Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

Background/Aims

We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes.

Methods

Consecutive patients (n = 126) with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50), OSA was defined as an apnea/hypopnea index ≥5. A carotid atherosclerotic plaque was defined as a focal thickening >1.3 mm.

Results

Prevalence of high OSA risk was similar in patients refusing or accepting PG (76% vs 68%, p = 0.17). Among those accepting PG, overall OSA prevalence was significantly higher in patients with F2-F4 fibrosis compared to those without (72% vs 44%; p = 0.04). Significant fibrosis was independently associated with mean nocturnal oxygen saturation (SaO₂)<95% (OR 3.21, 95%C.I. 1.02–7.34; p = 0.04). Prevalence of OSA tended to be higher in patients with, than in those without, carotid plaques (64% vs 40%; p = 0.08). Carotid plaques were independently associated with %time at SaO2<90% >1 (OR 6.30, 95%C.I. 1.02–12.3; p = 0.01).

Conclusions

In NAFLD patients with chronically elevated ALT at low prevalence of morbid obesity, OSA was highly prevalent and indexes of SaO₂ resulted independently associated with severity of liver fibrosis and carotid atherosclerosis. These data suggest to consider sleep disordered breathing as a potential additional therapeutic target in severe NAFLD patients.     

Association between Sleep Duration and Urinary Albumin Excretion in Patients with Type 2 Diabetes: The Fukuoka Diabetes Registry

Objective

Few studies have so far investigated the impact of sleep duration on chronic kidney disease in diabetic patients. The objective of the present study was to examine the relationship between sleep duration and albuminuria in type 2 diabetic patients.

Research Design and Methods

A total of 4,870 Japanese type 2 diabetic patients ≥20 years of age were divided into six groups according to self-reported sleep duration: less than 4.5 hours, 4.5–5.4 hours, 5.5–6.4 hours, 6.5–7.4 hours, 7.5–8.4 hours and more than 8.5 hours. The association between sleep duration and urinary albumin-creatinine ratio (UACR) was examined cross-sectionally.

Results

Both short and long sleep durations were significantly associated with higher UACR levels and higher proportions of patients with albuminuria (≥30 mg/g) and macroalbuminuria (≥300 mg/g) compared with a sleep duration of 6.5–7.4 hours (P for quadratic trend <0.001). A U-shaped association between sleep duration and UACR remained significant even after adjustment for potential confounders, including age, sex, duration of diabetes, current smoking habits, former smoking habits, current drinking habits, regular exercise habits, total energy intake, total protein intake, hypnotic use and estimated glomerular filtration rate. Furthermore, the association remained substantially unchanged after additional adjustment for body mass index, hemoglobin A_1c, systolic blood pressure, renin-angiotensin system inhibitor use and depressive symptoms.

Conclusions

Our findings suggest that sleep duration has a U-shaped association with the UACR levels in type 2 diabetic patients, independent of potential confounders.     

Association between Obstructive Sleep Apnea and Community-Acquired Pneumonia

BackgroundWe hypothesized that obstructive sleep apnea (OSA) can predispose individuals to lower airway infections and community-acquired pneumonia (CAP) due to upper airway microaspiration. This study evaluated the association between OSA and CAP.MethodsWe performed a case-control study that included 82 patients with CAP and 41 patients with other infections (control group). The controls were matched according to age, sex and body mass index (BMI). A respiratory polygraph (RP) was performed upon admission for patients in both groups. The severity of pneumonia was assessed according to the Pneumonia Severity Index (PSI). The associations between CAP and the Epworth Sleepiness Scale (ESS), OSA, OSA severity and other sleep-related variables were evaluated using logistic regression models. The associations between OSA, OSA severity with CAP severity were evaluated with linear regression models and non-parametric tests.FindingsNo significant differences were found between CAP and control patients regarding anthropometric variables, toxic habits and risk factors for CAP. Patients with OSA, defined as individuals with an Apnea-Hypopnea Index (AHI) ≥10, showed an increased risk of CAP (OR = 2·86, 95%CI 1·29–6·44, p = 0·01). Patients with severe OSA (AHI≥30) also had a higher risk of CAP (OR = 3·18, 95%CI 1·11–11·56, p = 0·047). In addition, OSA severity, defined according to the AHI quartile, was also significantly associated with CAP (p = 0·007). Furthermore, OSA was significantly associated with CAP severity (p = 0·0002), and OSA severity was also associated with CAP severity (p = 0·0006).ConclusionsOSA and OSA severity are associated with CAP when compared to patients admitted to the hospital for non-respiratory infections. In addition, OSA and OSA severity are associated with CAP severity. These results support the potential role of OSA in the pathogenesis of CAP and could have clinical implications. This link between OSA and infection risk should be explored to investigate the relationships among gastroesophageal reflux, silent aspiration, laryngeal sensory dysfunction and CAP.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01071421","term_id":"NCT01071421"}}NCT01071421     

Sleep and Multisystem Biological Risk: A Population-Based Study

BackgroundShort sleep and poor sleep quality are associated with risk of cardiovascular disease, diabetes, cancer, and mortality. This study examines the contribution of sleep duration and sleep quality on a multisystem biological risk index that is known to be associated with morbidity and mortality.MethodsAnalyses include a population-based sample from the Midlife Development in the United States survey recruited to the Biomarker substudy. A total of 1,023 participants aged 54.5 years (SD = 11.8), 56% female and 77.6% white, were included in the analyses. A multisystem biological risk index was derived from 22 biomarkers capturing cardiovascular, immune, lipid-metabolic, glucose-metabolic, sympathetic, parasympathetic, and hypothalamic-pituitary-adrenal systems. Self-reported average sleep duration was categorized as short (<5 hrs), below normal (5 to <6.5 hrs), normal (6.5 to <8.5 hrs), and long sleepers (8.5+ hrs). Sleep quality was determined using the Pittsburgh Sleep Quality Index categorized as normal (≤5) and poor quality (>5) sleep.FindingsLinear mixed effect models adjusting for age, gender, race, education, income, BMI, and health status were performed. As compared to normal sleepers, multisystem biological risk in both short (B(SE) = .38(.15), p<.01) and long sleepers (B(SE) = .28(.11), p<.01) were elevated. Poor quality sleep alone was associated with elevated multisystem biological risk (B(SE) = .15(.06), p = .01), but was not significant after adjustment for health status. All short sleepers reported poor sleep quality. However in the long sleepers, only those who reported poor sleep quality exhibited elevated multisystem biological risk (B(SE) = .93(.3), p = .002).ConclusionsSelf-reported poor sleep quality with either short or long sleep duration is associated with dysregulation in physiological set points across regulatory systems, leading to elevated multisystem biological risk. Physicians should inquire about sleep health in the assessment of lifestyle factors related to disease risk, with evidence that healthy sleep is associated with lower multisystem biological risk.     

Optimal Sleep Duration in the Subarctic with Respect to Obesity Risk Is 8–9 Hours

Introduction

Sleep duration, chronotype and social jetlag have been associated with body mass index (BMI) and abdominal obesity. The optimal sleep duration regarding BMI has previously been found to be 7–8 hours, but these studies have not been carried out in the subarctic or have lacked some central variables. The aims of our study were to examine the associations between sleep variables and body composition for people living in the subarctic, taking a range of variables into consideration, including lifestyle variables, health variables and biological factors.

Methods

The cross sectional population Tromsø Study was conducted in northern Norway, above the Arctic Circle. 6413 persons aged 30–65 years completed questionnaires including self-reported sleep times, lifestyle and health. They also measured height, weight, waist and hip circumference, and biological factors (non-fasting serum level of cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and glucose). The study period was from 1 October 2007 to 19 December 2008.

Results

The optimal sleep length regarding BMI and waist circumference was found to be 8–9 hours. Short sleepers (<6 h) had about 80% increased risk of being in the BMI≥25 kg/m2 group and male short sleepers had doubled risk of having waist circumference ≥102 cm compared to 8–9 hours sleepers. We found no impact of chronotype or social jetlag on BMI or abdominal obesity after controlling for health, lifestyle, and biological parameters.

Conclusions

In our subarctic population, the optimal sleep duration time regarding risk of overweight and abdominal obesity was 8–9 hours, which is one hour longer compared to findings from other studies. Short sleepers had 80% increased risk of being overweight, and men had a doubled risk of having abdominal obesity. We found no associations between chronotype or social jetlag and BMI or abdominal obesity, when we took a range of life-style, health and biological variables into consideration.     

Total Sleep Time Severely Drops during Adolescence

Restricted sleep duration among young adults and adolescents has been shown to increase the risk of morbidities such as obesity, diabetes or accidents. However there are few epidemiological studies on normal total sleep time (TST) in representative groups of teen-agers which allow to get normative data.

Purpose

To explore perceived total sleep time on schooldays (TSTS) and non schooldays (TSTN) and the prevalence of sleep initiating insomnia among a nationally representative sample of teenagers.

Methods

Data from 9,251 children aged 11 to 15 years-old, 50.7% of which were boys, as part of the cross-national study 2011 HBSC were analyzed. Self-completion questionnaires were administered in classrooms. An estimate of TSTS and TSTN (week-ends and vacations) was calculated based on specifically designed sleep habits report. Sleep deprivation was estimated by a TSTN – TSTS difference >2 hours. Sleep initiating nsomnia was assessed according to International classification of sleep disorders (ICSD 2). Children who reported sleeping 7 hours or less per night were considered as short sleepers.

Results

A serious drop of TST was observed between 11 yo and 15 yo, both during the schooldays (9 hours 26 minutes vs. 7 h 55 min.; p<0.001) and at a lesser extent during week-ends (10 h 17 min. vs. 9 h 44 min.; p<0.001). Sleep deprivation concerned 16.0% of chidren aged of 11 yo vs. 40.5% of those of 15 yo (p<0.001). Too short sleep was reported by 2.6% of the 11 yo vs. 24.6% of the 15 yo (p<0.001).

Conclusion

Despite the obvious need for sleep in adolescence, TST drastically decreases with age among children from 11 to 15 yo which creates significant sleep debt increasing with age.     

The CC Genotype of the Delta-Sarcoglycan Gene Polymorphism rs13170573 Is Associated with Obstructive Sleep Apnea in the Chinese Population

Obstructive sleep apnea (OSA) is a highly heterogeneous sleep disorder, and increasing evidence suggests that genetic factors play a role in the etiology of OSA. Airway muscle dysfunction might promote pharyngeal collapsibility, mutations or single nucleotide polymorphisms (SNPs) in the delta-sarcoglycan (SCGD) gene associated with muscle dysfunction. To evaluate if SCGD gene SNPs are associated with OSA, 101 individuals without OSA and 97 OSA patients were recruited randomly. The genotype distributions of SNPs (rs157350, rs7715464, rs32076, rs13170573 and rs1835919) in case and control populations were evaluated. The GG, GC and CC genotypes of rs13170573 in control and OSA groups were 51.5% and 37.1%, 36.6% and 35.1%, and 11.9% and 27.8%, respectively. Significantly fewer OSA patients possessed the GG genotype and significantly more possessed the CC genotype compared with controls. Further multivariate logistic regression analysis showed that the CC genotype was an independent risk factor for OSA, with an odds ratio (OR) of 2.17 (95% confidence interval [CI]: 1.19–6.01). Other factors, such as age ≥50 years, male gender, body mass index (BMI) ≥25 kg/m², low-density lipoprotein cholesterol (LDL-C) level ≥3.33 mg/dL, smoking and hypertension, were also independent risk factors for OSA in our multivariate logistic regression model.     

Sleep Extension Normalizes ERP of Waking Auditory Sensory Gating in Healthy Habitually Short Sleeping Individuals

Chronic sleep loss has been associated with increased daytime sleepiness, as well as impairments in memory and attentional processes. In the present study, we evaluated the neuronal changes of a pre-attentive process of wake auditory sensory gating, measured by brain event-related potential (ERP) – P50 in eight normal sleepers (NS) (habitual total sleep time (TST) 7 h 32 m) vs. eight chronic short sleeping individuals (SS) (habitual TST ≤6 h). To evaluate the effect of sleep extension on sensory gating, the extended sleep condition was performed in chronic short sleeping individuals. Thus, one week of time in bed (6 h 11 m) corresponding to habitual short sleep (hSS), and one week of extended time (∼ 8 h 25 m) in bed corresponding to extended sleep (eSS), were counterbalanced in the SS group. The gating ERP assessment was performed on the last day after each sleep condition week (normal sleep and habitual short and extended sleep), and was separated by one week with habitual total sleep time and monitored by a sleep diary. We found that amplitude of gating was lower in SS group compared to that in NS group (0.3 µV vs. 1.2 µV, at Cz electrode respectively). The results of the group × laterality interaction showed that the reduction of gating amplitude in the SS group was due to lower amplitude over the left hemisphere and central-midline sites relative to that in the NS group. After sleep extension the amplitude of gating increased in chronic short sleeping individuals relative to their habitual short sleep condition. The sleep condition × frontality interaction analysis confirmed that sleep extension significantly increased the amplitude of gating over frontal and central brain areas compared to parietal brain areas.     

The Impact of Obstructive Sleep Apnea on Metabolic and Inflammatory Markers in Consecutive Patients with Metabolic Syndrome

Background

Obstructive Sleep Apnea (OSA) is tightly linked to some components of Metabolic Syndrome (MetS). However, most of the evidence evaluated individual components of the MetS or patients with a diagnosis of OSA that were referred for sleep studies due to sleep complaints. Therefore, it is not clear whether OSA exacerbates the metabolic abnormalities in a representative sample of patients with MetS.

Methodology/Principal Findings

We studied 152 consecutive patients (age 48±9 years, body mass index 32.3±3.4 Kg/m²) newly diagnosed with MetS (Adult Treatment Panel III). All participants underwent standard polysomnography irrespective of sleep complaints, and laboratory measurements (glucose, lipid profile, uric acid and C-reactive protein). The prevalence of OSA (apnea-hypopnea index ≥15 events per hour of sleep) was 60.5%. Patients with OSA exhibited significantly higher levels of blood pressure, glucose, triglycerides, cholesterol, LDL, cholesterol/HDL ratio, triglycerides/HDL ratio, uric acid and C-reactive protein than patients without OSA. OSA was independently associated with 2 MetS criteria: triglycerides: OR: 3.26 (1.47–7.21) and glucose: OR: 2.31 (1.12–4.80). OSA was also independently associated with increased cholesterol/HDL ratio: OR: 2.38 (1.08–5.24), uric acid: OR: 4.19 (1.70–10.35) and C-reactive protein: OR: 6.10 (2.64–14.11). Indices of sleep apnea severity, apnea-hypopnea index and minimum oxygen saturation, were independently associated with increased levels of triglycerides, glucose as well as cholesterol/HDL ratio, uric acid and C-reactive protein. Excessive daytime sleepiness had no effect on the metabolic and inflammatory parameters.

Conclusions/Significance

Unrecognized OSA is common in consecutive patients with MetS. OSA may contribute to metabolic dysregulation and systemic inflammation in patients with MetS, regardless of symptoms of daytime sleepiness.     

Short Sleep Duration and Childhood Obesity: Cross-Sectional Analysis in Peru and Patterns in Four Developing Countries

Background

We aimed to describe the patterns of nutritional status and sleep duration in children from Ethiopia, India, Peru and Vietnam; to assess the association between short sleep duration and overweight and obesity, and if this was similar among boys and girls in Peru.

Methods and Findings

Analysis of the Young Lives Study, younger cohort, third round. In Ethiopia there were 1,999 observations, 2,011, 2,052 and 2,000 in India, Peru and Vietnam, respectively. Analyses included participants with complete data for sleep duration, BMI, sex and age; missing data: 5.9% (Ethiopia), 4.1% (India), 6.0% (Peru) and 4.5% (Vietnam). Exposure was sleep duration per day: short (<10 hours) versus regular (10–11 hours). Outcome was overweight and obesity. Multivariable analyses were conducted using a hierarchical approach to assess the effect of variables at different levels. Overweight/obesity prevalence was 0.5%/0.2% (Ethiopia), 1.3%/0.3% (India), 6.1%/2.8% (Vietnam), and 15.8%/5.4% (Peru). Only Peruvian data was considered to explore the association between short sleep duration and overweight and obesity, with 1,929 children, aged 7.9±0.3 years, 50.3% boys. Short and regular sleep duration was 41.6% and 55.6%, respectively. Multivariable models showed that obesity was 64% more prevalent among children with short sleep duration, an estimate that lost significance after controlling for individual- and family-related variables (PR: 1.15; 95%CI: 0.81–1.64). Gender was an effect modifier of the association between short sleep duration and overweight (p = 0.030) but not obesity (p = 0.533): the prevalence ratio was greater than one across all the models for boys, yet it was less than one for girls.

Conclusions

Childhood overweight and obesity have different profiles across developing settings. In a sample of children living in resource-limited settings in Peru there is no association between short sleep duration and obesity; the crude association was slightly attenuated by children-related variables but strongly diminished by family-related variables.     

Effects of Maternal Obstructive Sleep Apnoea on Fetal Growth: A Prospective Cohort Study

Objective

The objective of this study is to determine whether obstructive sleep apnea (OSA) is associated with reduced fetal growth, and whether nocturnal oxygen desaturation precipitates acute fetal heart rate changes.

Study Design

We performed a prospective observational study, screening 371 women in the second trimester for OSA symptoms. 41 subsequently underwent overnight sleep studies to diagnose OSA. Third trimester fetal growth was assessed using ultrasound. Fetal heart rate monitoring accompanied the sleep study. Cord blood was taken at delivery, to measure key regulators of fetal growth.

Results

Of 371 women screened, 108 (29%) were high risk for OSA. 26 high risk and 15 low risk women completed the longitudinal study; 14 had confirmed OSA (cases), and 27 were controls. The median (interquartile range) respiratory disturbance index (number of apnoeas, hypopnoeas or respiratory related arousals/hour of sleep) was 7.9 (6.1–13.8) for cases and 2.2 (1.3–3.5) for controls (p<0.001). Impaired fetal growth was observed in 43% (6/14) of cases, vs 11% (3/27) of controls (RR 2.67; 1.25–5.7; p = 0.04). Using logistic regression, only OSA (OR 6; 1.2–29.7, p = 0.03) and body mass index (OR 2.52; 1.09–5.80, p = 0.03) were significantly associated with impaired fetal growth. After adjusting for body mass index on multivariate analysis, the association between OSA and impaired fetal growth was not appreciably altered (OR 5.3; 0.93–30.34, p = 0.06), although just failed to achieve statistical significance. Prolonged fetal heart rate decelerations accompanied nocturnal oxygen desaturation in one fetus, subsequently found to be severely growth restricted. Fetal growth regulators showed changes in the expected direction- with IGF-1 lower, and IGFBP-1 and IGFBP-2 higher- in the cord blood of infants of cases vs controls, although were not significantly different.

Conclusion

OSA may be associated with reduced fetal growth in late pregnancy. Further evaluation is warranted to establish whether OSA may be an important contributor to adverse perinatal outcome, including stillbirth.     

Associations of a Short Sleep Duration,Insufficient Sleep,and Insomnia with Self-Rated Health among Nurses

Epidemiological evidence suggests that sleep duration and poor sleep are associated with mortality, as well as with a wide range of negative health outcomes. However, few studies have examined the association between sleep and self-rated health, particularly through the combination of sleep complaints. The objective of this study was to examine whether self-rated health is associated with sleep complaints, considering the combination of sleep duration, insomnia, and sleep sufficiency. This cross-sectional study was performed in the 18 largest public hospitals in the city of Rio de Janeiro, Brazil. A total of 2518 female nurses answered a self-filled multidimensional questionnaire. The adjusted odds ratios and 95% confidence intervals (CIs) estimated the chance of poor self-rated health in the presence of different combinations of sleep duration and quality. Compared with women who reported adequate sleep duration with no sleep quality complaints (reference group), the odds ratios (95% CI) for poor self-rated health were 1.79 (1.27–2.24) for those who reported only insufficient sleep, 1.85 (0.94–3.66) for only a short sleep duration, and 3.12 (1.94–5.01) for only insomnia. Compared with those who expressed all three complaints (short sleep duration, insomnia, and insufficient sleep), the odds ratio for poor self-rated health was 4.49 (3.25–6.22). Differences in the magnitude of the associations were observed, depending on the combination of sleep complaints. Because self-rated health is a consistent predictor of morbidity, these results reinforce the increasing awareness of the role of sleep in health and disease. Our findings contribute to the recognition of sleep as a public health matter that deserves to be better understood and addressed by policymakers.     

The Joint Effect of Sleep Duration and Disturbed Sleep on Cause-Specific Mortality: Results from the Whitehall II Cohort Study

Background

Both sleep duration and sleep quality are related to future health, but their combined effects on mortality are unsettled. We aimed to examine the individual and joint effects of sleep duration and sleep disturbances on cause-specific mortality in a large prospective cohort study.

Methods

We included 9,098 men and women free of pre-existing disease from the Whitehall II study, UK. Sleep measures were self-reported at baseline (1985–1988). Participants were followed until 2010 in a nationwide death register for total and cause-specific (cardiovascular disease, cancer and other) mortality.

Results

There were 804 deaths over a mean 22 year follow-up period. In men, short sleep (≤6 hrs/night) and disturbed sleep were not independently associated with CVD mortality, but there was an indication of higher risk among men who experienced both (HR = 1.57; 95% CI: 0.96–2.58). In women, short sleep and disturbed sleep were independently associated with CVD mortality, and women with both short and disturbed sleep experienced a much higher risk of CVD mortality (3.19; 1.52–6.72) compared to those who slept 7–8 hours with no sleep disturbances; equivalent to approximately 90 additional deaths per 100,000 person years. Sleep was not associated with death due to cancer or other causes.

Conclusion

Both short sleep and disturbed sleep are independent risk factors for CVD mortality in women and future studies on sleep may benefit from assessing disturbed sleep in addition to sleep duration in order to capture health-relevant features of inadequate sleep.     

Age-Group-Specific Associations between the Severity of Obstructive Sleep Apnea and Relevant Risk Factors in Male and Female Patients

Aim

To seek accurate and credible correlation manner between gender, age, and obesity; and the severity of obstructive sleep apnea (OSA) in large-scale population.

Methods

Totals of 1,975 male and 378 female OSA patients were sequentially recruited. Centralized covariant tendencies between age, body mass index (BMI), and waist hip ratio (WHR); and OSA severity, were explored in a gender-specific manner via multiple statistical analyses. The accuracies of observed correlations were further evaluated by adaptive multiple linear regression.

Results

All of age, BMI, WHR, smoking, drinking, and OSA severity differed between males and females. BMI and WHR were positively and (approximately) linearly associated with OSA severity in both males and females. Restricted cubic spline analysis was more effective than was the Pearson correlation approach in correlating age with AHI, and provided age crossover points allowing further piecewise linear modeling for both males and females. Multiple linear regression showed that increasing age was associated with OSA exacerbation in males aged ≤40 years and in females aged 45–53 years. BMI, WHR, and diabetes were independently associated with OSA severity in males with age-group-specific pattern. In females, only BMI was associated with OSA severity at all ages.

Conclusions

In male patients, BMI and WHR are prominent risk factors for OSA exacerbation. Age and diabetes are associated with OSA severity in males of particular ages. In females, BMI is also a prominent risk factor for severe OSA, and OSA severity increased with age in the range 45–53 years.     

The Potential Association between Obstructive Sleep Apnea and Diabetic Retinopathy in Severe Obesity—The Role of Hypoxemia

Background

Obstructive sleep apnea (OSA) is common in obese patients with type 2 diabetes mellitus (DM) and may contribute to diabetic microvascular complications.

Methods

To investigate the association between OSA, hypoxemia during sleep, and diabetic retinal complications in severe obesity. This was a prospective observational study of 93 obese patients mean (SD) age: 52(10) years; mean (SD) body mass index (BMI): 47.3(8.3) kg/m²) with DM undergoing retinal screening and respiratory monitoring during sleep. OSA was defined as apnea-hypopnea index (AHI) of ≥15 events/hour, resulting in two groups (OSA+ vs. OSA−).

Results

Forty-six patients were OSA+: median (95% CI) AHI = 37(23–74)/hour and 47 were OSA–ve (AHI = 7(4–11)/hour). Both groups were similar for ethnicity, BMI, cardiovascular co-morbidities, diabetes duration, HbA_1c, and insulin treatment (p>0.05). The OSA+ group was significantly more hypoxemic. There was no significant difference between OSA+ and OSA− groups for the presence of retinopathy (39% vs. 38%). More OSA+ subjects had maculopathy (22% vs. 13%), but this did not reach statistical significance. Logistic regression analyses showed that AHI was not significantly associated with the presence of retinopathy or maculopathy (p>0.05). Whilst minimum oxygen saturation was not significantly associated with retinopathy, it was an independent predictor for the presence of maculopathy OR = 0.79 (95% CI: 0.65–0.95; p<0.05), after adjustment.

Conclusions

The presence of OSA, as determined by AHI, was not associated with diabetic retinal complications. In contrast, severity of hypoxemia during sleep (minimum oxygen saturations) may be an important factor. The importance of hypoxia in the development of retinal complications in patients with OSA remains unclear and further studies assessing the pathogenesis of hypoxemia in patients with OSA and diabetic retinal disease are warranted.     

Obstructive Sleep Apnea Susceptibility Genes in Chinese Population: A Field Synopsis and Meta-Analysis of Genetic Association Studies

Background

Epidemiological studies to date have evaluated the association between genetic variants and the susceptibility to obstructive sleep apnea (OSA). However, the results of these studies have been inconclusive. In this current study we performed meta-analysis of genetic association studies (GAS) to pool OSA-susceptible genes in Chinese population, to perform a more precise evaluation of the association.

Methods

Various databases (i.e., PubMed, EMBASE, HuGE Navigator, Wanfang and CNKI) were searched to identify all eligible GAS-related variants associated with susceptibility to OSA. The generalized odds ratio metric (OR_G) and the odds ratio (OR) of the allele contrast were used to quantify the impact of genetic variants on the risk of OSA. Cumulative and recursive cumulative meta-analyses (CMA) were also performed to investigate the trend and stability of effect sizes as evidence was accumulated.

Results

Thirty-two GAS evaluating 13 polymorphisms in 10 genes were included in our meta-analysis. Significant associations were derived for four polymorphisms either for the allele contrast or for the OR_G. The variants TNF-α-308G/A, 5-HTTLPR, 5-HTTVNTR, and APOE showed marginal significance for OR_G (95% confidence interval [CI]): 2.01(1.31–3.07); 1.31(1.09–1.58); 1.85(1.16–2.95); 1.79(1.10–2.92); and 1.79(1.10–2.92) respectively. In addition, the TNF-α-308G/A, 5-HTTLPR, and 5-HTTVNTR variants showed significance for the allele contrast: 2.15(1.39–3.31); 2.26(1.58–3.24); 1.32(1.12–1.55); and 1.86(1.12–3.08) respectively. CMA showed a trend towards an association, and recursive CMA indicated that more evidence was needed to determine whether this was significant.

Conclusions

TNF-α, 5-HTT, and APOE genes can all be proposed as OSA-susceptibility genes in Chinese population. Genome-wide association studies (GWAS) are therefore urgently needed to confirm our findings within a larger sample of OSA patients in China.     

Relationship between Obstructive Sleep Apnea Severity and Sleep,Depression and Anxiety Symptoms in Newly-Diagnosed Patients

Obstructive sleep apnea (OSA) occurs in at least 10% of the population, and leads to higher morbidity and mortality; however, relationships between OSA severity and sleep or psychological symptoms are unclear. Existing studies include samples with wide-ranging comorbidities, so we assessed relationships between severity of OSA and common sleep and psychological disturbances in recently diagnosed OSA patients with minimal co-morbidities. We studied 49 newly diagnosed, untreated OSA patients without major co-morbidities such as mental illness, cardiovascular disease, or stroke; subjects were not using psychoactive medications or tobacco (mean ± std age: 46.8±9.1 years; apnea/hyponea index [AHI]: 32.1±20.5 events/hour; female/male: 12/37; weight <125 kg). We evaluated relationships between the AHI and daytime sleepiness (Epworth Sleepiness Scale; ESS), sleep quality (Pittsburg Sleep Quality Index; PSQI), depressive symptoms (Beck Depression Inventory-II; BDI), and anxiety symptoms (Beck Anxiety Inventory; BAI), as well as sex and body mass index (BMI). AHI was similar in females and males. Mean levels of all symptoms were above normal thresholds, but AHI was not correlated with age, ESS, PSQI, BDI, or BAI; only BMI was correlated with OSA severity. No differences in mean AHI appeared when subjects were grouped by normal versus elevated values of ESS, PSQI, BDI, or BAI. Consistent with other studies, a strong link between OSA severity and psychological symptoms did not appear in these newly diagnosed patients, suggesting that mechanisms additional to the number and frequency of hypoxic events and arousals occurring with apneas contribute to adverse health effects in OSA. OSA patients presenting with mild or moderate severity, and no major co-morbidities will not necessarily have low levels of sleep or psychological disturbances.     

Association of Genetic Loci with Sleep Apnea in European Americans and African-Americans: The Candidate Gene Association Resource (CARe)

Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI≥15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study.Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value<2×10⁻⁶. Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts.Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis.     

Effect of Acute Intermittent CPAP Depressurization during Sleep in Obese Patients

Background

Obstructive Sleep Apnea (OSA) describes intermittent collapse of the airway during sleep, for which continuous positive airway pressure (CPAP) is often prescribed for treatment. Prior studies suggest that discontinuation of CPAP leads to a gradual, rather than immediate return of baseline severity of OSA. The objective of this study was to determine the extent of OSA recurrence during short intervals of CPAP depressurization during sleep.

Methods

Nine obese (BMI = 40.4 ± 3.5) subjects with severe OSA (AHI = 88.9 ± 6.8) adherent to CPAP were studied during one night in the sleep laboratory. Nasal CPAP was delivered at therapeutic (11.1 ± 0.6 cm H₂0) or atmospheric pressure, in alternating fashion for 1-hour periods during the night. We compared sleep architecture and metrics of OSA during CPAP-on and CPAP-off periods.

Results

8/9 subjects tolerated CPAP withdrawal. The average AHI during CPAP-on and CPAP-off periods was 3.6 ± 0.6 and 15.8 ± 3.6 respectively (p<0.05). The average 3% ODI during CPAP-on and CPAP-off was 4.7 ± 2 and 20.4 ± 4.7 respectively (p<0.05). CPAP depressurization also induced more awake (p<0.05) and stage N1 (p<0.01) sleep, and less stage REM (p<0.05) with a trend towards decreased stage N3 (p = 0.064).

Conclusion

Acute intermittent depressurization of CPAP during sleep led to deterioration of sleep architecture but only partial re-emergence of OSA. These observations suggest carryover effects of CPAP.     

T Regulatory Lymphocytes and Endothelial Function in Pediatric Obstructive Sleep Apnea

Background

Obstructive sleep apnea (OSA) is a low-grade inflammatory disease affecting the cardiovascular and metabolic systems. Increasing OSA severity reduces T-regulatory lymphocytes (Tregs) in OSA children. Since Tregs modulate endothelial activation, and attenuate insulin resistance, we hypothesized that Tregs are associated with endothelial and metabolic dysfunction in pediatric OSA.

Methods

50 consecutively recruited children (ages 4.8–12 years) underwent overnight polysomnography and fasting homeostatic model (HOMA) of insulin resistance was assessed. Percentage of Tregs using flow cytometry, and endothelial function, expressed as the time to peak occlusive hyperemia (Tmax), were examined. In a subgroup of children (n = 21), in vitro Treg suppression tests were performed.

Results

Circulating Tregs were not significantly associated with either BMI z score or HOMA. However, a significant inverse correlation between percentage of Tregs and Tmax emerged (p<0.0001, r = −0.56). A significant negative correlation between Tregs suppression and the sleep pressure score (SPS), a surrogate measure of sleep fragmentation emerged (p = 0.02, r = −0.51) emerged, but was not present with AHI.

Conclusions

Endothelial function, but not insulin resistance, in OSA children is strongly associated with circulating Tregs and their suppressive function, and appears to correlate with sleep fragmentation. Thus, alterations in T cell lymphocytes may contribute to cardiovascular morbidity in pediatric OSA.