total of 426 participants (243 males) were recruited. Mean ± standard deviation body mass index (BMI) was 32.1 ± 7.1 kg/m2 and AHI 33.6 ± 28.9 events/h. PHQ-9 was 10.5 ± 6.1 and independently related to AHI (p < 0.001) and BMI (p < 0.001). In those without OSA, PHQ-9 ≥ 10 was more common in women, but no gender difference was evident with OSA. Of 293 patients offered CPAP, 228 were compliant (mean nightly use > 5 h) over 3 months of therapy. In them, with therapy, AHI decreased from 46.7 ± 27.4 to 6.5 ± 1.6 events/h, PHQ-9 from 11.3 ± 6.1 to 3.7 ± 2.9 and PHQ-9 ≥ 10 from 74.6% to 3.9% (p < 0.001 in each case). Magnitude of change in PHQ-9 was similar in men and women. Antidepressant use was constant throughout. CONCLUSIONS: Depressive symptoms are common in OSA and related to its severity. They improve markedly with CPAP, implying a relationship to untreated OSA.

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.

Physical Inactivity Is Associated with Moderate-Severe Obstructive Sleep Apnea.

STUDY OBJECTIVE: To investigate whether low levels of physical activity were associated with an increased occurrence of obstructive sleep apnea (OSA), OSA-related symptoms, and cardiometabolic risk. METHODS: A case-control study design was used. OSA cases were patients referred to a sleep clinic for suspected OSA (n = 2,340). Controls comprised participants from the Busselton community (n = 1,931). Exercise and occupational activity were derived from questionnaire data. Associations were modelled using logistic and linear regression and adjusted for confounders. RESULTS: In comparison with moderate exercise, the high, low, and nil exercise groups had an odds ratio (OR) for moderate-severe OSA of 0.6 (95% CI 0.5-0.8), 1.6 (95% CI 1.2-2.0), and 2.7 (95% CI 1.9-3.7), respectively. Relative to men in heavy activity occupations, men in medium, light and sedentary occupations had an OR for moderate-severe OSA of 1.7 (95% CI 1.1-2.5), 2.1 (95% CI 1.4-3.2), and 1.8 (95% CI 1.2-2.8), respectively. Relative to women in medium activity occupations, women in light and sedentary occupations had an OR for moderate-severe OSA of 4.2 (95% CI 2.6-7.2) and 3.5 (2.0-6.0). OSA patients who adequately exercised had lower: levels of doctor-diagnosed depression (p = 0.047); symptoms of fatigue (p < 0.0001); systolic (p = 0.015) and diastolic blood pressure (p = 0.015); and C-reactive protein (CRP) (p = 0.003). CONCLUSIONS: Low levels of physical activity were associated with moderate-severe OSA. Exercise in individuals with OSA is associated with lower levels of depression, fatigue, blood pressure and CRP.

A Comprehensive Evaluation of a Two-Channel Portable Monitor to "Rule in" Obstructive Sleep Apnea.

STUDY OBJECTIVES: We hypothesized that a dual-channel portable monitor (PM) device could accurately identify patients who have a high pretest probability of obstructive sleep apnea (OSA), and we evaluated factors that may contribute to variability between PM and polysomnography (PSG) results. METHODS: Consecutive clinic patients (N = 104) with possible OSA completed a home PM study, a PM study simultaneous with laboratory PSG, and a second home PM study. Uniform data analysis methods were applied to both PM and PSG data. Primary outcomes of interest were the positive likelihood ratio (LR+) and sensitivity of the PM device to "rule-in" OSA, defined as an apnea-hypopnea index (AHI) ≥ 5 events/h on PSG. Effects of different test environment and study nights, and order of study and analysis methods (manual compared to automated) on PM diagnostic accuracy were assessed. RESULTS: The PM has adequate LR+ (4.8), sensitivity (80%), and specificity (83%) for detecting OSA in the unattended home setting when benchmarked against laboratory PSG, with better LR+ (> 5) and specificity (100%) and unchanged sensitivity (80%) in the simultaneous laboratory comparison. There were no significant night-night (all p > 0.10) or study order effects (home or laboratory first, p = 0.08) on AHI measures. Manual PM data review improved case finding accuracy, although this was not statistically significant (all p > 0.07). Misclassification was more frequent where OSA was mild. CONCLUSIONS: Overall performance of the PM device is consistent with current recommended criteria for an "acceptable" device to confidently "rule-in" OSA (AHI ≥ 5 events/h) in a high pretest probability clinic population. Our data support the utility of simple two-channel diagnostic devices to confirm the diagnosis of OSA in the home environment. COMMENTARY: A commentary on this article appears in this issue on page 411.

Excessive daytime sleepiness increases the risk of motor vehicle crash in obstructive sleep apnea.

STUDY OBJECTIVES: (1) To describe the incidence rate of motor vehicle crashes (MVCs) in patients with obstructive sleep apnea (OSA); and (2) to investigate MVC risk factors in OSA patients. METHODS: A retrospective case-series observational study was conducted using data from the West Australian Sleep Health Study at a tertiary hospital-based sleep clinic. Participants were patients (N = 2,673) referred for assessment of suspected sleep disordered breathing. Questionnaire data were collected including age, sex, years of driving, near-misses and MVCs, sleepiness, and consumption of alcohol and caffeinated drinks. Overnight laboratory-based polysomnography was performed using standard methodology.(1) Poisson univariate and negative binomial multivariable regression models were used to investigate associations between risk factors and MVC and near-miss risk in patients with untreated OSA. RESULTS: In patients with untreated OSA, the crash rate was 0.06 MVC/person-year compared with the general community crash rate of 0.02 MVC/person-year. The rate ratio comparing very sleepy men with normal men was 4.68 (95% CI 3.07, 7.14) for near-misses and 1.27 (95% CI 1.00, 1.61) for crashes, after adjusting for confounders. In women there was a significant association with sleepiness score (p = 0.02) but no dose effect across quartiles. CONCLUSIONS: Untreated OSA is associated with an increased risk of near-misses in men and women and an increased risk of MVCs in very sleepy men. There is a strong association between excessive daytime sleepiness and increased report of near-misses. Our data support the observation that it is those patients with increased sleepiness regardless of OSA severity who are most at risk.