Endothelial dysfunction and inflammatory reactions of elderly and middle-aged men with obstructive sleep apnea syndrome

Introduction  Obstructive sleep apnea syndrome (OSAS) is considered to be associated with cardiovascular complications, and atherosclerosis could mediate this relationship. Cardiovascular risk factors of OSAS still need to be elucidated in elderly patients, since studies about the association between OSAS and cardiovascular diseases have been done mainly in middle-aged adults. To investigate whether endothelial dysfunction, as an early marker of atherosclerosis, and inflammatory responses in OSAS were affected by age, we studied flow-mediated dilatation (FMD) and C-reactive protein (CRP) in elderly and middle-aged patients with OSAS. Materials and methods  This study enrolled 161 male subjects of 117 middle-aged (35–59 years old) and 44 elderly (≥60 years old) patients with OSAS. After they finished nocturnal polysomnography (NPSG), FMD was measured on the brachial artery and blood samples were obtained to determine serum CRP levels. Results and discussion  FMD was significantly lower in the elderly patients (p = 0.04), but no difference was observed between two age groups in body mass index (BMI), neck circumference, waist-to-hip ratio, apnea hypopnea index (AHI), serum CRP level, or NPSG findings related with nocturnal hypoxemia such as average O₂ saturation, percentage of time below 90% O₂ saturation, and oxygen desaturation index (ODI). From the results of stepwise multiple linear regression analysis, the lowest oxygen saturation was a significant determinant of FMD (β = 0.25, p < 0.01, adjusted R ² = 6%), and BMI (β = 0.22, p < 0.05) and waist-to-hip ratio (β = 0.21, p < 0.05) were significant variables to explain CRP (adjusted R ² = 11%, p < 0.01) in the middle aged patients. In the elderly patients, no variable was significant for predicting FMD, but AHI was significant determinant of CRP (β = 0.46, p < 0.01, adjusted R ² = 19%, p < 0.01). In predicting cardiovascular risks of OSAS, both hypoxia and obesity should be considered in the middle-aged group, whereas nocturnal respiratory disturbances are important in the elderly group.     

Plasma pancreatic polypeptide levels are associated with differences in body fat distribution in human subjects

Aims/hypothesis Pancreatic polypeptide (PP) is produced by the F-cells of the pancreas, and its plasma concentration has been used as a marker of parasympathetic activity. Recent work in rodents suggests that there is both sympathetic and parasympathetic innervation of white adipose tissue and that parasympathetic activity is anabolic resulting in lipid accumulation. We have examined whether in humans increased PP levels are associated with increased intra-abdominal fat (IAF), and thereby insulin resistance. Materials and methods We measured PP levels in 177 non-diabetic subjects (75 male/102 female; age 32–75 years) 3 min after an i.v. glucose bolus during a frequently sampled intravenous glucose tolerance test. IAF and s.c. fat (SCF) areas were measured by CT scan. The insulin sensitivity index (S _I) was quantified using Bergman’s minimal model. Results PP levels were higher in men than in women (96.2 ± 72.2 vs 76.1 ± 55.0 pg/ml, mean ± SD, p = 0.037), as was IAF area (124.7 ± 67.4 vs 83.0 ± 57.7 cm², p < 0.001). While PP levels were significantly associated with IAF (r = 0.16, p = 0.031), WHR (r = 0.30, p < 0.001) and age (r = 0.37, p < 0.01), they were not associated with SCF (r = 0.02, p = 0.829). The association between PP and IAF was not independent of age and/or sex. S _I was negatively associated with PP levels (r = −0.17, p = 0.026) and IAF area (r = −0.65, p < 0.001). The association between S _I and PP disappeared after adjusting for IAF area, indicating that S _I was not a major determinant of PP levels. Conclusions/interpretation In humans, age and sex may modulate the association between plasma PP level and IAF area, suggesting that they may be determinants of parasympathetic activity and thus IAF accumulation.     

CPAP compliance in patients with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is characterized by repeated cessations of breathing during sleep. Major symptoms of this disease are excessive daytime sleepiness, snoring, and witnessed apnea. Most of the patients are treated with CPAP. In this study, we aimed to evaluate the factors affecting adherence to the CPAP treatment. Seventy-one patients were enrolled to this study. Patients were divided into three groups according to CPAP usage. Group I consisted of patients who had never used CPAP, group II consisted of patients who had used CPAP occasionally, and group-III patients had used CPAP treatment regularly. Group-III patients had higher apnea–hypopnea index (AHI) than groups I and II (respectively, 56.6 ± 27.7, 26.3 ± 7.5, and 32.3 ± 7.06; p < 0.000 for both). Oxygen desaturation index was significantly higher in group-III patients comparing to groups I and II (44.6 ± 22.3, 15.9 ± 8.3, and 25.6 ± 9.5; p < 0.000 for all). Our findings have shown that only very severe patients use the CPAP device regularly (mean AHI 56.6 ± 27.7). Compliance to CPAP treatment seemed to be poor in patients with moderate to severe, AHI about 30, OSAS. Considering the well-established benefits of CPAP treatment in patients with true indications, patients should be encouraged to use CPAP regularly, and complications of OSAS should be keynoted.     

Variations in the four and a half LIM domains 1 gene (<Emphasis Type="Italic">FHL1</Emphasis>) are associated with fasting insulin and insulin sensitivity responses to regular exercise

Aims/hypothesis The expression of the four and a half LIM domains 1 gene (FHL1) is increased in the muscle of individuals who show an improvement in insulin sensitivity index (S _I) after 20 weeks of exercise training. The aim of the present study was to investigate associations between three FHL1 single nucleotide polymorphisms (SNPs) and variables derived from an IVGTT, both in the sedentary state and in response to exercise training, in participants in the HERITAGE Family Study. Materials and methods SNPs were typed using fluorescence polarisation methodology. Analyses were performed separately by sex and in black and white individuals. Results In black participants, no associations were found with any of the SNPs. In white women (n = 207), SNP rs9018 was associated with the disposition index (D _I), which is calculated as S _I generated from the MINMOD program (×10⁻⁴ min⁻¹[μU/ml]⁻¹) multiplied by acute insulin response to glucose (AIR_g; pmol/l × 10 min), and the glucose disappearance index (K _g) training responses (p = 0.016 and p = 0.008, respectively). In white men (n = 222), all SNPs were associated with fasting glucose levels (p ≤ 0.05) and SNP rs2180062 with the insulin sensitivity index (S _I) (p = 0.04) in the sedentary state. Two SNPs were associated with fasting insulin training response. Fasting insulin decreased to a greater extent in carriers of the rs2180062 C allele (p = 0.01) and rs9018 T allele (p = 0.04). With exercise training, S _I (×10⁻⁴ min⁻¹[μU/ml]⁻¹: 0.68 ± 0.20 vs −0.77 ± 0.44, p = 0.046), D _I (319 ± 123 vs –528 ± 260, p = 0.006) and K _g (per 100 min: 0.09 ± 0.04 vs −0.14 ± 0.8, p = 0.03) improved more in the C allele carriers at rs2180062 than in the T allele carriers. Conclusions/interpretation Fasting insulin and S _I responses to exercise training were associated with DNA sequence variation in FHL1 in white men. Whether these associations exist only in white men remains to be investigated. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

The clinical significance of serum N-terminal pro-brain natriuretic peptide in systemic sclerosis patients

We evaluated the clinical significance of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level in systemic sclerosis (SSc). We studied 45 SSc patients (30 with limited and 15 with diffuse cutaneous SSc) of mean age ± SD 47.1 ± 12.9 years, mean duration of disease 10.2 ± 6.0 years, and 45 age- and sex-matched healthy controls. Pulmonary artery pressure was measured by echocardiography. Lung involvement was evaluated by pulmonary function testing and by using high-resolution computed tomography scores. Serum NT-proBNP levels were measured using a sandwich electrochemiluminescent immunoassay. Serum NT-proBNP levels were significantly higher in patients with SSc compared to healthy controls. When the patients were divided into clinical subsets, serum NT-proBNP was higher in diffuse SSc than in limited SSc. Serum NT-proBNP levels were found to be positively correlated with age, skin thickness score, and systolic pulmonary artery pressure and negatively correlated with percentage of carbon monoxide diffusion capacity (DLco). Multivariate analysis showed that serum NT-proBNP levels were positively correlated with age (p = 0.010), skin thickness score (p = 0.000), and blood pressure (p = 0.021) and negatively correlated with %DLco (p = 0.016). Fifty-seven percent of the variation in log (proBNP) can be explained by the multivariate model (R ² = 0.57). Serum NT-proBNP levels were higher in SSc patients (particularly the diffuse subset) than in healthy controls and were found to be correlated with skin thickness and %DLco. We conclude that serum NT-proBNP may be a biologic marker of skin fibrosis and pulmonary vascular involvement in SSc.     

Hypoxemia and obesity modulate plasma C-reactive protein and interleukin-6 levels in sleep-disordered breathing

C-reactive protein (CRP) and interleukin-6 (IL-6) are pro-inflammatory proteins and important risk factors for atherosclerosis. Plasma CRP levels in snoring children may or may not be elevated. Since obesity is prevalent among snoring children and is associated with elevated CRP levels, we aimed to investigate the relative contributions of sleep-disordered breathing (SDB) and obesity to the inflammatory processes in snoring children in this prospective study. Two hundred forty-four children (mean age 8.9 ± 3.4 years) underwent polysomnographic evaluation. CRP was measured the following morning, and plasma IL-6 levels from 111 randomly selected children were also examined. Plasma CRP and IL-6 levels were elevated in children with SDB. Log plasma CRP levels were higher in the moderate-severe SDB group (apnea/hypopnea index, AHI ≥ 5) compared to the mild SDB group (AHI ≥ 1 and <5; p < 0.0001) or the control group (AHI < 1; p = 0.0001). Log plasma CRP levels correlated with AHI, arousal index, relative BMI, and SpO₂ nadir (r = 0.30, p < 0.0001; r = 0.21, p = 0.002; r = 0.39, p < 0.0001, r = −0.36, p < 0.0001, respectively). Log plasma CRP levels were lower in children with SpO₂ nadir ≥90 (p < 0.0001). Sub-analysis of the 116 non-obese children in the cohort revealed similar findings. Log plasma IL-6 levels were increased in children with moderate–severe SDB compared to controls (p = 0.03) and correlated with AHI (r = 0.28, p = 0.003) and SpO₂ nadir (r = −0.24, p = 0.02). Children with SDB display significant severity-dependent increases in plasma CRP and IL-6 levels independent of obesity.     

Mandibular advancement splint titration in obstructive sleep apnoea

Introduction  Mandibular advancement splints (MAS) allowing self-adjustment may be better tolerated, but the optimum titration protocol needs systematic study. Aim  The aims of the study are to assess the effectiveness of a titratable MAS device in consecutive patients with body mass index (BMI) < 35 kg/m² and obstructive sleep apnoea [OSA, apnoea–hypopnoea index (AHI) 10–40/h] and compare two methods of adjustment [self-adjustment or adjustment after polysomnographic (PSG) feedback]. Materials and methods  Twenty-eight patients (24 M, mean age 49 years, mean BMI 27.6 kg/m²) with symptomatic (Epworth Sleepiness score > 8/24, snoring, choking or poor sleep quality) OSA (mean AHI 25.7/h, range 10–46/h) had a MAS set at 70% maximal protrusion and were randomised to subjective self-adjustment for 6 weeks (n = 16) or objective adjustment (n = 12; fixed position for 3 weeks, then PSG based feedback at 3 weeks with self-adjustment instructions). Primary outcome variable (AHI) and OSA symptoms were compared by t tests and chi-squared tests at baseline and after 6 weeks. Resolution of apnoea was defined as AHI < 5/h; improvement was defined as AHI decreased by >50% but still >5/h. Results  The groups had similar baseline demographics, OSA severity and occlusal type. MAS therapy improved or resolved OSA in 20 out of 28 (71%) and was reportedly used nightly by 91% of the objective group and 63% of the subjective group (p = 0.04). MAS were used all night by 75% of the objective group and 69% of the subjective group (p > 0.05). MAS adjustment following PSG feedback did not lower AHI further from 3 weeks (baseline 26.5 ± 12.0/h, 3 weeks 15.3 ± 13.5/h p = 0.01, 6 weeks 11.7 ± 10.0/h, p = 0.11). The overall improvement was similar to that achieved with subjective adjustment (baseline AHI 25.4 ± 7.4/h, 6 weeks 14.3 ± 10.7/h, p = 0.0002). Symptomatic benefit was reported by both groups. Conclusion  In selected patients, titratable MAS improved or resolved OSA in the majority of patients and was well tolerated. PSG-based feedback at 3 weeks allowed objective confirmation of efficacy and increased device use but did not result in greater improvement in AHI or symptoms. Neither titration method was significantly superior for us to provide firm endorsement. However, we recommend a follow-up sleep study to confirm MAS efficacy.     

Hyperinsulinaemia during exercise does not suppress hepatic glycogen concentrations in patients with type 1 diabetes: a magnetic resonance spectroscopy study

Aims/hypothesis We compared in vivo changes in liver glycogen concentration during exercise between patients with type 1 diabetes and healthy volunteers. Methods We studied seven men with type 1 diabetes (mean ± SEM diabetes duration 10 ± 2 years, age 33 ± 3 years, BMI 24 ± 1 kg/m², HbA_1c 8.1 ± 0.2% and VO₂ peak 43 ± 2 ml [kg lean body mass]⁻¹ min⁻¹) and five non-diabetic controls (mean ± SEM age 30 ± 3 years, BMI 22 ± 1 kg/m², HbA_1c 5.4 ± 0.1% and VO₂ peak 52 ± 4 ml [kg lean body mass]⁻¹ min⁻¹, before and after a standardised breakfast and after three bouts (EX1, EX2, EX3) of 40 min of cycling at 60% VO₂ peak. ¹³C Magnetic resonance spectroscopy of liver glycogen was acquired in a 3.0 T magnet using a surface coil. Whole-body substrate oxidation was determined using indirect calorimetry. Results Blood glucose and serum insulin concentrations were significantly higher (p < 0.05) in the fasting state, during the postprandial period and during EX1 and EX2 in subjects with type 1 diabetes compared with controls. Serum insulin concentration was still different between groups during EX3 (p < 0.05), but blood glucose concentration was similar. There was no difference between groups in liver glycogen concentration before or after the three bouts of exercise, despite the relative hyperinsulinaemia in type 1 diabetes. There were also no differences in substrate oxidation rates between groups. Conclusions/interpretation In patients with type 1 diabetes, hyperinsulinaemic and hyperglycaemic conditions during moderate exercise did not suppress hepatic glycogen concentrations. These findings do not support the hypothesis that exercise-induced hypoglycaemia in patients with type 1 diabetes is due to suppression of hepatic glycogen mobilisation. K. Chokkalingam and K. Tsintzas contributed equally to this study.     

Tissue specificity of insulin resistance in humans: fat in the liver rather than muscle is associated with features of the metabolic syndrome

Aims/hypothesis The aim of this study was to investigate whether intrahepatic and intramyocellular fat are related to insulin resistance in these respective tissues or to the metabolic syndrome. Methods Hepatic (insulin 1.8 pmol kg⁻¹ min⁻¹ combined with [3-³H]glucose) and muscle (insulin 6.0 pmol kg⁻¹ min⁻¹) insulin sensitivity were measured on separate occasions in 45 non-diabetic men (age 42 ± 1 years, BMI 26.2 ± 0.6 kg/m²) using the euglycaemic–hyperinsulinaemic clamp. Liver fat and intramyocellular lipid (IMCL) were measured by proton magnetic resonance spectroscopy and body composition by magnetic resonance imaging. We also determined fasting serum insulin and adiponectin concentrations, components of the metabolic syndrome and maximal oxygen consumption. Results In participants with high [median 12.0% (interquartile range 5.7–18.5%)] vs low [2.0% (1.0–2.0%)] liver fat, fasting serum triacylglycerols (1.6 ± 0.2 vs 1.0 ± 0.1 mmol/l, p = 0.002) and fasting serum insulin (55 ± 4 vs 32 ± 2 pmol/l, p < 0.0001) were increased and serum HDL-cholesterol (1.26 ± 0.1 vs 1.48 ± 0.1 mmol/l, p = 0.02) and fasting serum adiponectin (9.5 ± 1.2 vs 12.2 ± 1.2 μg/ml, p = 0.05) decreased. In participants with high [19.5% (16.0–26.0%)] vs low [5.0% (2.3–7.5%)] IMCL, these parameters were comparable. Liver fat was higher in participants with [10.5% (3.0–18.0%)] than in those without [2.0% (1.5–6.0%), p = 0.010] the metabolic syndrome, even independently of obesity, while IMCL was comparable. Insulin suppression of glucose rate of appearance and serum NEFA was significantly impaired in the high liver fat group. Conclusions/interpretation Fat accumulation in the liver rather than in skeletal muscle is associated with features of the metabolic syndrome, i.e. increased fasting serum triacylglycerols and decreased fasting serum HDL-cholesterol, as well as with hyperinsulinaemia and low adiponectin.     

Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion

Aims/hypothesis  We tested the hypothesis that the reversibility of insulin resistance and diabetes observed after biliopancreatic diversion (BPD) is related to changes in circadian rhythms of gastrointestinal hormones. Methods  Ten morbidly obese participants, five with normal glucose tolerance (NGT) and five with type 2 diabetes, were studied before and within 2 weeks after BPD. Within-day variations in glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP1) levels were assessed using a single cosinor model. Insulin sensitivity was assessed by euglycaemic–hyperinsulinaemic clamp. Results  Basal GLP1 relative amplitude (amplitude/mesor × 100) was 25.82–4.06% in NGT; it increased to 41.38–4.32% after BPD but was unchanged in diabetic patients. GLP1 and GIP mesor were shifted in time after surgery in diabetic patients but not in NGT participants. After BPD, the GLP1 AUC significantly increased from 775 ± 94 to 846 ± 161 pmol l⁻¹ min in NGT, whereas GIP AUC decreased significantly from 1,373 ± 565 to 513 ± 186 pmol l⁻¹ min in diabetic patients. Two-way ANOVA showed a strong influence of BPD on both GIP (p = 0.010) and GLP1 AUCs (p = 0.033), which was potentiated by the presence of diabetes, particularly for GIP (BPD × diabetes, p = 0.003). Insulin sensitivity was markedly improved (p < 0.01) in NGT (from 9.14 ± 3.63 to 36.04 ± 8.55 μmol [kg fat-free mass]⁻¹ min⁻¹) and diabetic patients (from 9.49 ± 3.56 to 38.57 ± 4.62 μmol [kg fat-free mass]⁻¹ min⁻¹). Conclusions/interpretation  An incretin circadian rhythm was shown for the first time in morbid obesity. The effect of BPD on the 24 h pattern of incretin differed between NGT and diabetic patients. GLP1 secretion impairment was reversed in NGT and could not be overcome by surgery in diabetes. On the other hand, GIP secretion was blunted after the operation only in diabetic patients, suggesting a role in insulin resistance and diabetes.     

Effects of dietary protein restriction on albumin and fibrinogen synthesis in macroalbuminuric type 2 diabetic patients

Aims/hypothesis Diabetic nephropathy is associated with hypoalbuminaemia and hyperfibrinogenaemia. A low-protein diet has been recommended in patients with diabetic nephropathy, but its effects on albumin and fibrinogen synthesis are unknown. Methods We compared the effects of a normal (NPD; 1.38 ± 0.08 g kg⁻¹ day⁻¹) or low (LPD; 0.81 ± 0.04 g kg⁻¹ day⁻¹) -protein diet on endogenous leucine flux (ELF), albumin and fibrinogen synthesis (l-[5,5,5,-²H₃]leucine infusion), and markers of inflammation in nine type 2 diabetic patients with macroalbuminuria. Six healthy participants on NPD served as control participants. Results In comparison with healthy participants, type 2 diabetic patients on an NPD had similar ELF, reduced serum albumin (38 ± 1.1 vs 42 ± 0.8 g/l; p < 0.05), similar fractional synthesis rates (FSR) and absolute synthesis rates (ASR) of albumin, and both increased plasma fibrinogen concentration [10.7 ± 0.6 vs 7.2 ± 0.5 μmol/l (3.64 ± 0.22 vs 2.45 ± 0.18 g/l); p < 0.05] and fibrinogen ASR [11.03 ± 1.17 vs 6.0 ± 1.8 μmol 1.73 m⁻² day⁻¹ (3.7 ± 0.4 vs 1.9 ± 0.3 g 1.73 m⁻² day⁻¹); p < 0.01]. After LPD, type 2 diabetic patients had the following changes in comparison with NPD: reduced proteinuria (2.74 ± 0.4 vs 4.51 ± 0.8 g/day; p < 0.05), ELF (1.93 ± 0.08 vs 2.11 ± 0.08 μmol kg⁻¹ min⁻¹; p < 0.05) and total fibrinogen pool; increased serum albumin (42 ± 1 vs 38 ± 1 g/l; p < 0.01) and albumin ASR (14.1 ± 1 vs 9.9 ± 1 g 1.73 m⁻² day⁻¹; p < 0.05); and reduced plasma IL-6 levels, which were correlated with albumin ASR (r = −0.749; p < 0.05). Conclusions/interpretation LPD in type 2 diabetic patients with diabetic nephropathy reduces low-grade inflammatory state, proteinuria, albuminuria, whole-body proteolysis and ASR of fibrinogen, while increasing albumin FSR, ASR and serum concentration. ISRCTN ID no: CCT-NAPN-16911     

Exercise under hyperinsulinaemic conditions increases whole-body glucose disposal without affecting muscle glycogen utilisation in type 1 diabetes

Aims/hypothesis We examined whole-body and muscle metabolism in patients with type 1 diabetes during moderate exercise at differing circulating insulin concentrations. Methods Eight men (mean ± SEM age 36.4 ± 1.5 years; diabetes duration 11.3 ± 1.4 years; BMI 24.6 ± 0.7 kg/m²; HbA_1c 7.9 ± 0.2% and VO₂ peak 44.5 ± 1.2 ml kg⁻¹ min⁻¹) with type 1 diabetes were studied on two occasions at rest (2 h) and during 45 min of cycling at 60% maximum VO₂ with insulin infused at the rate of either 15 (LO study) or 50 (HI) mU m⁻² min⁻¹ and blood glucose clamped at 8 mmol/l. Indirect calorimetry, insulin-glucose clamps and thigh muscle biopsies were employed to measure whole-body energy and muscle metabolism. Results Fat oxidation contributed 15 and 23% to total energy expenditure during exercise in the HI and LO studies, respectively. The respective carbohydrate (CHO) oxidation rates were 31.7 ± 2.7 and 27.8 ± 1.9 mg kg⁻¹ min⁻¹ (p < 0.05). Exogenous glucose utilisation rate during exercise was substantially greater (p < 0.001) in the HI study (18.4 ± 2.1 mg kg⁻¹ min⁻¹) than in the LO study (6.9 ± 1.2 mg kg⁻¹ min⁻¹). Muscle glycogen content fell by ∼40% during exercise in both trials. Muscle glycogen utilisation, muscle intermediary metabolism, and phosphorylation of protein kinase B/Akt, glycogen synthase kinase 3α/β and extracellular signal-regulated protein kinase 1 and 2 proteins were no different between interventions. Conclusions/interpretation In patients with type 1 diabetes, exercise under peak therapeutic insulin concentrations increases exogenous glucose utilisation but does not spare muscle glycogen utilisation. A disproportionate increase in exogenous glucose utilisation relative to the increase in CHO oxidation suggests an increase in glucose flux through non-oxidative pathways. Chokkalingam and Tsintzas are joint first authors.     

Efficacy and patient satisfaction with autoadjusting CPAP with variable expiratory pressure vs standard CPAP: a two-night randomized crossover trial

Expiratory pressure relief (C-Flex) technology monitors the patient’s airflow during expiration and reduces the pressure in response to the patient. Increased comfort levels associated with C-Flex therapy have potential to improve patient adherence to therapy. The purpose of this study was to assess the combination of autoadjusting CPAP (APAP) and C-Flex in terms of (1) treatment efficacy, and (2) patient preference when compared to standard CPAP. Fifteen patients who had previously undergone formal CPAP titration polysomnography were treated with either one night of the APAP with C-Flex or one night of conventional CPAP, in a crossover trial. Patient satisfaction levels were recorded using visual analog scales (VAS) on the morning after the study. Mean patient age was 50 ± 12 years, body mass index (BMI) was 36 ± 6 kg/m², baseline AHI was 53 ± 31 events/h, and CPAP Pressure was 11 ± 2 cm/H₂O. APAP with C-Flex was as effective as CPAP, with no differences detected in sleep latency (17 ± 5 vs 12.3 ± 3 min, p = 0.4), or respiratory indices (AHI of 4.2 ± 2 vs 2.4 ± 0.7 events/h, p = 0.1). VAS scores (scale 0–10) indicated a trend towards increased patient satisfaction while using APAP with C-Flex (7.9 vs 7.2, p = 0.07). 10 patients expressed a preference for APAP with C-Flex (VAS, 0 to10) over standard CPAP (total positive score of 68, mean score of 4.8 ± 4.3). One patient expressed no preference. Four patients expressed a preference for CPAP (total positive score of 13, mean score of 0.9 ± 1.9) (APAP with C-Flex vs standard CPAP, p < 0.01 paired t test). APAP with C-Flex eliminates sleep disordered breathing as effectively as standard CPAP. Patients indicated a preference for APAP with C-Flex suggesting a possible advantage in terms of patient adherence for this mode of treatment.     

Automated detection of sleep disordered breathing using a nasal pressure monitoring device

To assess the accuracy of a single channel portable monitoring device (RUSleeping™ RTS, Respironics, Murrysville, PA) that measures nasal pressure (a surrogate for airflow) to detect sleep disordered breathing (SDB). Twenty-five adult patients referred to a community sleep laboratory with suspected obstructive sleep apnea (OSA) participated in this investigation. The portable monitoring device was used in the sleep laboratory to acquire data concurrently with a standard multi-channel polysomnogram (PSG) to assess SDB. Respiratory events were scored manually on the PSG using standard criteria for clinical research to quantify an apnea–hypopnea index (AHI) based on events during sleep. The portable monitoring device automatically calculated an unedited respiratory event index (REI) based on recording time. These data were then compared using the Pearson product–moment correlation coefficient, Bland–Altman analysis, receiver operating characteristic (ROC) curves, and likelihood ratios. All 25 subjects completed the study. Mean age of subjects was 42.4 ± 12.9 years and mean body mass index was 31.0 ± 7.4 kg m⁻². There was good agreement between the REI and the AHI (R = 0.77, p < 0.001, mean difference 2.6 events per hour [2 SD: 39.8] using a Bland–Altman plot). The area under the ROC curve for detecting SDB (PSG AHI greater than or equal to five events per hour) with the REI was 0.94 (95% CI 0.84–1.0). For an REI >11.9 events per hour, the sensitivity was 0.89 (95% CI 0.65–0.99) and the specificity was 0.86 (95% CI 0.42–1.0) with a likelihood ratio of 6.2 for a positive test (LR+) and 0.13 for a negative test (LR−). Similar results were observed for detecting moderate–severe SDB (PSG AHI ≥ 15 events h⁻¹) using REI >15.2 events h⁻¹. In a population of subjects with suspected OSA, this portable monitoring device can automatically quantify an REI that compares well to the AHI scored manually on a concurrent PSG. Such a device may prove useful to assess SDB in high risk populations with self-administered testing in ambulatory settings such as the home. This study was performed at the Sleep Center of Greater Pittsburgh Sleep Laboratory.     

Reliability and validity studies of the Turkish version of the Epworth Sleepiness Scale

The Epworth Sleepiness Scale (ESS) is a self-administered eight-item questionnaire that is widely used in English speaking countries for assessment of daytime sleepiness in adults. The aim of this study was to investigate the reliability and validity of the ESS in the Turkish language. The Turkish version of the ESS (ESStr) was applied to 194 healthy controls and 150 consecutive subjects attending the sleep centre with symptoms of sleep-disordered breathing. Test–retest reliability of the ESStr was tested in a separate group of 30 subjects. The ESStr scores of 60 subjects with mild to severe obstructive sleep apnoea (OSA) were compared with the ESStr scores of 60 healthy controls matched for age, gender, and body mass index (BMI). Concurrent validity with the Functional Outcomes of Sleep Questionnaire (FOSQtr) was also assessed in 12 subjects. The questionnaire had a high level of internal consistency as measured by Cronbach’s alpha (≥0.86). The test–retest intraclass correlation coefficient was r  = 0.81 (95% confidence interval: 0.64–0.90) (p < 0.001) and Spearman’s correlation coefficient was r = 0.80 (p = 0.01). The control group had lower ESStr scores than subjects with sleep-disordered breathing (3.6 ± 3 vs 12.6 ± 6, respectively; p < 0.001). Subjects with mild sleep-disordered breathing also had lower scores of the ESStr than those with moderate and severe sleep-disordered breathing (10 ± 6.2 vs 14 ± 5. and 10 ± 6.2 vs 16 ± 5.4, respectively; both p < 0.05), but there were no significant differences between moderate and severe subjects with sleep apnoea. There were significant correlations between the ESStr and total FOSQtr and its subscales (r  = −0.22 to r = −0.92; all p  = 0.05). Factor analysis of item scores showed that the ESStr had only one factor. The ESStr is a reliable and valid measure of daytime sleepiness. These features and the simplicity of the ESStr make it a valuable measure for clinical management and research.     

The relation of serum vascular endothelial growth factor level with disease duration and activity in patients with rheumatoid arthritis

Vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of rheumatoid arthritis (RA). In order to elucidate the association between VEGF levels and RA disease activity, VEGF concentrations were measured in RA patients at different phases and severity levels. Thirty-eight healthy subjects and 40 patients with RA were prospectively included in the study. Subjects were further categorized into four subgroups (high, moderate, low, or remission) using the disease activity score-28 (DAS28) scoring system. VEGF levels were significantly higher in patients than controls (p < 0.001). VEGF levels differed significantly in controls, early and late-phase RA patients (p = 0.002). A significant difference was found between controls and patients with high RA disease activity scores (p < 0.0001). VEGF levels were not correlated with age (r = −0.016; p = 0.921) or sex (r = 0.209; p = 0.921). VEGF values were correlated with erythrocyte sedimentation rate (r = 0.445; p = 0.004), but was not correlated with serum rheumatoid factor levels (r = −0.130; p = 0.424) in the patient group. In conclusion, higher VEGF levels are associated with late phase and high disease activity in RA, independent of age and sex.     

Titratable mandibular repositioner appliances for obstructive sleep apnea syndrome: are they an option?

Mandibular repositioning appliances (tMRAs) designed with a titratable mechanism are effective to treat obstructive sleep apnea syndrome (OSAS) but are not widely used, although many studies have proven their value. The aim of the present study was to evaluate the efficacy of tMRAs in the treatment of OSAS on the criteria of the American Academy of Sleep Medicine (AASM; apnea/hypopnea index [AHI] < 5). Three hundred consecutive patients with a polysomnographic diagnosis of OSAS were referred for treatment with tMRAs between 2000 and 2003. Thirty-eight patients were excluded, and 262 concluded the titration protocol with tMRA that lasted 4 months. After titration, the patients were referred for a medical reassessment, and 83 patients (70 men) participated in the new polysomnographic exam with tMRA in place to access tMRA’s efficacy. The mean pre- and post-treatment AHI were 26 ± 17.7 and 4.8 ± 5.3 events per hour, respectively (p < 0.00005). Fifty-three (62.6%) of the 83 patients were treated successfully (AHI < 5). Twenty-three patients had severe OSAS, and 12 of them (52.1%) were treated successfully (AHI < 5). Forty patients had moderate OSAS, and 26 of them (65%) were treated successfully. Twenty patients had mild OSAS, and 15 (75%) were successfully treated. Even when applying more rigid criteria such as those of the AASM, the expressive success rate obtained with the treatment of different degrees of OSAS indicates that tMRAs are an additional valuable option even for cases of severe apnea in which the patient does not tolerate continuous positive airway pressure or cannot afford this treatment, a fact quite common in Brazil and other developing countries.     

Soluble receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin in ankylosing spondylitis: OPG is associated with poor physical mobility and reflects systemic inflammation

The objective of the study was to investigate the role of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in ankylosing spondylitis (AS). Serum levels of soluble RANKL (sRANKL) and OPG were measured in 42 AS patients and 26 healthy controls. We evaluated the AS patient's disease activity, functional ability, global assessment, and physical mobility and tested markers of systemic inflammation, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. Serum levels of sRANKL [mean (SD), 4.75 (1.88) vs. 3.70 (1.14) pmol/l, p = 0.015] and OPG [mean (SD), 5.18 (1.19) vs. 4.52 (0.85) pmol/l, p = 0.026] were significantly higher in the 42 AS patients than the 26 healthy controls. Interestingly, serum OPG levels correlated significantly with ESR (r = 0.417, p = 0.007), CRP (r = 0.524, p < 0.001), tragus-to-wall distance (r = 0.556, p < 0.001), fingertip-to-floor distance (r = 0.423, p = 0.007), and occiput-to-wall distance (r = 0.465, p = 0.002) and correlated inversely with modified Schober index (r = −0.525, p = 0.001), cervical rotation (r = −0.403, p = 0.022), lateral lumbar flexion (r = −0.587, p < 0.001), and chest expansion (r = −0.553, p < 0.001). Moreover, in the AS patients with higher (≥4.925 pmol/l, n = 21) serum OPG levels, there were significant increases in the tragus-to-wall distance (p = 0.007), fingertip-to-floor distance (p = 0.023), and CRP levels (p = 0.014) and decreased in the modified Schober index (p = 0.012), lateral lumbar flexion (p = 0.019), and chest expansion (p = 0.005). Serum levels of sRANKL and OPG are increased in the AS patients and may participate in the disease process of AS. Production of OPG has association with poor physical mobility and may reflect systemic inflammation in AS.     

Idiopathic deep venous thrombosis and arterial endothelial dysfunction in the elderly

Arterial and venous thrombosis have always been regarded as different pathologies and epidemiological studies have examined the association between venous thrombosis and indicators of atherosclerosis and/or arterial thromboembolic events. We measured the flow-mediated dilation (FMD), a well-known marker of arterial endothelial dysfunction, in young–middle-aged and old-aged patients with and without unprovoked deep venous thrombosis (DVT). The aim of this study was to investigate whether DVT was a significant predictor for impaired FMD, considering all the patients and young–middle-aged (age < 65 years) and old-aged (age ≥ 65 years) patients separately. FMD was measured in the brachial artery on a population of 120 subjects with the same atherosclerosis risk factors, 68 male and 52 female, 70 young–middle-aged subjects (mean age ± SD 49.5 ± 10.5 years) and 50 old-aged subjects (76.2 ± 7.7 years). Patients with DVT showed a significant decrease of FMD compared to patients without DVT (6.8 ± 5.5% vs. 10.9 ± 3.5%, p < 0.001). Moreover, old-aged patients showed a significant decrease of FMD compared to the young–middle-aged subjects (7.4 ± 4.1% vs. 9.8 ± 5.3%, p = 0.005). In the whole study population, DVT was strongly associated with FMD (risk factors adjusted β = −4.14, p < 0.001). A significant interaction between age and the presence of DVT on predicting FMD was found (p = 0.003) suggesting a differential behavior of DVT as predictor of FMD. In young–middle-aged group, multivariate model confirmed that DVT was the most significant predictor of continuous FMD (β = −6.06, p < 0.001). On the contrary, DVT was no more a predictor of FMD in the old age group (β = −0.73, p=0.556). Furthermore, old-aged patients without DVT showed a statistically significant decrease of FMD compared to the young–middle-aged subjects without DVT (8.2±2.1% vs. 12.6±2.7%, p<0.001) and old-aged patients with DVT showed a not statistically significant decrease of the FMD compared to the young–middle-aged patients with DVT (6.7±5.3% vs. 6.8±5.7%, p = 0.932). In conclusion, young–middle-aged patients with spontaneous DVT show an impaired FMD, whereas this impairment in old-aged subjects is evident independently from the presence or absence of DVT. Aging per se may be associated with physiologic abnormalities in the systemic arteries and with endothelial dysfunction.     

Psychometric evaluation of the Moroccan version of the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for use in patients with ankylosing spondylitis

The objectives of this study are to translate, adapt in the Moroccan cultural context, and validate in patients with ankylosing spondylitis (AS) the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The cross-cultural adaptation of the BASFI and BASDAI was obtained in accordance with the guidelines for translation of the health status measures. Eighty-five patients with AS were included in the study. The test–retest reliability and the internal consistency were analyzed, and both questionnaires were assessed for external construct validity. Structural validity was analyzed with correlation matrix. Twenty-four-hour test–retest reliability was good: BASFI intraclass correlation coefficient (ICC) = 0.96 (confidence interval (CI) at 95%, 0.93–0.97), BASDAI ICC = 0.93 (CI at 95%, 0.90–0.95). Cronbach’s alpha was 0.90 for the BASFI and 0.86 for BASDAI. The construct validity of the instruments was evaluated. The BASFI showed a strong validity when correlating its results with Schober’s test (r = −0.56), occipital wall distance (r = 0.46), chest expansion (r = −0.46), BASDAI (r = 0.54), Bath Ankylosing Spondylitis Metrology Index (r = 0.70), Bath Ankylosing Spondylitis Global Score (BAS-G; r = 0.58), Bath Ankylosing Spondylitis Radiology Index (r = 0.61), and the radiological changes in sacroiliac joints (r = 0.54). A good correlation was observed between the BASDAI and the spinal pain (r = 0.53), the number of nocturnal awakenings (r = 0.57), the morning stiffness (r = 0.65), the enthesic index (r = 0.47), the BAS-G (r = 0.53), the BASFI (r = 0.54), and the erythrocyte sedimentation rate (r = 0.41; for all p < 0.001). The correlation matrix showed an intermediate correlation between items. The Moroccan version of the BASFI and the BASDAI showed adequate reliability and validity. These instruments can be used in the clinical evaluation of Moroccan and Arabic-speaking patients with AS.