Sleep Apnea Syndromes: Gottlieb DJ

Collop NA, Anderson WM, Boehlecke B, Claman D, Goldberg R, Gottlieb DJ, Hudgel D, Sateia M, Schwab R, Anonymous00275. · Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21205, USA. · J Clin Sleep Med. · Pubmed #18198809 links to  free full text

Abstract: Based on a review of literature and consensus, the Portable Monitoring Task Force of the American Academy of Sleep Medicine (AASM) makes the following recommendations: unattended portable monitoring (PM) for the diagnosis of obstructive sleep apnea (OSA) should be performed only in conjunction with a comprehensive sleep evaluation. Clinical sleep evaluations using PM must be supervised by a practitioner with board certification in sleep medicine or an individual who fulfills the eligibility criteria for the sleep medicine certification examination. PM may be used as an alternative to polysomnography (PSG) for the diagnosis of OSA in patients with a high pretest probability of moderate to severe OSA. PM is not appropriate for the diagnosis of OSA in patients with significant comorbid medical conditions that may degrade the accuracy of PM. PM is not appropriate for the diagnostic evaluation of patients suspected of having comorbid sleep disorders. PM is not appropriate for general screening of asymptomatic populations. PM may be indicated for the diagnosis of OSA in patients for whom in-laboratory PSG is not possible by virtue of immobility, safety, or critical illness. PM may also be indicated to monitor the response to non-CPAP treatments for sleep apnea. At a minimum, PM must record airflow, respiratory effort, and blood oxygenation. The airflow, effort, and oximetric biosensors conventionally used for in-laboratory PSG should be used in PM. The Task Force recommends that PM testing be performed under the auspices of an AASM-accredited comprehensive sleep medicine program with written policies and procedures. An experienced sleep technologist/technician must apply the sensors or directly educate patients in sensor application. The PM device must allow for display of raw data with the capability of manual scoring or editing of automated scoring by a qualified sleep technician/technologist. A board certified sleep specialist, or an individual who fulfills the eligibility criteria for the sleep medicine certification examination, must review the raw data from PM using scoring criteria consistent with current published AASM standards. Under the conditions specified above, PM may be used for unattended studies in the patient's home. Afollow-up visit to review test results should be performed for all patients undergoing PM. Negative or technically inadequate PM tests in patients with a high pretest probability of moderate to severe OSA should prompt in-laboratory polysomnography.

Gottlieb DJ. · No affiliation provided · N Engl J Med. · Pubmed #16354898 No free full text.

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Gottlieb DJ. · No affiliation provided · Sleep. · Pubmed #16124655 No free full text.

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Gottlieb DJ. · No affiliation provided · N Engl J Med. · Pubmed #11832534 No free full text.

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Gottlieb DJ. · VA Boston Healthcare System and Boston University School of Medicine, Boston, Massachusetts 02118-2394, USA. · Curr Opin Pulm Med. · Pubmed #18812830 No free full text.

Abstract: PURPOSE OF REVIEW: The Sleep Heart Health Study began in 1994 as a prospective cohort study of cardiovascular disease. The results of longitudinal analysis are not yet available, but numerous analyses of cross-sectional data have been published. This review provides an overview of study results so far. RECENT FINDINGS: Recent findings covered in this review include a methodological study supporting the choice of a 4% oxyhemoglobin desaturation criterion for identification of hypopneas; evidence that sleepiness may modify the association of sleep apnea with hypertension; the association of sleep apnea with increased left ventricular mass in a pattern suggesting predominantly eccentric left ventricular hypertrophy; the association of restless legs syndrome with an increase in prevalent cardiovascular disease; and the results of a genome-wide association study of sleep and circadian phenotypes. SUMMARY: Although designed as a prospective cohort study, analysis of cross-sectional data from the Sleep Heart Health Study has contributed numerous insights to the field of sleep medicine.

Young T, Peppard PE, Gottlieb DJ. · Department of Population Health Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA. · Am J Respir Crit Care Med. · Pubmed #11991871 links to  free full text

Abstract: Population-based epidemiologic studies have uncovered the high prevalence and wide severity spectrum of undiagnosed obstructive sleep apnea, and have consistently found that even mild obstructive sleep apnea is associated with significant morbidity. Evidence from methodologically strong cohort studies indicates that undiagnosed obstructive sleep apnea, with or without symptoms, is independently associated with increased likelihood of hypertension, cardiovascular disease, stroke, daytime sleepiness, motor vehicle accidents, and diminished quality of life. Strategies to decrease the high prevalence and associated morbidity of obstructive sleep apnea are critically needed. The reduction or elimination of risk factors through public health initiatives with clinical support holds promise. Potentially modifiable risk factors considered in this review include overweight and obesity, alcohol, smoking, nasal congestion, and estrogen depletion in menopause. Data suggest that obstructive sleep apnea is associated with all these factors, but at present the only intervention strategy supported with adequate evidence is weight loss. A focus on weight control is especially important given the expanding epidemic of overweight and obesity in the United States. Primary care providers will be central to clinical approaches for addressing the burden and the development of cost-effective case-finding strategies and feasible treatment for mild obstructive sleep apnea warrants high priority.

DeMolles DA, Sparrow D, Gottlieb DJ, Friedman R. · VA Medical Center, Boston, MA 02130, USA. · Med Care. · Pubmed #15258478 No free full text.

Abstract: BACKGROUND: Continuous positive airway pressure (CPAP) is an effective therapy for obstructive sleep apnea syndrome (OSAS), although many patients have difficulty adhering to this therapy. The purpose of this study was to investigate the effectiveness of totally automated telephone technology in improving adherence to prescribed CPAP therapy. RESEARCH DESIGN: This pilot study was a randomized clinical trial in 30 patients being started on CPAP therapy for OSAS. Patients were randomly assigned to use of a computer telephone system designed to improve CPAP adherence (telephone-linked communications for CPAP [TLC-CPAP]) in addition to usual care (n = 15) or to usual care alone (n = 15) for a period of 2 months. TLC-CPAP is a computer-based system that monitors patients' self-reported behavior and provides education and reinforcement through a structured dialogue. MEASURES: A sleep symptoms checklist and the Functional Outcomes of Sleep Questionnaire were administered at study entry and at 2-month follow up. Hours of CPAP use at effective mask pressure were measured by the CPAP device, stored in its memory, and retrieved at the 2-month visit. RESULTS: At 2 months, patients randomized to TLC-CPAP had fewer reported sleep-related symptoms (9.4 vs. 13.4, P = 0.047) than those receiving usual care. The average nightly CPAP use in the TLC-CPAP group was 4.4 hours compared with 2.9 hours (P = 0.076) in the usual-care group. CONCLUSIONS: This pilot study suggests that patients with OSAS started on CPAP and a concurrently administered automated education and counseling system had better CPAP adherence and better control of OSAS symptoms.

Iber C, Redline S, Kaplan Gilpin AM, Quan SF, Zhang L, Gottlieb DJ, Rapoport D, Resnick HE, Sanders M, Smith P. · Department of Medicine, University of Minnesota, Minneapolis, MN, USA. · Sleep. · Pubmed #15164911 No free full text.

Abstract: STUDY OBJECTIVE: To compare polysomnographic recordings obtained in the home and laboratory setting. DESIGN AND SETTING: Multicenter study comparing unsupervised polysomnography performed in the participant's home with polysomnography supervised at an academic sleep disorders center, using a randomized sequence of study setting. Sleep Heart Health Study (SHHS) standardized polysomnographic recording and scoring techniques were used for both settings. PARTICIPANTS: 64 of 76 non-SHHS participants recruited from 7 SHHS field sites who had both a laboratory and home polysomnogram meeting acceptable quality criteria. MEASUREMENTS AND RESULTS: Median sleep duration was greater in the home than in the laboratory (375 vs 318 minutes, respectively, P < .0001) as was sleep efficiency (86% vs 82%, respectively, P < .0024). Very small, but significant increases in percentage of rapid eye movement sleep and decreases in stage 1 sleep were noted in the laboratory. Employing multiple definitions of respiratory disturbance index (RDI), median RDI was similar in both settings (for example, RDI with 3% desaturation: home 12.4, range 0.6-67; laboratory 9.5, range 0.1-93.4, P = .41). Quartile analysis of laboratory RDI showed moderate agreement with home RDI measurements. Based on the mean of laboratory and home RDI and using a cutpoint of 20, there was a biphasic distribution, with the RDI 3% above 20 being more common in the recordings performed in the laboratory than in the home and below 20 being more common in the recordings performed in the home than in the laboratory. These differences could not be attributed to quality of recording, age, sex, or body mass index. CONCLUSIONS: Using SHHS methodology, median RDI was similar in the unattended home and attended laboratory setting with differences of small magnitude in some sleep parameters. Differences in RDI between settings resulted in a rate of disease misclassification that is similar to repeated studies in the same setting.

Gottlieb DJ, Young TB. · VA Boston Healthcare System and Boston University School of Medicine, Boston, MA 02118-2394, USA. · Sleep. · Pubmed #19544745 No free full text.

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Kapur VK, Resnick HE, Gottlieb DJ, Anonymous00025. · Department of Medicine, University of Washington, Seattle, WA, USA. · Sleep. · Pubmed #18714785 links to  free full text

Abstract: STUDY 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-sectional. SETTING: Multicenter study. PARTICIPANTS: 6046 subjects from the Sleep Heart Health Study. MEASUREMENTS: 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 > or =30 compared to AHI <1.5, the adjusted odds ratio for hypertension was 2.83 (1.33-6.04) among those reporting sleepiness > or =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 (beta = 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.

Stamatakis K, Sanders MH, Caffo B, Resnick HE, Gottlieb DJ, Mehra R, Punjabi NM. · Johns Hopkins University, Baltimore, MD, USA. · Sleep. · Pubmed #18652097 links to  free full text

Abstract: STUDY OBJECTIVES: Commonly used definitions of sleep-disordered breathing (SDB) are based on identifying discrete events of breathing abnormalities during sleep that are accompanied by an oxyhemoglobin desaturation (delta SaO2) of at least 4%. However, it is not known whether disordered breathing events with oxyhemoglobin desaturation less than 4% are associated with clinical sequelae such as abnormalities in fasting glycemia. DESIGN: Cross-sectional study. SUBJECTS AND SETTING: Participants from the Sleep Heart Health Study (SHHS) with a fasting glucose measurement made within a year of the baseline polysomnogram. MEASUREMENTS AND RESULTS: SDB severity was defined using the apnea-hypopnea index (AHI) and the hypopnea index (HI) by counting events with different levels of oxyhemoglobin desaturation (0.0%-1.9%, 2.0%-2.9%, 3.0%-3.9%, > or = 4.0%). Fasting glucose levels were used to classify individuals into normal (<100 mg/dL), impaired (100-125 mg/dL), and diabetic (> or = 126 mg/dL) groups. Ordinal logistic regression was used to determine the adjusted relative odds of an abnormal glucose value across quartiles of the hypopnea index, independent of factors such as age, body mass index, waist circumference, and usual sleep duration. The prevalence of impaired and diabetic fasting glucose in the analytical sample was 32.9% and 5.8%, respectively. The covariate-adjusted relative odds of impaired or diabetic fasting glucose in the highest versus the lowest AHI quartile was 1.35 (95% CI: 1.04-1.76) for events with a delta SaO2 > or = 4.0%, 1.72 (95% CI: 1.20-2.48) for events with a delta SaO2 between 3.0%-3.9%, 1.41 (95% CI: 1.07-1.86) for events with a delta SaO2 between 2.0%-2.9%, and 1.07 (95% CI: 0.84-1.37) for events with a delta SaO2 between 0.0%-1.9%. The corresponding odds ratios for the HI were 1.47 (95% CI: 1.13-1.92), 2.25 (95% CI: 1.59-3.19), 1.44 (95% CI: 1.09-1.90), and 1.15 (95% CI: 0.90-1.47), respectively. CONCLUSIONS: The results of this study indicate that SDB events accompanied by oxyhemoglobin desaturation of between 2% to 4% are associated with fasting hyperglycemia. These findings suggest that milder degrees of SDB may predispose to adverse metabolic outcomes.

Wang W, Tretriluxana S, Redline S, Surovec S, Gottlieb DJ, Khoo MC. · Biomedical Engineering Department, University of Southern California, Los Angeles, CA 90089-0260, USA. · J Sleep Res. · Pubmed #18547374 No free full text.

Abstract: The goal of this study was to test the hypothesis that spectral indices of heart rate variability, such as high-frequency power (HFP), low-to-high frequency power (LHR), and their respiration-adjusted counterparts (HFPra, LHRra) are correlated with severity of sleep-disordered breathing (SDB), as quantified by the respiratory disturbance index (RDI). A total of 436 subjects, non-smoking, normotensive, and free of cardiovascular disease and diabetes were selected from the Sleep Heart Health Study (SHHS). Of these, 288 records with sufficiently high quality electrocardiogram signals were selected for further analysis [males/females: 221/67; age: 46.1 to 74.9 years; body mass index (BMI): 21.5 to 46.4 kg m(-2); 0.3 < RDI < 85.0(-1)]. From each polysomnogram, the respiration channels (thoracic and abdominal) and R-R interval (RRI) derived from the electrocardiogram were subjected to spectral analysis and autoregressive moving average modeling in consecutive 5-min segments. After adjusting for age and BMI, mean RRI was found to be negatively correlated with RDI in men in all sleep-wake states (all P < 0.001). HFP and HFPra were negatively correlated with RDI in men only during wakefulness (all P < 0.01). In women, LHR and LHRra were not correlated with RDI during wakefulness, but were positively correlated during non-rapid eye movement Stage 1 and 2 sleep (all P < 0.01). These findings suggest that the indices of cardiac autonomic control are correlated with SDB severity, but gender and state affect the nature of these correlations. In both genders, however, vagal modulation of heart rate increases while sympathetic modulation decreases from wakefulness to sleep.

Chami HA, Devereux RB, Gottdiener JS, Mehra R, Roman MJ, Benjamin EJ, Gottlieb DJ. · Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. · Circulation. · Pubmed #18458174 links to  free full text

Abstract: BACKGROUND: Whether sleep-disordered breathing (SDB) is a risk factor for left ventricular (LV) hypertrophy and dysfunction is controversial. We assessed the relation of SDB to LV morphology and systolic function in a community-based sample of middle-aged and older adults. METHODS AND RESULTS: The present study was a cross-sectional observational study of 2058 Sleep Heart Health Study participants (mean age 65+/-12 years; 58% women; 44% ethnic minorities) who had technically adequate echocardiograms. A polysomnographically derived apnea-hypopnea index (AHI) and hypoxemia index (percent of sleep time with oxyhemoglobin saturation < 90%) were used to quantify SDB severity. LV mass index was significantly associated with both AHI and hypoxemia index after adjustment for age, sex, ethnicity, study site, body mass index, current and prior smoking, alcohol consumption, systolic blood pressure, antihypertensive medication use, diabetes mellitus, and prevalent myocardial infarction. Adjusted LV mass index was 41.3 (SD 9.90) g/m(2.7) in participants with AHI < 5 (n=957) and 44.1 (SD 9.90) g/m(2.7) in participants with AHI > or = 30 (n=84) events per hour. Compared with participants with AHI < 5, those with AHI > or = 30 had an adjusted odds ratio of 1.78 (95% confidence interval 1.14 to 2.79) for LV hypertrophy. A higher AHI and higher hypoxemia index were also associated with larger LV diastolic dimension and lower LV ejection fraction, with a trend toward lower LV fractional shortening. LV wall thickness was significantly associated with the hypoxemia index but not with AHI. Left atrial diameter was not associated with either SDB measure. CONCLUSIONS: In a community-based cohort, SDB is associated with echocardiographic evidence of increased LV mass and reduced LV systolic function.

Thomas RJ, Mietus JE, Peng CK, Gilmartin G, Daly RW, Goldberger AL, Gottlieb DJ. · Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center Boston, MA 02215, USA. · Sleep. · Pubmed #18246985 links to  free full text

Abstract: STUDY OBJECTIVES: Complex sleep apnea is defined as sleep disordered breathing secondary to simultaneous upper airway obstruction and respiratory control dysfunction. The objective of this study was to assess the utility of an electrocardiogram (ECG)-based cardiopulmonary coupling technique to distinguish obstructive from central or complex sleep apnea. DESIGN: Analysis of archived polysomnographic datasets. SETTING: A laboratory for computational signal analysis. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The PhysioNet Sleep Apnea Database, consisting of 70 polysomnograms including single-lead ECG signals of approximately 8 hours duration, was used to train an ECG-based measure of autonomic and respiratory interactions (cardiopulmonary coupling) to detect periods of apnea and hypopnea, based on the presence of elevated low-frequency coupling (e-LFC). In the PhysioNet BIDMC Congestive Heart Failure Database (ECGs of 15 subjects), a pattern of "narrow spectral band" e-LFC was especially common. The algorithm was then applied to the Sleep Heart Health Study-I dataset, to select the 15 records with the highest amounts of broad and narrow spectral band e-LFC. The latter spectral characteristic seemed to detect not only periods of central apnea, but also obstructive hypopneas with a periodic breathing pattern. Applying the algorithm to 77 sleep laboratory split-night studies showed that the presence of narrow band e-LFC predicted an increased sensitivity to induction of central apneas by positive airway pressure. CONCLUSIONS: ECG-based spectral analysis allows automated, operator-independent characterization of probable interactions between respiratory dyscontrol and upper airway anatomical obstruction. The clinical utility of spectrographic phenotyping, especially in predicting failure of positive airway pressure therapy, remains to be more thoroughly tested.

Kushida CA, Nichols DA, Quan SF, Goodwin JL, White DP, Gottlieb DJ, Walsh JK, Schweitzer PK, Guilleminault C, Simon RD, Leary EB, Hyde PR, Holmes TH, Bloch DA, Green S, McEvoy LK, Gevins A, Dement WC. · Stanford Universit)y, Stanfbrd, CA, USA. · J Clin Sleep Med. · Pubmed #17561541 No free full text.

Abstract: STUDY OBJECTIVE: To assess the size, time course, and durability of the effects of long-term continuous positive airway pressure (CPAP) therapy on neurocognitive function, mood, sleepiness, and quality of life in patients with obstructive sleep apnea. DESIGN: Randomized, double-blinded, 2-arm, sham-controlled, multicenter, long-term, intention-to-treat trial of CPAP therapy. SETTING: Sleep clinics and laboratories at 5 university medical centers and community-based hospitals. Patients or Participants: Target enrollment is 1100 randomly assigned subjects across 5 clinical centers. INTERVENTIONS: Active versus sham (subtherapeutic) CPAP. Measurements and Results: A battery of conventional and novel tests designed to evaluate neurocognitive function, mood, sleepiness, and quality of life. CONCLUSIONS: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) is designed to study obstructive sleep apnea and test the effects of CPAP through a comprehensive, controlled, and long-term trial in a large sample of subjects with obstructive sleep apnea.

Patwardhan AA, Larson MG, Levy D, Benjamin EJ, Leip EP, Keyes MJ, Wang TJ, Gottlieb DJ, Vasan RS. · Boston University School of Medicine, Boston, MA, USA. · Sleep. · Pubmed #17068983 No free full text.

Abstract: STUDY OBJECTIVES: We hypothesized that alterations in cardiac hemodynamics associated with obstructive sleep apnea-hypopnea (OSAH) would be reflected in higher natriuretic peptide levels. We examined the association of OSAH with natriuretic peptides in a community-based sample. DESIGN: Cross-sectional, retrospective, observational study. SETTING: Framingham Heart Study Offspring Cohort and Sleep Heart Health Study. PARTICIPANTS: Community-based sample of 623 individuals. MEASUREMENTS: Full-montage home polysomnography was used to determine apnea-hypopnea index (AHI) and percentage of time with an oxyhemoglobin saturation < 90% (PctLt90). Sensitive immunoradiometric assays were used to measure plasma B-type (BNP) and N-terminal pro-atrial natriuretic peptide (NT-ANP). Multivariable regression was used to examine the relations between natriuretic peptides and indicators of OSAH, adjusting for age, sex, body mass index, and clinical covariates. RESULTS: No statistically significant relations between OSAH indices and BNP were observed in the multivariable model. Compared with an AHI < 5, relative levels of 1.20, 0.88, and 0.91 were observed forAHI categories 5-15, 15-30, >30 events per hour, respectively. For NT-ANP, no significant relations were seen with AHI in the multivariable model (relative levels of 0.98, 0.91, and 0.90). An inverse association was observed between NT-ANP and PctLt90 in age- and sex-adjusted models (relative levels of 0.93, 0.87, and 0.80), although this association became statistically nonsignificant after adjusting for body mass index. CONCLUSION: Lack of association of natriuretic peptides with OSAH indices suggests that undiagnosed OSAH may not be associated with major alterations in left ventricular function, as reflected in morning natriuretic peptide levels.

Gottlieb DJ, Redline S, Nieto FJ, Baldwin CM, Newman AB, Resnick HE, Punjabi NM. · The Pulmonary Center, Boston University School of Medicine, 715 Albany Street, R-304, Boston, MA 02118-2394, USA. · Sleep. · Pubmed #16944668 No free full text.

Abstract: STUDY OBJECTIVES: Limited experimental data suggest that sleep restriction acutely elevates blood pressure; however, little is known about the relationship between usual sleep duration and hypertension. This study assesses the relationship between usual sleep duration and hypertension in a community-based cohort. DESIGN: Cross-sectional observational study. SETTING: The Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing. PARTICIPANTS: Two thousand eight hundred thirteen men and 3097 women, aged 40 to 100 years. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Usual weekday and weekend sleep durations were obtained by questionnaire, and their weighted average were categorized as less than 6, 6 to less than 7, 7 to less than 8, 8 to less than 9, and 9 or more hours per night. Hypertension was defined as a systolic blood pressure of 140 mm Hg or greater, a diastolic blood pressure of 90 mm Hg or greater, or use of medication to treat hypertension. The relationship between sleep duration and hypertension was examined using categorical logistic regression with adjustment for age, sex, race, apnea-hypopnea index, and body mass index. Compared to subjects sleeping 7 to less than 8 hours per night, those sleeping less than 6 and between 6 and 7 hours per night had adjusted odds ratios for hypertension of 1.66 (95% confidence interval 1.35-2.04) and 1.19 (1.02-1.39), respectively, whereas those sleeping between 8 and 9 and 9 or more hours per night had adjusted odds ratios for hypertension of 1.19 (1.04-1.37) and 1.30 (1.04-1.62), respectively (p < .0001 for association of sleep duration with hypertension). These associations persisted when analyses were further adjusted for caffeine and alcohol consumption, current smoking, insomnia symptoms, depression symptoms, sleep efficiency, and prevalent diabetes mellitus or cardiovascular disease. CONCLUSIONS: Usual sleep duration above or below the median of 7 to less than 8 hours per night is associated with an increased prevalence of hypertension, particularly at the extreme of less than 6 hours per night.

Mehra R, Benjamin EJ, Shahar E, Gottlieb DJ, Nawabit R, Kirchner HL, Sahadevan J, Redline S, Anonymous00018. · Department of Medicine and Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA. · Am J Respir Crit Care Med. · Pubmed #16424443 links to  free full text

Abstract: RATIONALE: Sleep-disordered breathing recurrent intermittent hypoxia and sympathetic nervous system activity surges provide the milieu for cardiac arrhythmia development. OBJECTIVE: We postulate that the prevalence of nocturnal cardiac arrhythmias is higher among subjects with than without sleep-disordered breathing. METHODS: The prevalence of arrhythmias was compared in two samples of participants from the Sleep Heart Health Study frequency-matched on age, sex, race/ethnicity, and body mass index: (1) 228 subjects with sleep-disordered breathing (respiratory disturbance index>or=30) and (2) 338 subjects without sleep-disordered breathing (respiratory disturbance index<5). RESULTS: Atrial fibrillation, nonsustained ventricular tachycardia, and complex ventricular ectopy (nonsustained ventricular tachycardia or bigeminy or trigeminy or quadrigeminy) were more common in subjects with sleep-disordered breathing compared with those without sleep-disordered breathing: 4.8 versus 0.9% (p=0.003) for atrial fibrillation; 5.3 versus 1.2% (p=0.004) for nonsustained ventricular tachycardia; 25.0 versus 14.5% (p=0.002) for complex ventricular ectopy. Compared with those without sleep-disordered breathing and adjusting for age, sex, body mass index, and prevalent coronary heart disease, individuals with sleep-disordered breathing had four times the odds of atrial fibrillation (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.03-15.74), three times the odds of nonsustained ventricular tachycardia (OR, 3.40; 95% CI, 1.03-11.20), and almost twice the odds of complex ventricular ectopy (OR, 1.74; 95% CI, 1.11-2.74). A significant relation was also observed between sleep-disordered breathing and ventricular ectopic beats/h (p<0.0003) considered as a continuous outcome. CONCLUSIONS: Individuals with severe sleep-disordered breathing have two- to fourfold higher odds of complex arrhythmias than those without sleep-disordered breathing even after adjustment for potential confounders.

Kapur VK, Baldwin CM, Resnick HE, Gottlieb DJ, Nieto FJ. · Department of Medicine, University of Washington Sleep Disorders Center, Box 359803, 325 Ninth Avenue, Seattle, WA 98104, USA. · Sleep. · Pubmed #16171292 No free full text.

Abstract: BACKGROUND: Population-based studies suggest that complaints of sleepiness are absent in many individuals with sleep-disordered breathing. We investigated the prevalence of sleepiness as well as factors associated with sleepiness in individuals with moderate to severe sleep-disordered breathing (apnea-hypopnea index > or = 15). DESIGN: Cross-sectional study. SETTING: The Sleep Heart Health Study. PARTICIPANTS: Sleep Heart Health Study participants (N = 6440). MEASUREMENTS AND RESULTS: Sleepiness was defined as an Epworth Sleepiness Scale score >10 or a report of at least frequently feeling unrested or sleepy. Forty-six percent of participants with moderate to severe sleep-disordered breathing (n = 1149) reported sleepiness. Characteristics associated with sleepiness after adjustment for confounders included presence of respiratory disease, shorter self-reported weekday and weekend sleep, sleep durations, complaints of insufficient sleep, complaints of sleep maintenance insomnia, early morning awakening, habitual snoring, and complaints of awakening with leg cramps or leg jerks. Some respiratory polysomnography measures were associated with sleepiness, but sleep-stage percentages and measures of sleep disruption were not. CONCLUSIONS: In this community-based cohort, subjective sleepiness is absent in many individuals with significant sleep-disordered breathing. Comorbid conditions, including respiratory disease, sleep restriction, insomnia, and nocturnal leg complaints, are important risk factors for sleepiness in individuals with moderate to severe sleep-disordered breathing.

Gottlieb DJ, Chase C, Vezina RM, Heeren TC, Corwin MJ, Auerbach SH, Weese-Mayer DE, Lesko SM. · Department of Medicine, Slone Epidemiology Center, Boston University School of Medicine, Boston, Massachusetts 02118-2394, USA. · J Pediatr. · Pubmed #15480367 No free full text.

Abstract: OBJECTIVE: To assess the relation of sleep-disordered breathing (SDB) symptoms in children to neurocognitive function. STUDY DESIGN: A cross-sectional, population-based study of 205 5-year-old children. A parent-completed questionnaire was used to ascertain SDB symptoms, defined as frequent snoring, loud or noisy breathing during sleep, or witnessed sleep apnea. Polysomnography (PSG) data were available in 85% of children. Standardized neurocognitive tests were administered by a trained psychometrist unaware of the children's SDB status. Children with (n=61) and without SDB symptoms were compared using analysis of variance to adjust for demographic and respiratory health variables. RESULTS: Children with SDB symptoms scored significantly lower than those without SDB symptoms on tests of executive function (95.5 vs 99.9 on NEPSY Attention/Executive Core Domain, P=.02; 10.4 vs 11.2 on Wechsler Preschool and Primary Scale of Intelligence, Revised [WPPSI-R] Animal Pegs test, P=.03), memory (96.8 vs 103.0 on NEPSY Memory Domain, P=.02), and general intellectual ability (105.9 vs 111.7 on WPPSI-R Full Scale IQ, P=.02). There were no significant differences on a computerized continuous performance task. These findings persisted when children with PSG evidence of obstructive sleep apnea (OSA) were excluded from analysis. CONCLUSION: Even in the absence of OSA, SDB symptoms are associated with poorer executive function and memory skills and lower general intelligence in 5-year-old children.

Punjabi NM, Shahar E, Redline S, Gottlieb DJ, Givelber R, Resnick HE, Anonymous00373. · Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD21224, USA. · Am J Epidemiol. · Pubmed #15353412 links to  free full text

Abstract: Clinic-based studies suggest that sleep-disordered breathing (SDB) is associated with glucose intolerance and insulin resistance. However, in the available studies, researchers have not rigorously controlled for confounding variables to assess the independent relation between SDB and impaired glucose metabolism. The objective of this study was to determine whether SDB was associated with glucose intolerance and insulin resistance among community-dwelling subjects (n=2,656) participating in the Sleep Heart Health Study (1994-1999). SDB was characterized with the respiratory disturbance index and measurements of oxygen saturation during sleep. Fasting and 2-hour glucose levels measured during an oral glucose tolerance test were used to assess glycemic status. Relative to subjects with a respiratory disturbance index of less than 5.0 events/hour (the reference category), subjects with mild SDB (5.0-14.9 events/hour) and moderate to severe SDB (> or =15 events/hour) had adjusted odds ratios of 1.27 (95% confidence interval: 0.98, 1.64) and 1.46 (95% confidence interval: 1.09, 1.97), respectively, for fasting glucose intolerance (p for trend < 0.01). Sleep-related hypoxemia was also associated with glucose intolerance independently of age, gender, body mass index, and waist circumference. The results of this study suggest that SDB is independently associated with glucose intolerance and insulin resistance and may lead to type 2 diabetes mellitus.

Gottlieb DJ, DeStefano AL, Foley DJ, Mignot E, Redline S, Givelber RJ, Young T. · The Pulmonary Center, Boston University School of Medicine and VA Boston Healthcare System, MA 02118-2394, USA. · Neurology. · Pubmed #15326239 No free full text.

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.

Redline S, Kirchner HL, Quan SF, Gottlieb DJ, Kapur V, Newman A. · Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio, USA. · Arch Intern Med. · Pubmed #14980992 links to  free full text

Abstract: BACKGROUND: Polysomnography is used to assess sleep quality and to gauge the functional effect of sleep disorders. Few population-based data are available to estimate the variation in sleep architecture across the population and the extent to which sleep-disordered breathing (SDB), a common health condition, contributes to poor sleep independent of other factors. The objective of this study was to describe the population variability in sleep quality and to quantify the independent associations with SDB. METHODS: Cross-sectional analyses were performed on data from 2685 participants, aged 37 to 92 years, in a community-based multicenter cohort study. Dependent measures included the percentage time in each sleep stage, the arousal index, and sleep efficiency. Independent measures were age, sex, ethnicity, comorbidity status, and the respiratory disturbance index. RESULTS: Lighter sleep was found in men relative to women and in American Indians and blacks relative to other ethnic groups. Increasing age was associated with impaired sleep in men, with less consistent associations in women. Notably, women had, on average, 106% more slow wave sleep. Sleep-disordered breathing was associated with poorer sleep; however, these associations were generally smaller than associations with sex, ethnicity, and age. Current smokers had lighter sleep than ex-smokers or never smokers. Obesity had little effect on sleep. CONCLUSIONS: Sleep architecture varies with sex, age, ethnicity, and SDB. Individual assessment of the effect of SDB on sleep quality needs to account for other host characteristics. Men, but not women, show evidence of poorer sleep with aging, suggesting important sex differences in sleep physiology.

Gottlieb DJ, Vezina RM, Chase C, Lesko SM, Heeren TC, Weese-Mayer DE, Auerbach SH, Corwin MJ. · Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118-2394, USA. · Pediatrics. · Pubmed #14523179 links to  free full text

Abstract: OBJECTIVE: Sleep-disordered breathing (SDB) in children is reportedly associated with problem behaviors suggestive of attention-deficit/hyperactivity disorder; however, there are few data on the relation of SDB to problem behaviors in the general pediatric population. The goal of this study was to assess the prevalence of SDB symptoms in 5-year-old children and their relation to sleepiness and problem behaviors. METHODS: A population-based, cross-sectional survey was conducted of a birth cohort of children who were born in eastern Massachusetts. Subjects were 3019 5-year-old children (1551 boys, 1468 girls) who were enrolled in the Infant Care Practices Study and whose mothers were contacted within 3 months of their child's fifth birthday. A parent-completed questionnaire was used to ascertain the presence and intensity of snoring and other SDB symptoms and the presence of daytime sleepiness and problem behaviors. Parent-reported hyperactivity, inattention, and aggressiveness were each assessed by a single question that was validated against the Conners' Parent Rating Scale. SDB was defined as frequent or loud snoring; trouble breathing or loud, noisy breathing during sleep; or witnessed sleep apnea. RESULTS: Parent-reported hyperactivity (19%) and inattention (18%) were common, with aggressiveness (12%) and daytime sleepiness (10%) reported somewhat less often. SDB symptoms were present in 744 (25%) children. Compared with children without snoring or other symptoms of SDB, children with SDB symptoms were significantly more likely to have parent-reported daytime sleepiness (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.7-2.8) and problem behaviors, including hyperactivity (OR: 2.5; CI: 2.0-3.0), inattention (OR: 2.1; 95% CI: 1.7-2.6), and aggressiveness (OR: 2.1; 95% CI: 1.6-2.6). These associations remained significant after adjustment for sex, race/ethnicity, maternal education level, maternal marital status, household income, and respiratory health history. CONCLUSIONS: SDB symptoms are common in 5-year-old children and are associated with an increased risk of daytime sleepiness and with problem behaviors suggestive of attention-deficit/hyperactivity disorder.

Young T, Shahar E, Nieto FJ, Redline S, Newman AB, Gottlieb DJ, Walsleben JA, Finn L, Enright P, Samet JM, Anonymous00130. · Department of Population Health Sciences, University of Wisconsin, Madison, WI, USA. · Arch Intern Med. · Pubmed #11966340 links to  free full text

Abstract: 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.