Hongliang Yi

Effect of continuous positive airway pressure on lipid profile in patients with obstructive sleep apnea syndrome: A meta-analysis of randomized controlled trials

BACKGROUND Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for development of dyslipidemia. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. However, it is unclear whether CPAP improves lipid metabolism. OBJECTIVES To review the effect of CPAP on lipid profile of patients with OSAS. METHODS We searched PubMed, Embase, and the Cochrane Library to identify eligible articles published prior to October 30, 2013. Six randomized controlled trials (RCTs) were subjected to meta-analysis using Comprehensive Meta-Analysis software. RESULTS Six RCTs meeting the inclusion criteria were enrolled. The total numbers of measurements of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol, in CPAP intervention patients and sham/control groups, were 370 and 371, 330 and 328, 276 and 274, and 269 and 266 respectively. The pooled estimate of the difference in the mean TC level between the CPAP and sham CPAP/control groups was significantly different (-0.15 [95% confidence interval, -0.27 to -0.03]; p = 0.01). Subgroup analysis revealed that OSAS patients of younger age, who were more obese, and who had been treated via CPAP for a longer duration, showed a significant decrease in TC levels (the differences in the means were -0.27, -0.24, and -0.20; and the p values 0.001, 0.01, and 0.04, respectively). CONCLUSION We confirmed that CPAP decreases the TC level, especially in OSAS patients who are younger, more obese, and who use CPAP for a longer period. CPAP did not alter TG, LDL, or HDL levels, suggesting that CPAP may have no clinically important effect on lipid metabolism.

A systematic review and meta-analysis of the association between serotonergic gene polymorphisms and obstructive sleep apnea syndrome.

Background 5-Hydroxytryptamine receptor (5-HTR) and 5-hydroxytryptamine transporter (5-HTT) gene polymorphisms have been reported to be associated with susceptibility to obstructive sleep apnea syndrome (OSAS). The associations, derived from sporadic, inconsistent, small-sample-size studies, need to be evaluated further in a meta-analysis. Methods Relevant studies were identified by searching PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. Eligible data were extracted from each included study. Odds ratios (ORs) were calculated using a fixed-effects or a random-effects model. The ORs and 95% confidence interval (CI) were used to assess the strength of the association between serotonergic gene polymorphisms and OSAS in the dominant and recessive models, as well as alleles. The Q statistic was used to evaluate homogeneity and Begg’s test was used to assess publication bias. Results Eight studies were finally included in the meta-analysis of the association between 5-HTR2A gene variants (including 102T/C and 1438G/A), 5-HTT gene polymorphisms (including 5-HTT gene-linked promoter region (5-HTTLRP), and serotonin transporter intron 2 variable number tandem repeat (STin2VNTR) and OSAS risk. The G allele of 5-HTR2A 1438G/A, long 5-HTTLPR, and 10-tandem-repeats STin2VNTR were shown to increase OSAS susceptibility, with ORs of 2.33 (A vs. G, 95% CI 1.48–3.66), 1.24 (L vs. S, 95% CI: 1.04–1.49), and 2.87 (10 vs. 12, 95% CI: 1.38–5.97), respectively. These significant differences were determined in both dominant and recessive models. Of the 5-HTR2A 1438G/A gene polymorphism, the AA genotype increased the OSAS risk, with an OR of 4.21 (95% CI: 2.83–6.25) in a recessive model in male OSAS patients, but no significant association was found in females. Conclusions Our meta-analysis demonstrated that polymorphisms in the 5-HTR2A 1438G/A and 5-HTT genes contributed to susceptibility to OSAS. The A allele of the 1438G/A gene polymorphism is predominantly distributed in males and increased the OSAS risk significantly.

Distinct severity stages of obstructive sleep apnoea are correlated with unique dyslipidaemia: large-scale observational study

Background Dyslipidaemia is an intermediary exacerbation factor for various diseases but the impact of obstructive sleep apnoea (OSA) on dyslipidaemia remains unclear. Methods A total of 3582 subjects with suspected OSA consecutively admitted to our hospital sleep centre were screened and 2983 (2422 with OSA) were included in the Shanghai Sleep Health Study. OSA severity was quantified using the apnoea–hypopnea index (AHI), the oxygen desaturation index and the arousal index. Biochemical indicators and anthropometric data were also collected. The relationship between OSA severity and the risk of dyslipidaemia was evaluated via ordinal logistic regression, restricted cubic spline (RCS) analysis and multivariate linear regressions. Results The RCS mapped a nonlinear dose–effect relationship between the risk of dyslipidaemia and OSA severity, and yielded knots of the AHI (9.4, 28.2, 54.4 and 80.2). After integrating the clinical definition and RCS-selected knots, all subjects were regrouped into four AHI severity stages. Following segmented multivariate linear modelling of each stage, distinguishable sets of OSA risk factors were quantified: low-density lipoprotein cholesterol (LDL-C), apolipoprotein E and high-density lipoprotein cholesterol (HDL-C); body mass index and/or waist to hip ratio; and HDL-C, LDL-C and triglycerides were specifically associated with stage I, stages II and III, and stages II–IV with different OSA indices. Conclusions Our study revealed the multistage and non-monotonic relationships between OSA and dyslipidaemia and quantified the relationships between OSA severity indexes and distinct risk factors for specific OSA severity stages. Our study suggests that a new interpretive and predictive strategy for dynamic assessment of the risk progression over the clinical course of OSA should be adopted.

Independent Association between Sleep Fragmentation and Dyslipidemia in Patients with Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is independently associated with dyslipidemia. Previous studies have demonstrated that sleep fragmentation can impair lipid metabolism. The present study aimed to identify whether sleep fragmentation is independently associated with dyslipidemia, in a large-scale, clinic-based consecutive OSA sample. This cross-sectional study was conducted among 2,686 patients who underwent polysomnography (PSG) for suspicion of OSA from January 2008 to January 2013 at the sleep laboratory. Multivariate regression analyses were performed to evaluate the independent associations between the microarousal index (MAI) and lipid profiles adjusting for potential confounders, including metabolic syndrome components and nocturnal intermittent hypoxia. The adjusted odds ratios (ORs) for various types of dyslipidemia according to MAI quartiles, as determined by logistic regression were also evaluated. MAI was found positively associated with low-density lipoprotein cholesterol (LDL-c) but not with total cholesterol (TC), triglyceride (TG) or high-density lipoprotein cholesterol (HDL-c). Furthermore, the adjusted ORs (95% confidence interval) for hyper-LDL cholesterolemia increased across MAI quartiles, as follows: 1 (reference), 1.3 (1.1–1.7), 1.6 (1.2–2.0), and 1.6 (1.2–2.1) (p = 0.001, linear trend). Sleep fragmentation in OSA is independently associated with hyper-LDL cholesterolemia, which may predispose patients with OSA to a higher risk of cardiovascular disease.

An Effective Model for Screening Obstructive Sleep Apnea: A Large-Scale Diagnostic Study

Background Obstructive sleep apnea (OSA) causes high morbidity and mortality and is independently associated with an increased likelihood of multiple complications. The diagnosis of OSA is presently time-consuming, labor-intensive and inaccessible. Aim This study sought to develop a simple and efficient model for identifying OSA in Chinese adult population. Methods In this study, the efficiency of Epworth Sleepiness Scale (ESS) and a new established prediction model for screening OSA were evaluated in the test cohort (2,032 participants) and confirmed in an independent validation cohort (784 participants). Results In the test cohort, a high specificity (82.77%, 95% confidence interval [CI], 77.36–87.35) and a moderate sensitivity (61.65%, 95% CI, 59.35–63.91) were obtained at the threshold of nine for the ESS alone. Notably, sex-stratified analysis revealed different optimum cut-off points: nine for males and six for females. The new generated screening model, including age, waist circumference, ESS score, and minimum oxygen saturation (SaO2) as independent variables, revealed a higher sensitivity (89.13%, 95% CI, 87.60–90.53) and specificity (90.34%, 95% CI, 85.85–93.77) at the best cut-off point. Through receiver operating characteristics curve analysis, the area under the receiver operating characteristics curve of the model was found significantly larger than that of the ESS alone (0.955 vs. 0.774, P<0.0001). All these results were confirmed in the validation cohort. Conclusions A practical screening model comprising minimum SaO2 and other parameters could efficiently identify undiagnosed OSA from the high-risk patients. Additionally, a sex-specific difference should be considered if the ESS alone is used.

Effect of CPAP on Endothelial Function in Subjects With Obstructive Sleep Apnea: A Meta-Analysis

Obstructive sleep apnea (OSA) is related to endothelial dysfunction. CPAP is the first-line treatment for OSA. We conducted a meta-analysis to evaluate the effect of CPAP on endothelial function in subjects with OSA. The PubMed, Embase, and Cochrane Library databases were searched. The overall effects were measured by the weighted mean difference with a 95% CI. Subgroup and meta-regression analyses were used to explore the sources of between-study heterogeneity. Eleven studies were eligible for the meta-analysis. A random-effects model revealed that CPAP significantly improved endothelial function as assessed by flow-mediated dilation (weighted mean difference of 2.92, 95% CI 2.21–3.63, P < .001), whereas there was no significant improvement in endothelial function in response to nitroglycerin-mediated dilation (weighted mean difference of 0.90, 95% CI −1.63 to 3.43, P = .48). Age, sex, CPAP compliance and duration, and sleep-related variables had no effect on reduction in arterial stiffness after CPAP. Sensitivity analyses indicated that the protective effect of CPAP on endothelial function was robust. CPAP significantly improved flow-mediated dilation in subjects with OSA. Long-term randomized controlled trials with larger sample sizes are needed to confirm the positive effect of CPAP on endothelial function in subjects with OSA.

Obstructive sleep apnea predicts risk of metabolic syndrome independently of obesity: a meta-analysis

Introduction Obstructive sleep apnea (OSA) has been suggested to be associated with a high risk of metabolic syndrome (MS). However, results on whether the association between OSA and risk of MS is independent of obesity, and the effect of nocturnal intermittent hypoxia (IH) on MS, are conflicting. Our purpose was to estimate the magnitude of the independent association between OSA and risk of MS and further explore whether nocturnal IH in OSA plays a role in MS risk. Material and methods The PubMed and EMBASE databases were systematically searched (until January 21, 2015) for available observational evidence. Unadjusted and body mass index (BMI)-adjusted pooled odds ratios (ORs) for MS in OSA or higher nocturnal IH were calculated using fixed or random models. Tests of homogeneity, publication bias, and robustness of the results were performed. Results A total of 13 independent studies (involving 857 participants in 3 case-control studies and 7077 participants in 10 cross-sectional studies) were included. The OSA was significantly associated with an increased risk of MS in a meta-analysis of 10 studies (pooled OR = 1.72, 95% CI: 1.31–2.26, p < 0.001), with a BMI-adjusted pooled OR of 1.97 (95% CI: 1.34–2.88, p < 0.001). Pooled results from 3 studies on the oxygen desaturation index (ODI) and MS risk (OR = 1.96, 95% CI: 1.73–2.22, p < 0.001) and 3 studies on the cumulative percentage of sleep time with SpO2 below 90% (CT90) and MS risk (OR = 1.05, 95% CI: 1.02–1.07, p < 0.001) were also significant. Conclusions Our findings demonstrated a significant association between OSA and increased MS risk independent of BMI, and further indicated a role of nocturnal IH in this association.

Low prevalence of human papillomavirus in head and neck squamous cell carcinoma in Chinese patients

The aim of this study was to ascertain the prevalence and prognostic value of human papillomavirus (HPV) infection status in head and neck squamous cell carcinoma. Immunohistochemistry and GenoArray HPV genotyping assays were used to evaluate the HPV infection status of 256 Chinese patients with head and neck squamous cell carcinoma. Long‐term survival rates were calculated using the Kaplan–Meier method. Immunostaining for p16 was prevalent in 6.6% (17/256) of patients, whereas HPV infection was detected in 9 of 256 (3.5%) patients using the HPV genotyping test. None of the p16‐negative subjects were found to have HPV infection according to the HPV genotyping test. P16 positivity was more common among nonsmokers than smokers (16.3% vs. 4.7%, respectively; P = 0.02). Among nine HPV‐positive cases, seven were infected with HPV‐16, one with HPV‐33, and one with both HPV‐16 and HPV‐11. The 3‐year overall survival rate was 87.5% for p16‐positive/HPV‐positive patients, 75.0% for p16‐positive/HPV‐negative patients, and 76.9% for p16‐negative/HPV‐negative patients (P = 0.30). A very low rate of HPV infection was found among the study patients. HPV infection status may not be a useful prognostic marker for head and neck cancer patients. J. Med. Virol. 87:281–286, 2015.

Metabolomics Profiling for Obstructive Sleep Apnea and Simple Snorers

Few clinical studies have explored altered urinary metabolite levels in patients with obstructive sleep apnea (OSA). Thus, we applied a metabolomics approach to analyze urinary metabolites in three groups of participants: patients with polysomnography (PSG)-confirmed OSA, simple snorers (SS), and normal subjects. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and gas chromatography coupled with time-of-flight mass spectrometry were used. A total of 21 and 31 metabolites were differentially expressed in the SS and OSA groups, respectively. Patients with OSA had 18 metabolites different from those with SS. Of the 56 metabolites detected among the 3 groups, 24 were consistently higher or lower. A receiver operator curve analysis revealed that the combination of 4-hydroxypentenoic acid, arabinose, glycochenodeoxycholate-3-sulfate, isoleucine, serine, and xanthine produced a moderate diagnostic score with a sensitivity (specificity) of 75% (78%) for distinguishing OSA from those without OSA. The combination of 4-hydroxypentenoic acid, 5-dihydrotestosterone sulfate, serine, spermine, and xanthine distinguished OSA from SS with a sensitivity of 85% and specificity of 80%. Multiple metabolites and metabolic pathways associated with SS and OSA were identified using the metabolomics approach, and the altered metabolite signatures could potentially serve as an alternative diagnostic method to PSG.

Changes in cerebral metabolites in obstructive sleep apnea: a systemic review and meta-analysis.

Cognitive impairment is associated with changes in cerebral metabolites in patients with obstructive sleep apnea (OSA). Several studies have used magnetic resonance spectroscopy (MRS) to detect variations in cerebral metabolites; however, the results have been inconsistent. This meta-analysis summarizes the differences in cerebral metabolites between patients with OSA and controls. Two electronic databases, PubMed and Embase, were searched for articles (published before March 31, 2016) describing studies that used MRS to evaluate the cerebral metabolite changes. The overall effects were measured using the weighted mean difference with a 95% confidence interval. Subgroup analysis and sensitivity analysis were used to explore the sources of between-study heterogeneity and the stability of the results. Publication bias was also evaluated. Thirteen studies were ultimately included. In the hippocampus, the N-acetylaspartate (NAA)/creatine ratio was lower in patients with OSA. In the frontal lobe, only the NAA/choline ratio was lower in patients with OSA. Cerebral metabolites are significantly altered in the hippocampus in patients with OSA. Further clinical studies are needed to explore the underlying mechanisms between OSA and the changes in cerebral metabolites in the brain.