.: INSTITUTO DO SONO :.

XXXXXResearch developed by Professor Sergio Tufik at UNIFESP's Psychobiology Department in the late 1970s led to the formation of a group of researchers specializing in sleep. Initially, they examined effects of paradoxical (or REM) sleep deprivation in animals and this enabled the group to gain recognition in the international research scenario.

XXXXXThe Sleep Institute itself was founded in the early 1990s and is now involved with several activities, including research, sleep medicine training (specializations, graduate and post-graduate levels) and providing services in the area of sleep disturbance diagnoses.

XXXXXResearch accounts for the main part of the Sleep Institute's work. Current projects are exploring the basic mechanisms of sleep and possible clinical applications (diagnoses and treatment), as well as clinical research into sleep regulation in humans and the most effective types of treatment for different types of sleep disorders.

XXXXXIn 2000 the Sleep Institute joined a research program "Research, Expansion and Diffusion Centers" (Cepid) of the State of São Paulo's Research Support Foundation (FAPESP) under the coordination of professors Sergio Tufik (Coordinator - Research), and Luiz Eugênio de Araújo Moraes Mello (Coordinator - Innovation and Technology; e-mail: lemello@ecb.epm.br) and Roberto Frussa Filho (Coordinator - Dissemination; frussa.farm@epm.br).

XXXXXCepid/Sono's mission is primarily developing multidisciplinary research in the field of sleep medicine and building effective procedures for the transfer of knowledge to society.

XXXXXA highlight among the innovative aspects of Cepids is the education component. In addition to developing the usual research assistance programs for undergraduates and graduate students, the center also organizes extension courses in the field of basic education, such as research assistant programs for secondary school students and teachers, teacher training and scientific outreach courses. These activities, in addition to their intrinsic value, aim to help develop a culture in which researchers feel co-responsible for basic education in Brazil.

XXXXXAnother important aspect developed by CEPID / Sleep was the contribution and participation of its members to the thematic commission on health and environment (CTSMA) of the national road safety council (CONTRAN) which led to CONTRAN's resolution 267 making medical and psychological assessments a condition for obtaining professional drivers licenses. This is a very important point since an estimated 27% to 32% of all traffic accidents and 17% to 19% of deaths are caused by drivers falling asleep or becoming drowsy at the wheel, which may be due to sleep deprivation and/or sleep disorders, fatigue, excessive hours and/or alteration of the light- dark cycle.

XXXXXWhile the primary function of sleep remains unknown, the fact that prolonged sleep deprivation (SD) leads to death in humans and experimental animals indicates that sleep is essential for survival (Perspect. Biol. Med., 41(3):359-90, 1998). The biological significance of sleep is further signaled by the fact that it occurs in most species, despite being apparently maladaptative as concerns other biological properties such as feeding, avoiding predators, and reproducing. Most organisms literally "fall asleep" as a normal behavior, and will experience an increasingly strong urge to do so if deprived of sleep. That the consequences of this overpowering urge to sleep may be disastrous in a number of situations is exemplified in accidents involving motor vehicles or heavy machinery.

XXXXX The causes, mechanisms and consequences of SD and the physiological basis of the resulting need to sleep constitute the central focus of the research work proposed by our CEPID Center.Our goals are to expand scientific understanding of sleep functions by addressing the broad spectrum of consequences of sleep loss, and to develop and validate new diagnostic and therapeutic approaches to sleep-related conditions.

XXXXXUNIFESP is the most productive Brazilian university, taking into account the amount of published papers in international scientific journals in relation to the number of faculty members. Its graduation courses, post-graduate programs and health assistance are national references by the quality of their contents, the professionals' backgrounds and the technology they offer.

XXXXXAFIP is a private non-profit organization which was created by faculty member of the Psychobiology Department of UNIFESP in the 1980s. It is registered and certified as a public service organization at the municipal, state and federal levels, associated to the University. Its mandate is to provide financial support for teaching and research activities, expediting the purchasing of equipment and it also supplies and provides technical and administrative human resources support. AFIP is supported by a combination of grants from Brazilian government agencies (CNPq, CAPES, FINEP and FAPESP), funds from the Ministry of Health, from Central Agency for Medications (Central de Medicamentos), Banco do Brasil, the United Nations (UNFDAC/UNDCP), the Ministry of Justice, fees for laboratory analyses performed for the public health system, and trials performed for pharmaceutical companies in its Clinical Analyses Laboratories and Sleep Laboratory. AFIP's net worth is at present estimated to be about US$ 40 million.

XXXXX AFIP therefore currently provides physical and financial support to basic and clinical research at the Psychobiology Department, provides funds for research projects, travel to international meetings and congresses, training abroad, fees for international consultants, upkeep and maintenance of research laboratories (equipment, drugs, reagents, glassware); it also provided funds for the creation and maintenance of an animal vivarium, library services (including journal subscriptions, book purchases, reading room), computers and auditorium.

Sergio Tufik
Luiz Eugênio A. Mello
Roberto Frussa Filho
Lia A. Bittencourt
Marco Túlio de Mello

Summary of the research lines, results obtained, science developed at the Center and graphs illustrating some of the results obtained since the creation of the Center (past 8 years).

Figure 1: Articles published in peer-reviewed journals by researchers of the Instituto do Sono, from 1997 to February 2008. Cepid was granted towards the end of 2000.

XXXXXThe apnea-hypopnea index (AHI), measured by the number of apnea-hypopnea events per night, is the primary measure in the diagnosis of obstructive sleep apnea (OSA). However, there is no consensus as to how variable this index is from one night to another. We evaluated 20 OSA outpatients during four consecutive nights with polysomnographic (PSG) recordings and found a great individual variability in the stability of the index (J. Sleep Res., 10:245-51, 2001). The AHI classification changed in 50% of patients when comparing the first night with one of the subsequent 3 nights. This suggests that for adequate OSA diagnosis AHI should be used together with other clinical and polysomnographic parameters.

Figure 2: Apnea-hypopnea index (AHI) in the outpatients (50%) who had variable measures, during 4 consecutive nights and who would therefore receive different obstructive sleep apnea diagnosis if only one night were used for this purpuse (J. Sleep Res., 10:245-51, 2001).

XXXXXParaplegic individuals present frequent Periodic Leg Movement (PLM) (our data, e.g. Spinal Cord, 36:18-20, 1998). In an attempt to elucidate the key causative factors of this phenomenon, we proposed an animal model of PLM that involved observing the incidence of limb movements during sleep in spinal cord injured (SCI) rats in comparison to rats that underwent a sham procedure. Only SCI rats presented limb movement characteristic of PLM during Non-REM sleep, which were statistically different from those in the sham group from day 5 (D5). The results suggest that these movements may be generated in the spinal medulla without involvement of cortical structures (Brain Res., 1017:32-8, 2004).

Figure 3: Number of animals that presented limb movements during non-REM sleep after sham and Spinal Cord Injury (SCI) procedures at baseline (B) and the 7 days (D1-D7) following the operation. Only SCI animals presented such movements, which were statistically significant (*) in comparison to sham from day 5 (Brain Res., 1017:32-8, 2004).

XXXXXWe have demonstrated the involvement of oxidative stress in the amnestic effect of paradoxical sleep deprivation (PSD) in mice (Neuropharmacology, 46:895-903, 2004), the anti-amnestic effect of antioxidant agents (Neuropharmacology, 46:895-903, 2004) and the pro-amnestic effect of pro-oxidants (Prog. Neuropsychopharmacol. Biol. Psychiatry., 31:65-70, 2007) in mice submitted to PSD. In addition, we have shown that the amnestic effect of PSD in mice is also related to a concomitant anxiogenic effect of PSD (Neurobiol. Learn. Mem., 82:90-8, 2004), is not related to modifications in GABAergic transmission, but is mediated by noradrenergic transmission (Psychopharmacology, 176:115-22, 2004).

Figure 4: Involvement of hippocampal oxidative stress and the beneficial effects of antioxidant agents on the amnestic effect induced by paradoxical sleep deprivation in mice. (A) Latency (s) to enter the dark chamber in the test session of a passive avoidance task and (B) hippocampal levels of lipid peroxidation (mean ± S.E.) presented by control (CO) or 72 h-sleep-deprived (SD) mice that were treated i.p. with vehicle (TW/PG), 40 mg/kg vitamin E (VE), 5 mg/kg melatonin (MEL) or 200 mg/kg N-tert-butyl-?-phenylnitrone (PBN). *p<0.001 compared to all the other groups. ?p<0.05 compared to CO-TTW/PG group. p<0.05 compared to SD-TW/PG group (Neuropharmacology, 46:895-903, 2004).

HORMONE TREATMENT FACILITATES PENILE ERECTION IN CASTRATED RATS AFTER SLEEP DEPRIVATION

XXXXXSleep loss causes several behavioral responses some of which are under hormonal control such as sexual behaviour. The facilitation effect of paradoxical sleep deprivation (PSD) on spontaneous genital reflexes in rats associated with increased concentrations of progesterone provide a basis for exploring the neuro-endocrine mechanisms of erectile function. Our findings demonstrated that progesterone might be involved in paradoxical sleep regulation and consequently play a functional role in the regulation of genital mechanisms in males (J. Neuroendocrinol., 16:154-9, 2004).

Figure 5: Effect of saline (sal) or cocaine (coc - 7mg/kg, ip) on genital reflexes in paradoxical sleep deprived (PSD) and home-cage control (CTRL) rats. PSD stimulatory effect on genital reflexes such as penile erection (PE) and ejaculation (EJ) is dramatically potentiated by dopaminergic drugs such as cocaine, whereas the same dose in control rats has no effect. *different from the other groups, #different from CTRL+sal and CTRL+coc groups. Panel B: Mean SEM concentrations of progesterone (ng/mL) in non-castrated and castrated rats PSD and CTRL groups. different from respective control group. (J. Neuroendocrinol., 16:154-9, 2004).

XXXXXAdult Chiari malformation (CM), a syndrome of difficult diagnosis, is primarily characterized by herniation of the cerebellar tonsils through the foramen magnum. It has been described as associated to severe sleep respiratory disorders, such as respiratory failure and even death. The ventilatory responses to exogenous and endogenous stimuli, such as responses to hypoxia and hypercapnia, are usually diminished, and apnea may be manifested and detected during sleep, allowing for CM diagnosis. This review encourages studies on the relations between sleep apnoea and its relations with craniocervical malformations (Neurosurg. Rev., 28:169-76, 2005).

Figure 6: Illustration of Chiari I (adult) malformation. Note the tonsillar herniation (white arrow) (see Neurosurg Rev., 28:169-76, 2005).

XXXXXThe prolonged period of anestrus in paradoxical sleep deprived females indicates the long-lasting effects of sleep loss on reproductive function by altering hormonal/neurochemical mechanisms (Horm Behav., 49:433-40, 2006).

Figure 7: Vaginal estrous cycles of home-cage controls (CTRL, at left) and paradoxical sleep deprived (PSD, n=11, right) female rats submitted to PSD condition at diestrus. The solid bar on the abscissa represents the paradoxical sleep deprivation days of the period. Exposure of the female rats to PSD at the beginning of diestrus caused constant prolonged anestrus during the recovery period in PSD group. These data indicate that sleep deprivation presents distinct, long-lasting effects on estrous cycle, and may modulate the ovarian hormone release through alterations in hormonal-neurochemical mechanisms. P: proestrus; M: metestrus; E: estrus, and D: diestrus (Horm Behav., 49:433-40, 2006).

XXXXXThe hyperfagia/weight loss paradox is described in the experimental sleep literature and is contrary to findings in humans. We showed that sleep deprived animals do not lose weight while increasing food intake. Instead, they have difficulties in obtaining food to reach their energetic needs, especially during the first day of sleep deprivation, after which they adapt to the procedure (Sleep, 29:1233-8, 2006). Also, they present stereotyped behavior at the beginning of sleep deprivation procedures (see also Physiol. Behav., 93:229-34, 2008).

Figure 8: Changes in body weight and food intake (lines: daily; bars: period average) of rats living on several environmental conditions such as: sawdust-baseline (BL), metal floor (MF) positioned above the original floor consisting of a wire mesh grid, metal floor over water (MFW), 120 h of sleep deprivation by narrow platform (SD), sleep recovery on metal floor (RMF), baseline control condition (BC). Sleep deprived animals lose weight particularly on the first day due to difficulty in reaching for food (Sleep, 29:1233-8, 2006).

A DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER STUDY OF SILDENAFIL IN OBSTRUCTIVE SLEEP APNEA (OSA)

XXXXX This study assessed the effects of a single dose of 50 mg of sildenafil in men with OSA. Erectile dysfunction is prevalent among adult male populations, particularly in those with OSA. Patients often take sildenafil in the evening close to bedtime. We found that 50 mg, at bedtime, significantly worsens respiratory and Oxygen Saturation (SaO2) variables during sleep, when compared to placebo. This study was published in a special issue of Archives of Internal Medicine dedicated to sleep. It also reached the lay media, and was commented on masculine magazines over the United States of America, warning snorers who take sildenafil at bedtime (Arch. Intern. Med., 166:1763-7, 2006).

Figure 9: The figure shows patient's hypnogram (top) and Oxygen Saturation (bottom). It documents the significant worsening of SaO2 during sleep on the nights subjects took sildenafil (Arch. Intern. Med., 166:1763-7, 2006).

ACUPUNCTURE IS AN EFFECTIVE TREATMENT FOR MODERATE OBSTRUCTIVE SLEEP APNEA SYNDROME

XXXXXIn this study we investigated the efficacy of acupuncture in the treatment of moderate obstructive sleep apnea syndrome (OSAS), assessed by polysomnography (PSG) and questionnaires of functional quality of life (SF-36) and excessive daytime sleepiness (Epworth). This was a randomised, placebo-controlled (sham group), study with blinded evaluation on patients presenting an apnea/hypopnea index (AHI) of 15-30/h. There was also a control group, receiving no treatment (n = 12). Ten weekly sessions of acupuncture significantly improved the respiratory events of patients presenting with moderate OSAS in comparison to treatment with the sham procedure (needle insertion in non-acupoints) and to non-treated controls. Acupuncture also improved quality of life and decreased subjective sleepiness (Sleep Med., 8:43-50, 2007).

XXXXXThis study compares the prevalence of complaints of insomnia, excessive diurnal sleepiness, parasomnias, and sleep habits of the adult population in the city of São Paulo, Brazil, estimated in surveys carried out in 1987 and 1995 (1000 adults each; Braz. J. Med. Biol. Res., 40:1505-15, 2007). Difficulty in maintaining sleep, initiating sleep and early morning awakening significantly increased throughout time, mainly in women. Besides sleeping slightly less, interviewees went to bed and woke up later in 1995. These major changes over a little under a decade should be considered as an important public health issue.

Figure 10: Insomnia complaints by gender in surveys carried out in 1987 and 1995 in the city of São Paulo (representative samples of 1000 adults per survey). Sleep complaints increased in 1995. Data are reported as percentages ± confidence interval (CI) at 95% (Ztest).

XXXXXDonepezil is a commonly prescribed drug for Alzheimer's disease patients. Here, we found that this drug improves apnea hypopnea index and oxygen saturation during sleep in Alzheimer disease patients with Obstructive Sleep Apnea, despite REM sleep increase. This is the first controlled trial, showing this magnitude of improvement of respiratory parameters during sleep with one drug. Repercussion has been seen worldwide. Lay media in more than four countries and the scientific community are commenting on this data. Trial registration: ClinicalTrials.gov Identifier: NCT00480870 (Chest, 133:677-683, 2008).

Figure 11: Significant improvement (from baseline, 1, to post-treatment, 2) on percentage of sleep time of Oxygen Saturation bellow 90% in Alzheimer patients with Obstructive Sleep Apnea treated with donepezil (Chest, 133:677-683, 2008).

XXXXXParadoxical sleep deprivation (PSD) promotes a number of behavioural, physiological, as well as cellular functioning alterations, including gene expression in specific brain regions. A total of 55 genes were found to be differently expressed in rats after 96 hours of PSD. Interestingly, after 24 hours of sleep recovery (rebound), approximately 50% (n=25) of the PSD genes had their expression returned to control levels. Also, 200 transcripts, such as Adenosine A2B receptor, Insulin receptor substrate2, Corticotropin releasing hormone, and Homer1, were specifically altered when compared to the PSD condition (see table below). These data raise a number of potential candidates for the molecular basis of homeostatic mechanism of sleep regulation.

Figure 12: Examples of genes differently expressed after 96 h of sleep deprivation and 24 h of rebound sleep in rats. Unpublished data.

xxxxxxThe educational program of our Center comprises 6 main fronts of information dissemination. Our main achievements in each front are described bellow:

WEB Page: the address of the home page is www.sono.org.br. The page provides constantly updated information for the lay public with links to specialized sites in Portuguese and English. It offers easy readability information about sleep physiology, sleep hygiene, main sleep disturbances and snoring and apnoea.In addition, it provides information about how to make clinical appointments. As regards specific research information, the page offers an update description of the main scientific research activities of the Center as well as links to the main sleep centers in the world. It also provides information about special diffusion activities eventually offered by the center. Approximately 70,000 persons visit our web page per year.

Organization of artistic/scientific/educational events: our CEPID center has organized 5 artistic/scientific/educational events in which easy readability information about sleep physiology, sleep hygiene, main sleep disturbances, sleep-related drug abuse, snoring and apnoea were provided to the lay public.

EVENT	KIND	PLACE	No. OF PEOPLE REACHED	DATE
"Insone"	Artistic/ educational	Nações Unidas Shopping	15,000-20,000	November 13-17, 2000
"De Somno-Sleep and its misteries"	Artistic/ Scientific/ educational	SESC - Consolação	21,000	May 19-24, 2003
"Banco Itaú Event"	Scientific/ educational	Itaú Bank	1,000	September 22-24, 2004
"Brazilian Week of Science and Technology"	Scientific/ educational	Federal University of São Paulo	100	October 24, 2004
Morumbi Shopping Event	Scientific/ educational	Morumbi Shopping	500	August 23, 2005

Large scale dissemination of information related to sleep physiology, sleep hygiene and main sleep disturbances through newspapers, magazines, radio and television media.

	No. OF REPORTS/PROGRAMS	ISSUES/AUDIENCE
Newspapers	54	13,199,000
Magazines	51	24,993,500
Radio	26	4,112,500
Television	105	654,938,118

Elaboration and distribution of printed material: a thirty-page information brochure was produced by our staff in partnership with Johnson's & Johnson's. It was based on the recommendations of the National Sleep Foundation and was distributed to pregnant women and health professionals in São Paulo clinics and hospitals that offer services for pregnant women and infants. Specific themes disseminated: sleep physiology and sleep hygiene in newborn babies and infants.

Number of information brochure issues: 40,000.

Large scale dissemination through newspapers, magazines, radio and television media.

	No. OF REPORTS/PROGRAMS	ISSUES/AUDIENCE
Newspapers	10	1,762,500
Magazines	5	430,000
Radio	1	13,000
Television	8	16,094,300

A teaching module for high-school students was elaborated and tested as an alternative within Biological Sciences High School curriculum. Topics covered included: sleep physiology, sleep hygiene, dreams, main sleep disturbances, drug effects on sleep and experimental approaches to the study of sleep. The module was tested in the following schools: Waldorf Rudolf Steiner, Humboldt, Poliedro and São Paulo.

Large scale dissemination through newspapers, magazines, radio and television media.

Program of talks: a program of talks was prepared by our Center's staff and was offered to older individuals in clubs, universities and elderly meetings. This program of talks reached approximately 1000 elderly participants.

Large scale dissemination through newspapers, magazines, radio and television media.

Large scale dissemination through newspapers, magazines, radio and television media.

14 six-month long training courses for technicians were offered to 600 students.
07 850h specialization courses for medical doctors were offered to 62 medical doctors.
07 150h specialization courses for medical doctors were offered to 97 medical doctors.

The following books were produced and distributed for free to Brazilian universities:

Specific talks were presented in extracurricular courses and medical events by our Center's staff. Taken together we estimate that sleep information was disseminated to approximately 13,700 health care professionals through these specific talks.

xxxxxxIn our first annual reports concerning the Education and Dissemination activities we have quantitatively described all the activities performed as well as the contact rates for each of them. During the last years, we have also tried to objectively evaluate the repercussions of our Education and Dissemination activities. This study, entitled "Repercussions of a sleep medicine outreach program" was published in the Brazilian Journal of Medical and Biological Research (39:1057-1063, 2006).

xxxxxx In this study, it was demonstrated that, besides reaching a large number of persons, our Education and Dissemination activities were effective in producing a qualitative improvement in sleep medicine awareness. Considering such a finding and the fact that our education and dissemination activities have been recognized as "a major contribution", "very impressive" and "commendable" point of our Center by FAPESP reviewers, we propose here a continuation and a further quantitative and qualitative increment of such activities.

xxxxxxThus, the main education and dissemination proposals of our CEPID Center will be: 1-) large scale dissemination of general sleep-related information aimed to the lay public, and 2-) dissemination of sleep information specifically focusing on 2a) newborn babies and infants, 2b) school-age children and adolescents, 2c) elderly, 2d) shift workers and accidents due to sleep problems and 2e) health care professionals.

xxxxxxIn order to accomplish the above proposals we will continue to develop our Web site, to sensitize Brazilian TV, radio and print media to disseminate sleep-related information, to organize major educational events, to develop high school teaching modules, to offer training and specialization courses to health care professionals and to offer programs of talks and specific "sleep kits" to be distributed in schools, hospitals, etc…

xxxxxxAs additional initiatives for Education and Dissemination we will develop the project entitled "The virtual university: Production of videos on Sleep Themes". The planned series of videotapes will include:

1-) Sleep history
2-) The history of paradoxical sleep
3-) What happens when we sleep?
4-) Why is sleep important for health?
5-) How to tell if we have a sleep disturbance?
6-) How and where to find help if you have a sleep problem
7-) Drugs that cause insomnia
8-) Sleep in newborn babies
9-) Sleep and sudden infant death
10-) Sleep in infants
11-) Sleep in school-age children and adolescents
12-) Sleep in the elderly
13-) Sleep in Alzheimer disease patients
14-) Sleep in shift workers
15-) Accidents due to sleep problems
16-) Sleep laboratory
17-) Periodic leg movements
18-) Sleep and physical exercise
19-) Bruxism
20-) Sleep and genes
21-) Sleep and cellular death
22-) Sleep and immunology
23-) Sleep and nutrition
24-) Obstructive sleep apnoea
25-) Sleep and the cardiovascular system
26-) Sleep in the climatery
27-) Acupuncture and sleep
28-) Sleep and sex
29-) Sleep and memory
30-) Sleep and psychology
31-) Sleep and psychiatry disorders
32-) Sleep and drug abuse
33-) Sleep and post-traumatic stress
34-) Sleep and pain
35-) Teaching sleep medicine to medical doctors
36-) Sleep in São Paulo city

xxxxxxThe videos will be monthly produced by TV Unifesp, will be distributed in several Brazilian universities and São Paulo high schools and we will try to make them accessible on our Web site.

XXXXXThe effects of sleep deprivation have always been a research focus at the Sleep Institute, both for the purpose of discovering the functions of sleep, more specifically paradoxical or REM sleep, and the consequences of sleep deprivation, important when considering the frequency with which sleep deprivation or fragmentation is found in many sleep disorders, such as apnea, fibromyalgia and insomnia.

XXXXXThe Sleep Institute conducted three Epidemiological Surveys of sleeping patterns and symptoms in the city of São Paulo in 1987, 1995 ( see article) and 2007.

XXXXXThe 2007 survey was the biggest survey ever conducted in this field and combined questionnaires with polysomnography for a representative sample of 1056 volunteers from the city of São Paulo. Its main objectives are:

XXXXX a. building an epidemiological profile of sleep disturbances for the adult population of the city of São Paulo in 2007, using questionnaires to assess sleep patterns and sleep recording sessions for the entire sample;

XXXXX b. studying this population for associations between sleep patterns and disturbances and sociodemographics , anthropometrics, clinical history, activity / rest cycle , eating habits and physical activity, mood disorders, male sexual dysfunction, alcoholism and drug-addition, genetic markers, and biochemical, hematological, endocrinologal, immunological and inflammatory variables;

XXXXXc. evaluating compatibility across results from sleep epidemiological studies in the city of São Paulo conducted in 1987 and 1995, in order to track secular trends in the prevalence of sleep disturbances.

XXXXX The three stage agglomerated randomized sample comprised 1056 individuals from the city of São Paulo, in numbers proportional to gender, age group (over 20s ) and social class. Data collection involved: 1) questionnaires filled out at home 2) detailed records of sleep patterns and disturbances, with questionnaires and full-night sleep recording sessions at the Sleep Institute, and actigraphy data for at least three nights prior to the sessions; and 3) peripheral blood for biochemical, hematological, endocrinogical and genetic sampling.

XXXXX The association between heart diseases and sleep abnormalities has been known for many years. However, interest in this field has recently been newly instigated due to the increase in cardiovascular mortality in patients with sleep breathing disturbances. Research on risk stratification for obstructive sleep apnea seeks to determine the role of sleep apnea as a cardiovascular risk factor. All registered patients with sleep breathing disturbances are asked to take part in this study. Our testing protocol includes clinical evaluation, electrocardiogram with 12 derivations, spirometry, ergo-spirometric test, treadmill, actigraphy, three-dimensional ecocardiogram, laboratory evaluation, and autonomous nervous system evaluation. Patients are given test results and appropriate advice 15 days later. A subgroup is randomized for treatment with CPAP or SHAM CPAP developed by the group. At present some 500 patient and controls have been examined.