Sonia Maria Togeiro

Obstructive Sleep Apnea: A Cardiometabolic Risk in Obesity and the Metabolic Syndrome

Obstructive sleep apnea (OSA) is an underdiagnosed condition characterized by recurrent episodes of obstruction of the upper airway leading to sleep fragmentation and intermittent hypoxia during sleep. Obesity predisposes to OSA, and the prevalence of OSA is increasing worldwide because of the ongoing epidemic of obesity. Recent evidence has shown that surrogate markers of cardiovascular risk, including sympathetic activation, systemic inflammation, and endothelial dysfunction, are significantly increased in obese patients with OSA versus those without OSA, suggesting that OSA is not simply an epiphenomenon of obesity. Moreover, findings from animal models and patients with OSA show that intermittent hypoxia exacerbates the metabolic dysfunction of obesity, augmenting insulin resistance and nonalcoholic fatty liver disease. In patients with the metabolic syndrome, the prevalence of moderate to severe OSA is very high (∼60%). In this population, OSA is independently associated with increased glucose and triglyceride levels as well as markers of inflammation, arterial stiffness, and atherosclerosis. A recent randomized, controlled, crossover study showed that effective treatment of OSA with continuous positive airway pressure for 3 months significantly reduced several components of the metabolic syndrome, including blood pressure, triglyceride levels, and visceral fat. Finally, several cohort studies have consistently shown that OSA is associated with increased cardiovascular mortality, independent of obesity. Taken together, these results support the concept that OSA exacerbates the cardiometabolic risk attributed to obesity and the metabolic syndrome. Recognition and treatment of OSA may decrease the cardiovascular risk in obese patients.

CPAP and survival in moderate-to-severe obstructive sleep apnoea syndrome and hypoxaemic COPD

Obstructive sleep apnoea syndrome (OSAS) often coexists in patients with chronic obstructive pulmonary disease (COPD). The present prospective cohort study tested the effect of OSAS treatment with continuous positive airway pressure (CPAP) on the survival of hypoxaemic COPD patients. It was hypothesised that CPAP treatment would be associated with higher survival in patients with moderate-to-severe OSAS and hypoxaemic COPD receiving long-term oxygen therapy (LTOT). Prospective study participants attended two outpatient advanced lung disease LTOT clinics in São Paulo, Brazil, between January 1996 and July 2006. Of 603 hypoxaemic COPD patients receiving LTOT, 95 were diagnosed with moderate-to-severe OSAS. Of this OSAS group, 61 (64%) patients accepted and were adherent to CPAP treatment, and 34 did not accept or were not adherent and were considered not treated. The 5-yr survival estimate was 71% (95% confidence interval 53–83%) and 26% (12–43%) in the CPAP-treated and nontreated groups, respectively (p<0.01). After adjusting for several confounders, patients treated with CPAP showed a significantly lower risk of death (hazard ratio of death versus nontreated 0.19 (0.08–0.48)). The present study found that CPAP treatment was associated with higher survival in patients with moderate-to-severe OSAS and hypoxaemic COPD receiving LTOT.

The variability of the apnoea–hypopnoea index

This study was designed to evaluate the variability of the apnoea–hypopnoea index (AHI) in 20 patients with obstructive sleep apnoea–hypopnoea syndrome (OSAHS) and to determine possible relationships of this variability with other polysomnographic parameters. The subjects were recorded on four consecutive nights. The mean AHI values were not significantly altered throughout the four recording nights (P=0.67). The intraclass correlation coefficient of the AHI on the four nights was 0.92. However, the Bland and Altman plot showed that, individually, the AHI presented an important variability, which was not related to its initial value. In regard to the OSAHS severity, 50% of the patients changed the classification from the first to the subsequent nights. Thirteen of the 20 patients (65%) presented a variation in the AHI value equal or higher than 10 events h–1. When we evaluated the AHI mean values for a specific body position and sleep stage, no difference was observed among the nights. In both supine and lateral–ventral decubitus, higher AHI was observed during Stages 1 and 2 than the other stages. Additionally, the AHI during Stages 1 and 2 and REM sleep was higher on the supine than on the lateral–ventral decubitus. The AHI in OSAHS patients presented a good correlation among the four recording nights; however, a significant individual variability should be considered, especially when AHI is applied in OSAHS classification or as a criterion of therapeutic success.

Clinical, Anthropometric and Upper Airway Anatomic Characteristics of Obese Patients with Obstructive Sleep Apnea Syndrome

Background: Obese subjects are at increased risk of developing obstructive sleep apnea syndrome (OSAS). However, the individual role of local (i.e., upper airway-related) and general (clinical and whole-body anthropometric) characteristics in determining OSAS in obese patients is still controversial. Objectives: To contrast the clinical, anthropometric and upper airway anatomical features of obese subjects presenting or not presenting with OSAS. Methods: Thirty-seven obese (BMI ≧30 kg/m2) males with OSAS and 14 age- and gender-matched obese controls underwent clinical and anthropometric (BMI, waist-to-hip ratio and neck circumference) evaluation. In a subgroup of subjects (18 and 11 subjects, respectively), magnetic resonance imaging (MRI) during wakefulness was used to study the upper airway anatomy. Results: OSAS patients showed significantly higher BMI, waist-to-hip ratio and neck circumference as compared to controls (p < 0.05). They also referred to nonrepairing sleep, impaired attention, and previous car accidents more frequently (p < 0.05). The transversal diameter of the airways (TDAW) at the retroglossal level by MRI was found to be an independent predictor of the presence and severity of OSAS (p < 0.05). Parapharyngeal fat increase, however, was not related to OSAS. A TDAW >12 mm was especially useful to rule out severe OSAS (apnea-hypopnea index >30, negative predictive value = 88.9%, likelihood ratio for a negative test result = 0.19). Conclusions: MRI of the upper airway can be used in association with clinical and anthropometric data to identify obese males at increased risk of OSAS.

Consequences of obstructive sleep apnea on metabolic profile: A Population-Based Survey†

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.

Continuous positive airway pressure therapy improves hypoadiponectinemia in severe obese men with obstructive sleep apnea without changes in insulin resistance.

BACKGROUND Obstructive sleep apnea (OSA) is associated with several conditions that could facilitate the onset of cardiovascular and metabolic dysfunctions. Continuous positive airway pressure (CPAP) therapy has been shown to improve cardiovascular morbidity and mortality related to OSA, but the mechanisms underlying this association are not fully understood. OBJECTIVE The aim of the present study was to evaluate whether sleep apnea contributes to insulin resistance and inflammatory marker alterations and to evaluate the benefits of nasal CPAP therapy in severe obese patients with OSA. METHODS Plasma inflammatory cytokines and the homeostasis model assessment of insulin resistance index (HOMA-IR, Insulin Sensitivity Index [ISI]) were measured in severe obese male with OSA (n = 16) and compared with body mass index (BMI)-matched male controls without OSA (n = 13). Seven patients with severe sleep apnea (apnea-hypopnea index >30 events/h) were reevaluated after 3 months of nasal CPAP therapy. RESULTS OSA patients had a significantly lower adiponectin levels than obese controls (8.7 +/- 1.18 ng/mL vs. 15.0 +/- 2.55 ng/mL, P = 0.025). HOMA-IR, ISI, tumor necrosis factor-alpha (TNF-alpha, C-reactive protein (CRP), and interleukin-6 (IL-6) levels were not different between groups. Although insulin resistance index and BMI values did not change after 3 months of nCPAP therapy, adiponectin levels increased (P = 0.036) and the levels of TNF-alpha tended to decrease (P = 0.065). Changes in adiponectin levels during nCPAP therapy were positively correlated with an improvement in minimum oxygen saturation (r = 0.773; P = 0.041) and negatively correlated with changes in TNF-alpha levels (r = -0.885; P = 0.008). CONCLUSIONS nCPAP therapy reverses hypoadiponectinemia levels present in obese men with OSA, probably through reductions in hypoxia and inflammation activity.

Métodos diagnósticos nos distúrbios do sono

The aim of this manuscript is to describe the procedures, recommendations, findings and value of the diagnostic methods used in Sleep Disorders including questionnaires, Actigraph, Polysomnography and Multiple sleep latency test. Specific questionnaires including evaluation of sleep quality , hyper somnolence, Respiratory Sleep Disorders and Sleep-Wake rhythm are in general, used as a screening for the Sleep Disorders and indication of sleep studies. Polysomnogram and Multiple sleep latency test are considered the gold standard methods for the diagnosis of majority of sleep disorders and Narcolepsy respectively. Criteria for these disorders are reported bellow.

Effect of continuous positive airway pressure therapy on hypothalamic-pituitary-adrenal axis function and 24-h blood pressure profile in obese men with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) increases the risk of cardiovascular events. Sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis activation may be the mechanism of this relationship. The aim of this study was to evaluate HPA axis and ambulatory blood pressure monitoring in obese men with and without OSAS and to determine whether nasal continuous positive airway pressure therapy (nCPAP) influenced responses. Twenty-four-hour ambulatory blood pressure monitoring and overnight cortisol suppression test with 0.25 mg of dexamethasone were performed in 16 obese men with OSAS and 13 obese men controls. Nine men with severe apnea were reevaluated 3 mo after nCPAP therapy. Body mass index and blood pressure of OSAS patients and obese controls were similar. In OSAS patients, the percentage of fall in systolic blood pressure at night (P = 0.027) and salivary cortisol suppression postdexamethasone (P = 0.038) were lower, whereas heart rate (P = 0.022) was higher compared with obese controls. After nCPAP therapy, patients showed a reduction in heart rate (P = 0.036) and a greater cortisol suppression after dexamethasone (P = 0.001). No difference in arterial blood pressure (P = 0.183) was observed after 3 mo of nCPAP therapy. Improvement in cortisol suppression was positively correlated with an improvement in apnea-hypopnea index during nCPAP therapy (r = 0.799, P = 0.010). In conclusion, men with OSAS present increased postdexamethasone cortisol levels and heart rate, which were recovered by nCPAP.

Sleep disordered breathing in Parkinson's disease: a critical appraisal.

Parkinsons disease (PD) is the second most common neurodegenerative disorder, characterized by resting tremor, rigidity, bradykinesia and postural instability, and is associated with non-motor features, including sleep abnormalities. The high prevalence of excessive daytime sleepiness and snoring in PD patients has led to the suggestion that sleep disordered breathing (SDB) is more common in these individuals than in normal subjects. We aimed to review the literature on SDB prevalence and its clinical repercussions in PD. A PubMed search was performed to identify controlled studies, published from January 1990 through October 2012, which addressed the prevalence of SDB diagnosed by polysomnography in idiopathic PD. From the seven studies included, five reported similar or lower prevalence of SDB in patients when compared to healthy age-matched controls. Two studies reported less oxyhemoglobin desaturation during sleep among patients. These results did not support the idea that PD patients are at increased risk of SDB and indicate that they may not present significant hypoxemia. The prevalence of obstructive sleep apnea syndrome and the long-term outcomes of disordered breathing events during sleep have not been adequately studied in PD.

Disturbed sleep and musculoskeletal pain in the bed partner of patients with obstructive sleep apnea

BACKGROUND Obstructive sleep apnea (OSA) has been recognized as a distressing experience to the female partner, but a causal association remains controversial. Furthermore, a growing body of evidence supports a relationship of distress and sleep disruptions with musculoskeletal pain, also prevalent in middle-aged women. To test the hypothesis that sharing a bed with an OSA man may contribute to manifestations of distress and impaired sleep, we conducted a case-control study of 17 OSA wives and 17 wives of healthy sleepers. METHODS Clinical outcome variables were scores of the Fibromyalgia Impact Questionnaire (FIQ) and visual analog scales (VAS), tender point (TP) count and algometric index. Sleep outcome parameters were VAS scores for sleep quality and polysomnographic (PSG) parameters. Secondary outcomes were VAS scores for distress and marital relationship and coping strategies adopted by OSA wives. Clinical assessment and PSG scoring were conducted blindly. RESULTS After controlling for age and menopausal status, OSA wives exhibited lower sleep quality and higher distress scores than controls (p<0.05, all). Increase in pain threshold (TP count and algometric index) and in FIQ score were also observed, and in their PSG, there was an increase in awaken period and stage 1 amount during sleep, as well as in alpha power during slow wave sleep (p<0.05, all). These sleep parameters had substantial correlation with tiredness and poor sleep quality and were moderately correlated to pain assessments and distress scores. CONCLUSION Thus, independently of age and menopausal status of the group, wives of OSA patients exhibited an increase in pain threshold, distress and impaired sleep in comparison to controls.