Obstructive sleep apnoea during REM sleep and incident non-dipping of nocturnal blood pressure: a longitudinal analysis of the Wisconsin Sleep Cohort.

BACKGROUND: Non-dipping of nocturnal blood pressure (BP) is associated with target organ damage and cardiovascular disease. Obstructive sleep apnoea (OSA) is associated with incident non-dipping. However, the relationship between disordered breathing during rapid eye movement (REM) sleep and the risk of developing non-dipping has not been examined. This study investigates whether OSA during REM sleep is associated with incident non-dipping. METHODS: Our sample included 269 adults enrolled in the Wisconsin Sleep Cohort Study who completed two or more 24 h ambulatory BP studies over an average of 6.6 years of follow-up. After excluding participants with prevalent non-dipping BP or antihypertensive use at baseline, there were 199 and 215 participants available for longitudinal analysis of systolic and diastolic non-dipping, respectively. OSA in REM and non-REM sleep were defined by apnoea hypopnoea index (AHI) from baseline in-laboratory polysomnograms. Systolic and diastolic non-dipping were defined by systolic and diastolic sleep/wake BP ratios >0.9. Modified Poisson regression models estimated the relative risks for the relationship between REM AHI and incident non-dipping, adjusting for non-REM AHI and other covariates. RESULTS: There was a dose-response greater risk of developing systolic and diastolic non-dipping BP with greater severity of OSA in REM sleep (p-trend=0.021 for systolic and 0.024 for diastolic non-dipping). Relative to those with REM AHI<1 event/h, those with REM AHI≥15 had higher relative risk of incident systolic non-dipping (2.84, 95% CI 1.10 to 7.29) and incident diastolic non-dipping (4.27, 95% CI 1.20 to 15.13). CONCLUSIONS: Our findings indicate that in a population-based sample, REM OSA is independently associated with incident non-dipping of BP.

Obstructive sleep apnea during REM sleep and hypertension. results of the Wisconsin Sleep Cohort.

RATIONALE: Obstructive sleep apnea (OSA) is associated with hypertension. OBJECTIVES: We aimed to quantify the independent association of OSA during REM sleep with prevalent and incident hypertension. METHODS: We included adults enrolled in the longitudinal community-based Wisconsin Sleep Cohort Study with at least 30 minutes of REM sleep obtained from overnight in-laboratory polysomnography. Studies were repeated at 4-year intervals to quantify OSA. Repeated measures logistic regression models were fitted to explore the association between REM sleep OSA and prevalent hypertension in the entire cohort (n = 4,385 sleep studies on 1,451 individuals) and additionally in a subset with ambulatory blood pressure data (n = 1,085 sleep studies on 742 individuals). Conditional logistic regression models were fitted to longitudinally explore the association between REM OSA and development of hypertension. All models controlled for OSA events during non-REM sleep, either by statistical adjustment or by stratification. MEASUREMENTS AND MAIN RESULTS: Fully adjusted models demonstrated significant dose-relationships between REM apnea-hypopnea index (AHI) and prevalent hypertension. The higher relative odds of prevalent hypertension were most evident with REM AHI greater than or equal to 15. In individuals with non-REM AHI less than or equal to 5, a twofold increase in REM AHI was associated with 24% higher odds of hypertension (odds ratio, 1.24; 95% confidence interval, 1.08-1.41). Longitudinal analysis revealed a significant association between REM AHI categories and the development of hypertension (P trend = 0.017). Non-REM AHI was not a significant predictor of hypertension in any of the models. CONCLUSIONS: Our findings indicate that REM OSA is cross-sectionally and longitudinally associated with hypertension. This is clinically relevant because treatment of OSA is often limited to the first half of the sleep period leaving most of REM sleep untreated.

Sleep-disordered breathing and cancer mortality: results from the Wisconsin Sleep Cohort Study.

RATIONALE: Sleep-disordered breathing (SDB) has been associated with total and cardiovascular mortality, but an association with cancer mortality has not been studied. Results from in vitro and animal studies suggest that intermittent hypoxia promotes cancer tumor growth. OBJECTIVES: The goal of the present study was to examine whether SDB is associated with cancer mortality in a community-based sample. METHODS: We used 22-year mortality follow-up data from the Wisconsin Sleep Cohort sample (n = 1,522). SDB was assessed at baseline with full polysomnography. SDB was categorized using the apnea-hypopnea index (AHI) and the hypoxemia index (percent sleep time below 90% oxyhemoglobin saturation). The hazards of cancer mortality across levels of SDB severity were compared using crude and multivariate analyses. MEASUREMENTS AND MAIN RESULTS: Adjusting for age, sex, body mass index, and smoking, SDB was associated with total and cancer mortality in a dose-response fashion. Compared with normal subjects, the adjusted relative hazards of cancer mortality were 1.1 (95% confidence interval [CI], 0.5-2.7) for mild SDB (AHI, 5-14.9), 2.0 (95% CI, 0.7-5.5) for moderate SDB (AHI, 15-29.9), and 4.8 (95% CI, 1.7-13.2) for severe SDB (AHI ≥ 30) (P-trend = 0.0052). For categories of increasing severity of the hypoxemia index, the corresponding relative hazards were 1.6 (95% CI, 0.6-4.4), 2.9 (95% CI, 0.9-9.8), and 8.6 (95% CI, 2.6-28.7). CONCLUSIONS: Our study suggests that baseline SDB is associated with increased cancer mortality in a community-based sample. Future studies that replicate our findings and look at the association between sleep apnea and survival after cancer diagnosis are needed.

The impact of ageing and sex on the association between sleepiness and sleep disordered breathing.

The aim of our study was to investigate age-related changes in sleepiness symptoms associated with sleep disordered breathing (SDB). Wisconsin Sleep Cohort participants were assessed using polysomnography, the Epworth Sleepiness Scale (ESS) and the multiple sleep latency test (MSLT). SDB was defined as an apnoea/hypopnoea index ≥15 events·h(-1), and sleepiness as ESS ≥10 and MSLT ≤5 min. Odds ratios were calculated using generalised estimating equations associating sleepiness with SDB, and conditional logistic regression examining changes in longitudinal sleepiness status (ESS only). Models were a priori stratified by sex. ESS was measured in 1,281 participants and MSLT in 998 at multiple time-points (ESS n=3,695; MSLT n=1,846). Significant interactions were found between SDB and age in males, but not females. The odds ratios modelled for sleepiness in a 40-yr-old male with SDB were significant compared to a male without SDB (ESS 2.1 and MSLT 2.9); however, these associations were not significant at 60 yrs of age. The within-subject odds ratio for sleepiness was also significant at 40 yrs of age (OR 3.4), but not at 60 yrs of age. The age-related reductions in the association between sleepiness and SDB may have clinical implications for the diagnosis and treatment of SDB in older people as sleepiness is often used as a therapeutic target.

Effects of sleep-disordered breathing on cerebrovascular regulation: A population-based study.

RATIONALE: Cerebrovascular regulation is impaired in patients with moderate to severe obstructive sleep apnea; however, it is unknown whether this impairment exists in individuals with less severe sleep-disordered breathing. OBJECTIVES: To test the hypothesis that cerebrovascular responses to hypercapnia are attenuated in a nonclinical population-based cohort. METHODS: A rebreathing test that raised end-tidal CO2 tension by 10 mm Hg was performed during wakefulness in 373 participants of the Wisconsin Sleep Cohort. MEASUREMENTS AND MAIN RESULTS: We measured cerebral flow velocity (transcranial Doppler ultrasound); heart rate (electrocardiogram); blood pressure (photoplethysmograph); ventilation (pneumotachograph); and end-tidal CO2 (expired gas analysis). Cerebrovascular CO2 responsiveness was quantified as the slope of the linear relationship between flow velocity and end-tidal CO2 during rebreathing. Linear regression analysis was performed using cerebrovascular CO2 responsiveness as the outcome variable. Main independent variables were the apnea-hypopnea index and the mean level of arterial oxygen saturation during sleep. We observed a positive correlation between cerebrovascular CO2 responsiveness and the mean level of oxygen saturation during sleep that was statistically significant in unadjusted analysis and after adjustment for known confounders and the increase in arterial pressure during rebreathing. Each 5% decrease in Sa(O2) during sleep predicted a decrease in cerebrovascular reactivity of 0.4 ± 0.2 cm/second/mm Hg P(ET)CO2. In contrast, the negative correlation between cerebrovascular CO2 responsiveness and apnea-hypopnea index was statistically significant only in the unadjusted analysis. CONCLUSIONS: Hypercapnic vasodilation in the cerebral circulation is blunted in individuals with sleep-disordered breathing. This impairment is correlated with hypoxemia during sleep.

Dissociation of obstructive sleep apnea from hypersomnolence and obesity in patients with stroke.

BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) is seldom considered in the diagnostic investigation in the poststroke period although it is a stroke risk factor and has adverse prognostic implications after stroke. One reason might be that widely used clinical criteria for detection of OSA in the general community are not applicable in patients with stroke. We hypothesized that patients with stroke report less sleepiness and are less obese than subjects from a community sample with the same severity of OSA. METHODS: We performed polysomnography in 96 consecutive patients with stroke admitted to a stroke rehabilitation unit and in a community sample of 1093 subjects without a history of stroke. We compared the degrees of subjective sleepiness assessed by the Epworth Sleepiness Scale and body mass index between the 2 samples according to OSA categories assessed by the frequency of apneas and hypopneas per hour of sleep (<5, no OSA; 5 to <15 mild OSA; and >or=15, moderate to severe OSA). RESULTS: Compared with the community sample, patients with stroke with OSA had significantly lower Epworth Sleepiness Scale scores and body mass index for mild OSA (Epworth Sleepiness Scale 9.3+/-0.3 versus 5.6+/-0.5, P<0.001 and body mass index 33.1+/-0.5 versus 28.5+/-1.1, P<0.048) and for moderate to severe OSA (Epworth Sleepiness Scale 9.7+/-0.4 versus 7.1+/-0.9, P=0.043 and body mass index 36.4+/-0.8 versus 27.2+/-0.8 kg/m(2), P<0.025). CONCLUSIONS: For a given severity of OSA, patients with stroke had less daytime sleepiness and lower body mass index than subjects without stroke. These factors may make the diagnosis of OSA elusive in the poststroke period and preclude many such patients from the potential benefits of OSA therapy.

Prospective associations of insomnia markers and symptoms with depression.

Whether insomnia, a known correlate of depression, predicts depression longitudinally warrants elucidation. The authors examined 555 Wisconsin Sleep Cohort Study participants aged 33-71 years without baseline depression or antidepressant use who completed baseline and follow-up overnight polysomnography and had complete questionnaire-based data on insomnia and depression for 1998-2006. Using Poisson regression, they estimated relative risks for depression (Zung scale score > or =50) at 4-year (average) follow-up according to baseline insomnia symptoms and polysomnographic markers. Twenty-six participants (4.7%) developed depression by follow-up. Having 3-4 insomnia symptoms versus none predicted depression risk (age-, sex-, and comorbidity-adjusted relative risk (RR) = 3.2, 95% confidence interval: 1.1, 9.6). After multiple adjustments, frequent difficulty falling asleep (RR = 5.3, 95% confidence interval: 1.1, 27.9) and polysomnographically assessed (upper or lower quartiles) sleep latency, continuity, and duration (RRs = 2.2-4.7; P's < or = 0.05) predicted depression. Graded trends (P-trend < or = 0.05) were observed with increasing number of symptoms, difficulty falling asleep, and difficulty returning to sleep. Given the small number of events using Zung > or =50 (depression cutpoint), a limitation that may bias multivariable estimates, continuous depression scores were analyzed; mean values were largely consistent with dichotomous findings. Insomnia symptoms or markers increased depression risk 2.2- to 5.3-fold. These results support prior findings based on self-reported insomnia and may extend similar conclusions to objective markers. Heightened recognition and treatment of insomnia may prevent subsequent depression.

Extreme morning chronotypes are often familial and not exceedingly rare: the estimated prevalence of advanced sleep phase, familial advanced sleep phase, and advanced sleep-wake phase disorder in a sleep clinic population.

STUDY OBJECTIVES: Report the first prevalence estimates of advanced sleep phase (ASP), familial advanced sleep phase (FASP), and advanced sleep-wake phase disorder (ASWPD). This can guide clinicians on the utility of screening for extreme chronotypes both for clinical decision-making and to flag prospective participants in the study of the genetics and biology of FASP. METHODS: Data on morning or evening sleep schedule preference (chronotype) were collected from 2422 new patients presenting to a North American sleep center over 9.8 years. FASP was determined using a severity criterion that has previously identified dominant circadian mutations in humans. All patients were personally seen and evaluated by one of the authors (C.R.J.). RESULTS: Our results demonstrate an ASP prevalence of 0.33%, an FASP prevalence of 0.21%, and an ASWPD prevalence of at least 0.04%. Most cases of young-onset ASP were familial. CONCLUSIONS: Among patients presenting to a sleep clinic, conservatively 1 out of every 300 patients will have ASP, 1 out of every 475 will have FASP, and 1 out of every 2500 will have ASWPD. This supports obtaining a routine circadian history and, for those with extreme chronotypes, obtaining a family history of circadian preference. This can optimize treatment for evening sleepiness and early morning awakening and lead to additional circadian gene discovery. We hope these findings will lead to improved treatment options for a wide range of sleep and medical disorders in the future.

Longitudinal association of sleep-disordered breathing and nondipping of nocturnal blood pressure in the Wisconsin Sleep Cohort Study.

STUDY OBJECTIVES: The association of sleep-disordered breathing (SDB) and blunting of normal nocturnal lowering of blood pressure (BP) (nondipping) has only been examined cross-sectionally. The purpose of this study is to investigate whether SDB is prospectively associated with nondipping. METHODS: The longitudinal association between SDB and incident nondipping was examined in a subsample of 328 adults enrolled in the Wisconsin Sleep Cohort Study who completed 2 or more 24-hour ambulatory BP studies over an average of 7.2 years of follow-up. SDB identified by baseline in-laboratory polysomnography was defined by apnea-hypopnea index (AHI) categories. Systolic and diastolic nondipping was defined by systolic and diastolic sleep-wake BP ratios > 0.9. All models were adjusted for age, sex, body mass index at baseline and follow-up, smoking, alcohol consumption, hypertension, sleep time, length of follow-up time, and antihypertensive medication use. RESULTS: There was a dose-response increased odds of developing systolic nondipping in participants with SDB. The adjusted odds ratios (95% confidence interval) of incident systolic nondipping for baseline AHI 5 to < 15 and AHI > or = 15, versus AHI < 5, were 3.1 (1.3-7.7) and 4.4 (1.2-16.3), respectively (P trend = 0.006). The adjusted odds ratios (95% confidence interval) of incident diastolic nondipping for corresponding SDB categories were not statistically significant: 2.0 (0.8-5.6) and 1.3 (0.2-7.1). CONCLUSIONS: Our longitudinal findings of a dose-response increase in development of systolic nondipping of BP with severity of SDB at baseline in a population-based sample provide evidence consistent with a causal link. Nocturnal systolic nondipping may be a mechanism by which SDB contributes to increased cardiovascular disease.

Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort.

BACKGROUND: Sleep-disordered breathing (SDB) is a treatable but markedly under-diagnosed condition of frequent breathing pauses during sleep. SDB is linked to incident cardiovascular disease, stroke, and other morbidity. However, the risk of mortality with untreated SDB, determined by polysomnography screening, in the general population has not been established. METHODS: An 18-year mortality follow-up was conducted on the population-based Wisconsin Sleep Cohort sample (n = 1522), assessed at baseline for SDB with polysomnography, the clinical diagnostic standard. SDB was described by the number of apnea and hypopnea episodes/hour of sleep; cutpoints at 5, 15 and 30 identified mild, moderate, and severe SDB, respectively. Cox proportional hazards regression was used to estimate all-cause and cardiovascular mortality risks, adjusted for potential confounding factors, associated with SDB severity levels. RESULTS: All-cause mortality risk, adjusted for age, sex, BMI, and other factors was significantly increased with SDB severity. The adjusted hazard ratio (HR, 95% CI) for all-cause mortality with severe versus no SDB was 3.0 (1.4,6.3). After excluding persons who had used CPAP treatment (n = 126), the adjusted HR (95% CI) for all-cause mortality with severe versus no SDB was 3.8 (1.6,9.0); the adjusted HR (95% CI) for cardiovascular mortality was 5.2 (1.4,19.2). Results were unchanged after accounting for daytime sleepiness. CONCLUSIONS: Our findings of a significant, high mortality risk with untreated SDB, independent of age, sex, and BMI underscore the need for heightened clinical recognition and treatment of SDB, indicated by frequent episodes of apnea and hypopnea, irrespective of symptoms of sleepiness.

Periodic limb movements in sleep: Prevalence and associated sleepiness in the Wisconsin Sleep Cohort.

OBJECTIVES: Periodic limb movements in sleep (PLMS) are thought to be prevalent in elderly populations, but their impact on quality of life remains unclear. We examined the prevalence of PLMS, impact of age on prevalence, and association between PLMS and sleepiness. METHODS: We identified limb movements in 2335 Wisconsin Sleep Cohort polysomnograms collected over 12 years. Prevalence of periodic limb movement index (PLMI) ≥15 was calculated at baseline (n = 1084). McNemar's test assessed changes in prevalence over time. Association of sleepiness and PLMS evaluated using linear mixed modeling and generalized estimating equations. Models adjusted for confounders. RESULTS: Prevalence of PLMI ≥15 at baseline was 25.3%. Longitudinal prevalence increased significantly with age (p = 2.97 × 10-14). Sleepiness did not differ significantly between PLMI groups unless stratified by restless legs syndrome (RLS) symptoms. The RLS+/PLM+ group was sleepier than the RLS+/PLM- group. Multiple Sleep Latency Test trended towards increased alertness in the RLS-/PLM+ group compared to RLS-/PLM-. CONCLUSIONS: A significant number of adults have PLMS and prevalence increased with age. No noteworthy association between PLMI category and sleepiness unless stratified by RLS symptoms. SIGNIFICANCE: Our results indicate that RLS and PLMS may have distinct clinical consequences and interactions that can help guide treatment approach.

Correlates of sleep-onset REM periods during the Multiple Sleep Latency Test in community adults.

The diagnosis of narcolepsy without documented cataplexy is based on the observation of two or more sleep-onset REM periods (SOREMPs) during the Multiple Sleep Latency Test (MSLT). We report on the prevalence and correlates of SOREMPs in the community-based Wisconsin Sleep Cohort Study. MSLTs were conducted following nocturnal polysomnography (NPSG) and daily sleep diaries in 289 males and 267 females (age 35-70, 97% Caucasians). Multiple SOREMPs were observed in 13.1% of males and 5.6% of females. An MSLT mean sleep latency < or =8 min and > or =2 SOREMPs (diagnostic of narcolepsy) was observed in 5.9% (males) and 1.1% (females), all without cataplexy. Because of significant sex interactions, analyses were stratified by sex. Increased prevalence of HLA-DQB1*0602, a marker of narcolepsy, was observed in males but not in females with > or =2 SOREMPs. Males with multiple SOREMPs compared with those with no SOREMPs had shorter rapid eye movement (REM) latency during NPSG, were sleepier on the MSLT and reported increased sleepiness, hypnagogic hallucinations and cataplexy-like symptoms, suggesting a narcolepsy-like phenotype. In males only, the occurrence of SOREMPs increased with shift work and some indirect markers of sleep restriction, such as shorter sleep a day before NPSG. SOREMPs were unrelated to age, body mass index, depression (Zung Scale), anxiety (State-Trait Anxiety Scale) and the number of apnea and hypopnea events per hour of sleep (AHI), but were associated with decreased mean lowest oxygen saturation in males. Finally, we found that both males and females with SOREMPs reported taking more antidepressants, but those were of the types known not to suppress REM sleep. These results suggest a high prevalence of narcolepsy without cataplexy, as defined by the International Classification of Sleep Disorders, and/or a large number of false-positives for the MSLT.

Sleepiness and sleep in patients with both systolic heart failure and obstructive sleep apnea.

BACKGROUND: Adverse effects of obstructive sleep apnea (OSA), including sleep deprivation, can contribute to the progression of heart failure. The usual indication to diagnose and treat sleep apnea is subjective sleepiness. Previous studies suggest that patients with both heart failure and obstructive sleep apnea often do not complain of sleepiness, albeit their sleep time may be reduced. Therefore, we tested the hypothesis that patients with heart failure have less sleepiness and sleep less compared with subjects without heart failure for a given severity of OSA. METHODS: Sleepiness assessed with the Epworth Sleepiness Scale and sleep structure measured with polysomnography were compared among 155 consecutive patients with heart failure and from a random community sample (n = 1139) according to categories of the apnea-hypopnea index (<5, no OSA; 5-14, mild OSA; and > or =15, moderate to severe OSA). RESULTS: Compared with the community sample, for any given severity of OSA, patients with heart failure had lower mean +/- SE Epworth Sleepiness Scale scores (7.1 +/- 0.4 vs 8.3 +/- 0.2 [P = .005]; 6.7 +/- 0.7 vs 9.2 +/- 0.3 [P < .001]; and 7.8 +/- 0.7 vs 9.8 +/- 0.4 [P = .01]), indicating less sleepiness despite sleeping less (total sleep time mean +/- SE [in minutes]: 306 +/- 7 vs 384 +/- 2, 295 +/- 19 vs 384 +/- 5, and 285 +/- 13 vs 359 +/- 7 for no, mild, and moderate to severe OSA, respectively; P < .001 for all comparisons). CONCLUSIONS: Patients with heart failure have less subjective daytime sleepiness compared with individuals from a community sample, despite significantly reduced sleep time, whether or not they have OSA. In patients with heart failure, the absence of subjective sleepiness is not a reliable means of ruling out OSA.

Longitudinal associations of hypersomnolence and depression in the Wisconsin Sleep Cohort Study.

BACKGROUND: Hypersomnolence is common in depression, however longitudinal associations of excessive daytime sleepiness (EDS), long habitual sleep duration, and objective sleep propensity with depressive symptomatology are not well established. METHODS: Data from adults participating in the Wisconsin Sleep Cohort Study who had multiple assessments at 4-year intervals were utilized in analyses. Conditional (intrasubject) logistic regression estimated the likelihood of development of depression and three primary hypersomnolence measures: subjective EDS [Epworth Sleepiness Scale (ESS) >10], habitual sleep duration ≥9h/day, and increased physiological sleep propensity [multiple sleep latency test (MSLT) mean sleep latency <8min]. RESULTS: After adjusting for all covariates, the odds for development of depression were significantly increased 1.67-fold (95% CI 1.02-2.73, p=0.04) in participants who also developed subjective EDS. However, development of increased physiological sleep propensity on the MSLT was associated with a trend towards reduced odds for development of depression (odds ratio 0.50, 95% CI 0.24-1.06, p=0.07). No significant longitudinal association between excessive sleep duration and depression was observed. LIMITATIONS: Depression was not verified by psychiatric interview and an objective measure of sleep duration was not utilized. CONCLUSIONS: Our results demonstrate a significant longitudinal association between increased subjective EDS and depression. However, increased physiological sleep propensity on the MSLT was paradoxically marginally protective against the development of depression. Further research is indicated to determine the mechanism underling divergent effects of various aspects of hypersomnolence on the course of mood disorders.

Breathing Disturbances Without Hypoxia Are Associated With Objective Sleepiness in Sleep Apnea.

Study Objectives: To determine whether defining two subtypes of sleep-disordered breathing (SDB) events-with or without hypoxia-results in measures that are more strongly associated with hypertension and sleepiness. Methods: A total of 1022 participants with 2112 nocturnal polysomnograms from the Wisconsin Sleep Cohort were analyzed with our automated algorithm, developed to detect breathing disturbances and desaturations. Breathing events were time-locked to desaturations, resulting in two indices-desaturating (hypoxia-breathing disturbance index [H-BDI]) and nondesaturating (nonhypoxia-breathing disturbance index [NH-BDI]) events-regardless of arousals. Measures of subjective (Epworth Sleepiness Scale) and objective (2981 multiple sleep latency tests from a subset of 865 participants) sleepiness were analyzed, in addition to clinically relevant clinicodemographic variables. Hypertension was defined as BP ≥ 140/90 or antihypertensive use. Results: H-BDI, but not NH-BDI, correlated strongly with SDB severity indices that included hypoxia (r ≥ 0.89, p ≤ .001 with 3% oxygen-desaturation index [ODI] and apnea hypopnea index with 4% desaturations). A doubling of desaturation-associated events was associated with hypertension prevalence, which was significant for ODI but not H-BDI (3% ODI OR = 1.06, 95% CI = 1.00-1.12, p < .05; H-BDI OR 1.04, 95% CI = 0.98-1.10) and daytime sleepiness (ß = 0.20 Epworth Sleepiness Scale [ESS] score, p < .0001; ß = -0.20 minutes in MSL on multiple sleep latency test [MSLT], p < .01). Independently, nondesaturating event doubling was associated with more objective sleepiness (ß = -0.52 minutes in MSL on MSLT, p < .001), but had less association with subjective sleepiness (ß = 0.12 ESS score, p = .10). In longitudinal analyses, baseline nondesaturating events were associated with worsening of H-BDI over a 4-year follow-up, suggesting evolution in severity. Conclusions: In SDB, nondesaturating events are independently associated with objective daytime sleepiness, beyond the effect of desaturating events.

Prevalence and correlates of restless legs syndrome symptoms in the Wisconsin Sleep Cohort.

BACKGROUND AND PURPOSE: The aim of this study was to estimate the prevalence of restless legs syndrome (RLS) symptoms in the US adult population and to relate frequency of RLS symptoms to self-reported general health, depressive and anxiety symptoms, daytime sleepiness, and cardiovascular disease. PATIENTS AND METHODS: Data were obtained from a survey, conducted in 2002, of 2821 participants in the Wisconsin Sleep Cohort, a prospective community-based epidemiology study. Classification of RLS symptoms was based on the following four symptoms at the 2002 survey: 'repeated urge to move your legs' and 'strange and uncomfortable feelings in the legs', 'when sitting or lying down' which occur at least weekly, 'get better when you get up and start walking' and 'disrupt your sleep'. RESULTS: Prevalence of RLS symptoms occurring at least weekly was 10.6%, with no statistical difference between males (9.9%) and females (11.2%). Individuals with symptoms of RLS occurring at least weekly were older than those without such symptoms (P<0.02). Those with Daily RLS symptoms had statistically more frequent excessive daytime sleepiness, poorer self-reported general health, an elevation in depressive and anxiety symptoms, and an increased prevalence of cardiovascular disease compared to those with no RLS symptoms. All of these associations were stronger in subjects with Daily RLS symptoms than those with RLS symptoms 1-6 times per week. CONCLUSIONS: RLS symptoms are associated with multiple physical and psychological indices of impaired health. Longitudinal studies are required to determine whether RLS symptoms are causally related to excessive daytime sleepiness, poor general health, elevated depression and anxiety symptoms, and cardiovascular disease.

Subjective and Objective Measures of Hypersomnolence Demonstrate Divergent Associations with Depression among Participants in the Wisconsin Sleep Cohort Study.

STUDY OBJECTIVES: To examine associations of depression with habitual sleep duration, daytime sleepiness, and objective sleep propensity in a nonclinical population. METHODS: Data from adults participating in the Wisconsin Sleep Cohort Study were utilized in analyses. There were 1,287 adults (3,324 observations) who were used in the analysis of subjective hypersomnolence measures; 1,155 adults (2,981 observations) were used in the analysis of objective sleep propensity assessed by the multiple sleep latency test (MSLT). Repeated-measures logistic regression estimated associations between presence of depression (defined as modified Zung Self-Rating Depression Scale ≥ 50 or use of antidepressant medications) and three primary hypersomnolence measures: subjective excessive daytime sleepiness (Epworth Sleepiness Scale [ESS] ≥ 11), self-reported sleep duration ≥ 9 h/d, and objective sleep propensity (MSLT mean sleep latency < 8 min). RESULTS: After adjusting for age, sex, body mass index, chronic medical conditions, sedative hypnotic medication use, caffeine, tobacco, and alcohol use, sleep disordered breathing, as well as insomnia and sleep duration when appropriate, estimated odd ratios (95% confidence interval) for depression were: 1.56 (1.31,1.86) for ESS ≥ 11; 2.01 (1.49, 2.72) for habitual sleep time ≥ 9 h; and 0.76 (0.63-0.92) for MSLT mean sleep latency < 8 min. CONCLUSIONS: Our results demonstrate divergent associations between subjective and objective symptoms of hypersomnolence and depression, with subjective sleepiness and excessive sleep duration associated with increased odds of depression, but objective sleep propensity as measured by the MSLT associated with decreased odds of depression. Further research is indicated to explain this paradox and the impact of different hypersomnolence measures on the course of mood disorders. COMMENTARY: A commentary on this article appears in this issue on page 467.

Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study.

BACKGROUND: Sleep-disordered breathing (SDB) is common, but largely undiagnosed in the general population. Information on demographic patterns of SDB occurrence and its predictive factors in the general population is needed to target high-risk groups that may benefit from diagnosis. METHODS: The sample comprised 5615 community-dwelling men and women aged between 40 and 98 years who were enrolled in the Sleep Heart Health Study. Data were collected by questionnaire, clinical examinations, and in-home polysomnography. Sleep-disordered breathing status was based on the average number of apnea and hypopnea episodes per hour of sleep (apnea-hypopnea index [AHI]). We used multiple logistic regression modeling to estimate cross-sectional associations of selected participant characteristics with SDB defined by an AHI of 15 or greater. RESULTS: Male sex, age, body mass index, neck girth, snoring, and repeated breathing pause frequency were independent, significant correlates of an AHI of 15 or greater. People reporting habitual snoring, loud snoring, and frequent breathing pauses were 3 to 4 times more likely to have an AHI of 15 or greater vs an AHI less than 15, but there were weaker associations for other factors with an AHI of 15 or greater. The odds ratios (95% confidence interval) for an AHI of 15 or greater vs an AHI less than 15 were 1.6 and 1.5, respectively, for 1-SD increments in body mass index and neck girth. As age increased, the magnitude of associations for SDB and body habitus, snoring, and breathing pauses decreased. CONCLUSIONS: A significant proportion of occult SDB in the general population would be missed if screening or case finding were based solely on increased body habitus or male sex. Breathing pauses and obesity may be particularly insensitive for identifying SDB in older people. A better understanding of predictive factors for SDB, particularly in older adults, is needed.

Association of low ferritin with PLM in the Wisconsin Sleep Cohort.

OBJECTIVE: The origins of periodic leg movements (PLMs), a strong correlate of restless legs syndrome (RLS), are uncertain. This study was performed to assess the relationship between PLMs and peripheral iron deficiency, as measured with ferritin levels corrected for inflammation. METHODS: We included a cross-sectional sample of a cohort study of 801 randomly selected people (n = 1008 assays, mean age 58.6 ± 0.3 years) from Wisconsin state employee agencies. A previously validated automatic detector was used to measure PLMs during sleep. The patients were categorized into RLS symptoms-positive and RLS symptoms-negative based on a mailed survey response and prior analysis. Analyses were performed using a linear model with PLM category above and below 15 PLM/h (periodic leg movement index, PLMI) as the dependent variable, and adjusting for known covariates, including previously associated single-nucleotide polymorphisms (SNPs) within BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD. Ferritin and C-reactive protein (CRP) levels were measured in serum, and ferritin levels corrected for inflammation using CRP levels. RESULTS: After controlling for cofactors, PLMI ≥ 15 was associated with low (≤50 ng/mL) ferritin levels (OR = 1.55, p = 0.020). The best model was found using quasi-least squares regression of ferritin as a function of PLMI, with an increase of 0.0034 PLM/h predicted by a decrease of 1 ng/mL ferritin (p = 0.00447). CONCLUSIONS: An association was found between low ferritin and greater PLMs in a general population of older adults, independent of genetic polymorphisms, suggesting a role of low iron stores in the expression of these phenotypes. Patients with high PLMI may require to be checked for iron deficiency.