Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a meta-analysis.

OBJECTIVE: To systematically analyze the studies that have examined the effect of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with resistant hypertension and obstructive sleep apnea (OSA). METHODS: Design - meta-analysis of observational studies and randomized controlled trials (RCTs) indexed in PubMed and Ovid (All Journals@Ovid). participants: individuals with resistant hypertension and OSA; interventions - CPAP treatment. RESULTS: A total of six studies met the inclusion criteria for preintervention to postintervention analyses. The pooled estimates of mean changes after CPAP treatment for the ambulatory (24-h) SBP and DBP from six studies were -7.21 mmHg [95% confidence interval (CI): -9.04 to -5.38; P < 0.001; I² 58%) and -4.99 mmHg (95% CI: -6.01 to -3.96; P < 0.001; I² 31%), respectively. The pooled estimate of the ambulatory SBP and DBP from the four RCTs showed a mean net change of -6.74 mmHg [95% CI: -9.98 to -3.49; P < 0.001; I² 61%] and -5.94 mmHg (95% CI: -9.40 to -2.47; P = 0.001; I² 76%), respectively, in favor of the CPAP group. CONCLUSION: The pooled estimate shows a favorable reduction of BP with CPAP treatment in patients with resistant hypertension and OSA. The effects sizes are larger than those previously reported in patients with OSA without resistant hypertension.

Brain-derived neurotrophic factor gene polymorphism predicts interindividual variation in the sleep electroencephalogram.

Previous studies have suggested that brain-derived neurotrophic factor (BDNF) participates in the homeostatic regulation of sleep. The objective of this study was to investigate the influence of the Val66Met functional polymorphism of the BDNF gene on sleep and sleep EEG parameters in a large population-based sample. In total 337 individuals participating in the São Paulo Epidemiologic Sleep Study were selected for analysis. None of the participants had indications of a sleep disorder, as measured by full-night polysomnography and questionnaire. Spectral analysis of the EEG was carried out in all individuals using fast Fourier transformation of the oscillatory signals for each EEG electrode. Sleep and sleep EEG parameters in individuals with the Val/Val genotype were compared with those in Met carriers (Val/Met and Met/Met genotypes). After correction for multiple comparisons and for potential confounding factors, Met carriers showed decreased spectral power in the alpha band in stage one and decreased theta power in stages two and three of nonrapid-eye-movement sleep, at the central recording electrode. No significant influence on sleep macrostructure was observed among the genotype groups. Thus, the Val66Met polymorphism seems to modulate the electrical activity of the brain, predicting interindividual variation of sleep EEG parameters. Further studies of this and other polymorphic variants in potential candidate genes will help the characterization of the molecular basis of sleep.

Do circadian preferences influence the sleep patterns of night shift drivers?

OBJECTIVE: The objective of this study was to analyze the effect of individual circadian preferences of drivers with fixed night work schedules on sleep patterns. SUBJECTS AND METHODS: A total of 123 professional drivers, 32 indifferent preference drivers and 91 morning preference drivers of an intermunicipality and interstate bus transportation company were evaluated. All drivers underwent polysomnographic recordings after their shifts. Furthermore, they filled out a questionnaire that contained sociodemographic and health questions. The Horne and Östberg questionnaire was used to assess the subjects' morningness-eveningness preference. RESULTS: The mean age was 42.54 ± 6.98 years and 82 (66.66%) of the drivers had worked for ≥15 years. A significant effect on rapid eye movement (REM) was observed in the morning preference drivers. They showed an increased sleep latency and an REM sleep percentage of 5% of the total REM time. This reveals a significant effect on sleep architecture associated with work time. CONCLUSION: The drivers reported that morning preference had a significant effect on their sleep pattern indicating less REM sleep and longer REM sleep latency in the morning preference group. Thus, it is important to evaluate interactions between individual aspects of health and other parameters, such as sleep quality and work organizational factors, to promote night shift workers' health and well-being.

Consequences of obstructive sleep apnea on metabolic profile: a Population-Based Survey.

OBJECTIVE: Epidemiologic studies that control for potential confounders are needed to assess the independent associations of obstructive sleep apnea (OSA) with metabolic abnormalities. The aim of our study was to evaluate the associations of OSA with metabolic abnormalities among the adult population of Sao Paulo, Brazil. DESIGN AND METHODS: Questionnaires were applied face-to-face, full night polysomnography (PSG) was performed, and blood samples were collected in a population-based survey in Sao Paulo, Brazil, adopting a probabilistic three-stage cluster sample method. The metabolic profile included fasting glucose, insulin, and lipid levels. The hepatic insulin resistance index was assessed by the homeostasis model assessment-estimated insulin resistance (HOMAIR ). RESULTS: A total of 1,042 volunteers underwent PSG. Mild OSA and moderate to severe OSA comprised 21.2% and 16.7% of the population, respectively. Subjects with severe to moderate OSA were older, more obese, had higher fasting glucose, HOMAIR , and triglycerides (TG) levels than did the mild and non-OSA group (P < 0.001). Multivariate regression analyses showed that an apnea-hypopnea index (AHI) ≥ 15 and a time of oxy-hemoglobin saturation <90% were independently associated with impaired fasting glucose, elevated TG, and HOMAIR . CONCLUSIONS: The results of this large cross-sectional epidemiological study showed that the associations of OSA and metabolic abnormalities were independent of other risk factors.

Inhibitory effects of modafinil on emotional memory in mice.

Modafinil (MOD), a psychostimulant used to treat narcolepsy, excessive daytime sleepiness, and sleepiness due to obstructive sleep apnea, appears to promote a possible facilitatory effect on cognitive function. In the present study, we investigated the effects of the acute administration of MOD on the different steps of emotional memory formation and usage (acquisition, consolidation and retrieval) as well as the possible participation of the state-dependency phenomenon on the cognitive effects of this compound. Mice were acutely treated with 32, 64 or 128 mg/kg MOD before training or testing or immediately after training and were subjected to the plus-maze discriminative avoidance task. The results showed that although pre-training MOD administration did not exert any effects on learning, the doses of 32 or 64 mg/kg induced emotional memory deficits during testing. Still, the post-training acute administration of the higher doses of MOD (64 and 128 mg/kg) impaired associative memory consolidation. When the drug was administered pre-test, only the 32 mg/kg dose impaired the task retrieval. Importantly, the cognitive impairing effects induced by 32 mg/kg MOD were not related to the phenomenon of state-dependency. In all, our findings provide pre-clinical evidence of potential emotional memory amnesia induced by MOD. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

The human leucocyte antigen DQB1*0602 allele is associated with electroencephelograph differences in individuals with obstructive sleep apnoea syndrome.

Human leucocyte antigen (HLA) DQB1*0602 allele, a well-known genetic risk factor for narcolepsy, has been associated with sleep parameters in healthy subjects. We aimed to assess the association of this allele with daytime sleepiness and altered sleep electroencephalogram characteristics in the general population and in patients with obstructive sleep apnoea syndrome (OSAS). Eight hundred and ninety-four individuals from the Epidemiologic Study of Sleep were genotyped for the HLA DQB1*0602 allele. Full-night polysomnography was performed, and daytime sleepiness was analysed according to the Epworth Sleepiness Scale. HLA-DQB1*0602 allele-positive and -negative subjects in the general population, as well as in patients with OSAS, exhibited similar sleep parameters and levels of daytime sleepiness. However, spectral analysis showed that allele-positive individuals with OSAS exhibited higher theta power during sleep Stage 1 (P < 0.05) in occipital derivations, and lower delta power during sleep Stages 1 and 2 (P < 0.01) compared with individuals negative for the allele, even after correction for potential confounders as age, sex, body mass index and European ancestry. No significant differences in the electroencephalogram variables were found in individuals without OSAS. The data highlight the HLA-DQB1*0602 as a potential genetic factor influencing sleep physiology in individuals diagnosed with OSAS.

Prevalence of and risk factors for obstructive sleep apnea syndrome in Brazilian railroad workers.

OBJECTIVE: This study evaluated the prevalence of, and the risk factors for, obstructive sleep apnea syndrome (OSAS) among Brazilian railroad workers. METHODS: Male railroad workers (745) from a railway company in Brazil were analyzed after responding to questionnaires about their demographics, sleep habits, excessive daytime sleepiness (Epworth), and the likelihood of having apnea (Berlin). We also performed polysomnography and measured anthropometric data for all of the railroad workers. RESULTS: The results showed that 261 (35.03%) of the railroad workers presented with OSAS. These railroad workers were older (OSAS: 38.53±10.08 versus non-OSAS: 33.99±8.92 years), more obese according to body mass index (27.70±4.38 versus 26.22±3.92 kg/m(2)), and employed for a longer period of time (14.32±9.13 years) compared with those without OSAS (10.96±7.66 years). Among those with OSAS, 9.5% were smokers and 54.7% reported alcohol use. The associated risk factors were age (OR=2.51, 95% CI=1.76-3.57), BMI (OR=1.56, 95% CI=1.04-2.34), alcohol use (OR=1.28, 95% CI=0.90-1.81), and a high chance of having sleep apnea, as assessed by the Berlin questionnaire (OR=2.19, 95% CI=1.49-3.21). CONCLUSION: The prevalence of OSAS in Brazilian railroad workers was higher than that observed in the general population but similar to that found in the population of the city of São Paulo, Brazil. These results suggest that age, BMI, a high risk of developing apnea through subjective self-reporting (Berlin), and alcohol use are associated with a higher risk of developing OSAS. These data reinforce the need to be more attentive to this population because they have a higher propensity for accidents.

Addictive potential of modafinil and cross-sensitization with cocaine: a pre-clinical study.

Repeated or even a single exposure to drugs of abuse can lead to persistent locomotor sensitization, which is the result of an abundance of neuroplastic changes occurring within the circuitry involved in motivational behavior and is thought to play a key role in certain aspects of drug addiction. There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy that is increasingly being used as a cognitive enhancer and has been proposed as a pharmacotherapy for cocaine dependence. Male mice were used to investigate the ability of modafinil to induce locomotor sensitization after repeated or single administration in mice. Bidirectional cross-sensitization with cocaine and modafinil-induced conditioned place preference were also evaluated. Both repeated and single exposure to moderate and high doses of modafinil produced a pronounced locomotor sensitization that cross-sensitized in a bidirectional way with cocaine. Remarkably, when cocaine and modafinil were repeatedly administered sequentially, their behavioral sensitization was additive. Supporting these behavioral sensitization data, modafinil produced a pronounced conditioned place preference in the mouse. Taken together, the present findings provide pre-clinical evidence for the addictive potential of modafinil. Our data also strongly suggest that similar neural substrates are involved in the psychomotor/rewarding effects of modafinil and cocaine.

Androgen receptor CAG repeat polymorphism is not associated with erectile dysfunction complaints, gonadal steroids, and sleep parameters: data from a population-based survey.

Erectile dysfunction (ED) can be affected by androgen levels, which exert their action through the androgen receptor (AR). Androgenic action has been demonstrated to inversely correlate with a polymorphic trinucleotide CAG repeat region in the AR gene. We conducted an epidemiologic study to determine the potential association between the CAG repeat polymorphism of the AR gene and ED complaints, gonadal steroids, and sleep parameters in a large population-based sample in São Paulo, Brazil. AR CAG repeat was genotyped in 79 men with ED complaints and in 340 controls. Sleep and hormonal profiles were measured in all men. There was no association between the AR CAG repeat polymorphism and ED complaints. Moreover, there was no significant correlation among free and total testosterone, estradiol, follicle-stimulating hormone, and luteinizing hormone levels, as well as sleep parameters with the CAG repeat length, when evaluating the population as a whole, as well as subdivided into ED and control groups independently. The results were not affected when the data were analyzed in quartiles, divided by the median of the sample, or after correction for population stratification. AR CAG repeat polymorphism is not associated with ED complaints, gonadal steroids, and sleep parameters in men from a population-based sample in Brazil.

Prevalence of erectile dysfunction complaints associated with sleep disturbances in Sao Paulo, Brazil: a population-based survey.

INTRODUCTION: The aims of this study were to estimate the prevalence of erectile dysfunction (ED) complaints in a population-based sample from Sao Paulo and to determine the associations of ED prevalence with sleep disturbances, testosterone levels, age, body mass index (BMI), socioeconomic factors and selected medical history indicators. METHODS: The Epidemiologic Sleep Study (EPISONO) is a population-based study of sleep and risk factors for sleep disturbances in Brazil's largest city, Sao Paolo. This study adopted a probabilistic three-stage cluster sampling approach for the city of Sao Paulo. Questionnaires that covered medical conditions and sexual and erection complaints were administered and polysomnographies and fasting blood samples were collected. The patient cohort of the current study of ED consisted of 467 men, aged 20-80 years at the time of their enrollment in EPISONO. The percentage of men who participated in EPISONO but refused to participate in our study was 2.3%. RESULTS: The prevalence of ED complaints in the study cohort was 17.08% overall. ED complaints ranged from 7.3% in younger men (20-29 years old) to 63.25% in older men (>50years old) (adjusted odds ratio [OR]=21.65). The logistic regression model showed that both reduced time spent in REM sleep and fragmented sleep had significant effects as risk factors for ED complaints. Obesity (OR=1.8), low testosterone levels (OR=4.28), low quality of life (OR=4.4), an apnea-hypopnea index over 15 (OR=2.75), and obstructive sleep apnea syndrome (OR=2.13) were also significantly associated with a higher risk of ED complaints. CONCLUSION: EPISONO study indicates that ED complaints are relatively common phenomena, especially among older men. Adequate sleep patterns and normal or high levels of testosterone, which serve as markers for sexual motivation, may be protective against ED. The prevalence of sleep apnea showed a strong impact on erectile function and subsequently negatively affects sexual activity.

Angiotensin-converting enzyme polymorphism and erectile dysfunction complaints in the Brazilian population.

INTRODUCTION: Angiotensin-converting enzyme (ACE) is the major regulator of circulatory homeostasis. An insertion/deletion (I/D) polymorphism in the ACE gene has been associated with marked differences in serum ACE levels and with various cardiovascular diseases. Limited and conflicting data have been published on the influence of this genetic variant on the pathophysiology of erectile dysfunction (ED). AIM: To evaluate a potential association between ACE gene polymorphism and ED complaints in a population-based sample in São Paulo, Brazil. MAIN OUTCOME MEASURES: The prevalence of ED complaints was estimated according to previously validated 8 item questionnaire. METHODS: A total of 449 men were enrolled in the Epidemiologic Sleep Study and answered an 8-item questionnaire to ascertain sexual performance/ED and satisfaction. ACE gene polymorphism were genotyped using a standard polymerase chain reaction method. RESULTS: No significant case-control difference was observed for the ACE gene I/D polymorphism either by genotype or allele-wise. Because age is a significant risk factor for ED complaints in our sample, we carried out analyses stratifying the sample by age group. The ID and II genotypes were significantly more frequent in ED complaint cases (88.9%) compared with controls (57.1%) in the men between 40 and 55 years of age. The frequency of the I allele was also significantly higher in individuals complaining of ED (66.7%) compared with men with no complaints (39.0%) (odds ratio = 3.12; 95% confidence interval = 1.48-6.59). Correction for potential confounding variables, including genetic ancestry, did not affect the strength of the association. CONCLUSIONS: The findings of the present study suggest that the I/D polymorphism or another variant in close linkage disequilibrium with it may play a role in the development of ED in a specific age group and provides progress towards the understanding of the interaction between genetic factors and the risk of ED.

Chronobiological disorders: current and prevalent conditions.

In recent decades, the hectic lifestyle of industrialized societies has wrought its effects on the quality of sleep, and these effects are evidenced by a profusion of sleep-related disorders. Regular exposure to artificial light, coupled with social and economic pressures have shortened the time spent asleep. Otherwise, Circadian Rhythm Sleep Disorders are characterized by desynchronization between the intrinsic circadian clock and the extrinsic cycles of light/dark and social activities. This desynchronization produces excessive sleepiness and insomnia. The International Classification of Sleep Disorders describes nine sleep disorders under the category of Circadian Rhythm Sleep Disorders. Currently, this diagnosis is made based on the patient's history, a sleep log alone, or the sleep logs and actigraphy conducted for at least 7 days. This review contains an overview of current treatment options, including chronotherapy, timed bright light exposure, and administration of exogenous melatonin.

Paradoxical sleep deprivation: neurochemical, hormonal and behavioral alterations. Evidence from 30 years of research.

Sleep comprises approximately one-third of a person's lifetime, but its impact on health and medical conditions remains partially unrecognized. The prevalence of sleep disorders is increasing in modern societies, with significant repercussions on people's well-being. This article reviews past and current literature on the paradoxical sleep deprivation method as well as data on its consequences to animals, ranging from behavioral changes to alterations in the gene expression. More specifically, we highlight relevant experimental studies and our group's contribution over the last three decades.

Paradoxical sleep deprivation: neurochemical, hormonal and behavioral alterations: evidence from 30 years of research

Sleep comprises approximately one-third of a person's lifetime, but its impact on health and medical conditions remains partially unrecognized. The prevalence of sleep disorders is increasing in modern societies, with significant repercussions on people's well-being. This article reviews past and current literature on the paradoxical sleep deprivation method as well as data on its consequences to animals, ranging from behavioral changes to alterations in the gene expression. More specifically, we highlight relevant experimental studies and our group's contribution over the last three decades.

O sono ocupa cerca de um terço de nossas vidas, entretanto seu impacto na saúde e sua influência nas condições patológicas ainda não foi completamente elucidado. A prevalência dos distúrbios de sono é cada vez maior, sobretudo nas regiões mais industrializadas, repercutindo diretamente no bem-estar da população. Este artigo tem como objetivo sintetizar e atualizar a literatura a respeito do método de privação de sono paradoxal e seu panorama de conseqüências desde comportamentais até genéticas em animais. Ainda, destacamos a contribuição e relevância dos estudos experimentais realizados por nosso grupo nas ultimas três décadas.

Validation of a portable monitoring system for the diagnosis of obstructive sleep apnea syndrome.

STUDY OBJECTIVE: To evaluate if a portable monitor could accurately measure the apnea-hypopnea index (AHI) in patients with a suspicion of obstructive sleep apnea (OSA). DESIGN: Prospective and randomized. SETTING: Sleep laboratory. PARTICIPANTS: 80 participants: 70 patients with clinical OSA suspicion and 10 subjects without suspicion of OSA. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Three-order randomized evaluations were performed: (1) STD (Stardust II) used at the participants' home (STD home), (2) STD used simultaneously with PSG in the sleep lab (STD+PSG lab), and (3) PSG performed without the STD (PSG lab). Four AHI values were generated and analyzed: (a) STD home; (b) STD from STD+PSG lab; (c) PSG from STD+PSG (named PSG+STD lab); and (d) PSG lab. Two technicians, blinded to study details, performed the analyses of all evaluations. There was a strong correlation between AHI from the STD and PSG recordings for all 4 AHI values (all correlations above 0.87). Sensitivity, specificity, and positive and negative predictive values at AHI cut-off values of 5, 15, and 30 events/hour were calculated. AHI values from the PSG lab and PSG+STD lab were compared to STD home and STD+PSG lab and showed the best results when STD and PSG were performed simultaneously. In all analyses, the area under ROC curve was at least 0.90. With multiple comparisons, diagnostic agreement was between 91% and 75%. The Bland Altman analyses showed strong agreement between AHI values from the STD and PSG recordings, especially when comparing the AHI from simultaneous STD and PSG recordings. CONCLUSION: These data suggest that the STD is accurate in confirming the diagnosis of OSA where there is a suspicion of the disorder. Better agreement occurred during simultaneous recordings.

Clinical profile of menopausal insomniac women referred to sleep laboratory.

OBJECTIVE: The primary purpose of this study was to assess the overall clinical profile of menopausal women complaining of insomnia who were referred to a sleep laboratory. METHODS: A total of 206 menopausal women who had complaints related to insomnia were interviewed. Each participant completed a questionnaire in order to obtain data on general health, menopausal status, medications, and sleep patterns. RESULTS: The mean age of the participants was 55.9 years. Clinical profiles revealed that the most prevalent health problems were systemic arterial hypertension (33.9%) and osteoporosis (19%), though there was no association between insomnia and incidence of chronic disease. Our data demonstrate an overall prevalence of insomnia of 4-5 times a week in 62% of the women, with 68.9% complaining of hot flashes. However, there was no association between hot flashes and frequency of insomnia across the menopausal transition period. Only 7% of women had already undergone polysomnography. Less than 5% of the participants were undergoing treatment for menopause, while 8% were taking benzodiazepines for sleep problems. CONCLUSIONS: This study provides evidence that insomnia in postmenopausal women was not associated with incidence of chronic disease. In addition, the majority of the participants were not undergoing treatment for menopause or for sleep disturbance.

Effects of hormone therapy with estrogen and/or progesterone on sleep pattern in postmenopausal women.

OBJECTIVE: To investigate the effects of estrogen and progesterone on sleep in postmenopausal women. METHOD: The 33 participants were randomly assigned to an estrogen or placebo group after undergoing clinical and hormonal assessments and a polysomnogram, and they underwent the same tests again after 12 weeks. Then, while still taking estrogen or placebo, they all received progesterone for another 12 weeks and underwent a final polysomnogram. RESULTS: Estrogen plus progesterone was more effective than estrogen alone in decreasing the prevalence of periodic limb movement (PLM) (8.1% vs 2.8%), hot flashes (14.2% vs 0%), and bruxism (11.1% vs 0%) at night, or somnolence and attention difficulty during the day. The prevalences of breathing irregularities, arousal from sleep, anxiety, and memory impairment were decreased in both groups following progesterone treatment. CONCLUSION: While not significantly affecting sleep quality, hormone therapy decreased the prevalence of arousal in both groups and that of PLM in the group treated with estrogen plus progesterone.

Physical therapy reduces insomnia symptoms in postmenopausal women.

OBJECTIVE: Regular exercise has been highly promoted and recognized as the best non-pharmacological treatment for postmenopausal problems. It may also increase total sleep time and decrease the latency of sleep onset. One study assessed the effects of exercise on sleep symptoms in postmenopausal women. Tworoger et al. [Tworoger SS, Yasui Y, Vitiello MV, et al. Effects of a Yarlong moderate-intensity exercise and stretching intervention on sleep quality in postmenopausal women. Sleep 2003;26(7):830-6] observed that increased fitness was associated with an improvement in sleep. No studies have been published describing the effects of physiotherapeutic treatments for insomnia in postmenopausal women. This study examines two cases of symptomatic postmenopausal patients with insomnia. The two patients took part in an individual physiotherapeutic treatment program that involved one and a half hour sessions twice a week for 6 consecutive months. The treatment consisted of segmental and global stretching exercises, strengthening exercises, massotherapy and relaxation techniques. Patient 1 experienced a significant increase in REM sleep and in total sleep efficiency. Patient 2 experienced a reduction in sleep latency and an increase in slow wave sleep, as shown in the polysomnograph. Both patients reported an overall improvement in their condition.