Heart rate recovery post 6-minute walking test in obstructive sleep apnea: cycle ergometry versus 6-minute walking test in OSA patients.

PURPOSE: To examine the clinical usefulness of heart rate recovery (HRR) post 6-minute walking test (6MWT) as a simple marker of cardiovascular risk in obstructive sleep apnea (OSA) patients in comparison to HRR post cycle ergometry, the validated and more sophisticated protocol. METHODS: Seventy-four participants underwent full overnight polysomnography, cycle ergometry and 6MWT. The HRR at 1, 2 and 3 min (HRR-1, HRR-2 and HRR-3) 6MWT was compared to HRR at 1, 2, and 3 min post cycle ergometry in normal subjects and in moderate and severe OSA patients before and after 6-month CPAP treatment. RESULTS: The HRR-1, HRR-2 and HRR-3 in 6MWT were significantly different between normal, moderate and severe OSA patients with higher rates achieved in normal. The higher the severity of OSA the lower the HRR was. There were also no differences found between work rate and distance walked during cycle ergometry or 6MWT, respectively, concerning normal, moderate and severe OSA patients. Heart rate recovery was further associated with minimum saturation of oxygen during sleep independently of the duration of apnea episodes of BMI and ESS. The treatment with CPAP had a beneficial effect on HRR both post-6MWT and post cycle ergometry. CONCLUSIONS: Autonomic nervous system dysfunction in OSA can be found even with submaximal exertion. Heart rate recovery post-6MWT, such as HRR post cycle ergometry, was significantly impaired in OSA patients in comparison to normals and was favorably influenced from CPAP treatment. Furthermore, it was found to be more sensitive compared with distance walked in 6MWT in discriminating severity of OSA. The HRR post-6MWT was found to be an easily measured and reliable marker of OSA severity both before and after CPAP treatment.

Adherence to CPAP therapy improves quality of life and reduces symptoms among obstructive sleep apnea syndrome patients.

PURPOSE: The aim of the study was to asses quality of life and symptoms of obstructive sleep apnea syndrome (OSAS) patients after adhering to 6 months of continuous positive airway pressure (CPAP) treatment. METHODS: A group of 50 patients (41 men and 9 women) were diagnosed by polysomnography and treated with CPAP therapy for 6 months. Their symptoms and health-related quality of life were assessed by administering a validated and translated version of the sleep apnea quality of life index (SAQLI). Sleepiness was measured using the Epworth Sleepiness Scale (ESS) and through electronic monitoring of CPAP usage per night of sleep. RESULTS: Mean CPAP usage was 4.5 ± 0.5 h per night. Comparisons between quality of life indexes before and after CPAP treatment showed an improvement in the total SAQLI score (3.8 ± 0.9 vs. 5.8 ± 0.8 after CPAP, p < 0.01), in daily functioning (4.2 ± 1.4 vs. 6.0 ± 0.9, p < 0.01), social interactions (4.8 ± 1.3 vs.6.3 ± 0.7, p < 0.01), emotional functioning (4.4 ± 1.4 vs. 5.7 ± 1.0, p < 0.01), symptoms (1.6 ± 0.8 vs. 5.8 ± 1.2, p < 0.01), and in the ESS (13.7 ± 6.5 vs. 3.9 ± 3.8, p < 0.01). Regarding the patients' symptoms, improvement was noticed for "sleepiness while watching a spectacle" (96%), "reading" (95%), "carrying on a conversation" (95%), "driving" (92.9%), "restless sleep" (87.8%), and "urinating more than once per night" (84.8%). Smaller improvements were observed for the reported "dry mouth-throat upon awakening" (36.1%),"excessive fatigue" (54.5%), and "decreased energy" (55.3%). CONCLUSION: We conclude that OSAS patients who adhere to nighttime CPAP therapy show significant improvement of their quality of life, daytime sleepiness, and other symptoms after 6 months of treatment with CPAP.

Prediction of obstructive sleep apnea syndrome in a large Greek population.

PURPOSE: We aimed to evaluate the predictive value of anthropometric measurements and self-reported symptoms of obstructive sleep apnea syndrome (OSAS) in a large number of not yet diagnosed or treated patients. Commonly used clinical indices were used to derive a prediction formula that could identify patients at low and high risk for OSAS. METHODS: Two thousand six hundred ninety patients with suspected OSAS were enrolled. We obtained weight; height; neck, waist, and hip circumference; and a measure of subjective sleepiness (Epworth sleepiness scale--ESS) prior to diagnostic polysomnography. Excessive daytime sleepiness severity (EDS) was coded as follows: 0 for ESS ≤ 3 (normal), 1 for ESS score 4-9 (normal to mild sleepiness), 2 for score 10-16 (moderate to severe sleepiness), and 3 for score >16 (severe sleepiness). Multivariate linear and logistic regression analysis was used to identify independent predictors of apnea-hypopnea index (AHI) and derive a prediction formula. RESULTS: Neck circumference (NC) in centimeters, body mass index (BMI) in kilograms per square meter, sleepiness as a code indicating EDS severity, and gender as a constant were significant predictors for AHI. The derived formula was: AHIpred = NC × 0.84 + EDS × 7.78 + BMI × 0.91 - [8.2 × gender constant (1 or 2) + 37]. The probability that this equation predicts AHI greater than 15 correctly was 78%. CONCLUSIONS: Gender, BMI, NC, and sleepiness were significant clinical predictors of OSAS in Greek subjects. Such a prediction formula can play a role in prioritizing patients for PSG evaluation, diagnosis, and initiation of treatment.

The impact of positive airway pressure on cardiac status and clinical outcomes in patients with advanced heart failure and sleep-disordered breathing: a preliminary report.

INTRODUCTION: Heart failure (HF) is a major public health problem associated with high rates of morbidity and mortality. Patients with HF exhibit a high prevalence of sleep-disordered breathing (SDB). We have investigated the long-term impact of positive airway pressure (PAP) therapy on heart function and clinical outcomes in patients with advanced HF and concomitant SDB. MATERIALS AND METHODS: We assessed 18 patients with advanced HF (New York Heart Association (NYHA) functional classification III-IV) and concomitant SDB (diagnosed with polysomnography) either of obstructive or central type. Eleven patients who received PAP therapy (auto-titrating PAP or adaptive servo-ventilation) for 12 months were compared with seven patients who refused this therapy. All participants were assessed at both baseline and end of follow-up for NYHA functional status, left and right ventricular function, neurohormonal activation, and exercise tolerance. The rates of hospitalization, deaths, and the combination of both were also recorded. RESULTS: Patients treated with PAP achieved better functional status, higher left ventricular ejection fraction, improved longitudinal right ventricular contractile function, lower levels of b-type natriuretic peptide, and greater exercise performance compared to those who remained untreated. PAP-treated group had a significantly lower incidence of the prespecified combined end-point (i.e., hospital admissions and death) than the control group (87.5 vs. 18.2%, p = 0.013). Interestingly, the mortality rate was 28% (two out of seven patients) in the control group, while no deaths were recorded in the PAP-treated group. DISCUSSION: In this preliminary study, we found that treatment of SDB, irrespective of type, in stable patients with advanced HF receiving optimal medical therapy was associated with improvement in cardiac functional status, ventricular contraction, physical performance, and neurohormonal status, leading to better clinical outcomes.

How common is sleep-disordered breathing in patients with idiopathic pulmonary fibrosis?

BACKGROUND AND AIM: The frequency of obstructive sleep apnea-hypopnea syndrome (OSAHS) in patients with idiopathic pulmonary fibrosis (IPF) remains controversial. The aim of this study was to assess the frequency of OSAHS in newly diagnosed IPF patients and to identify possible correlations with body mass index and pulmonary function testing parameters. MATERIALS AND METHODS: Thirty-four newly diagnosed IPF patients were included. All subjects underwent attended overnight PSG. None of the included subjects was under any of the currently available IPF treatments or nocturnal supplemental oxygen therapy. RESULTS: Total apnea-hypopnea index (AHI) was <5, 5-15, and ≥ 15/h of sleep in 14 (41%), 15 (44%), and five patients (15%), respectively. REM AHI was statistically significant correlated with TLC [Total lung capacity] (p=0.03, r= -0.38). Diffusing capacity of the lung for carbon monoxide was correlated with mean oxygen saturation during sleep (p=0.02, r=0.39). CONCLUSIONS: Sleep-disordered breathing seems frequent, although remains usually under diagnosed in IPF patients. A decrease in TLC, reflecting the severity of pulmonary restriction, might predispose IPF patients in SDB, especially during the vulnerable REM sleep period.

Sleep breathing disorders in the U.S. female population.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a common disorder that remains underdiagnosed in adult females. The Berlin Questionnaire is a validated tool for identifying people at risk for OSAS. The aim of this report was to evaluate the prevalence of common symptoms of OSAS in women and to estimate the risk for OSAS among females in the United States. METHODS: This is an analysis of data from the 2007 Sleep in America Poll of the National Sleep Foundation. The NSF Poll is an annual telephone survey of a representative sample of U.S. adults. The 2007 NSF Poll included 1254 women in the United States, with an oversample of pregnant and postpartum women. We used the Berlin Questionnaire to estimate the risk for OSAS among the U.S. female population. This instrument includes questions about self-reported snoring, witnessed apneas, daytime sleepiness, hypertension, and obesity. Also included were questions about sleep habits, sleep problems, menstrual cycle status, and other medical disorders. RESULTS: Twenty-five percent of the female population was found to be at high risk for OSAS. Among women at high risk, such common symptoms of OSAS as habitual snoring (61%), observed apneas (7%), and daytime sleepiness (24%) were highly prevalent. Sleep onset insomnia (32%) or maintenance insomnia symptoms (19%) and restless legs syndrome (RLS) symptoms (33%) or body movements (60%) also were frequently reported. The risk increased with age (p < 0.05), obesity (p < 0.001), and menopause (p < 0.001). The presence of chronic medical disorders was more frequently reported among women at high risk. CONCLUSIONS: One in four women in America is at high risk of having OSAS. Awareness by the primary care medical community of this disorder in females should thus be increased.

Association of sleep apnea severity and obesity with insulin resistance, C-reactive protein, and leptin levels in male patients with obstructive sleep apnea.

Obesity is the major confounding factor in the relationship between obstructive sleep apnea and increased risk for cardiovascular disease. The aim of the study was to investigate the association of sleep apnea severity with insulin resistance, leptin, and CRP levels in a cohort of male patients. Sixty-seven men referred to our sleep laboratory for evaluation of suspected obstructive sleep apnea syndrome (OSAS) were divided into three groups according to apnea severity: non-OSAS group (n=15), mild to moderate OSAS group (n=26), and severe OSAS (n=26). Insulin resistance was estimated by the homeostasis model assessment method. HOMA values were similar in the three groups: (3.2+/-2.2 vs. 3.3+/-1.8 vs. 3.6+/-1.5, respectively, p=0.71). Leptin levels were higher in the mild to moderate OSAS group (23.1+/-21.8 ng/ml, p<0.05) and in the severe OSAS group (20.2+/-17.5 ng/ml, p<0.05) than in the non-OSAS group (9.4+/-6.4 ng/ml). CRP levels were significantly higher in severe sleep apnea (0.35+/-0.3 vs. 0.19+/-0.1 mg/dl, p<0.05). In multiple regression analyses, waist-to-hip ratio (WHR) was the most significant determinant of HOMA estimation for insulin resistance. WHR and the percentage of total sleep time spent with hypoxemia (%TST with SaO2 <90%) were significant predictors for leptin levels, while body mass index (BMI) and the %TST with SaO2 <90% were the best predicting parameters for CRP levels. Insulin resistance estimated by the HOMA method in male patients with OSAS was not associated with sleep apnea severity independent of obesity. The severity of nocturnal hypoxemia was associated with leptin and CRP levels independent of obesity.

Cytokines and pathological sleep.

Cytokines are proteins produced by leukocytes and other cells that function as intercellular mediators acting on several target tissues, resulting in multiple biologic actions. Over the last decade, medical research has explored the interaction between cytokines and sleep disorders. The aim of this review is to illustrate recent advances in knowledge about the relationship between cytokines and disorders of excessive sleepiness. Cytokines may have an important role in mediating excessive daytime sleepiness in sleep loss or insomnia. Alterations of the immune system have also been associated with narcolepsy. The relationship between cytokines and hormonal regulatory mechanisms may explain symptoms like fatigue and sleepiness in chronic inflammatory diseases. Cytokines may play an important role in the pathogenesis of obstructive sleep apnea and cardiovascular consequences of this condition. New biologic treatments targeting cytokines have been investigated in conditions characterized by sleep disturbance.

Cytokines and normal sleep.

PURPOSE OF REVIEW: Cytokines are mediators of immune system responses with multiple biologic actions on several target tissues. Over the past two decades, research has explored the interactions between cytokines and sleep mechanisms of the brain. This short review highlights selected findings that have advanced our understanding of the relation between cytokines and sleep. RECENT FINDINGS: A complex network of cytokines and their receptors exists in brain. Cytokines may either promote or inhibit sleep. Of cytokines studied thus far, evidence indicates that interleukin-1 and tumor necrosis factor play a role in the regulation of non-rapid eye movement sleep. Their sites of action for regulating such sleep likely include the hypothalamic preoptic area and the basal forebrain. Mechanisms of action include direct receptor-mediated effects on neurons and the synthesis and release of numerous transmitters, peptides, and hormones that lead to subsequent changes in sleep. Among others, the cascade of responses induced by cytokines that may lead to subsequent alterations in sleep includes alterations in nitric oxide synthesis and effects on neurohormonal systems such as growth hormone releasing hormone. The activation by cytokines of the hypothalamic-pituitary-adrenal axis also influences sleep. Studies suggest that there is a significant overlap between neurohormonal systems such as the somatotropic and hypothalamic-pituitary-adrenal axes and cytokines, particularly with regard to their effects on sleep-wake regulation. SUMMARY: There is increasing evidence of a role for cytokines in regulating spontaneous non-rapid eye movement sleep. The somatotropic hormonal system and hypothalamic-pituitary-adrenal axis mediate, in part, the effects of cytokines on sleep.

Gender and obstructive sleep apnea syndrome, part 2: mechanisms.

Epidemiologic studies have reported that obstructive sleep apnea syndrome (OSAS) is a common disorder affecting about four percent of adult males and two percent of adult females. This difference in OSAS prevalence suggests that the female gender may reduce the risk of sleep breathing disorders in adults. We review several interrelated factors that may explain the differences in risk related to gender. These include differences in obesity and the distribution of adipose tissue, upper-airway anatomy, upper-airway muscle function, control of ventilation, the effect of sex hormones and leptin. The gender related protective effect decreases in females who are postmenopausal and not on hormone replacement therapy.

Gender and obstructive sleep apnea syndrome, part 1: Clinical features.

In the two decades after obstructive sleep apnea syndrome (OSAS) was described, it was considered a disease primarily of males. As a result, for many years, epidemiologic studies of the general population examining the prevalence of OSAS included only males and investigators examined almost exclusively males in their pathophysiologic studies. It has been widely recognized that OSAS in women is not as rare as it was originally believed. Whereas early studies of clinic populations suggested that females made up about 10% or less of OSAS cases, later studies of the general population suggest that about a third of all cases are females. This suggests that there may be clinical under-recognition of OSAS in females. We explore the reasons for the male predominance of OSAS, and the clinical under-recognition in females by examining differences in clinical presentation and polysomnography findings between male and female patients.