The effect of continuous positive airway pressure treatment on insulin sensitivity in patients with obstructive sleep apnoea syndrome and type 2 diabetes

BACKGROUND: The obstructive sleep apnoea syndrome (OSA) is a frequent condition, as well as type 2 diabetes mellitus. Both diseases are characterized by insulin resistance. OBJECTIVES: The aim of this study was to establish whether OSA is an independent risk factor for increased insulin resistance in diabetics. For this purpose, we tested the hypothesis that the insulin sensitivity in patients with type 2 diabetes and OSA can be improved by 2 days or 3 months of continuous positive airway pressure (CPAP) treatment. METHODS: In 9 obese patients with type 2 diabetes and OSA [apnoea/hypopnoea index 43.1 +/- 21.3; body mass index (BMI) 37.3 +/- 5.6 kg/m2] and good glycaemic control on oral antidiabetics or on diet alone (HbA1c 6.4 +/- 0.7%), the insulin sensitivity index (ISI) was established by euglycaemic hyperinsulinaemic clamp tests at baseline, after 2 days and after 3 months of effective CPAP treatment. RESULTS: ISI was unchanged after 2 days of CPAP treatment, but was significantly improved after 3 months (4.38 +/- 2.94 vs. 2.74 +/- 2.25 at baseline; p = 0.021), without any significant changes in BMI. Glycaemic control was unaffected after 3 months (HbA1c 6.3 +/- 0.6%; not significant). Fasting leptin levels showed no significant changes. CONCLUSIONS: These results indicate that OSA itself is an independent risk factor for insulin resistance. This effect may be explained by the elevated sympathetic activity in OSA.     

Acylated ghrelin level in patients with OSA before and after nasal CPAP treatment

Background and objective: Patients with newly diagnosed OSA have been reported to have recent weight gain prior to diagnosis. Ghrelin stimulates food intake and increases weight gain. Plasma ghrelin is decreased in obese and increased in lean individuals. Of the two circulating forms of ghrelin, acylated and unacylated, the former is thought to be essential for the biological activity of ghrelin. Methods: The plasma levels of the two forms of ghrelin were measured in 21 OSA patients (with a mean of 46.2 sleep‐disordered events/h) before and after 1 month of nasal CPAP (nCPAP) treatment, and were compared with those in 14 untreated OSA patients and 13 individuals without OSA. Results: The BMI was significantly higher in the 21 OSA patients than in the non‐OSA group as were the baseline acylated (11.4 ± 5.86 vs 7.19 ± 3.80 fmol/mL, P = 0.03) and unacylated (84.2 ± 50.6 vs 48.3 ± 23.2 fmol/mL, P = 0.02) ghrelin levels. The total ghrelin level was positively correlated with the number of sleep‐disordered breathings (P = 0.002). After 1 month of nCPAP treatment, the acylated ghrelin level significantly decreased (P = 0.02) while the unacylated ghrelin level did not (P = 0.09). Conclusions: Treatment of OSA may play an important role in the management of obesity in these patients by reducing the acylated ghrelin level.     

Association between continuous positive airway pressure and changes in serum leptin in patients with obstructive sleep apnoea: a meta-analysis

Purpose

The role of leptin in the development of obstructive sleep apnoea (OSA) has been identified. However, the effects of OSA treatment using continuous positive airway pressure (CPAP) on serum leptin levels remain controversial. To address this issue, a meta-analysis was conducted to evaluate the effects of CPAP therapy on serum leptin levels in OSA.

Methods

A comprehensive literature search was performed to identify studies that focused on the effects of CPAP therapy (treatment duration, ≥4 weeks) on the serum leptin levels of OSA patients. Standardised mean difference (SMD) was used to analyse the summary estimates for CPAP therapy.

Results

Fifteen studies involving 427 patients were included in the meta-analysis. Results indicate that the overall SMD of the leptin levels before and after CPAP therapy was 0.137 (95 % confidence interval (CI) 0.002 to 0.272); test for overall effect z?=?1.99 (P?=?0.046). Sources of heterogeneity were not found by subgroup and meta-regression analyses. Subgroup analyses showed that differences in OSA severity, baseline body mass index, compliance, CPAP duration and leptin assay did not affect the effectiveness of CPAP therapy.

Conclusions

The evidence for the use of CPAP therapy on decrease of leptin levels in OSA patients is low, and stronger evidence is needed.     

Different effects of short- and long-term recombinant hGH administration on ghrelin and adiponectin levels in GH-deficient adults

OBJECTIVE: To evaluate circulating levels of ghrelin and adiponectin (ApN) in GH-deficient (GHD) adults before and after short- and long-term recombinant human GH (rhGH) administration. PATIENTS AND METHODS: Twenty-three patients were studied. Seventeen subjects (Group A, 12 men, five women) were evaluated at baseline and after 1 year rhGH therapy (dose mean +/- SD: 0.3 +/- 0.1 mg/day) with the assessment of serum IGF-I, ghrelin, ApN, leptin, insulin and glucose levels, percentage of body fat (BF%), HOMA-IR and QUICKI. Seventeen age-, sex- and body mass index (BMI)-matched healthy subjects were recruited for comparisons. Six patients (Group B, three men, three women) underwent IGF-I generation test (rhGH 0.025 mg/kg/day for 7 days), blood sampled at baseline and on day 8 for determination of IGF-I, ghrelin and ApN levels. RESULTS: Group A: at baseline GHD patients showed low IGF-I levels and BF% significantly higher than controls (31.4 +/- 2.5 vs. 26.4 +/- 1.3, P < 0.05). Glucose, insulin, leptin, tryglicerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, as well as HOMA-IR and QUICKI values were similar in the two series, while total cholesterol levels were higher in GHD. In GHD, ghrelin levels were significantly lower than in controls (193.9 +/- 27.1 vs. 298.1 +/- 32.5 pmol/l, respectively, P = 0.02), while ApN levels were similar (10.2 +/- 1.1 and 9 +/- 1 mg/l, respectively, P = ns). After 1 year of rhGH therapy, BF%, BMI, serum total and LDL cholesterol significantly decreased, serum leptin levels showed a trend to decrease, while HOMA-IR and QUICKI did not change. Ghrelin and ApN levels significantly increased from 193.9 +/- 27.1 to 232.4 +/- 26.3 pmol/l (P < 0.01) and from 8.6 +/- 0.8 to 10.3 +/- 1.1 mg/l (P < 0.05), respectively. In group B, the expected increase in IGF-I levels was associated with a significant decrease in ghrelin levels, while ApN did not change. CONCLUSION: GHD patients showed serum ghrelin lower than controls, probably due to the higher BF%. No difference in ApN was observed. Ghrelin and ApN increments induced by long-term treatment may be related to the significant BMI and BF% reduction that is the predominant metabolic effect of rhGH therapy. Conversely, the decrease in ghrelin levels observed after short-term rhGH administration may be consistent with an inhibitory feedback of GH and/or IGF-I on ghrelin release.     

Oxidative stress in obstructive sleep apnoea.

AIMS: Any sustained elevation of oxidative stress in patients with obstructive sleep apnoea (OSA) might help explain their increased risk for cardiovascular diseases. We tested the hypothesis that measures of oxidative stress are increased in otherwise healthy subjects with OSA when compared to closely matched OSA-free control subjects. METHODS AND RESULTS: Plasma indices of oxidative stress and lipid peroxidation [thiobarbituric acid-reactive substances (TBARS), oxidized LDL (oxLDL), isoprostanes] were measured in 41 moderate-severe OSA males without other diseases and in 35 matched controls first before sleep, then after 4 h of untreated OSA, and again in the morning after 4 h of effective treatment with continuous positive airway pressure (CPAP). Plasma levels of oxLDL, TBARS, and isoprostanes in OSA patients (n=34, 26, 17, respectively) were comparable to the controls (n=28, 27, 15 for the three markers, respectively). Neither untreated OSA nor CPAP treatment nor normal sleep affected levels of any of the three measures of oxidative stress. There was no association between the severity of sleep apnoea and any measure of oxidative stress. CONCLUSION: Otherwise healthy OSA patients, without any other co-morbidities, do not manifest evidence for higher oxidative stress and lipid peroxidation. Thus, oxidative stress and lipid peroxidation do not appear to be key mediators of increased cardiovascular disease in OSA patients.     

Atrial overdrive pacing compared to CPAP in patients with obstructive sleep apnoea syndrome.

AIMS: Obstructive sleep apnoea (OSA) is associated with oxygen desaturation, blood pressure increase, and neurohumoral activation, resulting in possible detrimental effects on the cardiovascular system. Continuous positive airway pressure (CPAP) is the therapy of choice for OSA. In a recent study, nocturnal atrial overdrive pacing (pacing) reduced the severity of sleep apnoea in pacemaker patients. We compared the effects of CPAP with those of pacing in patients with OSA but without pacemaker indication or clinical signs of heart failure. METHODS AND RESULTS: Ten patients with OSA on CPAP therapy were studied for three nights by polysomnography. During the nights that followed a night without any treatment (baseline), the patients were treated with CPAP or pacing in a random order. Pacing was performed with a temporary pacing lead. The pacing frequency was 15 b.p.m. higher than the baseline heart rate. The apnoea-hypopnoea index was 41.0 h(-1) (12.0-66.6) at baseline and was significantly lower during CPAP [2.2 h(-1) (0.3-12.4)] compared with pacing [39.1 h(-1) (8.2-78.5)]. Furthermore, duration and quality of sleep were significantly improved during CPAP when compared with pacing. CONCLUSION: Nocturnal atrial overdrive pacing is no alternative therapeutic strategy to CPAP for the treatment of OSA in patients without clinical signs of heart failure and without conventional indication for anti-bradycardia pacing.     

Cephalometric abnormalities in non-obese and obese patients with obstructive sleep apnoea.

The aim of this work was to comprehensively evaluate the cephalometric features in Japanese patients with obstructive sleep apnoea (OSA) and to elucidate the relationship between cephalometric variables and severity of apnoea. Forty-eight cephalometric variables were measured in 37 healthy males and 114 male OSA patients, who were classed into 54 non-obese (body mass index (BMI) <27 kg x m(-2), apnoea-hypopnoea index (AHI)=25.3+/-16.1 events x h(-1)) and 60 obese (BMI > or = 27 kg x m(-2), AHI=45.6+/-28.0 events h(-1)) groups. Diagnostic polysomnography was carried out in all of the OSA patients and in 19 of the normal controls. The non-obese OSA patients showed several cephalometric defects compared with their BMI-matched normal controls: 1) decreased facial A-P distance at cranial base, maxilla and mandible levels and decreased bony pharynx width; 2) enlarged tongue and inferior shift of the tongue volume; 3) enlarged soft palate; 4) inferiorly positioned hyoid bone; and 5) decreased upper airway width at four different levels. More extensive and severe soft tissue abnormalities with a few defects in craniofacial bony structures were found in the obese OSA group. For the non-obese OSA group, the stepwise regression model on AHI was significant with two bony structure variables as determinants: anterior cranial base length (S-N) and mandibular length (Me-Go). Although the regression model retained only linear distance between anterior vertebra and hyoid bone (H-VL) as an explainable determinant for AHI in the obese OSA group, H-VL was significantly correlated with soft tissue measurements such as overall tongue area (Ton), inferior tongue area (Ton2) and pharyngeal airway length (PNS-V). In conclusion, Japanese obstructive sleep apnoea patients have a series of cephalometric abnormalities similar to those described in Caucasian patients, and that the aetiology of obstructive sleep apnoea in obese patients may be different from that in non-obese patients. In obese patients, upper airway soft tissue enlargement may play a more important role in the development of obstructive sleep apnoea, whereas in non-obese patients, bony structure discrepancies may be the dominant contributing factors for obstructive sleep apnoea.     

The effects of continuous positive airway pressure therapy withdrawal on cardiac repolarization: data from a randomized controlled trial

Aims The preliminary evidence supports an association between obstructive sleep apnoea (OSA), disturbed cardiac repolarization, and consequent cardiac dysrhythmias. The aim of the current trial was to assess the effects of continuous positive airway pressure (CPAP) therapy withdrawal on the measures of cardiac repolarization in patients with OSA. Methods and results Forty-one OSA patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Polysomnography was performed, and indices of cardiac repolarization (QT(c), TpTe(c) intervals) and dispersion of repolarization (TpTe/QT ratio) were derived from 12-lead electrocardiography (ECG) at baseline and 2 weeks. Continuous positive airway pressure withdrawal led to a recurrence of OSA. Compared with therapeutic CPAP, subtherapeutic CPAP for 2 weeks was associated with a significant increase in the length of the QT(c) and TpTe(c) intervals (mean difference between groups 21.4 ms, 95% CI 11.3-1.6 ms, P < 0.001 and 14.4 ms, 95% CI 7.2-21.5 ms, P < 0.001, respectively) and in the TpTe/QT ratio (mean difference between groups 0.02, 95% CI 0.00-0.03, P = 0.020). There was a statistically significant correlation between the change in apnoea/hypopnoea index (AHI) from baseline, and both the change in the QT(c) interval and the TpTe(c) interval (r = 0.60, 95% CI 0.36-0.77, P < 0.001 and r = 0.45, 95% CI 0.17-0.67, P = 0.003, n = 41, respectively). Conclusion Continuous positive airway pressure withdrawal is associated with the prolongation of the QT(c) and TpTe(c) intervals and TpTe/QT ratio, which may provide a possible mechanistic link between OSA, cardiac dysrhythmias, and thus sudden cardiac death.     

慢性阻塞性肺疾病患者血浆瘦素和生长激素释放肽水平研究

目的探讨血浆瘦素和生长激素释放肽ghrelin与慢性阻塞性肺疾病（COPD）患者的营养状况和循环炎症因子水平的关系，以及排除营养因素的影响后，瘦素和ghrelin是否与COPD有关。方法检测53例稳定期COPD患者和26名健康对照者的血浆瘦素、总ghrelin、活性ghrelin、肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6）水平，评价去脂组织和脂肪组织重量。结果低体重COPD患者血浆瘦素水平[2．6（2．0-4．4）ng／L]显著低于正常体重的COPD患者[6．1（5．1-7．8）ng／L]和健康对照者[4．8（3．3-6．1）ng／L]，COPD患者的瘦素含量与脂肪组织重量和TNF-a水平呈显著正相关；校正脂肪组织重量等影响因素后，COPD患者血浆瘦素含量显著高于对照组，且与TNF-α水平显著相关。低体重COPD患者血浆总ghrelin和活性ghrelin水平[1090（860-2838）ng／L和63（50-97）ng／L]均显著高于正常体重的COPD患者[765（651-941）ng／L和47（41-56）ng／L]和健康对照者[844（676-1045）ng／L和54（41-60）ng／L]，COPD患者的总ghrelin水平、活性ghrelin水平均与体重指数呈显著负相关。结论营养不良的稳定期COPD患者血浆瘦素水平降低，总ghrdin和活性ghrelin水平升高，3种激素受营养状态影响，并且对稳定期COPD患者的营养状态起着生理性调节作用。在排除营养因素的影响后，COPD患者瘦素水平相对升高，并与TNF-α水平呈显著正相关，提示瘦素可能与COPD的疾病本身和全身炎症反应有关。     

Pulmonary hypertension in obstructive sleep apnoea: effects of continuous positive airway pressure: a randomized, controlled cross-over study.

AIMS: We tested the hypothesis that: (i) obstructive sleep apnoea (OSA) by itself originates pulmonary hypertension (PH); and (ii) the application of continuous positive airway pressure (CPAP) can reduce pulmonary pressure. METHODS AND RESULTS: In this randomized and cross-over trial, 23 middle-aged OSA (apnoea-hypopnoea index, 44.1 +/- 29.3 h(-1)) and otherwise healthy patients and 10 control subjects were included. OSA patients randomly received either sham or effective CPAP for 12 weeks. Echocardiographic parameters, blood pressure recordings, and urinary catecholamine levels were obtained at baseline and after both treatment modalities. At baseline, OSA patients had higher pulmonary artery systolic pressure than control subjects (29.8 +/- 8.8 vs. 23.4 +/- 4.1 mmHg, respectively, P = 0.036). Ten out of 23 patients [43%, (95% CI: 23-64%)] and none of the control subjects had PH at baseline (P = 0.012). Two patients were removed from the study because of inadequate CPAP compliance. Effective CPAP induced a significant reduction in the values for pulmonary systolic pressure (from 28.9 +/- 8.6 to 24.0 +/- 5.8 mmHg, P < 0.0001). The reduction was greatest in patients with either PH or left ventricular diastolic dysfunction at baseline. CONCLUSION: Severe OSA is independently associated with PH in direct relationship with disease severity and presence of diastolic dysfunction. Application of CPAP reduces pulmonary systolic pressure levels.     

Increased incidence of nonfatal cardiovascular events in stroke patients with sleep apnoea: effect of CPAP treatment

Obstructive sleep apnoea (OSA) is a risk factor for stroke, but little is known about the effect of OSA and continuous positive airway pressure (CPAP) on the incidence of long-term, nonfatal cardiovascular events (CVE) in stroke patients. A prospective observational study was made in 223 patients consecutively admitted for stroke. A sleep study was performed on 166 of them. 31 had an apnoea/hypopnoea index (AHI) <10 events · h(-1); 39 had an AHI between 10 and 19 events · h(-1) and 96 had an AHI ≥ 20 events · h(-1). CPAP treatment was offered when AHI was ≥ 20 events · h(-1). Patients were followed up for 7 yrs and incident CVE data were recorded. The mean ± SD age of the subjects was 73.3 ± 11 yrs; mean AHI was 26 ± 16.7 events · h(-1). Patients with moderate-to-severe OSA who could not tolerate CPAP (AHI ≥ 20 events · h(-1); n = 68) showed an increased adjusted incidence of nonfatal CVE, especially new ischaemic strokes (hazard ratio 2.87, 95% CI 1.11-7.71; p = 0.03), compared with patients with moderate-to-severe OSA who tolerated CPAP (n = 28), patients with mild disease (AHI 10-19 events · h(-1); n = 36) and patients without OSA (AHI <10 events · h(-1); n = 31). Our results suggest that the presence of moderate-to-severe OSA is associated with an increased long-term incidence of nonfatal CVE in stroke patients and that CPAP reduces the excess of incidence seen in these patients.     

Decrease in haematocrit with continuous positive airway pressure treatment in obstructive sleep apnoea patients.

Previous preliminary results have shown an overnight decrease in haematocrit and red cell count after the first night of treatment with nasal continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) patients. The present study was designed to confirm these preliminary data, and to analyse the long-term effects of CPAP. The haematocrit and red cell count (RCC) were measured in 80 OSA patients on two consecutive mornings, after an untreated night and after a CPAP treatment night. The haematocrit and RCC significantly decreased with CPAP (from 44.0 +/- 0.5 to 42.4 +/- 0.4%, p less than 0.0001 and from 4.769 +/- 0.051 to 4.597 +/- 0.052 x 10(12) red cells.l-1, p less than 0.0001, respectively). Neither the decrease in haematocrit nor the decrease in RCC were correlated with the decrease in urine volume or flow which occurred with CPAP. Thirty five of these patients remained untreated for 45 +/- 4 days, before home treatment with CPAP was initiated. The haematocrit and RCC had returned to values close to those before initial treatment and decreased again after the first treatment night. Twenty one of the patients were re-evaluated after at least one year of home treatment with CPAP, again on two consecutive nights either with CPAP or untreated. The follow-up, post-CPAP haematocrit and RCC were slightly and nonsignificantly higher than after the baseline CPAP night, but still lower than after the baseline untreated night (p less than 0.02). After the untreated follow-up night, no significant change in haematocrit was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efecto a largo plazo de la presión positiva automática en la vía aérea sobre la proteína C reactiva y la interleucina-6 en varones con síndrome de apnea obstructiva del sueño

Background and objectives

Obstructive sleep apnoea (OSA) has been increasingly linked to cardiovascular disease. Inflammatory processes associated with OSA may contribute to this morbidity. Some studies have reported serum levels of high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) to be increased in these patients. Primary objective: investigate the impact of short and long-term autoadjusting positive airway pressure (APAP) therapy on IL-6 and hs-CRP serum levels in patients with moderate to severe obstructive sleep apnoea. Secundary Objective: evaluate the basal hs-CRP and IL-6 levels in OSA patients and its possible relation to OSA severity, independently of confounders and compare the hs-CRP levels in OSA patients with those in community controls.

Patients and methods

This is a prospective study including 98 male patients with moderate to severe OSA confirmed by domiciliary sleep study. Malignancy and chronic inflammatory diseases were exclusion criteria. hs-CRP and IL-6 serum levels were evaluated before APAP, 9 days and 6 months after therapy. Community controls (n=103) were selected using random digit dialling, and matched by age and body mass index (BMI) for comparison of hs-CRP levels at baseline.

Results

The studied population had a mean age of 55.3±10.7 years, mean BMI 33.2±5.0 kg/m², mean apnoea-hypopnoea index 51.7±21.3/h and mean desaturation index 86.3±5.3/h. The APAP compliance was good: 91.27%±20.45 days usage and 5.76±1.59 h/night of usage.Mean basal hs-CRP and IL-6 serum values were 0.52±0.53 μg/l and 17.7±22.5 μg/l, respectively. CRP levels at baseline correlated significantly with apnoea-hypopnoea index, desaturation index and minimum nocturnal oxygen saturation. IL-6 levels at baseline correlated significantly and negatively with minimum nocturnal oxygen saturation. When adjusting for confounding factors found in this study, all these relations lost significance.CRP is significantly increased in patients when compared to controls (p=0.002) and when considering hs-CRP cardiovascular risk stratified categories, cases had significantly more patients at high risk of cardiovascular events than controls (p=0.002).After adjustment for BMI and arterial hypertension, cases had an almost twofold moderate risk of cardiovascular events and more than a twofold severe risk of cardiovascular events when compared to controls.We found no significant difference between hs-CRP and IL-6 concentrations pre-treatment and in two moments post-treatment (9 days and 6 months) (CRP: p=0.720 and p=0.387, respectively; IL-6: p=0.266 and p=0.238, respectively).

Conclusions

OSA is associated with a low-grade inflammatory process; hs-CRP serum levels are elevated in OSA patients when comparing to community controls, independently of age and BMI and the former have a significantly higher risk of cardiovascular events when compared to the latter. There was no significant decrease of both inflamatory mediators (hs-CRP, IL-6) after short and long-term APAP therapy.     

Endothelin-1 plasma levels are not elevated in patients with obstructive sleep apnoea.

Endothelin-1 (ET-1), a potent vasoconstrictor, is released mainly by vascular endothelial cells under the influence of hypoxia and other stimuli. ET-1 is related to endothelial dysfunction, as well as arterial and pulmonary hypertension, all of which are thought to be associated with obstructive sleep apnoea (OSA). This study evaluated venous plasma concentrations of ET-1 and noradrenaline and 24-h systemic blood pressure in 29 patients with OSA (age=56.9+/-1.6 yrs; body mass index=29.5+/-0.7 kg x m2 (mean+/-SEM)). Blood samples were taken in the morning, evening and during sleep. In the same way, the patients were assessed during a night of continuous positive airway pressure (CPAP) and after 13.9+/-1.4 months while still on CPAP. ET-1 levels were compared to those of control subjects, who were selected from in- and outpatients and were matched to patients for age, sex, presence of arterial hypertension and coronary artery disease. ET-1 plasma levels were not elevated in the patients compared to the controls (41.6+/-2.2 and 44.9+/-1.3 pg x mL(-1), respectively, p=0.20). The ET-1 concentration did not change significantly, neither during sleep nor in the first night on CPAP therapy, nor under long-term treatment with CPAP. ET-1 neither correlated to the severity of OSA nor to that of systemic hypertension. The results suggest that endothelin-1 does not play a crucial role in the pathophysiology of obstructive sleep apnoea.     

Falls in blood pressure in patients with obstructive sleep apnoea after long-term nasal continuous positive airway pressure treatment

OBJECTIVES: Effective treatment of obstructive sleep apnoea (OSA) with nasal continuous positive airway pressure (nCPAP) lowers blood pressure (BP). The long-term effects of nCPAP treatment on BP in OSA patients are not well known. The time period of such treatment sufficient to lower BP in OSA patients is also not known. We investigated compliance with long-term nCPAP therapy and its effects on BP. METHODS: This observational study involved 66 OSA patients [59 men, seven women; mean age, 51 (48-54) years; body mass index (BMI), 28.7 (27.7-29.7) kg/m; apnoea and hypopnoea, 50.3 (45.6-55.0)/h; 95% confidence intervals]. BP and BMI were measured before the study and at two checkpoints after usage of nCPAP [620 (552-688) and 1071 (1000-1143) days]. RESULTS: The different times between the first and second checkpoints for detecting objective compliance were 17 (4-30) min (P = 0.003). Diastolic BP decreased by 5.9 (3.1-8.7) mmHg after 600 days nCPAP treatment and by 4.6 (2.0-7.2) mmHg after 1000 days (P = 0.0006). Systolic BP and BMI did not change significantly. Usage of nCPAP treatment for a daily average of 3 h was needed to achieve a significant decrease in diastolic BP [7.4 (4.3-10.6) mmHg, P < 0.0001]. Diastolic BP of normotensive OSA patients did not change significantly by nCPAP treatment, but that of hypertensive OSA patients decreased significantly within 1 month-3 years of nCPAP treatment whether or not medication was used. CONCLUSIONS: In patients with severe OSA, the use of nCPAP for a daily average of 3 h would be sufficient to decrease the diastolic BP of hypertensive OSA patients.     

Ghrelin levels are increased in alcoholism

BACKGROUND: The neuropeptides leptin and ghrelin are involved in the appetite regulating network consisting of distinct orexigenic (ghrelin) and anorexigenic (leptin) circuitries. Recently, it has been shown that elevated leptin levels are associated with alcohol craving in patients suffering from alcoholism. Therefore, the aim of the present pilot study was to determine whether the gut-derived peptide ghrelin which increases hunger and food intake is altered and associated with alcohol craving in alcoholic patients METHODS: Two types of alcoholic inpatients, group A (active drinker, acutely intoxicated, n=97) and group B (early abstainer, who had stopped drinking 24-72 hrs before, n=21) were consecutively included in a prospective study from the first day of hospitalization. Ghrelin plasma levels and craving data were assessed on days 0, 1, 2 and 7(-10) and compared to those of 24 healthy controls RESULTS: At each time-point ghrelin plasma levels of alcoholic patients were significantly increased compared to healthy subjects. Furthermore, early abstainers showed significantly higher ghrelin levels than active drinkers. In the group of active drinkers ghrelin plasma levels were significantly increased at each time point compared to baseline. No correlations were found between ghrelin levels and craving data measured by the visual analogue scale or the Obsessive Compulsive Drinking Scale CONCLUSIONS: Ghrelin levels are elevated in alcoholism and seem to further increase during alcohol withdrawal. However, ghrelin levels do not seem to be associated with alcohol craving.     

Continuous positive airway pressure in heart failure patients with obstructive sleep apnoea

Background: The aim of the study was to study the effect of 6 months of continuous positive airway pressure (CPAP) in community heart failure (HF) patients with obstructive sleep apnoea (OSA). Methods: Clinically stable outpatients with HF and OSA (left ventricular ejection fraction (LVEF) <45%, apnoea/hypopnoea index >15/h, n = 19) treated with CPAP and a control group (LVEF <45%, apnoea/hypopnoea index <10/h, n = 7) were compared at baseline and at 6 months by Minnesota heart failure score, Epworth sleepiness score, shuttle walk distance, brain natriuretic peptide, urinary catecholamines and echocardiographic indices using paired t‐test, McNemar’s tests and effect sizes. Results: In HF patients with OSA, CPAP improved LVEF (35.9 ± 6.1% to 40.6 ± 8.0%, P = 0.015), decreased LV end‐systolic volume (152 ± 74 to 135 ± 62 cm³, P = 0.03), systolic blood pressure (P = 0.04) and sleepiness (Epworth sleepiness score 8.8 ± 4.8 to 6.3 ± 3.2, P = 0.01), whereas walk distance, catecholamines, brain natriuretic peptide levels and symptoms were unchanged. These outcomes did not change in the HF control group. Conclusion: In community HF patients with OSA, CPAP therapy over 6 months improved LVEF, systolic blood pressure and sleepiness, but not sympathetic activation, brain natriuretic peptide or exercise levels. Acceptance was relatively low, potentially limiting therapeutic effectiveness.     

Ghrelin secretion in severely obese subjects before and after a 3-week integrated body mass reduction program

Ghrelin, the endogenous ligand of GH-secretagogue receptors, has been implicated in the regulation of feeding behavior and energy balance. Aim of the study was to investigate ghrelin levels in fasting conditions and after a standard meal test in obese subjects before and after a 3-week integrated body weight reduction (BWR) program (consisting of energy-restricted diet, exercise training, psychological counselling and nutritional education). Weight, height, fat mass, fat free mass (by impedentiometry), circulating ghrelin, insulin and leptin levels were evaluated in 10 obese subjects (3 male, 7 female; mean age: 35 +/- 9.3 yr; body mass index BMI: 45.2 +/- 10.6 kg/m2) before and after weight reduction. At baseline, obese subjects showed significantly lower ghrelin levels than controls, which were negatively correlated with BMI, weight, insulin and leptin levels. Fasting ghrelin levels were not modified by standard meal test in obese subjects (from 110.8 +/- 69.7 to 91.8 +/- 70.2 pmol/l p=ns), while a significant reduction was observed in controls (from 352.4 +/- 176.7 to 199.0 +/- 105.2 pmol/l; p<0.01). After a 3-week integrated BWR program obese subjects significantly reduced weight, BMI and leptin levels, while no significant changes were found both in fasting ghrelin and in ghrelin response after the meal. In conclusion, 5% weight loss obtained after a short-term period of integrated BWR program is not sufficient to normalize fasting ghrelin levels nor to restore the normal ghrelin suppression after a meal in severely obese subjects.     

Auto-titrating continuous positive airway pressure therapy in patients with chronic heart failure and obstructive sleep apnoea: a randomized placebo-controlled trial.

AIMS: Obstructive sleep apnoea (OSA) is highly prevalent in patients with chronic heart failure (CHF) and may contribute to CHF progression. We aimed to determine whether treatment of OSA with continuous positive airway pressure (CPAP) would improve subjective and objective measures of heart failure severity in patients with CHF and OSA. METHODS AND RESULTS: Twenty-six patients with stable symptomatic CHF and OSA were randomized to nocturnal auto-titrating CPAP or sham CPAP for 6 weeks each in crossover design. Study co-primary endpoints were changes in peak VO(2) and 6 min walk distance. Secondary endpoints were changes in left ventricular ejection fraction, VE/VCO(2) slope, plasma neurohormonal markers, and quality-of-life measures. Twenty-three patients completed the study protocol. Mean CPAP and sham CPAP usage were 3.5 +/- 2.5 and 3.3 +/- 2.2 h/night, respectively (P = 0.31). CPAP treatment was associated with improvements in daytime sleepiness (Epworth Sleepiness Score 7 +/- 4 vs. 8 +/- 5, P = 0.04) but not in other quality-of-life measures. There were no changes in other study endpoints. CONCLUSION: In patients with CHF and OSA, auto-titrating CPAP improves daytime sleepiness but not other subjective or objective measures of CHF severity. These data suggest that the potential therapeutic benefits of CPAP in CHF are achieved by alleviation of OSA rather than by improvement in cardiac function.