- 作者列表："Skirko JR","James KT","Garrison LP","Weaver EM
Importance:With the increasing emphasis on economic evaluations, there is a need for additional methods of measuring patient utility in the obstructive sleep apnea population. Objective:To develop and validate a utility scoring algorithm for a sleep apnea-specific quality-of-life instrument. Design, Setting, and Participants:Development and validation were conducted at 2 tertiary referral sleep centers and associated sleep clinics and included patients with newly diagnosed obstructive sleep apnea from a randomized clinical trial and an associated observational cohort study. Baseline participants were randomly divided into a model development group (60%) and a cross-validation group (40%). Main Outcomes and Measures:Utility scoring of the Symptoms of Nocturnal Obstruction and Related Events (SNORE-25) was mapped from the SF-6D utility index through multiple linear regression in the development sample using the Akaike information criterion to determine the best model. Results:A total of 500 participants (development, n = 300; validation, n = 200) were enrolled; the analyzed sample of 500 participants included 295 men (59%), and the mean (SD) age was 48.6 (12.8) years, with a range of 18 to 90 years. The mean (SD) SF-6D utility among participants with untreated sleep apnea was 0.61 (0.08; range, 0.40-0.85) with similar utility across sleep apnea severity groups. The best-fit model (the SNORE Utility Index) was the natural log conversion of the instrument subscales (r2 = 0.32 in the development sample). The SNORE Utility Index retained this association within the validation sample (r2 = 0.33). Conclusions and Relevance:The SNORE Utility Index provides a validated, disease-specific, preference-weighted utility instrument that can be used in future studies of patients with obstructive sleep apnea.
重要性: 随着对经济评价的日益重视，需要额外的方法来测量阻塞性睡眠呼吸暂停人群中的患者效用。 目的: 开发并验证睡眠呼吸暂停特异性生活质量仪的效用评分算法。 设计、设置和参与者: 在 2 个三级转诊睡眠中心和相关睡眠诊所进行了开发和验证，纳入了来自一项随机临床试验和相关观察性队列研究的新诊断阻塞性睡眠呼吸暂停患者。基线参与者被随机分为模型开发组 (60%) 和交叉验证组 (40%)。 主要结局和措施: 夜间梗阻症状和相关事件的效用评分 (打鼾-25) 利用 Akaike 信息准则在开发样本中通过多元线性回归从 SF-6D 效用指数进行映射，确定最佳模型。 结果: 共纳入 500 例参与者 (发育，n = 300; 验证，n = 200); 500 例参与者的分析样本包括 295 例男性 (59%), 平均 (SD) 年龄为 48.6 (12.8) 岁，范围为 18 ~ 90 岁。未经治疗的睡眠呼吸暂停参与者的平均 (SD) SF-6D 效用为 0.61 (0.08; 范围，0.40-0.85)，在睡眠呼吸暂停严重程度组中的效用相似。最佳拟合模型 (鼾声效用指数) 是仪器分量表的自然对数转换 (开发样本中 r2 = 0.32)。鼾声效用指数在验证样本中保留了这种相关性 (r2 = 0.33)。 结论和相关性: SNORE 效用指数提供了一个经过验证的、疾病特异性的、偏好加权的效用指数，可用于未来阻塞性睡眠呼吸暂停患者的研究。
METHODS:OBJECTIVE:The functions and molecular regulatory mechanisms of miR-193a-3p in cardiac injury induced by obstructive sleep apnea (OSA) are poorly understood. This study aimed to explore the role of miR-193a-3p in intermittent hypoxia(IH)-induced human umbilical vein endothelial cells (HUVECs) injury. RESULTS:In this study, we found that IH significantly decreased viability but enhanced cell apoptosis. Concurrently, the miR-193a-3p expression level was increased in HUVECs after IH. Subsequent experiments showed that IH-induced injury was ameliorated through miR-193a-3p silence. Fas apoptotic inhibitory molecule 2 (FAIM2) was predicted by bioinformatics analysis and further identified as a direct target gene of miR-193a-3p. Interestingly, the effect of miR-193a-3p inhibition under IH could be reversed by down-regulating FAIM2 expression. CONCLUSION:In conclusion, our study first revealed that miR-193a-3p inhibition could protect HUVECs against intermittent hypoxia-induced damage by negatively regulating FAIM2. These findings could advance our understanding of the underlying mechanisms for OSA-related cardiac injury. METHODS:We exposed HUVECs to IH condition; the expression levels of miR-193a-3p were detected by RT-qPCR. Cell viability, and the expressions of apoptosis-associated proteins were examined via CCK-8, and western blotting, respectively. Target genes of miR-193a-3p were confirmed by dual-luciferase reporter assay.
METHODS:RATIONALE:Obstructive sleep apnea-hypopnea syndrome, a sleep breathing disorder in which chronic intermittent hypoxia (CIH) is the primary pathology, is associated with multiple cardiovascular diseases. However, whether and how CIH may affect cardiac remodeling following myocardial infarction (MI) remains unknown. OBJECTIVE:To determine whether CIH exposure at different periods of MI may exacerbate post-MI heart failure and to identify the mechanisms underlying CIH-exacerbated post-MI remodeling. METHODS AND RESULTS:Adult male mice were subjected to MI (4 weeks) with and without CIH (4 or 8 weeks). CIH before MI (CIH+MI) had no significant effect on post-MI remodeling. However, double CIH exposure (CIH+MI+CIH) or CIH only during the MI period (MI+CIH) significantly exacerbated pathological remodeling and reduced survival rate. Mechanistically, CIH activated TGF-β (tumor growth factor-β)/Smad (homologs of both the Drosophila protein MAD and the C. elegans protein SMA) signaling and enhanced cardiac epithelial to mesenchymal transition, markedly increasing post-MI cardiac fibrosis. Transcriptome analysis revealed that, among 15 genes significantly downregulated (MI+CIH versus MI), Ctrp9 (a novel cardioprotective cardiokine) was one of the most significantly inhibited genes. Real-time polymerase chain reaction/Western analysis confirmed that cardiomyocyte CTRP9 expression was significantly reduced in MI+CIH mice. RNA-sequencing, real-time polymerase chain reaction, and dual-luciferase reporter assays identified that microRNA-214-3p is a novel Ctrp9 targeting miRNA. Its upregulation is responsible for Ctrp9 gene suppression in MI+CIH. Finally, AAV9 (adeno-associated virus 9)-mediated cardiac-specific CTRP9 overexpression or rCTRP9 (recombinated CTRP9) administration inhibited TGF-β/Smad and Wnt/β-catenin pathways, attenuated interstitial fibrosis, improved cardiac function, and enhanced survival rate in MI+CIH animals. CONCLUSIONS:This study provides the first evidence that MI+CIH upregulates miR-214-3p, suppresses cardiac CTRP9 (C1q tumor necrosis factor-related protein-9) expression, and exacerbates cardiac remodeling, suggesting that CTRP9 may be a novel therapeutic target against pathological remodeling in MI patients with obstructive sleep apnea-hypopnea syndrome.
METHODS:STUDY OBJECTIVES:Sleep apnea (SA) is prevalent among patients with coronary artery disease (CAD) and increases cardiovascular risk. A previous study showed that 1 month of cardiac rehabilitation (CR) reduced severity of SA in patients with CAD by reducing fluid accumulation in the legs during the day and the amount of fluid shifting rostrally into the neck overnight. The aim of this study was to evaluate whether CR will lead to longer-term attenuation of SA in patients with CAD. METHODS:Fifteen patients with CAD and SA who had participated in a 1-month randomized trial of the effects of exercise training on SA were followed up until they completed 6 months of CR (age: 65 ± 10 years; body mass index: 27.0 ± 3.9 kg/m²; apnea-hypopnea index [AHI]: 39.0 ± 16.7). The AHI was evaluated at baseline by polysomnography and then at 6 months by portable monitoring at home. Cardiorespiratory fitness (VO2peak) was evaluated via a graded cardiopulmonary exercise test at baseline and 6 months later. The 6-month CR program included once weekly, 90-minute, in-facility exercise sessions, and 4 days per week at-home exercise sessions. RESULTS:After 6 months of CR, there was a 54% reduction in the AHI (30.5 ± 15.2 to 14.1 ± 7.5, P < .001). Body mass index remained unchanged, but VO2peak increased by 27% (20.0 ± 6.1 to 26.0 ± 8.9 mL/kg/min, P = .04). CONCLUSIONS:Participation in CR is associated with a significant long-term decrease in the severity of SA. This finding suggests that attenuation of SA by exercise could be a mechanism underlying reduced mortality following participation in CR in patients with CAD and SA. CLINICAL TRIAL REGISTRATION:This study is registered at www.controlled-trials.com with identifier number ISRCTN50108373.