Increasing systemic chronic inflammation mediated the association between poor sleep during pregnancy and gestational cardiovascular health.

OBJECTIVES: This study aimed to examine the association between sleep behaviors and cardiovascular health (CVH) during pregnancy and test whether high-sensitivity C-reactive protein (hs-CRP) mediates this association. METHODS: The study included 4204 pregnant women from the Maternal and Infant Health cohort study in Hefei (MIH-Hefei). Information on sleep (chronotype, sleep duration, snoring, daytime sleepiness, and insomnia) was collected through a touch-screen structured questionnaire at 16-23 weeks' gestation. CVH (body mass index, blood pressure, total cholesterol, glucose, and smoking) and hs-CRP were measured at 24-28 weeks' gestation. The role of hs-CRP in the association between sleep and CVH was explored in a mediation analysis, while adjusting for multiple confounding factors. RESULTS: Poor sleep score was significantly associated with poor gestational CVH metrics, including an RR of 0.872 (95% CI, 0.810, 0.938) for having all ideal (vs. any nonideal) CVH metrics; hs-CRP level was significantly associated with poor gestational CVH metrics, including an RR of 0.531 (95% CI, 0.432, 0.609) for having all ideal (vs. any nonideal) CVH metrics. Sleep scores were positively correlated with hs-CRP level (ß, 0.020, 95% CI, 0.006, 0.034). Mediation analysis revealed that the association between sleep and CVH mediated by hs-CRP was 12.31% (indirect effect, -0.0095, 95% CI, -0.0167, -0.0042). CONCLUSIONS: Poor sleep during pregnancy, particularly late chronotype and snoring, may worsen CVH by increasing systemic chronic inflammation.

Impact of autoimmune comorbidity on fatigue, sleepiness and mood in myasthenia gravis.

BACKGROUND: Disease burden in myasthenia gravis (MG) and in other autoimmune disorders is often determined by common accompanying symptoms such as fatigue, sleepiness and mood disturbances. Many MG patients have a second autoimmune disease, but it is unclear whether autoimmune comorbidities add to the severity of fatigue, sleepiness and mood disturbances. METHODS: We ascertained the presence of autoimmune comorbidities in 69 well-characterized MG patients. To assess fatigue, sleepiness and mood disturbances, we applied the Fatigue Severity Scale (FSS), the Fatigue Impact Scale (FIS), the Epworth Sleepiness Scale (ESS), as well as the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) to all patients. RESULTS: Thirteen MG patients had concomitant autoimmune thyroid disease (AITD), including 1 patient with rheumatoid arthritis as third autoimmune disease. Fatigue (68.1%), excessive daytime sleepiness (14.5%), moderate-severe depression (20.3%) and anxiety (26.1%) were common, but MG patients with and without autoimmune comorbidities had similar FSS, FIS, ESS, BDI and STAI scores. The presence of autoimmune comorbidities was not associated with altered clinical and immunological MG characteristics, but MG patients with autoimmune comorbidities have more often been treated with corticosteroids than patients without autoimmune comorbidities (92.3% vs. 60.7%; p = 0.03). CONCLUSIONS: While many MG patients were affected by fatigue, sleepiness, depression and anxiety, the present study does not suggest that coexisting autoimmune diseases substantially contribute to the magnitude of these cumbersome comorbid symptoms. However, the higher frequency of steroid treatment may have counterbalanced the effects of the autoimmune comorbidity.

[Hypercalcemic crisis and hypocalcemic tetany]. / Hyperkalzämische Krise und hypokalzämische Tetanie.

A serum calcium level >3.5 mmol/l together with clinical symptoms such as muscle weakness, fatigue, nausea, vomiting, pancreatitis or even coma are characteristic for a hypercalcemic crisis (HC). Primary hyperparathyroidism (1HPT) and malignancy-associated hypercalcemia are the most frequent causal diseases for a HC. The analysis of serum levels for calcium, phosphorous, intact parathyroid hormone, electrophoresis and renal function parameters indicate which further radiological, scintigraphic or serum diagnostic steps are adequate to identify the cause of the patient's acute situation (i. e. most frequently 1HPT or malignant disease with bone involvement, e. g. myeloma) and thus to initiate the required surgical or oncological intervention. However, the primary goals in the treatment of HC include correcting dehydration and improving kidney function, lowering calcium levels and decreasing osteoclastic bone resorption. The goals are accomplished by volume repletion, forced diuresis, antiresorptive agents and hemodialysis on an intensive care unit. Hypocalcemic tetany (HT) is the consequence of severely lowered calcium levels (<2.0 mmol/l), usually in patients with chronic hypocalcemia. The causal disease for hypocalcemic tetany is frequently a lack of parathyroid hormone (PTH), (e. g. as a complication of thyroid surgery) or, rarely, resistance to PTH. HT due to severe and painful clinical symptoms requires rapid i. v. calcium replacement by central venous catheter on an intensive care unit. For the treatment of chronic hypocalcemia oral calcium and 25OH-vitamin D or even 1,25(OH)2-vitamin D3 and magnesium supplements may be necessary to achieve the desired low normal calcium levels. Thiazides are useful to reduce renal calcium loss and to stabilize the calcium levels. Some patients continue to exhibit clinical symptoms despite adequate calcium levels; in these cases s. c. parathyroid hormone 1-84 should be considered to stabilize calcium levels and to lower the dosage of calcium and vitamin D supplements.

Objective, but Not Subjective, Sleepiness is Associated With Inflammation in Sleep Apnea.

Study objectives: Objective and subjective measures of excessive daytime sleepiness (EDS) are only weakly associated. No study, however, has examined whether these two measures of EDS differ in terms of underlying mechanisms and prognostic value. Pro-inflammatory cytokines, that is, interleukin-6 (IL-6) appear to promote sleepiness/fatigue, while the stress hormone cortisol promotes vigilance. We hypothesized that objective sleepiness is associated with increased levels of IL-6 and decreased levels of cortisol. Methods: We studied 58 obstructive sleep apnea (OSA) patients with clinical EDS and/or cardiovascular comorbidities who underwent 8-hour in-lab polysomnography for four consecutive nights. Objective and subjective daytime sleepiness were measured by Multiple Sleep Latency Test (MSLT), Epworth Sleepiness Scale (ESS), and Stanford Sleepiness Scale (SSS), respectively. Twenty-four-hour profiles of IL-6 and cortisol levels were assessed on the fourth day. Results: The agreement between objective and subjective EDS in OSA patients was fair (kappa = 0.22). Objective EDS (lower MSLT) in OSA patients was associated with significantly elevated 24-hour (ß = -0.34, p = .01), daytime (ß = -0.30, p = .02) and nighttime (ß = -0.38, p < .01) IL-6 levels, and significantly decreased daytime (ß = 0.35, p = .01) cortisol levels. In contrast, subjective EDS (higher ESS/SSS) was not associated with either elevated IL-6 levels or decreased cortisol levels. Conclusions: Our findings suggest that OSA with objective EDS is the more severe phenotype of the disorder associated with low-grade inflammation, a link to cardiometabolic morbidity and mortality. Compared to subjective EDS, objective EDS is a stronger predictor of OSA severity and may be useful in the clinical management of the disorder.

Changes at Mean Platelet Volume and Platelet Distribution Width Levels After Septoplasty and Its Correlation With Epworth Sleepness Scale.

OBJECTIVE: Nasal septum deviation may affect cardiopulmonary system. Those effects can be determined via blood tests and Epworth sleepness scale (ESS). In this study, it was aimed to measure mean platelet volume (MPV) and platelet distribution width (PDW) in patients with nasal septum deviation and to assess changes at their levels after septoplasty. Furthermore, it was purposed to document the correlation between ESS score and MPV, PDW levels. METHODS: Eighty-one patients who underwent septoplasty and 50 healthy controls composed the study group. Epworth sleepness scale was performed to all patients preoperatively and patients were divided into 2 groups in terms of ESS scores. Mean platelet volume and PDW levels were measured preoperatively and it was repeated postoperatively. RESULTS: In Group A (ESS <10), MPV reduced from 8.48 ±â€Š0.38 fl to 8.47 ±â€Š0.36 fl (P >0.05), PDW reduced from 14.56 ±â€Š1.27% to 14.43 ±â€Š1.03% after surgery (P >0.05). On the other hand, in Group B (ESS ≥10), MPV reduced from 9.54 ±â€Š0.68 fl to 8.87 ±â€Š0.44 fl (P <0.001), PDW reduced from 17.15 ±â€Š1.75% to 15.35 ±â€Š1.29% postoperatively (P <0.001). CONCLUSIONS: Statistically significant improvements at MPV and PDW levels after surgery were noticed only at patients with excessive daytime sleepness whose ESS score was 10 or above. According to this, it would be preferable to operate these patients earlier to protect them from systemic effects.

Daytime sleepiness is associated with hyperhomocysteinemia in rural area of China: A cross-sectional study.

OBJECTIVE: To ascertain whether sleep abnormalities including daytime sleepiness, snoring, apnea, sleep disruption and sleep duration abnormity are significantly associated with hyperhomocysteinemia (Hhcy). METHODS: A total of 5992 participants were involved in the cross-sectional study. Sleep abnormalities were evaluated by a structured questionnaire. Hhcy was defined as plasma levels of homocysteine ≥15µm/L. RESULTS: After adjustment for age, gender, education, current smoking status and current drinking status, daytime sleepiness (OR, 1.597; 95%CI, 1.210-2.110, P=0.001), sleep duration <6h (OR, 1.273; 95%CI, 1.063-1.524, P=0.009) and sleep duration >8h (OR, 1.205; 95%CI, 1.065-1.364, P=0.003) were significantly associated with Hhcy. While snoring (OR, 1.065; 95%CI, 0.950-1.195, P=0.279), apnea (OR, 1.170; 95%CI, 0.924-1.482, P=0.193), and sleep disruption (OR, 1.065; 95%CI, 0.852-1.331, P=0.580) were not. After further adjustment for body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, total cholesterol, physical activity, diabetes, coronary heart disease, stroke, depression, glomerular filtration rate, hypertension and hyperuricemia, still the increased OR could be found in the daytime sleepiness group (OR, 1.569; 95%CI, 1.145-2.150, P=0.005). However, sleep duration <6h (OR, 1.067; 95%CI, 0.788-1.445, P=0.676) and sleep duration >8h groups (OR, 1.080; 95%CI, 0.883-1.320, P=0.453) were no longer significantly associated with Hhcy. CONCLUSIONS: Daytime sleepiness, but not sleep duration abnormity, snoring, apnea and sleep disruption was an independent risk factor for Hhcy.

IL-1ß and BDNF are associated with improvement in hypersomnia but not insomnia following exercise in major depressive disorder.

Given the role of sleep in the development and treatment of major depressive disorder (MDD), it is becoming increasingly clear that elucidation of the biological mechanisms underlying sleep disturbances in MDD is crucial to improve treatment outcomes. Sleep disturbances are varied and can present as insomnia and/or hypersomnia. Though research has examined the biological underpinnings of insomnia in MDD, little is known about the role of biomarkers in hypersomnia associated with MDD. This paper examines biomarkers associated with changes in hypersomnia and insomnia and as predictors of improvements in sleep quality following exercise augmentation in persons with MDD. Subjects with non-remitted MDD were randomized to augmentation with one of two doses of aerobic exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for 12 weeks. The four sleep-related items on the clinician-rated Inventory of Depressive Symptomatology (sleep onset insomnia, mid-nocturnal insomnia, early morning insomnia and hypersomnia) assessed self-reported sleep quality. Inflammatory cytokines (tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-6) and brain-derived neurotrophic factor (BDNF) were assessed in blood samples collected before and following the 12-week intervention. Reduction in hypersomnia was correlated with reductions in BDNF (ρ = 0.26, P = 0.029) and IL-1ß (ρ = 0.37, P = 0.002). Changes in these biomarkers were not associated with changes in insomnia; however, lower baseline levels of IL-1ß were predictive of greater improvements in insomnia (F = 3.87, P = 0.050). In conclusion, improvement in hypersomnia is related to reductions in inflammatory markers and BDNF in persons with non-remitted MDD. Distinct biological mechanisms may explain reductions in insomnia.

Sleepiness, inflammation and oxidative stress markers in middle-aged males with obstructive sleep apnea without metabolic syndrome: a cross-sectional study.

BACKGROUND: The simultaneous occurrence of metabolic syndrome and excessive daytime sleepiness are very common in obstructive sleep apnea (OSA) patients. Both conditions, if present in OSA, have been reported to be associated with inflammation and disruption of oxidative stress balance that impair the cardiovascular system. To verify the impact of daytime sleepiness on inflammatory and oxidative stress markers, we evaluated OSA patients without significant metabolic disturbance. METHODS: Thirty-five male subjects without diagnostic criteria for metabolic syndrome (Adult Treatment Panel III) were distributed into a control group (n = 10) (43 ± 10.56 years, apnea-hypopnea index - AHI 2.71 ± 1.48/hour), a non-sleepy OSA group (n = 11) (42.36 ± 9.48 years, AHI 29.48 ± 22.83/hour) and a sleepy OSA group (n = 14) (45.43 ± 10.06 years, AHI 38.20 ± 25.54/hour). Excessive daytime sleepiness was considered when Epworth sleepiness scale score was ≥ 10. Levels of high-sensitivity C-reactive protein, homocysteine and cysteine, and paraoxonase-1 activity and arylesterase activity of paraoxonase-1 were evaluated. RESULTS: Patients with OSA and excessive daytime sleepiness presented increased high-sensitivity C-reactive protein levels even after controlling for confounders. No significant differences were found among the groups in paraoxonase-1 activity nor arylesterase activity of paraoxonase-1. AHI was independently associated and excessive daytime sleepiness tended to have an association with high-sensitivity C-reactive protein. CONCLUSIONS: In the absence of metabolic syndrome, increased inflammatory response was associated with AHI and daytime sleepiness, while OSA was not associated with abnormalities in oxidative stress markers.

Sleep duration and abnormal serum lipids: the China Health and Nutrition Survey.

OBJECTIVE: To examine the associations between sleep duration and total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), and lipoprotein (a) [Lp(a)]. METHODS: The present study analyzed 8574 adults from the China Health and Nutrition Survey (2009). Sleep duration was classified into < or = 6, 7, 8, 9, and > or = 10 h. Age, education, occupation, current smoking, current drinking, physical activity, body mass index, hypertension, and diabetes were adjusted as confounders in gender-stratified multiple logistic regression models. RESULTS: Compared with women reporting 8h sleep duration, the odds ratios (ORs) and 95% confidence intervals (CIs) of high TC for those with < or = 6, 7, 9, and > or = 10 h were 1.65 (1.32-2.06), 1.19 (1.00-1.43), 1.11 (0.89-1.39), and 1.27 (1.02-1.60) after adjusting for confounders. Likewise, the ORs (95% CIs) of high LDL-C were 1.71 (1.28-2.29), 1.36 (1.05-1.76), 1.04 (0.74-1.46), and 1.09 (0.78-1.53), whereas those of high ApoB were 1.80 (1.34-2.42), 1.15 (0.88-1.52), 0.95 (0.66-1.35), and 1.00 (0.70-1.43) for women with < or = 6, 7, 9, and > or = 10 h sleep duration, respectively. These associations were not statistically significant in men. CONCLUSIONS: Both shorter and longer sleep durations were associated with higher risks of abnormal serum lipid profiles in women but not in men.

Sleep-wake and melatonin pattern in craniopharyngioma patients.

OBJECTIVE: To assess the influence of craniopharyngioma or consequent surgery on melatonin secretion, and the association with fatigue, sleepiness, sleep pattern and sleep quality. DESIGN: Cross-sectional study. METHODS: A total of 15 craniopharyngioma patients were individually matched to healthy controls. In this study, 24-h salivary melatonin and cortisol were measured. Sleep-wake patterns were characterised by actigraphy and sleep diaries recorded for 2 weeks. Sleepiness, fatigue, sleep quality and general health were assessed by Multidimensional Fatigue Inventory, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Short-Form 36. RESULTS: Patients had increased mental fatigue, daytime dysfunction, sleep latency and lower general health (all, P≤0.05), and they tended to have increased daytime sleepiness, general fatigue and impaired sleep quality compared with controls. The degree of hypothalamic injury was associated with an increased BMI and lower mental health (P=0.01). High BMI was associated with increased daytime sleepiness, daytime dysfunction, mental fatigue and lower mental health (all, P≤0.01). Low midnight melatonin was associated with reduced sleep time and efficiency (P≤0.03) and a tendency for increased sleepiness, impaired sleep quality and physical health. Midnight melatonin remained independently related to sleep time after adjustment for cortisol. Three different patterns of melatonin profiles were observed; normal (n=6), absent midnight peak (n=6) and phase-shifted peak (n=2). Only patients with absent midnight peak had impaired sleep quality, increased daytime sleepiness and general and mental fatigue. CONCLUSION: Craniopharyngioma patients present with changes in circadian pattern and daytime symptoms, which may be due to the influence of the craniopharyngioma or its treatment on the hypothalamic circadian and sleep regulatory nuclei.

Excessive daytime sleepiness is associated with longer culprit lesion and adverse outcomes in patients with coronary artery disease.

STUDY OBJECTIVES: We assessed whether excessive daytime sleepiness was associated with coronary plaque phenotype and subsequent adverse cardiovascular events. METHODS: Prospective cohort study. Intravascular ultrasound (IVUS) examination of the culprit coronary stenosis was performed. The Epworth Sleepiness Scale (ESS) questionnaire was administered, and the patients were divided into 2 groups-(1) sleepier and (2) less sleepy-based on the ESS score. Adverse cardiovascular outcomes were defined as cardiac death, myocardial infarction, stroke, unplanned revascularization, or heart failure admission. RESULTS: One hundred seventeen patients undergoing urgent or non-urgent coronary angiography were recruited. Compared with the less sleepy group (ESS ≤ 10, n = 87), the sleepier group (ESS > 10, n = 30) had higher serum levels of total cholesterol and of low-density-lipoprotein cholesterols (p < 0.05 for both). The IVUS examinations indicated coronary stenoses were longer in the sleepier group than in the less sleepy group (p = 0.011). The cumulative incidence of adverse cardiovascular events at 16-month follow-up was higher in the sleepier than the less sleepy group (12.5% versus 6.9%, p = 0.03). Cox regression analysis adjusting for age and smoking showed increased hazard of adverse cardiovascular events in sleepier group as compared to less sleepy group (HR = 3.44, 95% CI 1.01-11.72). CONCLUSION: In patients presenting with coronary artery disease, excessive daytime sleepiness based on ESS > 10 was associated with longer culprit lesions and future adverse cardiovascular events.

Obstructive sleep apnea, excessive daytime sleepiness, and morning plasma TNF-α levels in Greek children.

BACKGROUND: Obstructive sleep apnea (OSA) has been associated with increased frequency of excessive daytime sleepiness (EDS). Increased plasma TNF-α levels may mediate this association in adults, but conflicting results have been reported in children. We hypothesized that: (i) the higher the OSA severity in childhood, the higher the frequency of EDS and morning plasma TNF-α levels; and (ii) high TNF-α levels predict presence of EDS. METHODS: Children without and with snoring underwent polysomnography. EDS was determined by parental response to specific questions, and plasma TNF-α levels were measured. RESULTS: Children with moderate-to-severe OSA (n = 24; 5.7 ± 2 years; apnea-hypopnea index [AHI] 11.5 ± 5.1/h), but not participants with mild OSA (n = 22; 6 ± 2.5 years; AHI 2.1 ± 1/h) were at significantly higher risk for EDS than controls (n = 22; 6.8 ± 2.1 years; AHI 0.5 ± 0.3/h) (OR [95% CI] adjusted for age, gender, and obesity: 9.2 [1.7-50.2] and 3.8 [0.7-21.8], respectively). The 3 groups did not differ regarding TNF-α concentration (0.63 ± 0.2 vs 0.65 ± 0.18 vs 0.63 ± 0.17 pg/mL; P > 0.05). TNF-α levels were associated significantly with body mass index z-score (P < 0.05) and not with polysomnography indices (P > 0.05). Subjects with high TNF-α levels (> 0.57 pg/mL) were not at higher risk for EDS than participants with low levels (OR [95% CI] adjusted for age, gender, and obesity: 1.7 [0.5-5.7]). CONCLUSIONS: Increasing severity of OSA is associated with increasing frequency of EDS, but not with elevated plasma TNF-α concentration. High TNF-α levels cannot be used as predictor for the presence of EDS in children with sleep apnea.

Does physical exercise reduce excessive daytime sleepiness by improving inflammatory profiles in obstructive sleep apnea patients?

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is associated with a variety of long-term consequences such as high rates of morbidity and mortality, due to excessive diurnal somnolence as well as cardiovascular and metabolic diseases. Obesity, recurrent episodes of upper airway obstruction, progressive hypoxemia, and sleep fragmentation during sleep cause neural, cardiovascular, and metabolic changes. These changes include activation of peripheral sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, insulin sensitivity, and inflammatory cytokines alterations, which predispose an individual to vascular damage. DISCUSSION: Previous studies proposed that OSAS modulated the expression and secretion of inflammatory cytokines from fat and other tissues. Independent of obesity, patients with OSAS exhibited elevated levels of C-reactive protein, tumor necrosis factor-α and interleukin-6, which are associated with sleepiness, fatigue, and the development of a variety of metabolic and cardiovascular diseases. OSAS and obesity are strongly associated with each other and share many common pathways that induce chronic inflammation. Previous studies suggested that the protective effect of exercise may be partially attributed to the anti-inflammatory effect of regular exercise, and this effect was observed in obese patients. Although some studies assessed the effects of physical exercise on objective and subjective sleep parameters, the quality of life, and mood in patients with OSAS, no study has evaluated the effects of this treatment on inflammatory profiles. In this review, we cited some studies that directed our opinion to believe that since OSAS causes increased inflammation and has excessive daytime sleepiness as a symptom and being that physical exercise improves inflammatory profiles and possibly OSAS symptoms, it must be that physical exercise improves excessive daytime sleepiness due to its improvement in inflammatory profiles.

[The study on AHI, LSaO2 and ET-1 in patients with obstructive sleep apnea-hypopnea syndrome after H-UPPP].

OBJECTIVE: To explore the treatment effect of H-UPPP on patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHOD: Seventy-nine patients were enrolled in our study. Among which 49 patients were done with H-UPPP, and the other 30 patients were done with UPPP. AHI and LSaO2 were monitored by polysomnography and plasma endothelins-1 were tested with enzyme linked immunosorbent assay (ELISA) before and after operation. RESULT: Forty-one patients were improved with reduced snoring and daytime sleepiness one year after operation in H-UPPP group,and the overall efficiency was 83.7%. Twenty-six patients were improved with reduced snoring and daytime sleepiness one year after operation in UPPP group, and the overall efficiency was 86.7%. There were significant differences of AHI, LSaO2 and ET-1 before and after operation between the two groups. Negative correlation was showed between AHI and LSaO2, also between LSaO2 and ET-1. CONCLUSION: Both H-UPPP and UPPP were proved to be effective to patients with OSAHS. The perioperative complications with H-UPPP was less than UPPP.

Endothelial function in patients with post-CPAP residual sleepiness.

STUDY OBJECTIVES: The significance of residual excessive daytime sleepiness (EDS) on cardiovascular markers in patients with adequately treated obstructive sleep apnea (OSA) remains unclear. The objective of this study was to investigate flow-mediated dilatation (FMD) and inflammatory markers (C-reactive protein [CRP], tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6) in continuous positive airway pressure (CPAP)-compliant patients with residual EDS compared with CPAP-compliant patients without residual EDS. METHODS: FMD of the brachial artery was measured by ultrasound in 12 CPAP-compliant patients with OSA who had residual EDS and 12 age-, sex-, and body mass index-matched CPAP-compliant patients with OSA who did not have residual EDS on week 8 after initiation of CPAP. Twelve otherwise-healthy subjects without sleep disordered breathing were used as control subjects. Serum concentrations of CRP, TNF-alpha, and IL-6 were quantified by enzyme-linked immunosorbent assays. RESULTS: Baseline FMD was comparable among CPAP-compliant patients with residual EDS (7.2 +/- 2.3), CPAP-compliant patients without residual EDS (8.6 +/- 2.1), and control subjects (7.7 +/- 1.4) (p = 0.37). The concentrations of CRP, TNF-alpha, and IL-6 were also not significantly different between subjects with CPAP-compliant residual EDS and those without residual EDS (p = 0.44, p = 0.37, and p = 0.42; respectively). CONCLUSIONS: Residual EDS in patients with adequately treated OSA may not represent a risk factor for cardiovascular diseases.

Iron stores, periodic leg movements, and sleepiness in obstructive sleep apnea.

STUDY OBJECTIVES: Most clinical sleep studies are performed for suspected obstructive sleep apnea (OSA), yet one-quarter to one-half show periodic leg movements (PLMs), for reasons that remain unknown. Several other disparate sleep disorders also increase the risk for PLMs. We examined the novel hypotheses that OSA as a representative sleep disorder could promote lower body iron stores, as reflected by serum ferritin levels, and, through downstream effects on dopaminergic transmission, increase PLMs and daytime sleepiness. METHODS: Subjects were recruited as they underwent laboratory-based polysomnography for suspected OSA. Serum ferritin levels were measured the next morning. Each subject completed an Epworth Sleepiness Scale and a brief questionnaire to assess for restless legs syndrome (RLS). RESULTS: The frequency of apneic events showed no association with serum ferritin levels, before or after adjustment for age, sex, body mass index, and likely RLS (each p value > 0.3). Serum ferritin levels did not predict the frequency of PLMs (p = 0.7) or Epworth scores (p = 0.8). Iron deficiency as a dichotomous variable, determined by ferritin levels less than < 50 microg/L or in combination with low transferrin saturation or mean corpuscular volume, showed similar results. In exploratory analyses, contrary to expectations, lower minimum oxygen saturation and increased sleep-stage shifts predicted increased rather than decreased ferritin levels (p = 0.03 and p = 0.02, respectively). CONCLUSIONS: Results of this study, powered to detect small to moderate effect sizes, strongly suggest that OSA does not cause lower serum ferritin levels, which, in turn, cannot explain PLMs or daytime sleepiness in these patients.

[Association between residual sleepiness and central sleep apnea events in patients with obstructive sleep apnea syndrome].

OBJECTIVE: To investigate the possible association between residual sleepiness (RS) and central sleep apnea events in patients with obstructive sleep apnea syndrome (OSAS) following continuous positive airway pressure (CPAP) treatment, as well as the effects of adaptive servo-ventilation (ASV) on RS. METHODS: Following correct application of CPAP treatment and exclusion of other sleepiness-associated disorders, 50 patients with moderate-to-severe OSAS were recruited, including 26 patients with RS (RS group) and 24 patients without RS (control group). The treatment of one month's auto-CPAP (AutoCPAP) followed by one week ASV with autoCS2 ventilator was performed. Comparisons were made separately before treatment, on AutoCPAP and ASV treatments in both groups of the following parameters: polysomnographic parameters including central sleep apnea index (CSAI), micro-arousal index (MAI), etc; daytime Epworth sleepiness score (ESS), and possibly sleepiness-associated factor, i.e., plasma tumor necrosis factor-alpha (TNF-alpha). Plasma TNF-alpha levels were measured by enzyme linked immunosorbent assay (ELISA). t test and single factor analysis of variances were used for comparison between two groups and within group respectively. q test was used for couple comparison within group at 3 different stages. Pearson correlation test was performed for correlation analysis between 2 variables. RESULTS: Before treatment there was no significant difference between two groups in apnea hypopnea index (AHI), MAI, minimal pulse oxygen saturation (minSpO2), ESS and plasma TNF-alpha levels (t: 0.630, 1.223, 0.691, 0.764 and 0.19 2, all P > 0.05). However, the CSAI in RS group was significantly higher than that in the control group [(7.19 +/- 1.75) times/h vs (3.37 +/- 1.04) times/h, t = 4.097, P < 0.05)]. After 1 month's AutoCPAP treatment there was a significant decrease in AHI, CSAI, MAI and ESS in both groups (q: 0.87-112.55, all P < 0.05), but CSAI, MAI and ESS in the RS group than those in the control group [CSAI: (7.19 +/- 1.75) times/h vs (3.37 +/- 1.04) times/h, t = 9.473, P < 0.05; MAI: (9.00 +/- 1.95) times/h vs (2.36 +/- 0.66) times/h, t = 14.385, P < 0.05; ESS: 9.54 +/- 0.51 vs 5.42 +/- 1.32, t = 2.857, P < 0.05). On one weeks' ASV treatment there was such a further significant decrease in CSAI, MAI and daytime ESS in the RS group and the control group. In addition, compared with the plasma TNF-alpha level before treatment in the RS group, there was no statistical difference on AutoCPAP treatment but a significant decrease on ASV treatment. Plasma TNF-alpha levels were positively correlated with ESS (r = 0.503, P < 0.01) and MAI (r = 0.545, P < 0.01). CONCLUSIONS: RS in OSAS patients following CPAP treatment was associated with their CSAI before and during treatment. By effectively eliminating CSA events with ASV, RS was significantly improved, which suggested that ASV was effective in treatment of RS. The elevation of plasma TNF-alpha level was correlated with the severity of sleepiness and may be involved in the pathogenesis of RS.

Association between serum neopterin, obesity and daytime sleepiness in patients with obstructive sleep apnea.

OBJECTIVE: Obesity and obstructive sleep apnea (OSA) and systemic inflammation may interact through biochemical pathways. Neopterin (NP) is a monocyte/macrophage activation marker produced by macrophages in response to interferon-gamma secreted by activated T-lymphocytes. This study examines the association between NP, obesity and OSA. PATIENTS AND METHODS: The study included 22 newly diagnosed OSA (+) patients and 18 OSA (-) patients. Subjects with history of coronary artery disease, transplant patients, history of alcohol and drug abuse, history of HIV and any other significant medical illnesses such as active infections, autoimmune disease, malignancy, liver disease, pulmonary disease (COPD, asthma,...), neuromuscular disease, patients on immunomodulating therapy or HMG-CoA reductase inhibitors were excluded. RESULTS: There were no significant differences in age, body mass index (BMI), and smoking habits of the OSA (+) patients and OSA (-) patients. Serum NP levels did not show any significant difference between the OSA (+) patients and OSA (-) patients, however, NP levels were positively correlated with BMI (r=0.320, p=0.044). There was no significant correlation between NP and any of the polysomnographic parameters. The result of stepwise regression analyses (r(2)=0.320, p<0.001) showed that high serum NP levels (p=0.004) and apnea-hypopnea index (AHI) were a risk factor for elevated Epworth sleepiness score, independent of BMI. CONCLUSION: We suggest that serum NP levels correlate with BMI. There was a significant relationship between serum NP levels and excessive daytime sleepiness in OSA patients.

Prostaglandin D synthase (beta-trace) in healthy human sleep.

STUDY OBJECTIVES: The prostaglandin D system plays an important role in animal sleep. In humans, alterations in the prostaglandin D system have been found in diseases exhibiting sleep disturbances as a prominent symptom, such as trypanosoma infection, systemic mastocytosis, bacterial meningitis, major depression, or obstructive sleep apnea. Assessment of this system's activity in relation to human physiologic sleep was the target of the present study. DESIGN: Serum concentrations of lipocalin-type prostaglandin D synthase (L-PGDS, former beta-trace), and plasma levels of the pineal hormone melatonin were measured in 20 healthy humans (10 women, 10 men; aged: 23.3 +/- 2.39 years) at 4-hour intervals over a period of 5 days and nights, which included physiologic sleep, rapid eye movement sleep deprivation, and total sleep deprivation. In addition, the serum L-PGDS and plasma melatonin levels of 6 subjects were determined under conditions of bright white (10,000 lux) or dark red light (< 50 lux) in a crossover design during total sleep deprivation. Nocturnal blood sampling was performed by a through-the-wall tube system. L-PGDS was measured by an automated immunonephelometric assay, and melatonin was analyzed by direct radioimmunoassay. RESULTS: Serum L-PGDS concentrations showed marked time-dependent changes with evening increases and the highest values at night (P < .0005). This nocturnal increase was suppressed during total sleep deprivation (P < .05), independent of external light conditions and melatonin secretion. Rapid eye movement sleep deprivation had no impact on circulating L-PGDS levels. CONCLUSIONS: The circadian L-PGDS pattern and its suppression by total sleep deprivation indicate an interaction of the prostaglandin D system and human sleep regulation. L-PGDS measurements may well provide new insights into physiologic and pathologic sleep regulation in humans.

Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders.

OBJECTIVE: To identify antinuclear antibodies (ANA) specific for chronic fatigue syndrome (CFS), and in related conditions such as fibromyalgia (FM) or psychiatric disorders. METHODS: One hundred and fourteen CFS patients and 125 primary and secondary FM patients were selected based on criteria advocated by the Centers for Disease Control and Prevention and by the American College of Rheumatology, respectively. As controls, healthy subjects and patients with either various psychiatric disorders or diffuse connective tissue diseases were included. Autoantibodies were examined by immunoblot utilizing HeLa cell extracts as the antigen. RESULTS: Autoantibodies to a 68/48 kDa protein were present in 13.2 and 15.6% of patients with CFS and primary FM, respectively. In addition, autoantibodies to a 45 kDa protein were found in 37.1 and 21.6% of the patients with secondary FM and psychiatric disorders, respectively. Meanwhile, these two autoantibodies were not found at all in connective tissue disease patients without FM, nor in healthy subjects (P<0.05). As a group, the anti-68/48 kDa-positive CFS patients presented more frequently with hypersomnia (P<0.005), short-term amnesia (P<0.07) or difficulty in concentration (P<0.05) than those CFS patients without the antibodies. CONCLUSIONS: The presence of the anti-68/48 kDa protein antibodies in a portion of both CFS and primary FM patients suggests the existence of a common immunological background. These antibodies may find utility as possible markers for a clinicoserological subset of CFS/FM patients with hypersomnia and cognitive complaints.