Longtitudinal Changes In Sleep Structure: Implications For Health Outcomes
Naresh Punjabi, Associate Professor
Medicinejohns Hopkins University
Grant 5R01HL086862-02 from National Heart, Lung, And Blood Institute, IRG: ASG
Abstract: Advancing age is accompanied by several alterations in sleep-wake behavior including nocturnal sleep disruption and an increase in daytime sleep tendency. Age is also associated with a number of medical disorders that can impact sleep quality. Population-based data show that sleep-disordered breathing (SDB), a chronic condition that is characterized by profound alterations in sleep structure, is also common in middle- aged and older adults. Although the biology of sleep has been a topic of intense research, the distinct effects of age versus age-associated illness on sleep structure have not been adequately addressed. The overall objective of this application is to delineate the distinct effects of age and SDB on sleep structure and determine whether the alterations in sleep structure predict cardiovascular and non-cardiovascular endpoints, specifically daytime sleepiness and quality of life, across the adult life span. Novel analytical methods that draw upon the expertise of various scientific disciplines are proposed to analyze the electroencephalographic data collected during sleep to (1) characterize the independent effects of age and SDB on sleep structure; and (2) determine the role of sleep structure as a putative intermediate in the causal pathway toward cardiovascular and non-cardiovascular outcomes. The current application will utilize data collected by the Sleep Heart Health Study, a multi-center longitudinal study on the cardiovascular consequences of SDB. The investigative team, which spans multiple disciplines including epidemiology, biostatistics, sleep medicine, and the engineering sciences, brings the necessary expertise to examine trajectories of sleep structure with healthy aging and age-associated illnesses. The significance of this application is that it will make a valuable contribution by providing a better understanding of the mechanistic role of sleep in increasing the age-related vulnerability to various conditions that impact general health. Insight will also be gained into the degree to which other conditions such as cardiovascular and pulmonary disease impact sleep. Although basic ´mechanistic´ links cannot be directly addressed, questions related to which aspects of sleep (e.g., EEC activity, recurrent sleep-stage shift) best discriminate clinical outcomes. Finally, we expect to also provide new and much needed information on how factors such as gender and race influence sleep and quantify the adverse sleep-related effects of behaviors such alcohol use, cigarette smoking, and caffeine consumption
Keywords: aging, disease /disorder proneness /risk, sleep, sleep apnea cardiovascular disorder risk, longitudinal human study, quality of life, sleep disorder clinical research, electroencephalography, human data, human middle age (35-64), human old age (65+), polysomnography
Project start date: 2007-07-05
Project end date: 2011-06-30
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Grants awarded to Naresh Punjabi
Sleep Apnea And Longitudinal Changes In Glycemia And Inflammation In Older Men
Naresh Punjabi, Associate Professor
Medicinejohns Hopkins University
Grant 1R01HL089467-01A1 from National Heart, Lung, And Blood Institute, IRG: CIDO
Abstract: Though long part of our common wisdom, the fact that inadequate sleep quantity and quality lead to serious health implications have only recently come under scientific scrutiny. Many of the findings have been striking and frightful. Most germane, it is now evident that normal sleep and health are intimately related. People who sleep less or have sleep-disordered breathing (SDB) are at risk for a variety of complications including fasting hyperglycemia and systemic inflammation. SDB is a chronic condition characterized by recurrent collapse of the upper airway during sleep. It is a common disorder in the general population with prevalence estimates that steadily increase with age. In addition, chronic sleep loss has also become a pervasive problem with increasing number of adults of all ages sleeping less at night than ever before. Ultimately, the long-term goal of our proposed research is to understand the mechanisms by which SDB and chronic sleep debt lead to adverse health consequences. For the sake of expediency, frugality, and scientific rigor, we will examine how SDB and short sleep duration are associated with fasting hyperglycemia, insulin resistance, markers of systemic inflammation (i.e., CRP, IL-6, and TNF-1), adipocytokine secretion (leptin) and hypothalamic-pituitary-adrenal (HPA) activity (cortisol). To speed our process of discovery, we will utilize the infrastructure of on ongoing epidemiologic study (The MrOS study) to address the following two specific aims (1) To assess the cross-sectional and longitudinal associations between indices of SDB severity, glucose metabolism, systemic inflammation, and HPA activity; and (2) To delineate the cross-sectional and longitudinal associations between usual sleep duration, glucose metabolism, systemic inflammation, and HPA activity. The MrOS study is a multi-center cohort study of older men who have been closely followed for seven-year period. Participants have also undergone actigraphy for assessments of usual sleep patterns and polysomnography for the presence and severity of SDB. In addition, DXA- and CT-derived measures of total body and regional fat distribution, respectively, are also available. The current proposal aims to utilize this rich collection of data along with the availability of serum samples which were collected over multiple clinic visits. Together, the proposed studies will address not only whether sleep deprivation and SDB are associated with abnormalities in glucose metabolism and systemic inflammation but will also yield important insight into the basic physiologic mechanisms by which chronic sleep debt and SDB may lead to medical conditions such as hypertension, type 2 diabetes mellitus, and cardiovascular disease. PUBLIC HEALTH RELEVANCE The overall purpose this research proposal is to determine whether sleep apnea and short sleep duration are related to higher fasting glucose and insulin levels in older community-dwelling men. In addition, we also seek to determine whether men that have sleep apnea and habitually sleep less than other have abnormalities in their cortisol levels and other inflammatory markers that are known risk factors for cardiovascular disease
Project start date: 2008-06-15
Project end date: 2012-05-31
Naresh Punjabi, Associate Professor
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5U01HL053937-10 from National Heart, Lung, And Blood Institute, IRG: ZHL1
Abstract: The Sleep Heart Health Study (SHHS) was started in 1994 as a multicenter cohort study of the cardiovascular consequences of sleep-disordered breathing (SDB). The study s principal aims are to assess SDB as a risk factor for adverse cardiovascular outcomes, including incident CHD events, stroke, and hypertension, and accelerated increase in blood pressure with age. The SHHS protocol added an assessment of SDB to ongoing cohort studies of cardiovascular and other diseases, including the Framingham Offspring and Omni cohorts, the Hagerstown and Minneapolis/St. Paul sites of the Atherosclerosis Risk in Communities (ARIC) Study, the Hagerstown, Sacramento, and Pittsburgh sites of the Cardiovascular Health Study (CHS), the Strong Heart Study sites in South Dakota, Oklahoma, and Arizona, and cohort studies of respiratory disease in Tucson and of hypertension in New York. During its first four years (1994-1998), the SHHS was successfully started with full and high quality polysomnography (PSG) data obtained in the home from 6,440 participants and scored at the Central Reading Center. The SHHS cohort includes 3,039 men and 3,401 women 40 years of age or more, of whom 8.2 percent are African American, 9.6 percent are American Indian, 1.3 percent are Asian, and 4.2 percent are Hispanic. In addition to PSG, data collection covered snoring and sleepiness and quality of life (QOL). Outcome assessment protocols are in place for all cohorts and the second SHHS exam is now in progress. Initial cross-sectional findings show that SDB is common and associated with hypertension and self-reported cardiovascular disease (CVD). This application requests five years of additional support to continue the SHHS. Further follow-up is needed for sufficient power to test the primary SHHS hypotheses. Additionally, in Years 7-9, PSG will be repeated to further characterize SDB in the participants and to describe the natural history of SDB. During the first five years, the SHHS has shown that large-scale research on sleep, SDB, and disease risk can be conducted in the community. Follow-up of the SHHS cohort will provide the data needed to characterize the cardiovascular consequences of SDB, along with its natural history. This application describes plans for continued data collection and follow-up by the SHHS Field Centers. A separate application for continuation of the Reading Center is being submitted and a new Coordinating Center will be selected.
Keywords: cardiovascular disorder, disease /disorder proneness /risk, respiratory airflow disorder, sleep apnea, sleep disorder, cardiovascular disorder epidemiology, comorbidity, cooperative study, hypertension, longitudinal human study, clinical research, human subject, polysomnography
Project start date: 1994-09-30
Project end date: 2004-08-31
5U01HL053937-10 (2003): $15576
5U01HL053937-14 (2007): $1
5U01HL053937-12 (2005): $104588
2U01HL053937-11 (2004): $102559
The Effects Of Sleep Apnea On Metabolic Function
Naresh Punjabi, Associate Professor
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5R01HL075078-04 from National Heart, Lung, And Blood Institute, IRG: ZHL1
Abstract: Sleep apnea is a chronic condition associated with an increased risk of hypertension and cardiovascular disease. Recent data suggest that sleep apnea is also associated with metabolic dysfunction that is characterized by glucose intolerance and insulin resistance. Although several studies indicate that the association between sleep apnea and metabolic dysfunction is independent of confounders including obesity, it remains to be determined whether the association is causal. Moreover, whether intermittent hypoxemia and/or sleep fragmentation are in the putative causal pathway is unknown. The major objective of our proposal is to determine whether sleep apnea produces metabolic dysfunction and delineate the underlying mechanisms. Our primary hypothesis is that intermittent hypoxemia and recurrent arousals from sleep lead to acute and chronic changes in metabolic function. In Specific Aim 1, we will examine whether nighttime and daytime profiles of metabolic function differ between patients with sleep apnea and control subjects matched on age, race, gender, and obesity. We hypothesize that, compared to control subjects, patients with sleep apnea will demonstrate a) marked abnormalities in nighttime profiles of glucose, insulin, and insulin secretion rate; b) impairment in daytime glucose tolerance, insulin sensitivity, and glucose effectiveness; and c) an increase in sympathetic activity and serum levels of leptin, cortisol, IL-6, and TNF-ct that are independently correlated with the severity of intermittent hypoxemia and frequency of arousals. In Specific Aim 2, we will examine whether experimental sleep fragmentation and sleep apnea (sleep fragmentation with intermittent hypoxemia) alter metabolic dysfunction in normal subjects. We hypothesize that a) sleep fragmentation in normal individuals will alter nighttime profiles of glucose, insulin, and insulin secretion rate and worsen daytime measures of glucose tolerance, insulin resistance, and glucose effectiveness; b) intermittent hypoxemia in association with sleep fragmentation will potentiate the adverse effects of sleep fragmentation alone; and c) experimental sleep fragmentation and sleep apnea will increase sympathetic activity and serum levels of cortisol, leptin, TNF-alpha and IL-6 in association with impaired glucose homeostasis. Novel experimental paradigms have been developed to determine the independent roles of sleep fragmentation and sleep apnea on metabolic function. Given the epidemic of obesity and diabetes, understanding the role of sleep apnea as a risk factor for metabolic dysfunction has public health significance in terms of prevention and treatment of diabetes, hypertension, and cardiovascular disease.
Keywords: disease /disorder proneness /risk, metabolic syndrome, sleep apnea, arousal, cortisol, disease /disorder etiology, glucose tolerance, hypoxia, insulin, insulin sensitivity /resistance, interleukin 6, leptin, metabolism, pathologic process, tumor necrosis factor alpha, blood chemistry, clinical research, human subject, patient oriented research, polysomnography
Project start date: 2003-09-30
Project end date: 2008-07-31
5R01HL075078-04 (2006): $399144
5R01HL075078-03 (2005): $408750
5R01HL075078-02 (2004): $408750
Effects Of Sleep Apnea On Metabolic Function
Naresh Punjabi, Associate Professor
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 1R01HL075078-01 from National Heart, Lung, And Blood Institute, IRG: ZHL1
Abstract: Sleep apnea is a chronic condition associated with an increased risk of hypertension and cardiovascular disease. Recent data suggest that sleep apnea is also associated with metabolic dysfunction that is characterized by glucose intolerance and insulin resistance. Although several studies indicate that the association between sleep apnea and metabolic dysfunction is independent of confounders including obesity, it remains to be determined whether the association is causal. Moreover, whether intermittent hypoxemia and/or sleep fragmentation are in the putative causal pathway is unknown. The major objective of our proposal is to determine whether sleep apnea produces metabolic dysfunction and delineate the underlying mechanisms. Our primary hypothesis is that intermittent hypoxemia and recurrent arousals from sleep lead to acute and chronic changes in metabolic function. In Specific Aim 1, we will examine whether nighttime and daytime profiles of metabolic function differ between patients with sleep apnea and control subjects matched on age, race, gender, and obesity. We hypothesize that, compared to control subjects, patients with sleep apnea will demonstrate a) marked abnormalities in nighttime profiles of glucose, insulin, and insulin secretion rate; b) impairment in daytime glucose tolerance, insulin sensitivity, and glucose effectiveness; and c) an increase in sympathetic activity and serum levels of leptin, cortisol, IL-6, and TNF-ct that are independently correlated with the severity of intermittent hypoxemia and frequency of arousals. In Specific Aim 2, we will examine whether experimental sleep fragmentation and sleep apnea (sleep fragmentation with intermittent hypoxemia) alter metabolic dysfunction in normal subjects. We hypothesize that a) sleep fragmentation in normal individuals will alter nighttime profiles of glucose, insulin, and insulin secretion rate and worsen daytime measures of glucose tolerance, insulin resistance, and glucose effectiveness; b) intermittent hypoxemia in association with sleep fragmentation will potentiate the adverse effects of sleep fragmentation alone; and c) experimental sleep fragmentation and sleep apnea will increase sympathetic activity and serum levels of cortisol, leptin, TNF-alpha and IL-6 in association with impaired glucose homeostasis. Novel experimental paradigms have been developed to determine the independent roles of sleep fragmentation and sleep apnea on metabolic function. Given the epidemic of obesity and diabetes, understanding the role of sleep apnea as a risk factor for metabolic dysfunction has public health significance in terms of prevention and treatment of diabetes, hypertension, and cardiovascular disease.
Keywords: disease /disorder proneness /risk, metabolic syndrome, sleep apnea, arousal, cortisol, disease /disorder etiology, glucose tolerance, hypoxia, insulin, insulin sensitivity /resistance, interleukin 6, leptin, metabolism, pathologic process, tumor necrosis factor alpha, blood chemistry, clinical research, human subject, patient oriented research, polysomnography
Project start date: 2003-09-30
Project end date: 2007-07-31
1R01HL075078-01 (2003): $408750
EARLY IDENTIFICATION AND TREATMENT OF SLEEP APNEA
Naresh Punjabi, Associate Professor
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5K23HL004065-05 from National Heart, Lung, And Blood Institute, IRG: ZHL1
Abstract: Dr. Naresh Punjabi is a promising young investigator who has made a substantial commitment to an academic career in clinical research. His commitment is evident in his pursuit of advanced clinical and research training, including completion of an residency in Internal Medicine, a fellowship in Pulmonary and Critical Care Medicine, and enrollment in the Graduate Training Program in Clinical Investigation at the Johns Hopkins University School of Hygiene and Public Health. This background provides a solid foundation for him to address challenging questions related to the diagnosis and management of sleep apnea, a pervasive problem with potentially significant consequences. Sleep apnea is one of the most common sleep disorders and is estimated to affect 18 million middle-aged adults in the United States. This disorder, which is especially prevalent in the elderly, is associated with hypertension, coronary artery disease, cognitive impairment, mood disturbances, diminished quality of life, and an increased risk for motor vehicle accidents. Despite the numerous effects of this disorder on health and society, a majority of affected individuals remain unrecognized. The proposed research in this application builds on Dr. Punjabi s previous research and addresses questions of fundamental importance related to the diagnosis and management of sleep apnea. The primary objective of this proposal is to develop and incorporate a risk-stratification approach for sleep apnea in clinical care. To this end, we propose three related studies a) a retrospective study to develop a risk- stratification approach for sleep apnea using the clinical characteristics that are associated with an increased risk; b) a prospective validation study of this approach in a sleep-clinic and primary-care patient sample; and c) a randomized intervention trial to determine whether treatment is associated with improved patient outcomes. The principal investigator will also be strengthening his knowledge base in the methodology of clinical investigation in a supervised environment guided by exceptionally talented mentors. By combining the resources of the Johns Hopkins Medical Institutions and the practical experience in the pursuit of the outlined aims, the Mentored Patient-Orientated Research Career Development Award will provide Dr. Punjabi the opportunity to reach his full potential as a clinical investigator.
Keywords: disease /disorder proneness /risk, early diagnosis, respiratory disorder diagnosis, sleep apnea, diagnosis design /evaluation, epidemiology, human therapy evaluation, quality of life, respiratory therapy, clinical research, human subject, polysomnography
Project start date: 1999-08-01
Project end date: 2004-07-31
5K23HL004065-05 (2003): $129497
5K23HL004065-03 (2001): $160128
5K23HL004065-02 (2000): $154618
1K23HL004065-01 (1999): $130937
Effects Of Aging On Sleep Architecture
Naresh Punjabi, Associate Professor
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5R21AG025553-02 from National Institute On Aging, IRG: ECDA
Abstract: Advancing age is associated with a decline in functional status and an increase in the prevalence of chronic medical conditions. Disturbed nighttime sleep is also a common finding in older individuals. Epidemiologic data indicate that more than 50% of the adults over the age of 65 years have some form of a chronic sleep-related complaint. Numerous studies have documented that disruption of nocturnal sleep architecture is associated with daytime sleepiness and alterations in neuroendocrine function. Although studies with overnight polysomnography have examined the changes in sleep architecture with increasing age, the distinct effects of healthy aging and age-associated illnesses have not been rigorously investigated. The major objectives of this application are to describe the age-related changes in sleep architecture in the general population. Using the baseline polysomnographic data collected by the Sleep Heart Health Study, the current application will employ novel analytical techniques including multi-state survival analysis and spectral analysis to characterize the macro- and micro-alterations in sleep architecture across the age spectrum. The Specific Aims of this application are as follows (1) To characterize the independent effects of healthy aging on sleep micro-architecture in a community-based sample of middle-aged and older adults without medical co-morbidity; (2) To delineate the independent effects of sleep apnea on nocturnal sleep micro-architecture in middle-aged and older adults; and (3) To examine the combined effects of aging and sleep apnea on nocturnal sleep micro-architecture. The research proposed in this application will offer a unique perspective on sleep in the aging adult from the most extensive collection of polysomnographic data. Segregating the effects of normal aging from age-associated illness will identify potential sources of variability in sleep that occurs in older adults. Moreover, a comprehensive summary of the changes in sleep structure with increasing age will provide the necessary foundation for ongoing studies of aging cohorts to determine whether disruption of sleep architecture plays a significant role in the age-related predisposition to cardiovascular, metabolic, and neurobehavioral consequences.
Keywords: aging, sleep, age difference, comorbidity, sleep apnea, electroencephalography, human data, polysomnography
Project start date: 2005-08-15
Project end date: 2007-07-31
5R21AG025553-02 (2006): $169680
1R21AG025553-01A1 (2005): $207878
Longtitudinal Changes In Sleep Structure: Implications For Health Outcomes
Naresh Punjabi, Associate Professor
Medicinejohns Hopkins University
Grant 5R01HL086862-02 from National Heart, Lung, And Blood Institute, IRG: ASG
Abstract: Advancing age is accompanied by several alterations in sleep-wake behavior including nocturnal sleep disruption and an increase in daytime sleep tendency. Age is also associated with a number of medical disorders that can impact sleep quality. Population-based data show that sleep-disordered breathing (SDB), a chronic condition that is characterized by profound alterations in sleep structure, is also common in middle- aged and older adults. Although the biology of sleep has been a topic of intense research, the distinct effects of age versus age-associated illness on sleep structure have not been adequately addressed. The overall objective of this application is to delineate the distinct effects of age and SDB on sleep structure and determine whether the alterations in sleep structure predict cardiovascular and non-cardiovascular endpoints, specifically daytime sleepiness and quality of life, across the adult life span. Novel analytical methods that draw upon the expertise of various scientific disciplines are proposed to analyze the electroencephalographic data collected during sleep to (1) characterize the independent effects of age and SDB on sleep structure; and (2) determine the role of sleep structure as a putative intermediate in the causal pathway toward cardiovascular and non-cardiovascular outcomes. The current application will utilize data collected by the Sleep Heart Health Study, a multi-center longitudinal study on the cardiovascular consequences of SDB. The investigative team, which spans multiple disciplines including epidemiology, biostatistics, sleep medicine, and the engineering sciences, brings the necessary expertise to examine trajectories of sleep structure with healthy aging and age-associated illnesses. The significance of this application is that it will make a valuable contribution by providing a better understanding of the mechanistic role of sleep in increasing the age-related vulnerability to various conditions that impact general health. Insight will also be gained into the degree to which other conditions such as cardiovascular and pulmonary disease impact sleep. Although basic ´mechanistic´ links cannot be directly addressed, questions related to which aspects of sleep (e.g., EEC activity, recurrent sleep-stage shift) best discriminate clinical outcomes. Finally, we expect to also provide new and much needed information on how factors such as gender and race influence sleep and quantify the adverse sleep-related effects of behaviors such alcohol use, cigarette smoking, and caffeine consumption
Keywords: aging, disease /disorder proneness /risk, sleep, sleep apnea cardiovascular disorder risk, longitudinal human study, quality of life, sleep disorder clinical research, electroencephalography, human data, human middle age (35-64), human old age (65+), polysomnography
Project start date: 2007-07-05
Project end date: 2011-06-30
1R01HL086862-01A1 (2007): $369000
Related Publications
Characterizing sleep structure using the hypnogram. J Clin Sleep Med. 2008 Aug 15; 4( 4): 349-55. PMID: 18763427 Fasting glycemia in sleep disordered breathing: lowering the threshold on oxyhemoglobin desaturation. Sleep. 2008 Jul 1; 31( 7): 1018-24. PMID: 18652097 Subjective and objective sleep quality in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the sleep heart health study. Am J Kidney Dis. 2008 Aug; 52( 2): 305-13. Epub 2008 Jul 9. PMID: 18617308 
Sleep: a nourisher in life's feast? Sleep Med Rev. 2008 Aug; 12( 4): 253-5. No abstract available. PMID: 18603218 Sleep-disordered breathing and type 2 diabetes: a report from the International Diabetes Federation Taskforce on Epidemiology and Prevention. Diabetes Res Clin Pract. 2008 Jul; 81( 1): 2-12. PMID: 18544448 Contribution of male sex, age, and obesity to mechanical instability of the upper airway during sleep. J Appl Physiol. 2008 Jun; 104( 6): 1618-24. Epub 2008 Apr 17. PMID: 18420722 Sleep-disordered breathing and cardiovascular disease: an outcome-based definition of hypopneas. Am J Respir Crit Care Med. 2008 May 15; 177( 10): 1150-5. Epub 2008 Feb 14. PMID: 18276938 
Sleep-disordered breathing and impaired glucose metabolism in normal-weight and overweight/obese individuals: the Sleep Heart Health Study. Diabetes Care. 2008 May; 31( 5): 1001-6. Epub 2008 Feb 11. PMID: 18268072 The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc. 2008 Feb 15; 5( 2): 136-43. Review. PMID: 18250205 Sleep problems reported by patients entering opioid agonist treatment. J Subst Abuse Treat. 2008 Oct; 35( 3): 328-33. Epub 2008 Jan 14. PMID: 18248944 Cross-sectional and prospective study of lung function in adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) study. Diabetes Care. 2008 Apr; 31( 4): 741-6. Epub 2007 Dec 4. PMID: 18056886 Power spectral analysis of EEG activity during sleep in cigarette smokers. Chest. 2008 Feb; 133( 2): 427-32. Epub 2007 Oct 9. PMID: 17925420 
Long sleep duration: a risk to health or a marker of risk? Sleep Med Rev. 2007 Oct; 11( 5): 337-9. Review. No abstract available. PMID: 17854737 Elevated levels of neopterin in sleep-disordered breathing. Chest. 2007 Oct; 132( 4): 1124-30. Epub 2007 Jul 23. PMID: 17646222 Relation of sleep-disordered breathing to carotid plaque and intima-media thickness. Atherosclerosis. 2008 Mar; 197( 1): 125-31. Epub 2007 Apr 11. PMID: 17433330 C-reactive protein is associated with sleep disordered breathing independent of adiposity. Sleep. 2007 Jan 1; 30( 1): 29-34. PMID: 17310862 Sleep apnea in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the Sleep Heart Health Study. J Am Soc Nephrol. 2006 Dec; 17( 12): 3503-9. Epub 2006 Nov 2. PMID: 17082238 Association of usual sleep duration with hypertension: the Sleep Heart Health Study. Sleep. 2006 Aug 1; 29( 8): 1009-14. PMID: 16944668 Cigarette smoking and nocturnal sleep architecture. Am J Epidemiol. 2006 Sep 15; 164( 6): 529-37. Epub 2006 Jul 7. PMID: 16829553