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Rationale: Previous genetic studies of obstructive sleep apnea (OSA) have limitations in terms of precise case definition, integrated quantitative traits, and interpretation of genetic functions; thus, the heritability of OSA remains poorly explained. Objectives: To identify novel genetic variants associated with OSA and objective sleep-related traits and to explore their functional roles. Methods: A genome-wide association study was performed in 20,590 Han Chinese individuals (5,438 OSA and 15,152 control samples). Human samples and point mutation knockin mice were used for follow-up investigation of gene functions. Measurements and Main Results: Two characteristic study-wide significant loci (P < 2.63 × 10-9) for OSA were identified: the PACRG intronic variant rs6455893 on 6q26 (odds ratio [OR] = 1.62; 95% confidence interval [CI], 1.39-1.89; P = 6.98 × 10-10) and the missense variant rs3746804 (p.Pro267Leu) in the riboflavin transporter SLC52A3 on 20p13 (OR = 0.83; 95% CI, 0.79-0.88; P = 7.57 × 10-10). In addition, 18 genome-wide significant loci associated with quantitative OSA and objective sleep-related traits were identified, 5 of which exceeded the study-wide significance threshold. Rs3746804 was associated with elevated serum riboflavin concentrations, and the corresponding mutation in mice increased riboflavin concentrations, suggesting that this variant may facilitate riboflavin uptake and riboflavin-dependent physiological activity. Conclusions: We identified several novel genome-wide significant loci associated with OSA and objective sleep-related traits. Our findings provide insight into the genetic architecture of OSA and suggest that SLC52A3 might be a therapeutic target, whereas riboflavin might be a therapeutic agent.
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Estudo de Associação Genômica Ampla , Apneia Obstrutiva do Sono , Animais , Humanos , Camundongos , População do Leste Asiático , Proteínas de Membrana Transportadoras/genética , Proteínas dos Microfilamentos/genética , Chaperonas Moleculares/genética , Riboflavina , Sono , Apneia Obstrutiva do Sono/genéticaRESUMO
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.
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Apolipoproteínas/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/sangue , Apneia Obstrutiva do Sono/sangue , Triglicerídeos/sangue , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/complicações , Dislipidemias/complicações , Dislipidemias/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Polissonografia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/etiologiaRESUMO
BACKGROUND: Lipid metabolism disorder is recognized to be associated with obstructive sleep apnea (OSA); however, inconsistent results have been reported. The aim of this study was to evaluate the association between lipid profile and OSA with adjustments for multiple confounding factors. METHODS: In total, 2983 subjects were recruited from the Shanghai Sleep Health Study (SSHS) during 2007-2013. Data for overnight polysomnography (PSG) parameters, serum lipids, fasting blood glucose, insulin levels, and anthropometric measurements were collected. Multivariable logistic regression analyses were used to determine the correlation between lipid profile and OSA with adjustments for confounders including lipids, age, gender, Epworth sleepiness scale, body mass index, waist/hip ratio, glucose, insulin resistance, hypertension, and smoking. RESULTS: The prevalence of hyper total cholesterol (TC), hyper triglycerides, hypo high-density lipoprotein cholesterol, hyper low-density lipoprotein cholesterol (LDL-C), hyper apolipoprotein (apo) A-I, and hyper apoB differed significantly between the non-OSA and OSA patients. Without considering the interaction across different lipids, TC, LDL-C, and apoB were independently associated with OSA in primary multivariable logistic regression analyses; the odds ratios (ORs) and 95 % confidence intervals (CIs) were 1.262 (1.109-1.438), 1.432 (1.233-1.664), and 5.582 (2.643-11.787), respectively. However, only LDL-C (OR = 1.430, 95 % CI = 1.221-1.675) was found to be an independent risk factor for OSA in further multivariable logistic regression analyses. CONCLUSIONS: We demonstrated that patients with OSA had a higher percentage of dyslipidemia than subjects without OSA. Of the various components in serum lipid, only LDL-C was independently associated with OSA.
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LDL-Colesterol/sangue , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/diagnóstico , Adulto , Idoso , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , China , Estudos Transversais , Feminino , Humanos , Hipercolesterolemia/epidemiologia , Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Polissonografia , Apneia Obstrutiva do Sono/epidemiologia , Estatística como AssuntoRESUMO
INTRODUCTION: This study investigated the effect of sound therapy combined with drug therapy (SDT) on gap detection threshold and speech recognition scores in patients with sudden sensorineural hearing loss (SSNHL). METHODS: Patients with SSNHL were grouped randomly into SDT and drug therapy (DT) groups. All patients received standard drug treatment and patients in the SDT group additionally received sound stimulation for the affected ears for 6 days. Pure tone audiogram, speech recognition scores at normal and time-compressed rates under quiet and noisy conditions, and the gap detection threshold of the SDT and DT groups before treatment and on day 6 and 30 after treatment were compared. RESULTS: There were 20 patients in the SDT group and 24 in the DT group. The pure tone thresholds of affected ears were significantly lower in the SDT group on day 6 after treatment than those in the DT group at 125 and 250 Hz. Significantly lower gap detection thresholds and higher speech recognition scores under noisy conditions were observed at the normal and time-compressed rates in the SDT group than those in the DT group on day 6 and 30 after treatment. Significant correlations were observed between the gap thresholds and speech recognition scores in a noisy environment at normal and time-compressed rates on day 6 and 30. CONCLUSIONS: SDT may improve the recovery of hearing abilities, such as the gap in noise thresholds and speech recognition in noise, in the case of SSNHL. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17012262.
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Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Humanos , Audiometria de Tons Puros , Limiar Auditivo/fisiologia , Audição , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Súbita/tratamento farmacológico , Estudos ProspectivosRESUMO
INTRODUCTION: We aimed to retrospectively analyze the therapeutic outcomes of using glucocorticoid combined with a vasodilator, breviscapine, versus glucocorticoid alone in patients with sudden sensorineural hearing loss (SSNHL) and to explore the impact on different audiometric curves. METHODS: Data from 154 patients were collected between January 2017 and December 2018. Patients received treatments of either glucocorticoid combined with breviscapine (GC + Bre) or glucocorticoid alone (GC). These two groups were stratified into low frequencies SSNHL (LF-SSNHL), high frequencies SSNHL (HF-SSNHL), all frequencies SSNHL (AF-SSNHL), and total deafness SSNHL (TD-SSNHL) subgroups according to their corresponding audiograms. The hearing level was evaluated by pure tone audiometry, and hearing recovery was calculated by comparing the pure tone average (PTA) at pretreatment and 4 weeks after therapy. RESULTS: Hearing recovery was significantly greater for GC + Bre than GC-only treatment in the AF-SSNHL and TD-SSNHL subgroups (P < 0.05) and to a lesser extent in the LF-SSNHL and HF-SSNHL subgroups (P > 0.05). Logistic regression analysis also showed a favorable outcome for SSNHL in the GC + Bre group (odds ratio 2.848, P < 0.05). CONCLUSION: Treating SSNHL using glucocorticoid combined with breviscapine could be more beneficial than using glucocorticoid alone, especially for patients with AF-SSNHL and TD-SSNHL. TRIAL REGISTRATION NUMBER: ChiCTR18000170072.
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Flavonoides/uso terapêutico , Glucocorticoides/uso terapêutico , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Súbita/tratamento farmacológico , Adulto , Audiometria de Tons Puros , Quimioterapia Combinada , Feminino , Audição/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Excessive daytime sleepiness is a common symptom in obstructive sleep apnea (OSA). Previous studies have showed that excessive daytime sleepiness is associated with some individual components of metabolic syndrome. We performed a large cross-sectional study to explore the relationship between excessive daytime sleepiness and metabolic syndrome in male OSA patients. METHODS: A total of 2241 suspected male OSA patients were consecutively recruited from 2007 to 2013. Subjective daytime sleepiness was assessed using the Epworth sleepiness scale. Anthropometric, metabolic, and polysomnographic parameters were measured. Metabolic score was used to evaluate the severity of metabolic syndrome. RESULTS: Among the male OSA patients, most metabolic parameters varied by excessive daytime sleepiness. In the severe group, male OSA patients with excessive daytime sleepiness were more obese, with higher blood pressure, more severe insulin resistance and dyslipidemia than non-sleepy patients. Patients with metabolic syndrome also had a higher prevalence of excessive daytime sleepiness and scored higher on the Epworth sleepiness scale. Excessive daytime sleepiness was independently associated with an increased risk of metabolic syndrome (odds ratio =1.242, 95% confidence interval: 1.019-1.512). No substantial interaction was observed between excessive daytime sleepiness and OSA/ obesity. CONCLUSIONS: Excessive daytime sleepiness was related to metabolic disorders and independently associated with an increased risk of metabolic syndrome in men with OSA. Excessive daytime sleepiness should be taken into consideration for OSA patients, as it may be a simple and useful clinical indicator for evaluating the risk of metabolic syndrome.
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Obstructive sleep apnea (OSA) is associated with dyslipidemia. However, no study has focused on dyslipidemia in women with OSA. The aim of this study was to determine the prevalence and risk factors for dyslipidemia in women with OSA. Between 2007 and 2013, 570 eligible female patients with suspected OSA were consecutively recruited. The analyzed data consisted of polysomnography parameters, biochemical indicators, and anthropometric measurements. Serum lipid levels and dyslipidemia were compared. Binary logistic regression and multivariate linear regression models were used to determine the independent risk factors influencing serum lipids. After multivariate adjustment, there were essentially no major differences in serum lipid levels among patients with no to mild, moderate, and severe OSA nor did serum lipid levels change with OSA severity. Dyslipidemia in total cholesterol, triglycerides, low-density lipoprotein cholesterol, apolipoproteins(apo) B and apoE increased with OSA severity, but only in non-obese subjects and those <55 years of age. Age, body mass index, waist to hip ratio, glucose and insulin were major risk factors for most serum lipids after multivariate adjustments. Our results indicate that, in women with OSA, age, obesity/central obesity, and insulin resistance are major determinants of dyslipidemia.
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Dislipidemias/sangue , Apneia Obstrutiva do Sono/sangue , Adulto , Apolipoproteínas/sangue , Biomarcadores/sangue , Índice de Massa Corporal , Colesterol/sangue , Dislipidemias/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/complicações , Triglicerídeos/sangueRESUMO
BACKGROUND: To explore the feasibility, the efficacy, and the mechanism of mandibular advancement devices (MAD) in the treatment of persistent sleep apnea after surgery. METHODS: Nineteen patients who failed uvulopalatopharyngoplasty (UPPP) or UPPP plus genioglossus advancement and hyoid myotomy (GAHM) were given a non-adjustable MAD for treatment. All patients had polysomnography (PSG) at least 6 months post-UPPP with and without the MAD. Seventeen patients had computed tomography (CT) examinations. RESULTS: After the application of MAD, the apnea hypopnea index (AHI) decreased significantly from 41.2 ± 13.1/h to 10.1 ± 5.6/h in the responder group. The response rate was 57.9 % (11/19). During sleep apnea/hypopnea acquired from sedated sleep, the cross-sectional area and anterior-posterior and lateral diameters of the velopharynx enlarged significantly from 4.2 ± 6.0 mm2 to 17.5 ± 15.3 mm2, 1.9 ± 2.3 mm to 6.5 ± 4.1 mm, and 1.1 ± 1.3 mm to 2.6 ± 2.1 mm, respectively (P < 0.01) in the responder group with MAD. The velopharyngeal collapsibility also decreased significantly from 83.3 ± 21.8 % to 46.5 ± 27.1 %. The glossopharyngeal collapsibility decreased from 39.8 ± 39.1 % to -22.9 ± 73.2 % (P < 0.05). CONCLUSION: MAD can be an effective alternative treatment for patients with moderate and severe OSAHS after surgery. The principal mechanisms underlying the effect of MAD are expansion of the lateral diameter of the velopharynx, the enlargement of the velopharyngeal area, the reduction of velopharyngeal and glossopharyngeal collapsibility, and the stabilization of the upper airway.
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Avanço Mandibular/métodos , Síndromes da Apneia do Sono/cirurgia , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Falha de Tratamento , Resultado do TratamentoRESUMO
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.
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Dislipidemias/epidemiologia , Dislipidemias/etiologia , Apneia Obstrutiva do Sono/complicações , Privação do Sono/complicações , Adulto , Análise Química do Sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Privação do Sono/etiologiaRESUMO
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.
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Modelos Biológicos , Oxigênio/sangue , Apneia Obstrutiva do Sono , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/patologia , Apneia Obstrutiva do Sono/fisiopatologiaRESUMO
OBJECTIVE: To explore effectiveness of maxillomandibular advancement (MMA) in the treatment of obstructive sleep apnea/hypopnea syndrome (OSAHS). METHODS: MMA was performed in 10 OSAHS patients with mandibular dysplasia diagnosed by mandibular protrusion angle (SNB) < 75 degrees and a posterior airway space (PAS) < 11 mm. Six patients had uvulopalatopharyngoplasty (UPPP) also. Six patients had over 6 months postoperative follow up. RESULTS: The blood loss was about 250-600 ml in the operation, and the serious complications didn't happen. The patients were satisfied with the postoperative facial change. Based on success criteria of 2009, of 5 patients showed highly responsive result and 1 patient was responsive (valid). rate was 83% and the responsive rate 100%. The snoring loudness score and Epworth sleepy score were reduced from preoperative 8 (6-10) and 15 (11-24) to postoperative 2 (0-4) and 5 (1-8). AHI was reduced from preoperative 52.2 (23.7-83.8) to postoperative 12.6 (7.6-31.8), lowest mean oxygen saturation increased from 0.64 (0.57-0.83) to 0.82 (0.78-0.93). Percentage of time with oxyhemoglobin saturation below 0.90 (CT90) reduced from 21.0% (12.0%-37.2%) to 2.0% (0%-8.0%). CONCLUSIONS: MMA is effective for the OSAHS patients with mandibular dysplasia.