@article {1523, title = {Relation of sleepiness to respiratory disturbance index: the Sleep Heart Health Study.}, journal = {Am J Respir Crit Care Med}, volume = {159}, year = {1999}, month = {1999 Feb}, pages = {502-7}, abstract = {

Obstructive sleep apnea syndrome is a well recognized cause of excessive sleepiness; however, the relation of sleepiness to mild sleep-disordered breathing (SDB), which affects as much as half the adult population, is uncertain. In order to explore this relation, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study, a longitudinal study of the cardiovascular consequences of SDB. The study sample comprises 886 men and 938 women, with a mean age of 65 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Sleep-disordered breathing was quantified by the respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, measured during in-home polysomnography. When RDI was categorized into four groups (< 5, 5 to < 15, 15 to < 30, >/= 30), a significantly progressive increase in mean ESS score was seen across all four levels of SDB, from 7.2 (4.3) in subjects with RDI < 5 to 9.3 (4.9) in subjects with RDI >/= 30 (p < 0.001). There was no significant modification of this effect by age, sex, body mass index, or evidence of chronic restriction of sleep time or periodic limb movement disorder. The percentage of subjects with excessive sleepiness, defined as an ESS score >/= 11, increased from 21\% in subjects with RDI < 5 to 35\% in those with RDI >/= 30 (p < 0. 001). We conclude that SDB is associated with excess sleepiness in community-dwelling, middle-aged and older adults, not limited to those with clinically apparent sleep apnea.

}, keywords = {Aged, Cardiovascular Diseases, Cross-Sectional Studies, Disorders of Excessive Somnolence, Female, Humans, Male, Middle Aged, Polysomnography, Respiration, Retrospective Studies, Severity of Illness Index, Sleep Apnea Syndromes, Surveys and Questionnaires}, issn = {1073-449X}, doi = {10.1164/ajrccm.159.2.9804051}, author = {Gottlieb, D J and Whitney, C W and Bonekat, W H and Iber, C and James, G D and Lebowitz, M and Nieto, F J and Rosenberg, C E} } @article {623, title = {Does snoring predict sleepiness independently of apnea and hypopnea frequency?}, journal = {Am J Respir Crit Care Med}, volume = {162}, year = {2000}, month = {2000 Oct}, pages = {1512-7}, abstract = {

Obstructive apneas and hypopneas during sleep are a well recognized cause of excessive daytime sleepiness. Snoring is also associated with excess sleepiness, although it is not known whether this reflects an independent effect of snoring or whether snoring is simply a marker for obstructive sleep apnea. To further explore the relation of snoring to sleepiness, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study. The study sample comprises 2,737 men and 3,040 women with a mean age of 64 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Snoring history was obtained via a self-completion questionnaire. The respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, was measured during in-home polysomnography. The ESS score increased progressively with increasing RDI, from a mean of 7.1 (4.2) in subjects with RDI < 1.5 to 8.8 (4.8) in subjects with RDI >/= 15 (p < 0.001). A progressive increase in ESS score was also seen across five categories of snoring frequency, from 6.4 (4.2) in current nonsnorers to 9.3 (4.8) in subjects who snored six to seven nights per week (p < 0.001). The prevalence of excessive daytime sleepiness, defined as an ESS score >/= 11, increased from 15\% in never-snorers to 39\% in those who snored six to seven nights per week. The relation of snoring to sleepiness was seen at all levels of RDI, with no significant change in the relation of snoring to ESS score after adjustment for RDI in multivariate models. The effects of snoring and RDI on sleepiness were little affected by adjustment for age, sex, race, body mass index, or questionnaire evidence of insufficient sleep time or nocturnal leg jerks or cramps. We conclude that both snoring and RDI are independently associated with excess sleepiness in community-dwelling, middle-aged and older adults.

}, keywords = {Adult, Aged, Arousal, Cohort Studies, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Polysomnography, Risk Factors, Sleep Apnea, Obstructive, Snoring, Wakefulness}, issn = {1073-449X}, doi = {10.1164/ajrccm.162.4.9911073}, author = {Gottlieb, D J and Yao, Q and Redline, S and Ali, T and Mahowald, M W} } @article {609, title = {Effects of varying approaches for identifying respiratory disturbances on sleep apnea assessment.}, journal = {Am J Respir Crit Care Med}, volume = {161}, year = {2000}, month = {2000 Feb}, pages = {369-74}, abstract = {

Varying approaches to measuring the respiratory disturbance index (RDI) may lead to discrepant estimates of the severity of sleep-disordered breathing (SDB). In this study, we assessed the impact of varying the use of corroborative data (presence and degree of desaturation and/or arousal) to identify hypopneas and apneas. The relationships among 10 RDIs defined by various definitions of apneas and hypopneas were assessed in 5,046 participants in the Sleep Heart Health Study (SHHS) who underwent overnight unattended 12-channel polysomnography (PSG). The magnitude of the median RDI varied 10-fold (i.e., 29.3 when the RDI was based on events identified on the basis of flow or volume amplitude criteria alone to 2.0 for an RDI that required an associated 5\% desaturation with events). The correlation between RDIs based on different definitions ranged from 0.99 to 0.68. The highest correlations were among RDIs that required apneas and hypopneas to be associated with some level of desaturation. Lower correlations were observed between RDIs that required desaturation as compared with RDIs defined on the basis of amplitude criteria alone or associated arousal. These data suggest that different approaches for measuring the RDI may contribute to substantial variability in identification and classification of the disorder.

}, keywords = {Adult, Aged, Aged, 80 and over, Arousal, Diagnosis, Differential, Female, Humans, Lung Volume Measurements, Male, Middle Aged, Observer Variation, Oxygen, Oxyhemoglobins, Polysomnography, Risk Factors, Sleep Apnea Syndromes}, issn = {1073-449X}, doi = {10.1164/ajrccm.161.2.9904031}, author = {Redline, S and Kapur, V K and Sanders, M H and Quan, S F and Gottlieb, D J and Rapoport, D M and Bonekat, W H and Smith, P L and Kiley, J P and Iber, C} } @article {662, title = {Echocardiographic features of the right heart in sleep-disordered breathing: the Framingham Heart Study.}, journal = {Am J Respir Crit Care Med}, volume = {164}, year = {2001}, month = {2001 Sep 15}, pages = {933-8}, abstract = {

The effect of sleep-disordered breathing (SDB) on right heart structure and function is controversial. Studies of patients referred for evaluation of possible sleep apnea have yielded conflicting results, and the impact of SDB on the right heart has not been investigated in the general population. We examined the echocardiographic features of subjects with SDB at the Framingham Heart Study site of the Sleep Heart Health Study. Of 1,001 polysomnography subjects, 90 with SDB defined as a respiratory disturbance index (RDI) score > 90th percentile (mean RDI = 42) were compared with 90 low-RDI subjects (mean RDI = 5) matched for age, sex, and body mass index. Right heart measurements, made without knowledge of clinical status, were compared between groups. The majority of the subjects were male (74\%). After multivariable adjustment, right ventricle (RV) wall thickness was significantly greater (p = 0.005) in subjects with SDB (0.78 +/- 0.02 cm) than in the low-RDI subjects (0.68 +/- 0.02 cm). Right atrial dimensions, RV dimensions, and RV systolic function were not found to be significantly different between subjects with SDB and the low-RDI subjects. We conclude that in this community-based study of SDB and right heart echocardiographic features, RV wall thickness was increased in subjects with SDB. Whether the RV hypertrophy observed in persons with SDB is associated with increased morbidity and mortality remains unknown.

}, keywords = {Adult, Age Factors, Aged, Cohort Studies, Cross-Sectional Studies, Data Interpretation, Statistical, Echocardiography, Female, Forced Expiratory Volume, Humans, Hypertrophy, Right Ventricular, Linear Models, Male, Middle Aged, Obesity, Observer Variation, Polysomnography, Prospective Studies, Sex Factors, Sleep Apnea Syndromes, Ventricular Function, Right, Vital Capacity}, issn = {1073-449X}, doi = {10.1164/ajrccm.164.6.2001092}, author = {Guidry, U C and Mendes, L A and Evans, J C and Levy, D and O{\textquoteright}Connor, G T and Larson, M G and Gottlieb, D J and Benjamin, E J} } @article {798, title = {APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study.}, journal = {Neurology}, volume = {63}, year = {2004}, month = {2004 Aug 24}, pages = {664-8}, abstract = {

BACKGROUND: Obstructive sleep apnea/hypopnea (OSAH) has a strong heritable component, although its genetic basis remains largely unknown. One epidemiologic study found a significant association between the APOE epsilon4 allele and OSAH in middle-aged adults, a finding that was not replicated in a cohort of elderly adults. The objective of this study was to further examine the association of the APOE epsilon4 allele with OSAH in a community-dwelling cohort, exploring age dependency of the association.

METHODS: A genetic association study was performed, nested within a prospective cohort study of the cardiovascular consequences of OSAH. Unattended, in-home nocturnal polysomnography was used to measure apnea-hypopnea index (AHI) in 1,775 participants age 40 to 100 years. OSAH was defined as an AHI > or = 15. The relation of APOE genotype to prevalent OSAH was analyzed using generalized estimating equations to account for non-independent observations of individuals from the same sibship.

RESULTS: At least one APOE epsilon4 allele was present in 25\% of subjects, with 1.3\% epsilon4/epsilon4 homozygotes. The prevalence of OSAH was 19\%. After adjustment for age, sex, and BMI, the presence of any APOE epsilon4 allele was associated with increased odds of OSAH (OR 1.41, 95\% CI 1.06 to 1.87, p = 0.02). The effect was approximately twice as great in subjects <75 (OR 1.61, CI 1.02 to 2.54) as in those > or =75 years old (OR 1.32, CI 0.91 to 1.90). Exploratory analyses revealed that the strongest effect of APOE epsilon4 was in subjects age <65 (OR 3.08, CI 1.43 to 6.64), and was stronger in those with hypertension or cardiovascular disease than in those without.

CONCLUSION: The APOE epsilon4 allele is associated with increased risk of OSAH, particularly in individuals under age 65. The mechanisms underlying this association are uncertain. Age-dependency of the APOE-OSAH association may explain previous conflicting results.

}, keywords = {Adult, Age Distribution, Aged, Aged, 80 and over, Alleles, Apolipoprotein E4, Apolipoproteins E, Cardiovascular Diseases, Cohort Studies, Comorbidity, Female, Genetic Predisposition to Disease, Genotype, Humans, Hyperlipidemias, Hypertension, Male, Middle Aged, Obesity, Polysomnography, Sleep Apnea, Obstructive, Smoking}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000134671.99649.32}, author = {Gottlieb, D J and DeStefano, A L and Foley, D J and Mignot, E and Redline, S and Givelber, R J and Young, T} } @article {6566, title = {Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.}, journal = {Mol Psychiatry}, volume = {20}, year = {2015}, month = {2015 Oct}, pages = {1232-9}, abstract = {

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 {\texttimes} 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 {\texttimes} 10(-4)). The strongest combined association was at rs1823125 (P=1.5 {\texttimes} 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

}, keywords = {Adult, African Americans, Aged, Dyssomnias, European Continental Ancestry Group, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Self Report, Sleep}, issn = {1476-5578}, doi = {10.1038/mp.2014.133}, author = {Gottlieb, D J and Hek, K and Chen, T-H and Watson, N F and Eiriksdottir, G and Byrne, E M and Cornelis, M and Warby, S C and Bandinelli, S and Cherkas, L and Evans, D S and Grabe, H J and Lahti, J and Li, M and Lehtim{\"a}ki, T and Lumley, T and Marciante, K D and P{\'e}russe, L and Psaty, B M and Robbins, J and Tranah, G J and Vink, J M and Wilk, J B and Stafford, J M and Bellis, C and Biffar, R and Bouchard, C and Cade, B and Curhan, G C and Eriksson, J G and Ewert, R and Ferrucci, L and F{\"u}l{\"o}p, T and Gehrman, P R and Goodloe, R and Harris, T B and Heath, A C and Hernandez, D and Hofman, A and Hottenga, J-J and Hunter, D J and Jensen, M K and Johnson, A D and K{\"a}h{\"o}nen, M and Kao, L and Kraft, P and Larkin, E K and Lauderdale, D S and Luik, A I and Medici, M and Montgomery, G W and Palotie, A and Patel, S R and Pistis, G and Porcu, E and Quaye, L and Raitakari, O and Redline, S and Rimm, E B and Rotter, J I and Smith, A V and Spector, T D and Teumer, A and Uitterlinden, A G and Vohl, M-C and Widen, E and Willemsen, G and Young, T and Zhang, X and Liu, Y and Blangero, J and Boomsma, D I and Gudnason, V and Hu, F and Mangino, M and Martin, N G and O{\textquoteright}Connor, G T and Stone, K L and Tanaka, T and Viikari, J and Gharib, S A and Punjabi, N M and R{\"a}ikk{\"o}nen, K and V{\"o}lzke, H and Mignot, E and Tiemeier, H} }