A pathway underlying the impact of CPAP adherence on intimate relationship with bed partner in men with obstructive sleep apnea.

PURPOSE: Our aim was to determine the pathway underlying the effects of continuous positive airway pressure (CPAP) adherence on intimate relationship with bed partner in men with obstructive sleep apnea (OSA). We hypothesized that CPAP with good adherence affected the intimate relationship with bed partner directly and indirectly, and it was mediated through daytime sleepiness and activity level in men with OSA. METHODS: Data were obtained from an education program for enhancing CPAP adherence. Men who were newly diagnosed of OSA and CPAP therapy naïve were recruited in a tertiary teaching hospital. RESULTS: Self-reported quality of life [Functional Outcomes of Sleep Questionnaire], daytime sleepiness [Epworth Sleepiness Scale (ESS)], and negative emotion symptoms [depression, anxiety, stress scale] were assessed before and after CPAP treatment at 1-year assessment. Seventy-three men were included in the data analysis, with a mean ± SD age of 52 ± 10 years, body mass index of 29.0 ± 5.2 kg/m(2), ESS of 9.5 ± 5.6, and median [interquartile range(IR)] apnea and hypopnea index of 31 (21, 56) events/h. The median (IR) CPAP daily usage was 4.3(0, 6.1) h/day. From the path analysis, CPAP therapy was shown to improve intimate relationship directly (ß = 0.185) and indirectly (ß = 0.050) by reducing daytime sleepiness and increasing activity level. However, negative emotion symptoms were not the mediators between CPAP adherence and the intimate relationship. CONCLUSIONS: CPAP therapy with good adherence is related directly and indirectly to a better intimate relationship with bed partner in men with OSA. It was possibly attributed to reduced daytime sleepiness and increased activity level.

Plasma EGFR Mutation Detection Associated With Survival Outcomes in Advanced-Stage Lung Cancer.

UNLABELLED: We confirmed the performance of an array method for plasma epidermal growth factor receptor (EGFR) mutation detection and showed the association of plasma EGFR mutation with survival outcomes. BACKGROUND: Noninvasive detection of epidermal growth factor receptor (EGFR) mutation in plasma is feasible and could be adjunct for therapeutic monitoring especially when repeated biopsy of tumor tissue is challenging. The aims of this study were to establish the diagnostic performance of peptide nucleic acid-locked nucleic acid polymerase chain reaction followed by custom array for plasma EGFR mutation and to evaluate the association of detection with clinical characteristics and survival outcomes. MATERIALS AND METHODS: Plasma genomic DNA from consecutive advanced lung cancer subjects was tested for EGFR mutations before anticancer treatment, and compared with mutation status in tumor tissue. Clinical characteristics were compared between patients who were EGFR-mutant and wild type; and within EGFR mutants, whether EGFR mutations could be detected in plasma. RESULTS: In 74 lung cancer patients, the sensitivity, specificity, and positive and negative predictive values of plasma EGFR detection were 79.1%, 96.8%, 97.1%, and 76.9%, respectively. EGFR mutants with concomitant detection of plasma EGFR mutation showed worse survival compared with mutants with no concomitant plasma mutation detected in biopsy specimens. CONCLUSION: Plasma EGFR mutation detected using this method demonstrated high diagnostic performance. In EGFR mutants, plasma EGFR mutation detection correlated not only EGFR mutation status in biopsy but was also associated with worse prognosis compared with EGFR mutant without plasma EGFR mutation detection.

The efficacy of a brief motivational enhancement education program on CPAP adherence in OSA: a randomized controlled trial.

BACKGROUND: Poor adherence to CPAP treatment in OSA adversely affects the effectiveness of this therapy. This randomized controlled trial (RCT) examined the efficacy of a brief motivational enhancement education program in improving adherence to CPAP treatment in subjects with OSA. METHODS: Subjects with newly diagnosed OSA were recruited into this RCT. The control group received usual advice on the importance of CPAP therapy and its care. The intervention group received usual care plus a brief motivational enhancement education program directed at enhancing the subjects' knowledge, motivation, and self-efficacy to use CPAP through the use of a 25-min video, a 20-min patient-centered interview, and a 10-min telephone follow-up. Self-reported daytime sleepiness adherence-related cognitions and quality of life were assessed at 1 month and 3 months. CPAP usage data were downloaded at the completion of this 3-month study. RESULTS: One hundred subjects with OSA (mean ± SD, age 52 ± 10 years; Epworth Sleepiness Scales [ESS], 9 ± 5; median [interquartile range] apnea-hypopnea index, 29 [20, 53] events/h) prescribed CPAP treatment were recruited. The intervention group had better CPAP use (higher daily CPAP usage by 2 h/d [Cohen d = 1.33, P < .001], a fourfold increase in the number using CPAP for ≥ 70% of days with ≥ 4 h/d [P < .001]), and greater improvements in daytime sleepiness (ESS) by 2.2 units (P = .001) and treatment self-efficacy by 0.2 units (P = .012) compared with the control group. CONCLUSIONS: Subjects with OSA who received motivational enhancement education in addition to usual care were more likely to show better adherence to CPAP treatment, with greater improvements in treatment self-efficacy and daytime sleepiness. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01173406; URL: www.clinicaltrials.gov.

Linguistic and psychometric validation of the Chinese version of the self-efficacy measures for sleep apnea questionnaire.

OBJECTIVES: The self-efficacy measure for sleep apnea (SEMSA) questionnaire was shown to be an effective tool to assess adherence-related cognitions on continuous positive airway pressure (CPAP) therapy in obstructive sleep apnea (OSA) subjects. SEMSA helps to solicit fundamental information for formulating strategies to promote CPAP adherence for better treatment outcomes. The objective of our study was to perform a linguistic and psychometric evaluation of a Chinese version of the SEMSA (SEMSA-C). METHODS: Data were obtained from 100 subjects in a randomized controlled trial (RCT) on CPAP education. Subjects were newly diagnosed of OSA and naïve to CPAP therapy. RESULTS: A 26-item SEMSA-C was obtained by a rigorous linguistic validation process. Internal consistency was high with Cronbach α>0.88. One-week test-retest intraclass correlation coefficient (ICC) ranged from 0.70 to 0.82. Principal component factor analysis identified three of the same hypothesized factors (perceived risks, outcome expectancies, and treatment self-efficacy) as in the original version. CPAP adherence was associated with outcome expectancies and treatment self-efficacy at 3-month assessment. Further, SEMSA-C demonstrated an improvement in self-efficacy after CPAP use. CONCLUSIONS: SEMSA-C shows similar psychometric properties as the original English version. It is a reliable and responsive instrument to measure perceived risks, outcome expectancies, and treatment self-efficacy in Chinese subjects with OSA.

Impact of nephrotic edema of the lower limbs on obstructive sleep apnea: gathering a unifying concept for the pathogenetic role of nocturnal rostral fluid shift.

BACKGROUND: Nocturnal rostral fluid shift has been suggested to be a risk factor for obstructive sleep apnea (OSA) in healthy subjects after lower body positive pressurization. It remains unclear whether this may apply to subjects with nephrotic lower limb edema and, if so, whether disease remission may reverse the accompanying OSA. METHODS: Patients who presented with steroid-responsive primary nephrotic syndrome with lower limb edema as the predominant presenting clinical feature were recruited. They underwent one overnight polysomnography (PSG) before treatment and a repeat testing after achieving remission of the nephrotic edema. RESULTS: Among 23 consecutive nephrotic subjects, 11 (48%) had polysomnographic evidence of sleep apnea [apnea-hypopnea index (AHI)≥5] upon presentation. After steroid-based treatment, there was remission of proteinuria associated with complete disappearance of lower limb edema, significant reduction of body mass index, waist, hip and calf circumferences and total body water mainly in the extracellular compartment. Repeat PSG, performed 8.1±2.6 months later, showed that the overall (N=23) respiratory disturbance index (RDI) and AHI fell from 17.3±5.0 to 8.7±2.5 (P<0.05) and from 16.3±5.1 to 7.8±2.3 (P=0.057), respectively. Among the 11 subjects with sleep apnea detected at baseline, their AHI and RDI fell from 33.4±7.8 to 15.0±3.7 (P<0.05) and from 34.8±7.6 to 16.5±4.0 (P<0.05), respectively. There was also concomitant improvement in sleep efficiency, mean nocturnal oxygen saturation, shorter duration during sleep with oxygen saturation<95 and <90% and reduced desaturation index. There was also subjective improvement in self-reported daytime sleepiness. CONCLUSIONS: Nephrotic lower limb edema is associated with disturbed respiratory breathing and increased propensity to OSA, which was reversed upon remission of the nephrosis. This gathers a unifying concept for the role of nocturnal rostral fluid shift in the pathogenesis of OSA.

Increased serum levels of advanced glycation end-products is associated with severity of sleep disordered breathing but not insulin sensitivity in non-diabetic men with obstructive sleep apnoea.

BACKGROUND: Patients with diabetes mellitus are known to have increased serum levels of advanced glycation end-products (AGEs), and this is also associated with insulin resistance. This study aimed to investigate the relationship between serum AGEs and insulin sensitivity in non-diabetic subjects with obstructive sleep apnoea (OSA). METHODS: Adult males with no known comorbidities were recruited from the sleep clinic of a university teaching hospital. They underwent overnight in-laboratory polysomnography. Fasting blood was taken to measure serum AGE and plasma glucose levels. Insulin sensitivity was estimated using the short insulin tolerance test. RESULTS: In total, 105 subjects with a mean age of 43.5 (standard deviation [SD] 9.2)years, mean body mass index of 27.1 (SD 4.0)kg/m(2), and median apnoea-hypopnoea index (AHI) of 17 (interquartile range 5-46) were analysed. Serum AGE levels were significantly higher in subjects with OSA (AHI ≥5), compared with those without OSA (AHI <5) (3.9 [SD 1.2] vs. 3.2 [SD 0.8]µg/ml, respectively; P=0.037) after adjusting for confounders. AGE levels were positively correlated with AHI (r=0.318, P=0.001), but not with insulin sensitivity. AGE levels decreased in subjects with moderate-to-severe OSA who received continuous positive airway pressure (CPAP) treatment for three months (n=18, P=0.017). CONCLUSIONS: Serum AGE levels correlate with AHI in non-diabetic adult males. This relationship cannot be explained by insulin sensitivity. Supporting the hypothesis of a direct relationship between AHI and AGEs, AGE levels were found to decline with CPAP therapy.

The efficacy of oral appliances in the treatment of severe obstructive sleep apnea.

OBJECTIVES: The purpose of this study is to evaluate the efficacy of oral appliance (OA) treatment for subjects with severe obstructive sleep apnea (OSA) and to determine the dental parameters associated with treatment outcomes. STUDY DESIGN: This study uses a prospective longitudinal design. METHODS: Consecutive Chinese subjects with severe OSA who refused continuous positive airway pressure treatment were recruited. Their dental measurements were taken from lateral cephalometric radiographs. Polysomnograms with OA were repeated at 3 months and 1 year. Blood pressure was taken in the morning after sleep studies. RESULTS: Thirty-four subjects were evaluated at 3 months and 1 year according to the principle of intention-to-treat analysis. OA reduced AHI significantly in subjects with favorable responses, from 49.3 (37.4-67) to 12.5 (6.1-15.7), p < 0.001 at 3 months and from 47.5 (41.1-72.9) to 13.1 (6.0-14.0), p < 0.001 at 1 year. These OSA subjects had an increased overjet at baseline compared to those with unfavorable responses (p ≤ 0.05). Systolic blood pressure was significantly reduced in those hypertensive OSA subjects after 3 months and 1 year of treatment. CONCLUSIONS: OA reduces the severity of sleep apnea, and the effect is maintained at 1 year in subjects with retrognathism. OA appears to reduce systolic blood pressure in hypertensive OSA subjects at 3 months and 1 year.

Advantages of video trigger in problem-based learning.

BACKGROUND: Traditionally, paper cases are used as 'triggers' to stimulate learning in problem-based learning (PBL). However, video may be a better medium because it preserves the original language, encourages the active extraction of information, avoids depersonalization of patients and allows direct observation of clinical consultations. In short, it exposes the students to the complexity of actual clinical problems. AIM: The study aims to find out whether students and facilitators who are accustomed to paper cases would prefer video triggers or paper cases and the reasons for their preference. METHOD: After students and facilitators had completed a video PBL tutorial, their responses were measured by a structured questionnaire using a modified Likert scale. RESULTS: A total of 257 students (92%) and 26 facilitators (100%) responded. The majority of students and facilitators considered that using video triggers could enhance the students' observational powers and clinical reasoning, help them to integrate different information and better understand the cases and motivate them to learn. They found PBL using video triggers more interesting and preferred it to PBL using paper cases. CONCLUSION: Video triggers are preferred by both students and facilitators over paper cases in PBL.

Prevalence and recognition of obstructive sleep apnea in Chinese patients with type 2 diabetes mellitus.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with disorders of glucose metabolism. Previous studies revealed a high prevalence of OSA among subjects with type 2 diabetes mellitus (DM). The aims of this study were to determine the prevalence of OSA and associated clinical factors in Chinese patients with DM. METHODS: All records of the DM clinic at a teaching hospital in Hong Kong were screened between January 2007 and June 2008. Inclusion criteria for patients were Chinese, aged 18 to 75 years, with type 2 DM. Patients with unstable medical illnesses, gestational diabetes, or on renal replacement therapy were excluded. RESULTS: Of 3,489 records screened, 1,859 subjects were eligible. A random sample of 663 (mean age, 58.2 ± 10.8; mean BMI, 26.0 ± 4.6), except six with known OSA, were invited for polysomnography (PSG). Of 165 subjects on which PSG was performed, OSA was diagnosed (apnea-hypopnea index [AHI] ≥ 5.0/h) in 89 subjects (53.9%, median Epworth Sleepiness Scale, 6 [interquartile range 3, 10]). Fifty-four (32.7%) had moderate/severe OSA (AHI ≥ 15/h). The estimated OSA prevalence in this diabetic cohort was 17.5% (24.7% in men, 10.3% in women). Regression analysis identified that AHI was associated independently with higher BMI, advanced age, male sex, and higher diastolic BP (R(2) = 29.6%). The adjusted OR of requiring three or more antihypertensive drugs in moderate/severe OSA was 2.48 (95% CI, 1.05-5.87). No association between glycemic control (HbA1c) and sleep was identified. CONCLUSIONS: In conclusion, OSA is more prevalent in Chinese adults with DM than in the general population. A high index of suspicion for OSA in patients with DM is warranted, because they may not have overt daytime sleepiness.

Obstructive sleep apnoea: definitions, epidemiology & natural history.

Obstructive sleep apnoea (OSA) is increasingly being recognized as an important health issue in the last two to three decades. It is characterized by frequent episodes of upper airway collapse during sleep, causing recurrent arousals, intermittent hypoxaemia, sleep fragmentation and poor sleep quality. There is accumulating evidence that OSA is being considered as an independent risk factor for hypertension, glucose intolerance / diabetes mellitus, cardiovascular diseases and stroke, leading to increased cardiometabolic morbidity and mortality. The prevalence rates of OSA have been estimated in the range of 2 to 10 per cent worldwide, and the risk factors for obstructive sleep apnoea include advanced age, male sex, obesity, family history, craniofacial abnormalities, smoking and alcohol consumption. The common clinical presenting symptoms are heavy snoring, witnessed apnoeas and daytime hypersomnolence, which would help to identify the affected individuals. With increasing awareness of this disease entity and associated complications in our society, there have been increased referrals to sleep physicians or expertise for further investigations and diagnostic evaluation. Early recognition and treatment of obstructive sleep apnoea may prevent from adverse health consequences. Some of the epidemiological aspects of obstructive sleep apnoea in adults are reviewed.

Sleep & the metabolic syndrome.

Sleep is an essential part of our daily living, and sleep disturbances may intervene with the biological and physiological processes in human body leading to the development of metabolic dysfunction. Short sleep duration and poor sleep quality have adverse effects on metabolism and hormonal processes, contributing to increased cardiovascular risk. Obstructive sleep apnoea is a chronic condition characterized by repetitive upper airway collapse during sleep, causing intermittent hypoxaemia, recurrent arousals and sleep fragmentation. Sleep disturbances can increase sympathetic activity, provoke systemic inflammation and oxidative stress, and impair vascular endothelial function. Obstructive sleep apnoea is increasingly recognized to be an independent cardiovascular risk factor. There is intense research interest in the association between obstructive sleep apnoea and the metabolic syndrome - the constellation of inter-related metabolic derangements including central obesity, hypertension, insulin resistance and dyslipidaemia, which appears to directly promote the development of atherosclerosis. The underlying pathophysiologic pathways or mechanistic links between obstructive sleep apnoea and metabolic syndrome have not been well delineated. This article reviews the current knowledge of the relationship between sleep disturbances, sleep-disordered breathing and the metabolic syndrome in adults.

Determinants of daytime blood pressure in relation to obstructive sleep apnea in men.

This study investigated the roles of different potential pathophysiological mechanisms in the determination of blood pressure in relation to obstructive sleep apnea. The study was designed as a cross-sectional study. Consecutive healthy male subjects who were to undergo polysomnography were recruited. Demographic and anthropometric data were collected. Blood pressure measurements were taken in the evening before sleep and the next morning on waking. Overnight urinary samples for catecholamines and fasting blood for cortisol, insulin, glucose, and lipids were taken. Ninety-four men were analyzed, with a mean age of 43.7 +/- 9.3 years and mean apnea-hypopnea index (AHI) of 27.5 +/- 26.2 events/h. Sixty-nine patients (73%) had obstructive sleep apnea (AHI >or= 5). Urinary catecholamines were positively correlated with severity of sleep apnea, independent of obesity. Blood pressure measurements correlated with age, obesity, severity of sleep apnea, and urinary catecholamines. Regression analysis showed that sleep indices and urinary catecholamines were independent determinants of morning systolic and diastolic blood pressure, respectively, while total cholesterol and waist circumference were respective additional factors. Urinary catecholamines and waist circumference were determinants of evening blood pressure, with morning cortisol being an additional determinant for diastolic blood pressure. Obstructive sleep apnea and related sympathetic activity contributed significantly to the determination of daytime blood pressure in overweight middle-aged men without overt cardiometabolic diseases, and other contributing factors include abdominal obesity, total cholesterol, and cortisol levels.

Implantation of a breathing pacemaker in a tetraplegic patient in Hong Kong.

A 38-year-old man had been tetraplegic and ventilator-dependent after sustaining a traumatic cervical spine fracture at the C1/C2 level in 1991, at the age of 22 years. He had been bedbound and mechanically ventilated since then. A multidisciplinary management team approached him in 2003 and helped him to become ambulatory and independent in his daily activities of living. We successfully implanted the diaphragm pacing stimulation system in this patient in 2004. Diaphragm pacing by phrenic nerve stimulation is well accepted in western countries, and has been in clinical application for children and adults for decades. Its use facilitates ambulation and improves the quality of life of tetraplegic individuals with chronic ventilatory failure.

Obstructive sleep apnea and the metabolic syndrome.

Obstructive sleep apnea (OSA) and the metabolic syndrome have a strong association with each other owing to their common feature of obesity, but an association independent of obesity has been demonstrated in several studies. There is also evidence, of varying strengths, from epidemiologic and clinical studies, for the independent association between OSA and individual core components of the metabolic syndrome, including hypertension, insulin resistance and dyslipidemia. To date, the data are strongest for hypertension, while data for adverse glucose or lipid metabolism are more controversial. Obesity and other factors, such as alcohol drinking and smoking, obviously pose major confounding hurdles to the clarification of the causal or aggravational role of OSA on cardiometabolic risks. Recurrent episodes of obstructed breathing notably result in intermittent hypoxemia and sleep fragmentation, and these may in turn lead to many adverse body responses, including sympathetic activation, neurohumeral changes and inflammation, which are the seeds for cardiometabolic dysfunctions, such as atherosclerosis and diabetes mellitus. Evidence from translational studies or animal/cell work are forthcoming in the delineation of these pathogenetic mechanisms.

Hypoadiponectinemia is related to sympathetic activation and severity of obstructive sleep apnea.

STUDY OBJECTIVES: Hypoadiponectinemia is associated with cardiovascular morbidity and diabetes mellitus. We hypothesize that adiponectin may be downregulated in sleep apnea through various mechanisms, contributing to cardiometabolic risks. This study investigated the relationship between serum adiponectin and sleep disordered breathing and its potential determinants. DESIGN: Cross-sectional study. SUBJECTS AND SETTING: Adult men without prevailing medical comorbidity from the sleep clinic in a teaching hospital. MEASUREMENTS & RESULTS: One hundred thirty-four men underwent polysomnography, with mean age of 43.9 (9.8) years, and median apnea-hypopnea index (AHI) of 17.1 (5.7, 46.6). Overnight urine samples for catecholamines and blood samples for analyses of insulin, glucose and adiponectin levels from fasting subjects were taken. Insulin resistance was estimated by homeostasis model assessment (HOMA-IR). Magnetic resonance imaging was performed to quantify the amount of abdominal visceral fat. Serum adiponectin level, adjusted for age, body mass index, and visceral fat volume, was significantly lower in subjects with severe obstructive sleep apnea (AHI > or =30) compared with those with an AHI of less than 30: 4.0 (3.1, 5.4) versus 5.4 (3.6, 7.9) microg/mL, P = 0.039. After we adjusted for adiposity, adiponectin levels remained negatively correlated with AHI (P = 0.037), arousal index (P = 0.022), HOMA-IR/fasting insulin (P < 0.001), and urinary norepinephrine and normetanephrine (P < 0.008). In a multiple stepwise regression model, the independent determinants of adiponectin after adjustment for adiposity were HOMA-IR (P < 0.001) and urinary norepinephrine and normetanephrine (P = 0.037). CONCLUSIONS: Adiponectin was suppressed in subjects with severe obstructive sleep apnea, independent of obesity. Adiponectin levels were determined by insulin resistance and sympathetic activation, factors that may be totally or partially attributed to sleep disordered breathing.

An update on obstructive sleep apnea and the metabolic syndrome.

PURPOSE OF REVIEW: Patients with obstructive sleep apnea are often overweight or obese, and they frequently exhibit metabolic aberrations, collectively known as the metabolic syndrome, an established cardiovascular risk factor. We review recent data on the relationship between obstructive sleep apnea and metabolic syndrome or its components, including abdominal obesity, insulin resistance, hypertension, and dyslipidemia. RECENT FINDINGS: There is accumulating evidence for an independent association between obstructive sleep apnea and metabolic syndrome or its components. Recent epidemiologic and clinical data suggest a causal role of severe obstructive sleep apnea in development of hypertension, but findings for insulin resistance and dyslipidemia are controversial. Visceral obesity remains a confounding issue in analyses. Animal models and translational studies indicate that obstructive sleep apnea may promote metabolic dysfunction through cycles of intermittent hypoxia; proposed underlying pathophysiologic mechanisms include oxidative stress, sympathetic activation, and inflammation. SUMMARY: There is suggestive evidence, but independent associations between obstructive sleep apnea and metabolic syndrome or its components are not fully established because of the confounding effect of obesity. Large randomized interventional trials are needed to identify any cause-effect relationship. Long-term follow-up studies would help to clarify the role of treatment of sleep apnea in reducing cardio-metabolic morbidity.

Randomised study of three non-surgical treatments in mild to moderate obstructive sleep apnoea.

BACKGROUND: Patients with mild to moderate obstructive sleep apnoea (OSA) may be managed with different treatment options. This study compared the effectiveness of three commonly used non-surgical treatment modalities. METHODS: Subjects with mild to moderate OSA were randomised to one of three treatment groups for 10 weeks: conservative measures (sleep hygiene) only, continuous positive airways pressure (CPAP) in addition to conservative measures or an oral appliance in addition to conservative measures. All overweight subjects were referred to a weight-reduction class. OSA was assessed by polysomnography. Blood pressure was recorded in the morning and evening in the sleep laboratory. Daytime sleepiness was assessed with the Epworth Sleepiness Scale. Health-related quality of life (HRQOL) was assessed with the 36-Item Short-Form Health Survey (SF-36) and Sleep Apnoea Quality of Life Index (SAQLI). RESULTS: 101 subjects with a mean (SEM) apnoea-hypopnoea index (AHI) of 21.4 (1.1) were randomised to one of the three groups. The severity of sleep-disordered breathing was decreased in the CPAP and oral appliance groups compared with the conservative measures group, and the CPAP group was significantly better than the oral appliance group. Relief from sleepiness was significantly better in the CPAP group. CPAP was also better than the oral appliance or conservative measures in improving the "bodily pain" domain, and better than conservative measures in improving the "physical function" domain of SF-36. Both CPAP and the oral appliance were more effective than conservative measures in improving the SAQLI, although no difference was detected between the CPAP and oral appliance groups. CPAP and the oral appliance significantly lowered the morning diastolic blood pressure compared with baseline values, but there was no difference in the changes in blood pressure between the groups. There was also a linear relationship between the changes in AHI and body weight. CONCLUSION: CPAP produced the best improvement in terms of physiological, symptomatic and HRQOL measures, while the oral appliance was slightly less effective. Weight loss, if achieved, resulted in an improvement in sleep parameters, but weight control alone was not uniformly effective.

Advanced glycation endproducts in nondiabetic patients with obstructive sleep apnea.

SUBJECT OBJECTIVE: The formation and accumulation of advanced glycation endproducts (AGEs) has been implicated in the progression of age-related diseases such as diabetes mellitus and atherosclerosis. We hypothesize that AGE concentrations may be increased in subjects with obstructive sleep apnea (OSA), a condition associated with increased oxidative stress. METHODS: One hundred nineteen nondiabetic patients with OSA and 234 age-matched healthy controls and 134 patients with type 2 diabetes were recruited for participation in the study. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay using a polyclonal rabbit antisera raised against AGE-RNase. RESULTS: Serum AGEs were increased in OSA subjects, as compared with controls, but were less increased than the AGEs of patients with type 2 diabetes (control: 3.22 +/- 0.54 unit per mL; OSA: 3.68 +/- 0.39; diabetes mellitus: 4.11 +/- 0.99; analysis of variance p < .01). In the subjects with OSA, serum AGEs correlated with the duration of nocturnal desaturation (r = 0.21, p = .025) and plasma total 8-isoprostane concentration, a biochemical marker of oxidative stress (r = 0.22, p = .015), but not with fasting glucose level. On general linear model univariate analysis, the association between serum AGEs and 8-isoprostane was independent of age, sex, body mass index, smoking status, and glucose. CONCLUSION: Serum levels of AGEs were increased in nondiabetic subjects with OSA and were associated with the severity of OSA. Whether increased AGE formation contributes significantly to the high cardiovascular risk associated with OSA remains to be determined.

HDL dysfunction in obstructive sleep apnea.

OBJECTIVE: HDL is anti-atherogenic and has antioxidant property. HDL dysfunction has been reported in patients with coronary heart disease and we hypothesize that HDL may also be dysfunctional in obstructive sleep apnea (OSA), a condition associated with increased oxidative stress. METHODS: 128 OSA patients and 82 controls were recruited. HDL dysfunction was determined by evaluating the ability of HDL to inhibit LDL oxidation ex vivo. Plasma HDL was incubated with native LDL in the presence of dichlorofluorescein which fluoresced upon interaction with lipid oxidation products. Plasma levels of oxidized LDL and 8-isoprostane were measured by ELISA and a specific enzyme immunoassay, respectively. RESULTS: Plasma total 8-isoprostane levels were elevated in OSA subjects (p<0.01). Despite having similar concentrations of plasma lipids and apolipoproteins as controls, OSA subjects had greater degree of HDL dysfunction (p<0.01) and increased oxidized LDL levels (p<0.05). The apnea-hypopnea index was the main determinant of HDL dysfunction in OSA, accounting for 30% of its variance, with oxidized LDL and apolipoprotein AI contributing to 8% and 5% of its variance respectively (p<0.001). CONCLUSION: HDL is dysfunctional in preventing the formation and inactivation of oxidized lipids in OSA subjects and may partly contribute to their increased cardiovascular risk.