SLEEP

Pack, Allan I.; Platt, Alec B.; Pien, Grace W.

doi: 10.5665/sleep/31.8.1067pmid: N/A

Merlino, Giovanni; Serafini, Anna; Gigli, Gian Luigi

doi: 10.5665/sleep/31.8.1069pmid: N/A

Young, Terry; Finn, Laurel; Peppard, Paul E.; Szklo-Coxe, Mariana; Austin, Diane; Nieto, F. Javier; Stubbs, Robin; Hla, K. Mae

doi: 10.5665/sleep/31.8.1071pmid: N/A

AbstractBackground: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.

Marshall, Nathaniel S.; Wong, Keith K. H.; Liu, Peter Y.; Cullen, Stewart R. J.; Knuiman, Matthew W.; Grunstein, Ronald R.

doi: 10.5665/sleep/31.8.1079pmid: N/A

AbstractBackground:Previously published cohort studies in clinical populations have suggested that obstructive sleep apnea (OSA) is a risk factor for mortality associated with cardiovascular disease. However, it is unknown whether sleep apnea is an independent risk factor for all-cause mortality in a community-based sample free from clinical referral bias.Methods:Residents of the Western Australian town of Busselton underwent investigation with a home sleep apnea monitoring device (MESAM IV). OSA was quantified via the respiratory disturbance index (RDI). Mortality status was determined in 397/400 participants (99.3%) after up to 14 years (mean follow-up 13.4 years) by data matching with the Australian National Death Index and the Western Australian Death Register. Univariate analyses and multivariate Cox proportional hazards modelling were used to ascertain the association between sleep apnea and mortality after adjustment for age, gender, body mass index, mean arterial pressure, total cholesterol, high-density lipoprotein cholesterol, diabetes, and medically diagnosed angina in those free from heart attack or stroke at baseline (n = 380).Results:Among the 380 participants, 18 had moderate-severe OSA (RDI ≥15/hr, 6 deaths) and 77 had mild OSA (RDI 5 to <15/hr, 5 deaths). Moderate-to-severe OSA was independently associated with greater risk of all-cause mortality (fully adjusted hazard ratio [HR] = 6.24, 95% CL 2.01, 19.39) than non-OSA (n = 285, 22 deaths). Mild OSA (RDI 5 to <15/hr) was not an independent risk factor for higher mortality (HR = 0.47, 95% CL 0.17, 1.29).Conclusions:Moderate-to-severe sleep apnea is independently associated with a large increased risk of all-cause mortality in this community-based sample.

Gangwisch, James E.; Heymsfield, Steven B.; Boden-Albala, Bernadette; Buijs, Ruud M.; Kreier, Felix; Opler, Mark G.; Pickering, Thomas G.; Rundle, Andrew G.; Zammit, Gary K.; Malaspina, Dolores

doi: 10.5665/sleep/31.8.1087pmid:

Goodwin, Renee D.; Marusic, Andrej

doi: 10.5665/sleep/31.8.1097pmid: N/A

AbstractObjective:To determine the association between sleep, mental disorders, and suicidal ideation (SI) and suicide attempt (SA) among adults in the community.Design:Cross-sectional.Setting:National Comorbidity Survey (n = 8098).Participants:A representative sample of adults in the United States.Measurements and Results:Multiple logistic regression analyses were used to determine the association between usual number of hours of sleep during a 24-h period and SI and SA (past 12 months and lifetime). Analyses were adjusted for differences in demographic characteristics and comorbid mental disorders. Additional analyses examined the relationship between hours of sleep and the odds of SA among adults with SI, compared with SI without SA. Short sleep was associated with significantly increased odds of SI (OR 2.5, 95% CI: 1.6–3.9) and SA (OR 3.0, 95% CI: 1.4–6.4), and with SA among those with SI (past 12 months). These associations persisted after adjusting for differences in demographic characteristics and mental disorders, though the links between short sleep and SA among those with SI were no longer statistically significant after adjusting for panic, mood, and substance use disorders.Conclusions:Short sleep appears to be associated with increased likelihood of SI and SA, independent of the effects of comorbid mental disorders, among adults in the community. Among adults with SI, short sleep is associated with increased odds of SA, and this association seems largely related to the presence of panic attacks, mood, and substance use disorders. Future studies should investigate the nature of these relationships, and whether and how mental health problems may play a role.

Cross, Rebecca L.; Kumar, Rajesh; Macey, Paul M.; Doering, Lynn V.; Alger, Jeffry R.; Yan-Go, Frisca L.; Harper, Ronald M.

doi: 10.5665/sleep/31.8.1103pmid: N/A

AbstractStudy Objectives:Depressive symptoms are common in obstructive sleep apnea (OSA) patients, and brain injury occurs with both OSA and depression independently. The objective was to determine whether brain alterations in OSA bear relationships to depressive symptoms.Design:Cross-sectional study.Setting:University-based medical center.Participants:40 treatment-naive OSA subjects and 61 control subjects without diagnosed psychopathology.Interventions:None.Measurements and Results:Whole-brain maps of T2 relaxation time, a measure sensitive to injury, were calculated from magnetic resonance images, transformed to common space, and smoothed. Control and OSA groups were classified by Beck Depression Inventory (BDI)- II scores (≥12 symptomatic, <10 asymptomatic for depressive symptoms). The OSA group separated into 13 symptomatic (mean ± SD: BDI-II 21 ± 8; age 47.6 ± 11; apnea hypopnea index [AHI] 28.3 ± 17), and 27 asymptomatic (4 ± 3; 47.5 ± 8; 31.5 ± 16) subjects. The control group included 56 asymptomatic (BDI-II 2.5 ± 2.6; age 47.3 ± 9) subjects. Asymptomatic OSA subjects exhibited higher AHI. T2 maps were compared between groups (ANCOVA), with age and gender as covariates. Injury appeared in symptomatic vs asymptomatic OSA subjects in the mid- and anterior cingulate, anterior insular, medial pre-frontal, parietal, and left ventrolateral temporal cortices, left caudate nucleus, and internal capsule. Relative to asymptomatic controls, symptomatic OSA patients showed damage in the bilateral hippocampus and caudate nuclei, anterior corpus callosum, right anterior thalamus, and medial pons.Conclusions:Neural injury differed between OSA patients with and without depressive symptoms. Depressive symptoms may exacerbate injury accompanying OSA, or introduce additional damage in affective, cognitive, respiratory, and autonomic control regions.

Lessov-Schlaggar, Christina N.; Bliwise, Donald L.; Krasnow, Ruth E.; Swan, Gary E.; Reed, Terry

doi: 10.5665/sleep/31.8.1111pmid: N/A

AbstractStudy Objectives:Clinical rating scales, self-reports, and diagnostic instruments measuring depression often inquire about daytime fatigue and tiredness. Excessive daytime sleepiness refers specifically to the tendency to feel drowsy or fall asleep during waking hours and is considered conceptually and operationally independent from the fatigue, tiredness, and sleeping difficulties that characterize depression. The objective of this study was to examine whether daytime sleepiness assessed using the Epworth Sleepiness Scale and depressive symptoms assessed using the Geriatric Depression Scale are genetically related.Design/Setting:Cross-sectional data were collected via questionnaire in 1998-2000.Participants:Population-based sample of more than 5,000 male elderly twins aged 69-82 years old at the time of survey.Interventions:N/AMeasurements and Results:There was evidence for moderate heritability for daytime sleepiness (36.9%) and depressive symptoms (30.7%). There was evidence for a significant genetic correlation (0.40) between the 2 measures, suggesting that both daytime sleepiness and depressive symptoms have some genes in common. The genetic correlation was reduced to 0.21 after adjustment for several covariates.Conclusions:The results showed that the often reported phenotypic correlation between daytime sleepiness and depressive symptoms is due, in part, to modest overlap in genetic factors, at least in elderly men. However, the majority of individual variation in daytime sleepiness and depressive symptoms, in particular after covariate adjustment, was attributable to individual-specific environmental factors.

Mishima, Kazuo; Fujiki, Nobuhiro; Yoshida, Yasushi; Sakurai, Takeshi; Honda, Makoto; Mignot, Emmanuel; Nishino, Seiji

doi: 10.5665/sleep/31.8.1119pmid: N/A

AbstractStudy Objective:To determine whether hypocretin receptor gene ( hcrtR1 and hcrtR2) expression is affected after long-term hypocretin ligand loss in humans and animal models of narcolepsy.Design:Animal and human study. We measured hcrtR1 and hcrtR2 expression in the frontal cortex and pons using the RT-PCR method in murine models (8-week-old and 27-week-old orexin/ataxin-3 transgenic (TG) hypocretin cell ablated mice and wild-type mice from the same litter, 10 mice for each group), in canine models (8 genetically narcoleptic Dobermans with null mutations in the hcrtR2 , 9 control Dobermans, 3 sporadic ligand-deficient narcoleptics, and 4 small breed controls), and in humans (5 narcolepsy-cataplexy patients with hypocretin deficiency (average age 77.0 years) and 5 control subjects (72.6 years).Measurement and Results:27-week-old (but not 8-week-old) TG mice showed significant decreases in hcrtR1 expression, suggesting the influence of the long-term ligand loss on the receptor expression. Both sporadic narcoleptic dogs and human narcolepsy-cataplexy subjects showed a significant decrease in hcrtR1 expression, while declines in hcrtR2 expression were not significant in these cases. HcrtR2-mutated narcoleptic Dobermans (with normal ligand production) showed no alteration in hcrtR1 expression.Conclusions:Moderate declines in hcrtR expressions, possibly due to long-term postnatal loss of ligand production, were observed in hypocretin-ligand deficient narcoleptic subjects. These declines are not likely to be progressive and complete. The relative preservation of hcrtR2 expression also suggests that hypocretin based therapies are likely to be a viable therapeutic options in human narcolepsy-cataplexy.

Kapur, Vishesh K.; Resnick, Helaine E.; Gottlieb, Daniel J.; ,

doi: 10.5665/sleep/31.8.1127pmid: N/A

AbstractStudy Objectives:Epidemiologic studies that demonstrate increased risk of hypertension in persons with sleep disordered breathing indicate that only a minority of these persons report significant subjective sleepiness. Studies also suggest that presence of self-reported sleepiness may identify a subset of persons with sleep disordered breathing who are at greatest risk of cardiovascular sequelae, including hypertension. We explore whether self-reported sleepiness modifies the relationship between sleep disordered breathing and prevalent hypertension.Design:Cross-sectionalSetting:Multicenter studyParticipants:6046 subjects from the Sleep Heart Health StudyMeasurements:Polysomnography, systolic and diastolic blood pressure, antihypertensive medication use, questionnaire determined excessive sleepiness and Epworth Sleepiness Scale, and covariates.Results:The odds of hypertension at higher apnea hypopnea index categories were larger in participants identified as sleepy based on responses to a frequency of sleepiness question or the Epworth score. For example, for those with AHI ≥30 compared to AHI <1.5, the adjusted odds ratio for hypertension was 2.83 (1.33–6.04) among those reporting sleepiness ≥5 days per month, but only 1.22 (0.89–1.68) among those reporting less frequent daytime sleepiness. In adjusted logistic regression models, there was statistical evidence for effect modification by frequency of sleepiness (P = 0.033) of the association between apnea hypopnea index and hypertension. In adjusted models that included the Epworth score as a continuous variable, the interaction term fell slightly short of statistical significance (β = 0.010, P = 0.07).Conclusion:This study finds that the association of sleep disordered breathing with hypertension is stronger in individuals who report daytime sleepiness than in those who do not.