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Background: The SERVE-HF study has raised questions concerning the higher mortality under adaptive servoventilation. The ventilatory mode was discussed as a possible aggravating factor., Objectives: We wondered if the data recorded by the adaptive servo-ventilation (ASV)-devices in heart failure patients with CSA-CSR ± OSA are different in terms of respiratory parameters and therapeutic pressures compared to patients with CPAP-resistant/emergent-CSA with normal BNP/NT-pro-BNP., Methods: Patients were included, if ASV had normalized respiratory disturbance index in the first night of application and after at least 6 weeks. ASV-device data were analyzed in terms of respiratory rate (RR), min ventilation (MV), endexpiratory (EEP), peak inspiratory pressure (Ppeak) and median pressure., Results: Compared to CPAP-resistant/emergent-CSA with normal BNP/NT-pro-BNP (n = 25), CSA-CSR- (n = 13) CSA-CSR+OSA-patients (n = 32) with elevated BNP/NT-pro-BNP had higher RR (p < 0.01) in the first night of ASV therapy and during follow-up (15.3 ± 1.3 vs. 17.3 ± 2.4/min) with similar MV (6.5 ± 1.3 vs. 6.6 ± 1.3 L), resulting in significantly lower tidal volumes. EEP (5.6 ± 1.1 vs. 5.5 ± 1.1 hPa), Pmedian and Ppeak (9.8 ± 1.5 vs. 9.7 ± 1.2 hPa) were comparable. Ventilatory parameters were not different between LVEF < 40, 40-49, and ≥50%, neither within the whole group nor the group of CSA-CSR ± OSA and heart failure., Conclusion: Patients with heart failure and CSA-CSR ± OSA have higher RRs but similar MV under ASV-therapy than patients with CSA and normal BNP. This indicates higher dead space ventilation. EF was not found to have an influence on the ventilatory parameters., (© 2018 S. Karger AG, Basel.)

Background: Endothelial dysfunction has been recognized to occur in the context of obstructive sleep apnea (OSA) or tobacco smoking. However, the deleterious effect on vascular function with concurrence of both conditions is largely unknown., Objective: To investigate whether the concurrence of OSA and smoking poses an additive detriment to endothelial dysfunction., Methods: Chinese men without a history of chronic medical illness were invited to complete a questionnaire including smoking pack-year exposure, polysomnography and peripheral arterial tonometry (PAT) for endothelial function. Serum 8-isoprostane, advanced oxidation protein products (AOPP) and monocyte chemo-attractant protein-1 (MCP-1) were measured., Results: 114 men were successfully enrolled. PAT ratio, adjusted for age and body mass index, correlated inversely with overall severity of OSA: apnea-hypopnea index (AHI), r = -0.160 (p = 0.092); oxygen desaturation index, r = -0.214 (p = 0.024); duration of oxygen saturation <90%, r = -0.219 (p = 0.020); and minimum oxygen saturation, r = 0.250 (p = 0.008). The PAT ratio decreased with increasing pack-year group (p = 0.018). It was lower with concurrent smoking history and moderate-severe OSA (AHI ≥15/h) compared to having one or neither factor (p = 0.011). Serum levels of 8-isoprostane and AOPP were positively related to severity of OSA, while MCP-1 correlated with smoking quantity. Multiple linear regression analyses showed that severity of intermittent hypoxia, MCP-1 and pack-year exposure were independent predictors of PAT ratio., Conclusion: While OSA, in particular intermittent hypoxemia, and tobacco smoking were independent risk factors, the concurrence of moderate-severe OSA and smoking was associated with the most severe impairment in endothelial function., (© 2016 S. Karger AG, Basel.)

Background: Obstructive sleep apnea (OSA) is associated with nocturnal intermittent hypoxia, which may be responsible for increased circulating levels of vascular endothelial growth factor (VEGF) and inflammatory mediators, such as metalloproteinases (MMPs), and which contributes to the pathogenesis of systemic hypertension. Why some OSA patients remain normotensive is poorly understood. Relaxin-2, a pregnancy hormone, may sometimes circulate in men and could increase in hypoxic conditions. It exerts a vasodilatory activity and can modulate the release of molecules, such as MMPs and VEGF., Objectives: The objective of this study was to explore if circulating relaxin-2 in male OSA subjects may be related to OSA severity, to circulating levels of MMPs, of their inhibitors (tissue inhibitors of metalloproteinases; TIMPs), and of VEGF, and if it may protect from hypertension., Patients and Methods: Fifty untreated male subjects with suspected OSA were recruited. After nocturnal polysomnography, a morning venous blood sample was withdrawn. Then, 24-hour ambulatory blood pressure (BP) monitoring was performed., Results: The respiratory disturbance index in the sample was 30.4 [interquartile range (IQR) 15.6-55.2]. Relaxin-2 was detectable in 20 subjects. These subjects did not differ in OSA severity or diurnal and nocturnal BP from subjects with undetectable relaxin-2, but they showed lower TIMP-1 (126.8 ± 29.1 vs. 156.9 ± 41.7 pg/ml, respectively; p = 0.007) and a marginally higher MMP-9/TIMP-1 molar ratio [0.58 (IQR 0.23-1.35) vs. 0.25 (IQR 0.15-0.56); p = 0.052]., Conclusions: Relaxin-2 in male subjects was not related to OSA severity, but it was associated with lower TIMP-1. As it was often undetectable, even when BP values were normal, it is unlikely that it plays a role as a major factor protecting from hypertension in OSA., (© 2016 S. Karger AG, Basel.)

Background: Obstructive sleep apnea syndrome (OSAS) and obesity frequently occur together. The relationship between increased appetite and obesity is well known; however, despite existing knowledge about the relationship between OSAS and obesity, it is not fully understood., Objectives: This study aimed to evaluate the relationship between OSAS and the appetite-suppressing hormone nesfatin-1 independent of body mass index (BMI)., Methods: A total of 134 cases were included in the study; 102 with OSAS (OSAS group) and 32 healthy controls (control group). All cases underwent polysomnography, and nesfatin-1 levels were determined., Results: Nesfatin-1 levels were significantly lower in the OSAS group compared to the control group (3,776.5 ± 204.8 and 4,056.2 ± 101.5 pg/ml, respectively; p < 0.001). In addition, there was a statistically significant negative correlation between nesfatin-1 and the apnea hypopnea index (r = -0.543; p < 0.001). The statistically significant relationship persisted after adjusting for confounding intergroup factors such as age, gender and BMI (p < 0.001). In the OSAS group, there was a statistically significant correlation between nesfatin-1 and neck circumference (r = -0.304; p = 0.02) but not between nesfatin-1 and BMI and waist circumference. There was no statistically significant difference in nesfatin-1 levels between the sexes., Conclusion: OSAS patients have lower nesfatin-1 levels compared to controls, and a greater nesfatin-1 deficit corresponds to an increased severity of OSAS and an increased neck circumference. Replacement therapy may be a potential treatment for obese OSAS patients who have lower nesfatin-1 levels, which may have additional benefits through appetite suppression and weight loss., (© 2015 S. Karger AG, Basel.)

Background: Clinical and epidemiological studies indicate that obstructive sleep apnea syndrome (OSAS) has a strong genetic basis., Objectives: To investigate the apolipoprotein E (APOE) alleles as a genetic risk factor in OSAS., Methods: A total of 73 patients (37 male) were included. All underwent full-night polysomnography and were evaluated for APOE alleles., Results: The mean age was 51 ± 12 years. Forty-two of the patients had OSAS. The APOE3 allele was found in 97.3% (71/73) of the study population. The most common APOE genotype was E3/E3 (55/73, 75.3%). Compared to the individuals with no APOE2 alleles (E3/E3, E3/E4), the individuals with at least one APOE2 allele (E2/E3, E2/E4) had a 9.37-fold greater OSAS risk (OR = 9.37, 95% CI 1.13-77.7, p = 0.019). The individuals with APOE2 alleles (E2/E3, E2/E4) compared to the individuals with only an E3/E3 allele genotype had a 10-fold greater OSAS risk (OR = 10.3, 95% CI 1.24-86.61, p = 0.0308). Compared to the individuals with no APOE4 alleles (E2/E3, E3/E3), the individuals with APOE4 alleles (E2/E4, E3/E4) had a high but insignificant risk for OSAS (OR = 2.9, 95% CI 0.55-15.05, p = 0.286). The individuals with APOE4 alleles (E2/E4, E3/E4) compared to APOE3 alleles (E3/E3) had an increased but insignificant risk for OSAS (OR = 3.62, 95% CI 0.96-19.05, p = 0.127)., Conclusion: Specific APOE genotypes are associated with OSAS in a high-risk population.

Background: Obstructive sleep apnea has been associated with impaired endothelial function; however, the mechanisms underlying this association are not completely understood. Cell-derived microparticles may provide a link between obstructive sleep apnea and endothelial dysfunction., Objectives: This randomized controlled trial aimed to examine the effect of a 2-week withdrawal of continuous positive airway pressure (CPAP) therapy on levels of circulating microparticles., Methods: Forty-one obstructive sleep apnea patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continuing therapeutic CPAP, for 2 weeks. Polysomnography was performed and circulating levels of microparticles were analyzed by flow cytometry at baseline and 2 weeks., Results: CPAP withdrawal led to a recurrence of obstructive sleep apnea. Levels of CD62E+ endothelium-derived microparticles increased significantly in the CPAP withdrawal group compared to the continuing therapeutic CPAP group (median difference in change +32.4 per µl; 95% CI +7.3 to +64.1 per µl, p = 0.010). CPAP withdrawal was not associated with a statistically significant increase in granulocyte, leukocyte, and platelet-derived microparticles when compared with therapeutic CPAP., Conclusions: Short-term withdrawal of CPAP therapy leads to a significant increase in endothelium-derived microparticles, suggesting that microparticle formation may be causally linked to obstructive sleep apnea and may promote endothelial activation., (Copyright © 2012 S. Karger AG, Basel.)

Background: Vitamin D insufficiency and high levels of parathyroid hormone (PTH) appear to be emerging risk factors for metabolic syndrome (MS), diabetes and cardiovascular disease, conditions that occur frequently in patients with obstructive sleep apnea syndrome (OSAS)., Objectives: This study examined whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH were associated with the presence of MS, diabetes and hypertension among an OSAS population., Methods: A total of 826 patients (635 men and 191 women) with newly diagnosed OSAS were studied. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III clinical criteria. Serum levels of 25(OH)D, PTH, glucose, triglycerides, cholesterol, HDL cholesterol, creatinine and uric acid were determined., Results: In 55.3% of the men and in 63.2% of the women, the serum 25(OH)D level was less than 30 ng/ml (insufficient status). After adjusting for age, sex and seasonality, there was a significant trend of decreasing odds for diabetes [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.33-0.94, ptrend = 0.038] and MS (OR 0.34, 95% CI 0.21-0.56, ptrend < 0.001) with increasing vitamin D levels. Higher PTH levels were associated with a higher prevalence of obesity (OR 2.05, 95% CI 1.06-3.09, ptrend < 0.001) and hypertension (OR 1.83, 95% CI 1.01-3.05, ptrend = 0.049)., Conclusions: These data suggest an inverse association of 25(OH)D with diabetes and MS and a positive association of PTH with obesity and hypertension among patients with OSAS. Based on our observational study, the causative nature of the associations cannot be established. These findings require further examination in prospective studies including clinical trials., (Copyright © 2012 S. Karger AG, Basel.)

Background: The obstructive sleep apnea syndrome (OSAS) is characterized by repeated upper airway obstruction during sleep together with decreases in oxygen saturation leading to a series of pathological events, primarily in the cardiovascular system. Elevated plasma homocysteine levels have recently been considered as an independent risk factor for vascular disease, and increased levels are attributed to cardiovascular diseases., Objectives: We aimed to investigate the possible relationship between homocysteine levels and echocardiographic findings in OSAS patients at different stages of disease., Methods: Thirty-eight patients (23 males and 15 females) with polysomnographically verified OSAS (mean age, 49 +/- 12 years, range 27-74) and a mean body mass index of 31.27 +/- 5.24 kg/m(2) (range 22.60-47.90) were prospectively studied. Plasma levels of homocysteine, cholesterols, triglycerides, vitamin B(12) and high-sensitive C-reactive protein (hsCRP), as well as echocardiographic and lung function parameters were assessed., Results: Homocysteine levels were elevated in all OSAS groups and were statistically significantly different between the mild and moderate/severe groups. Significant differences were present between the variables nocturnal oxygen desaturation (NOD), respiratory arousal and light sleep among the mild and moderate/severe groups. We found a significant positive correlation between homocysteine levels and NOD duration, and hsCRP levels were positively correlated with the apnea-hypopnea index and NOD duration., Conclusions: In all OSAS groups, homocysteine levels were elevated regardless of the presence of cardiac dysfunction. Echocardiographic abnormalities were primarily left-ventricular (LV) hypertrophy and LV diastolic dysfunction and could be observed in all OSAS severity groups., (2009 S. Karger AG, Basel.)

Background: Obesity and obstructive sleep apnea (OSA) are both associated with the prevalence of major cardiovascular illnesses and certain common factors they are considered responsible for, such as stress oxidative increase, sympathetic tonus and resistance to insulin., Objective: The aim of the present study was to compare the effect of continuous positive airway pressure (CPAP) on oxidative stress and adiponectin levels in obese patients with and without OSA., Methods: Twenty-nine obese patients were categorized into 3 groups: group 1: 10 individuals without OSA (apnea-hypopnea index, AHI or=20) who did not use CPAP; group 3: 9 patients with moderate to severe OSA (AHI >or=20) who used CPAP., Results: Group 3 showed significant differences before and after the use of CPAP, in the variables of diminished production of superoxide, and increased nitrite and nitrate synthesis and adiponectin levels. Positive correlations were seen between the AHI and the superoxide production, between the nitrite and nitrate levels and the adiponectin levels, between superoxide production and the HOMA-IR, and between AHI and the HOMA-IR. Negative correlations were found between AHI and the nitrite and nitrate levels, between the superoxide production and that of nitric oxide, between the superoxide production and the adiponectin levels, between AHI and the adiponectin levels, and between the nitrite and nitrate levels and the HOMA-IR., Conclusions: This study demonstrates that the use of CPAP can reverse the increased superoxide production, the diminished serum nitrite, nitrate and plasma adiponectin levels, and the metabolic changes existing in obese patients with OSA., (Copyright 2009 S. Karger AG, Basel.)

Background: Obstructive sleep apnea syndrome (OSAS) is associated with impaired glucose metabolism and insulin resistance. Retinol-binding protein-4 (RBP-4) is an adipokine, hypothesized to induce insulin resistance., Objectives: The aim of the study was to explore the association between serum RBP-4 levels and OSAS severity in nondiabetic, adherent to therapy OSAS patients and to investigate the role of continuous positive airway pressure (CPAP) in the alteration of RBP-4 levels., Methods: OSAS patients (n = 62) without comorbidities or medication use were included. Fasting RBP-4, glucose and insulin levels, HbA(1c), homeostatic model assessment of insulin resistance index and lipid profile were measured at baseline and after 6 months of CPAP use. Patients were divided into group A (with fasting glucose levels <110 mg/dl, n = 47), and group B (with impaired fasting glucose (IFG), i.e. fasting glucose levels ≥110 mg/dl, n = 15)., Results: RBP-4 levels were not associated with apnea-related indices, anthropometric characteristics or markers of glycemic control, insulin resistance or lipid profile. In group A (but not in group B), a significant reduction was observed in RBP-4 (p = 0.046), HbA(1c) (p = 0.005), LDL cholesterol (p = 0.034), and high-sensitivity C-reactive protein (hs-CRP, p = 0.033) levels after 6 months of CPAP use., Conclusions: RBP-4 levels were not correlated with sleep, anthropometric characteristics, markers of glycemic control and insulin sensitivity. OSAS patients without IFG respond well to CPAP use as evidenced by the significant reduction in RBP-4, HbA(1c) and, additionally, hs-CRP and LDL- cholesterol levels. This treatment effect is not observed in patients with IFG., (Copyright © 2010 S. Karger AG, Basel.)

Background: Considerable evidence implicates CD40 signaling in the pathogenesis of atheromas. Exposure to CD40 ligand induces platelet-leukocyte conjugation, a heightened expression of inflammatory cytokines, matrix-degrading enzymes, and procoagulant factors., Objectives: To investigate the association between plasma soluble CD40 ligand (sCD40L) and platelet-monocyte aggregates in patients with obstructive sleep apnea (OSA) and to determine whether treatment of OSA with nasal continuous positive airway pressure (nCPAP) alters this relationship., Methods: Twelve patients with OSA who were free of other diseases and 12 healthy controls matched for age, gender, and body mass index had blood drawn for sCD40L and platelet-monocyte aggregate measurements. A repeat assessment was obtained following 8 weeks of nCPAP therapy., Results: Subjects with OSA had significantly higher plasma sCD40L levels and exhibited elevated platelet-monocyte aggregates compared to nonapneic subjects (7.6 +/- 4.3 versus 1.7 +/- 1.1, p = 0.004; and 41.3 +/- 23.7 versus 6.7 +/- 4.9, p = 0.001, respectively). Both parameters correlated positively with the percentage of time spent with SpO(2) <90% (r = 0.69, p = 0.01 and r = 0.6, p = 0.03, respectively). After 8 weeks of nCPAP treatment, sCD40 levels declined by 47% (p = 0.003) and platelet-monocyte aggregates by 42% (p = 0.002). None of the controls showed any changes in either sCD40L or platelet- monocyte aggregates after nCPAP therapy., Conclusions: OSA is associated with upregulation of circulating sCD40L levels and platelet-monocyte aggregation that may account for the increased incidence of cardiovascular events in this population. Treatment with nCPAP may alleviate this risk., ((c) 2008 S. Karger AG, Basel.)

Background: Cardiovascular (CV) diseases are a leading cause of mortality and they are frequent in patients with the obstructive sleep apnea syndrome (OSAS)., Objectives: In this study we investigated if OSAS influences CV function independently of other CV risk factors frequently present in these patients (e.g. obesity, high blood pressure)., Methods: We compared plasma markers of endothelial dysfunction, asymmetric dimethylarginine (ADMA) and endothelin-1 (ET-1), and atherosclerosis progression (soluble fraction of the CD40 ligand, sCD40L) in OSAS patients with (n = 23) and without (n = 18) concurrent CV risk factors, as well as in healthy subjects (n = 23)., Results: Plasma ADMA (p < 0.01) and sCD40L (p < 0.05) were abnormally increased in patients with OSAS versus healthy controls, but they were not influenced by the presence or absence of CV risk factors in OSAS. ET-1 levels were not different between the three groups of subjects studied., Conclusions: OSAS is associated with endothelial injury and atherosclerosis progression independently of other CV risk factors., ((c) 2008 S. Karger AG, Basel.)

Background: Although obstructive sleep apnea (OSA) severity is evaluated by the apnea-hypopnea index (AHI), the value of AHI in evaluating cardiovascular risks, especially in mild to moderate OSA, is unclear., Objectives: The purpose of this study is to evaluate the validity of a new index, the integrated area of desaturation (IAD), to detect the incidence of cardiovascular events (CVEs) in such patients., Methods: We enrolled 230 consecutive patients with mild to moderate OSA and 354 with severe OSA diagnosed by polysomnography, of whom 53 and 112, respectively, had CVEs. The IAD was calculated by dividing the area of desaturation by total sleep time in polysomnography. C-reactive protein (CRP) was also measured for all patients., Results: In the mild to moderate OSA patients, the mean IAD of the CVEs group was significantly higher than that of the non-CVE group (94.4 +/- 82.7 vs. 62.3 +/- 50.8, p = 0.001), whereas mean AHI and 3% oxygen desaturation index were similar in both groups. Multivariate analysis demonstrated that the IAD was an independent variable for CVEs (OR 1.006, 95% confidence interval 1.001-1.012, p = 0.031). Moreover, the IAD level of the high CRP group was significantly higher than that of the low CRP group (92.9 +/- 84.8 vs. 63.9 +/- 54.5, p = 0.009). There was no significant difference in AHI, IAD or other polysomnographic parameters in the severe OSA patients., Conclusions: IAD might be superior to AHI alone in the evaluation of the history of CVEs in mild to moderate OSA patients, and it deserves attention as a possible predictor of future CVEs., ((c) 2009 S. Karger AG, Basel.)

Background: Obstructive sleep apnoea syndrome (OSAS) has been suggested to be an independent risk factor for non-alcoholic fatty liver disease (NAFLD), possibly via intermittent hypoxia that influences blood pressure, lipid levels and insulin resistance, factors themselves known to cause NAFLD. In observational studies, OSAS has been associated with elevated levels of liver enzymes. Continuous positive airway pressure (CPAP) is the treatment for OSAS, but the effects of CPAP on liver enzymes have not been studied in a randomized controlled trial., Objective: To determine if 4 weeks of CPAP influence alanine-aminotransferase (ALT) and aspartate-aminotranferase (AST) levels., Methods: 94 patients with moderate-to-severe OSAS were randomized to therapeutic or sub-therapeutic CPAP treatment. Plasma ALT and AST were measured before and after 4 weeks of CPAP., Results: Results are means +/- SD. ALT levels decreased from 39.1 +/- 26.3 to 30.3 +/- 16.4 IU/l in patients treated with therapeutic CPAP, but also decreased from 36.9 +/- 20.7 to 31.5 +/- 16.5 IU/l in patients treated with sub-therapeutic CPAP (difference between mean changes -3.4, 95% CI -7.8 to 1.0 IU/l, p = 0.13 between groups). AST levels did not change significantly with therapeutic CPAP (from 29.1 +/- 14.7 to 30.2 +/- 13.6 IU/l), nor with sub-therapeutic CPAP (from 28.2 +/- 16.2 to 29.5 +/- 12.6 IU/l; difference between mean changes -0.2, 95% CI -3.0 to 2.6 IU/l, p = 0.87 between groups)., Conclusions: Four weeks of active CPAP has no beneficial effect on aminotransferase levels when compared to sub-therapeutic CPAP in patients with OSAS. Therefore, CPAP does not seem to improve biochemical markers of potential NAFLD in OSAS patients.

Background: Leptin levels have been reported to be higher in patients with obstructive sleep apnea (OSA) than in control subjects with matching age and body mass index (BMI). Although animal studies have shown that leptin augments hypercapnic ventilatory response (HCVR), the effect of leptin on HCVR has not been clarified in OSA., Objectives: To investigate whether leptin could augment HCVR during wakefulness in patients with OSA., Methods: Of 134 consecutive patients with OSA, 13 eucapnic and 16 hypercapnic patients with OSA, and 12 control subjects matched for sex, age, and BMI were selected. Fasting serum leptin levels were collected, and HCVR during wakefulness assessed by the slope between minute ventilation and end-tidal PCO(2)., Results: There was a significant positive relationship between serum leptin levels and HCVR in the group including control subjects and eucapnic patients with OSA (r = 0.42, p < 0.05). Subgroup analyses suggest that serum leptin levels and HCVR were significantly higher in eucapnic patients with OSA than in control subjects. On the other hand, hypercapnic patients had lower HCVR than eucapnic patients (p < 0.05), whereas serum leptin levels were similar between the two OSA subgroups., Conclusion: Leptin levels and HCVR are correlated as long as the eucapnic condition is maintained. We speculate that a stimulating effect of leptin on HCVR may be masked by the hypoventilation state., (2007 S. Karger AG, Basel)

Background: The obstructive sleep apnea syndrome (OSAS) is closely associated with cardiovascular and metabolic disorders., Objectives: The aim of this study was to evaluate the influence of OSAS on plasma adiponectin levels independent of obesity in our study group. We also investigated the association between plasma adiponectin, plasma tumor necrosis factor-alpha (TNF-alpha), obesity, cardiovascular disease (CVD) and OSAS., Methods: The patients were classified into controls or OSAS patients according to the apnea-hypopnea index (AHI): patients with an AHI <5 constituted the control group (n = 32) and patients with an AHI > or =5 constituted the OSAS group (n = 106). Plasma TNF-alpha and adiponectin levels were measured in both groups., Results: Plasma adiponectin levels were negatively correlated with AHI, body mass index (BMI) and SpO(2) <90% and positively correlated with minimum oxygen saturation. The plasma levels of TNF-alpha were positively correlated with SpO(2) <90%, BMI and fasting plasma glucose levels. In addition, there was a significant negative correlation between plasma TNF-alpha and adiponectin levels in theOSAS group. Compared with thenon-obese OSAS group, subjects with obesity and OSAS had lower adiponectin levels and SpO(2) <90%, and higher TNF-alpha levels. Obese OSAS patients had higher rates of CVD with lower plasma adiponectin levels when compared with obese control subjects., Conclusion: Serum adiponectin is significantly lower in patients with OSAS and it is independent of obesity. This might explain the high incidence of CVD and metabolic syndrome in patients with OSAS., (Copyright 2008 S. Karger AG, Basel.)

Background: Obstructive sleep apnea (OSA) is closely related to systemic inflammation. Resistin is an adipocyte-derived cytokine (adipokine) that may link obesity with inflammation., Objective: We aimed to investigate whether incremental changes in OSA severity, from normal to severe, primarily affect the levels of resistin and other adipokines., Methods: Serum levels of resistin, interleukin-6 (IL-6) and leptin were examined in 31 men with OSA and 10 men without OSA, matched for age, body mass index (BMI) and several metabolic profiles. In 11 of the 31 men with OSA, these mediators were reexamined after 3 months of nasal continuous airway pressure (nCPAP) therapy., Results: Levels of resistin and IL-6 were simultaneously elevated in men with OSA compared with those in men without OSA (p < 0.05), while levels of leptin did not differ. The resistin and IL-6 levels tended to increase with increasing disease severity (p < 0.05), which was based on the apnea-hypopnea index (AHI). The average oxyhemoglobin saturation during sleep (p < 0.01) and IL-6 (p < 0.05) emerged as significant determinants of resistin, even after adjustments for age, BMI, leptin levels and metabolic risk factors. After nCPAP therapy, the elevated levels of resistin and IL-6 decreased, reaching almost baseline levels of controls. Before treatment, AHI correlated positively with the reduction rate in resistin (p < 0.05)., Conclusion: In OSA patients, resistin production can be enhanced by hypoxic stress during sleep, possibly mediating systemic inflammatory processes. nCPAP therapy may play a beneficial role in the control of resistin production., ((c) 2008 S. Karger AG, Basel.)

Background: Nonobese diabetics with diabetic autonomic neuropathy (DAN) show an elevated prevalence of obstructive sleep apnea-hypopnea (OSAH)., Objective: It was the aim of this study to assess if the presence of DAN could further increase the risk of developing OSAH in obese diabetics., Methods: Eighteen obese diabetic patients, 8 with DAN [age 57 +/- 5 years, body mass index (BMI) 35 +/- 4] and 10 without DAN (age 56 +/- 8 years, BMI 37 +/- 5), were recruited. Ten age-matched obese subjects were studied as controls (age 53 +/- 12 years, BMI 34 +/- 3). All subjects underwent a cardiorespiratory sleep study in the in-hospital sleep laboratory to obtain the apnea-hypopnea index (AHI) and oxygen desaturation indices., Results: Diabetics with DAN (Ob-DAN+) had a higher AHI than diabetics without DAN (Ob-DAN-) and controls, amounting to 39.5 +/- 13 versus 15.8 +/- 12 (p < 0.01) and 19.3 +/- 21 (p < 0.05), respectively. A moderate-to-severe OSAH (AHI > or = 15) occurred in all Ob-DAN+ and only in 4 Ob-DAN- and 4 control patients. Moreover, the indices reflecting the impairment of oxygen saturation (SaO(2)) during sleep such as the mean lowest SaO(2) and sleep time with a SaO(2) <90% were more severely affected in Ob-DAN+ patients compared with the other groups and were associated with longer obstructive respiratory events., Conclusions: Apneas-hypopneas are more frequent and last longer in Ob-DAN+ than in other obese subjects, with or without diabetes., (2007 S. Karger AG, Basel)

Background: Although certain studies report high levels of vascular endothelial growth factor (VEGF) in obstructive sleep apnea syndrome (OSAS), the effect of systemic hypoxia on circulating VEGF remains controversial., Objectives: To study the association of serum VEGF and OSAS in a large group of patients., Methods: One hundred patients with OSAS (mean age 58.1+/-12.4 years, mean body mass index 30.6+/-5.4 kg/m2) were tested for serum VEGF levels, and the findings were correlated with the severity of OSAS, as determined by the apnea-hypopnea index (AHI) on the basis of polysomnography and background data., Results: The mean AHI was 40.0+/-21.2 (range 10-106). Mean minimal oxygen saturation was 80.6+/-11.7% (range 43-98%) and mean time of oxygen saturation under 90% was 50.0+/-75.0 min (range 0-300 min). The mean VEGF level was 445.2+/-289.8 pg/ml in the study group (vs. 280 pg/ml reported in normal controls). The mean platelet count was 233.8+/-64.4 10(3)/ml and the mean VEGF/platelet ratio was 1.95+/-1.40 pg/10(6). There was no association of VEGF or VEGF/platelets with the severity of OSAS. However, both factors showed a significant correlation with patient age (r=0.224, p=0.01 and r=0.425, p=0.01, respectively). Age was the only parameter to significantly predict VEGF and VEGF/platelets on multivariate analysis (R2=0.713, p=0.001 and R2=0.844, p=0.001, respectively)., Conclusion: The elevation of serum VEGF in OSAS is not associated with the severity of the disease, but it is associated with patient age. VEGF might be involved in the long-term adaptive mechanism in OSAS, and its age-dependent increase might partly explain the reduced mortality in elderly OSAS patients., (Copyright (c) 2007 S. Karger AG, Basel.)

Background: Obstructive sleep apnea syndrome (OSAS)-induced hypoxic stress modulates circulating inflammatory mediators causing accelerated atherogenesis., Objectives: We hypothesized that OSAS-induced hypoxia might result in cardiovascular disease due to increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the endothelial surface., Methods: Thirty-nine subjects with moderate-to-severe OSAS and 34 non-apneic controls matched for age, gender, body mass index (BMI), smoking history, and cardiovascular disease were included in this prospective study. Overnight polysomnography was performed. Circulating ICAM-1 and VCAM-1 levels in the serum were measured by enzyme-linked immunosorbent assay., Results: Circulating levels of both ICAM-1 (480.1 +/- 216.7 vs. 303.4 +/- 98.6 ng/ml, p < 0.0001) and VCAM-1 (1,156.6 +/- 79.8 vs. 878.8 +/- 71.1 ng/ml, p = 0.002) were significantly increased in the OSAS group compared to the control group. For an ICAM-1 cutoff level of 375 ng/ml, predictive sensitivity and specificity for OSAS were 69.2% (95% confidence interval, CI: 52.4-83.0%) and 82.4% (95% CI: 65.5-93.2%), respectively. For a VCAM-1 cutoff level of 859 ng/ml, predictive sensitivity and specificity for OSAS were 74.4% (95% CI: 57.9-86.9%) and 64.7% (95% CI: 46.5-80.2%), respectively. There was a significant positive correlation between circulating levels of ICAM-1 and ln of AHI (r = 0.276, p = 0.018). Multiple logistic regression analyses showed that OSAS was associated with high ICAM-1 and high VCAM-1 levels independent of age, gender, BMI, smoking status and cardiovascular disease., Conclusion: We conclude that OSAS can independently increase circulating levels of adhesion molecules, (Copyright 2007 S. Karger AG, Basel.)

Background: Adiponectin has been found to be associated with the pathogenesis of diabetes, obesity and some cardiovascular diseases, which usually coexist with obstructive sleep apnea hypopnea syndrome (OSAHS). However, an association between adiponectin and OSAHS has rarely been reported., Objectives: To investigate the levels of serum adiponectin in adult male patients with OSAHS., Methods: Following polysomnographic examination, 86 adult male habitual snorers were divided into simple snorers (control group) and OSAHS patients (OSAHS group) who were further divided into mild, moderate and severe OSAHS subgroups based on their apnea hypopnea index (AHI). There was no significant difference in age, body mass index (BMI), fasting blood glucose (FBG) and insulin resistance expressed as homeostasis model assessment (HOMA) between the two groups. The serum adiponectin levels were measured by radioimmunoassay., Results: Serum adiponectin levels were significantly lower in the OSAHS group than in the control (p < 0.01). Such a decrease in adiponectin level was most significant in patients with moderate and severe OSAHS. Pearson correlation analysis showed that in OSAHS patients, serum adiponectin level was negatively correlated with BMI, waist (WC) and neck (NC) circumferences, AHI and HOMA, but positively correlated with nadir pulse oxyhemoglobin saturation (nadir SpO2). After controlling for HOMA, BMI, NC and WC in OSAHS patients, a partial correlation analysis showed that adiponectin levels were negatively correlated with AHI but positively correlated with nadir SpO2. Multiple logistic regression analysis indicated that adiponectin was independently associated with OSAHS., Conclusions: Serum adiponectin levels were significantly lower in OSAHS patients than in simple snorers. OSAHS may cause a decrease in serum adiponectin level., (Copyright 2006 S. Karger AG, Basel.)

Background: Leptin is a protein produced by adipose tissue that circulates to the brain and interacts with receptors in the hypothalamus to inhibit eating. In obese humans, serum leptin is up to four times higher than in lean subjects, indicating that human obesity is associated with a central resistance to the weight-lowering effects of leptin. Although the leptin-deficient mouse (ob/ob) develops obesity hypoventilation syndrome (OHS), in humans with OHS, serum leptin is a better predictor of awake hypercapnia in obesity than the body mass index (BMI). This suggests that central leptin resistance may promote the development of OHS in humans. We speculated that the reversal of OHS by regular non-invasive ventilation (NIV) therapy decreases leptin levels., Objectives: The aim of this study was to investigate whether ventilatory treatment of OHS would alter circulating leptin concentrations., Method: We measured fasting serum leptin levels, BMI, spirometry and arterial blood gases in 14 obese hypercapnic subjects undergoing a diagnostic sleep study., Results: The average age of the subjects was (mean +/- SE) 62 +/- 13 years, BMI 40.9 +/- 2.2 kg/m(2), PaCO(2) 6.7 +/- 0.2 kPa, PaO(2 )8.9 +/- 0.4 kPa and total respiratory disturbance index 44 +/- 35 events/hour. Subjects were clinically reviewed after a median of 2.3 years (range 1.6-3) with repeat investigations. Nine patients were regular NIV users and 5 were non-users. NIV users had a significant reduction in serum leptin levels (p = 0.001), without a change in BMI. In these patients, there was a trend towards an improved daytime hypercapnia and hypoxemia, while in the 5 non-users, no changes in serum leptin, BMI or arterial blood gases occurred., Conclusion: Regular NIV use reduces serum leptin in OHS. Leptin may be a modulator of respiratory drive in patients with OHS.

Background: Leptin is a hormone with well-investigated functions concerning body composition, energy homeostasis and feeding behavior in humans. The obstructive sleep apnea syndrome (OSAS) is strongly associated with obesity, which is known to be closely associated with hyperleptinemia. More recently, ghrelin, a hormone that also influences appetite and energy homeostasis, has been discovered., Objectives: The aim of this study was to investigate serum leptin and ghrelin levels in obese patients with OSAS in comparison with equally obese controls without OSAS., Methods: Thirty untreated obese patients with moderate-severe OSAS (apnea-hypopnea index: AHI > or =15) and 22 obese controls (AHI <5) were studied. To confirm the diagnosis, all patients underwent standard polysomnography in our sleep disorders center. Serum samples were taken at 08:00 h in the morning after overnight fasting., Results: Significantly higher serum leptin levels were found in OSAS patients compared to controls (p = 0.012), but there was no significant difference in serum ghrelin levels between OSAS patients and controls. Serum leptin levels were significantly correlated with body mass index in both OSAS patients (r = 0.55, p = 0.002) and controls (r = 0.46, p = 0.028), but only in OSAS patients was the leptin level significantly correlated with AHI (r = 0.38, p = 0.036)., Conclusion: These data support findings suggesting that leptin is a hormonal factor affected by OSAS and not determined by obesity alone. Further studies are needed to investigate the relationship between serum ghrelin and OSAS., ((c) 2005 S. Karger AG, Basel)

Background: Orexin-A, also known as hypocretin, is a neuropeptide implicated in appetite and sleep regulation. Because the obstructive sleep apnea syndrome (OSAS) is characterized by obesity and excessive daytime sleepiness, we hypothesized that orexin-A levels may be abnormal in patients with OSAS. Further, since treatment with continuous positive airway pressure (CPAP) in patients with OSAS is very effective in normalizing daytime sleepiness, we also hypothesized that the chronic use of CPAP may influence plasma levels of orexin-A in these patients., Objective: To evaluate plasma levels of orexin-A in patients with OSAS and the effect of CPAP treatment., Patients and Methods: We compared the plasma levels of orexin-A in 13 healthy controls, 27 untreated patients with OSAS and 14 patients treated with CPAP during at least 1 year (4.5 +/- 0.5 h/night; mean +/- SEM). All patients had severe OSAS (apnea-hypopnea index, 57 +/- 4 h(-1))., Results: Orexin-A plasma levels were significantly lower in untreated (9.4 +/- 1.9 pg.ml(-1), p < 0.01) and treated patients with OSAS (4.2 +/- 1.5 pg.ml(-1), p < 0.001) than in healthy subjects (20.6 +/- 4.5 pg.ml(-1)). In untreated patients, orexin-A levels were not significantly related to daytime somnolence assessed by Epworth scale (r = -0.18, p = 0.37) or the body mass index (r = -0.13, p = 0.52)., Conclusions: Orexin-A plasma levels are abnormally low in patients with OSAS, independently of the level of somnolence and/or presence of obesity. These results suggest that these low orexin-A levels may be related to the pathogenesis of OSAS.

Background: Adiponectin is an adipocyte-derived hormone with anti-inflammatory and insulin-sensitizing properties. Insulin resistance is a typical feature of the obstructive sleep apnea syndrome (OSAS)., Objectives: Since nasal continuous positive airway pressure (nCPAP) treatment improves insulin sensitivity in patients with OSAS, we investigated serum adiponectin levels before and during nCPAP treatment to clarify possible interactions between the adiponectin levels and insulin sensitivity in patients with OSAS., Methods: Thirty nondiabetic, obese patients with OSAS (mean age 56.4 +/- 11.1 years; apnoea-hypopnoea index (AHI) 46.03 +/- 19.57) underwent CPAP treatment. Adiponectin levels and the levels of proinflammatory cytokines and proteins reflecting platelet activation [regulated on activation normally T cell expressed and secreted (RANTES) and soluble P-selectin (sCD62p)], as well as the insulin sensitivity index were measured before, and after 2 days and 3 months of CPAP treatment., Results: Insulin sensitivity increased significantly under nCPAP treatment, whereas adiponectin levels decreased after 2 days of nCPAP treatment, but returned to baseline levels after 3 months of nCPAP treatment. The increase in insulin sensitivity was more pronounced in patients with the highest adiponectin levels at baseline (p = 0.021) after adjustment for body fat (p = 0.003). During treatment, changes in adiponectin levels were highly predictable by the insulin sensitivity index., Conclusions: We found a significant relation between adiponectin and the insulin sensitivity index in overweight patients with OSAS. The lack of a long-lasting change in adiponectin may be explained by the overwhelming influence of the body mass index on adiponectin secretion, which was unchanged during nCPAP treatment.

Background: Polysomnography (PSG) tests are very complicated and time consuming, despite their clinical benefits in the diagnosis of patients with obstructive sleep apnea hypopnea syndrome (OSAHS). A plasma marker would be desirable to select patients suspected of OSAHS for further PSG studies. We have recently reported that orexin-A concentrations in plasma collected immediately after waking early in the morning were significantly lower in patients with OSAHS than in controls., Objectives: We conducted the present study to assess the clinical usefulness of the measurement of orexin-A concentrations in plasma obtained in the daytime as a diagnostic predictor to screen patients with OSAHS., Methods: Blood samples were collected in the daytime from 19 male patients with suspected sleep-disordered breathing. Plasma orexin-A concentrations were measured by radioimmunoassay before performing PSG., Results: PSG was conducted in all 19 subjects. PSG showed that 14 subjects had OSAHS and 5 subjects did not. Plasma orexin-A concentrations were significantly lower in patients with OSAHS (4.9 +/- 0.8 pmol/l, mean +/- SE, n = 14) than in control subjects (12.3 +/- 1.9 pmol/l, n = 5) (p = 0.0004)., Conclusions: These findings suggest that the orexin-A concentration in plasma obtained even in the daytime may be a useful plasma marker for screening OSAHS., (Copyright 2004 S. Karger AG, Basel)

Background: In previous studies, significantly elevated levels of vascular endothelial growth factor (VEGF) have been reported in patients with severe obstructive sleep apnea-hypopnea syndrome (OSAHS). On the other hand, plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) have been significantly higher in mild sleep apneics than in normal controls. However, this study included a small number of patients and milder cases of OSAHS., Objectives and Methods: To assess the involvement of IL-6 and TNF-alpha in VEGF increases in patients with severe OSAHS, serum levels of IL-6 and TNF-alpha were determined in patients with severe OSAHS (n=110) and compared to those of controls (n=45) using an enzyme-linked immunosorbent assay., Results: No significant increase in IL-6 or TNF-alpha was detected in the present study cohort. However, the body mass index was significantly correlated with the severity of the apnea-hypopnea index., Conclusions: These data suggest that the elevation in VEGF is not directly related to IL-6 or TNF-alpha levels. However, the question of whether VEGF is the cause or the result of OSAHS remains to be determined. Further studies are needed to clarify the role of IL-6 and TNF-alpha in the pathogenesis of OSAHS, in which obesity should be entered as an independent factor., (Copyright 2004 S. Karger AG, Basel)

Obstructive sleep apnea syndrome (OSAS) afflicts about 5% of adults in Western countries and is thought to play an important role in the pathogenesis of cardiovascular disorders and diabetes mellitus. Although the etiology of OSAS is uncertain, intense local and systemic inflammation are present in these patients. In the upper airway, this process may promote oropharyngeal inspiratory muscle dysfunction and amplify upper airway narrowing and collapsibility thereby worsening the frequency and duration of apneas during sleep. The presence of systemic inflammation, characterized by elevated levels of certain potent pro-inflammatory mediators, such as C-reactive protein, leptin, TNF-alpha, IL-1beta, IL-6, reactive oxygen species and adhesion molecules, may predispose to the development of cardiovascular complications observed in patients with OSAS. Treatment with nasal CPAP abrogates, in part, local and systemic inflammation in these patients. Whether therapeutic interventions aimed at abating inflammation could be a useful adjunct in the treatment of OSAS merits further investigation., (Copyright 2003 S. Karger AG, Basel)