Responses to CPAP treatment in obese and lean sleep apnea patients

肥胖和瘦睡眠呼吸暂停患者对 CPAP 治疗的反应

• 批准号: 7613229
• 负责人: SAMUEL T. KUNA
• 金额: $ 28.9万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7613229
• 关键词: Abdomen; Accounting; Address; Adipose tissue; Adult; Aftercare; Area; Arteries; Arts; Atherosclerosis; Biological Markers; Blood Pressure; Blood Vessels; Body Weight; Body mass index; Cardiovascular Diseases; Cardiovascular system; Central obesity; Chronic; Clinical; Clinical Management; Conflict (Psychology); Continuous Positive Airway Pressure; Data; Disease; Dose; Enrollment; Ensure; Event; Excretory function; Fatty acid glycerol esters; Future; Goals; Health; Hour; Hypertension; Individual; Inflammation; Inflammatory; Insulin Resistance; Interleukin-10; Interleukin-6; Intervention Studies; Isoprostanes; Left Ventricular Mass; Magnetic Resonance Imaging; Measurement; Measures; Mediator of activation protein; Metabolic; Methods; Modeling; Newly Diagnosed; Norepinephrine; Obesity; Obstructive Sleep Apnea; Outcome; Oxidative Stress; Participant; Patients; Physiologic pulse; Plasma; Population; Process; Protocols documentation; Randomized Controlled Clinical Trials; Reaction Time; Relative (related person); Research; Residual state; Resolution; Risk; Risk Factors; Role; Sample Size; Screening procedure; Serum; Severities; Sleep; Sleep Apnea Syndromes; Source; Stratification; Sympathetic Nervous System; Testing; Thick; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Visceral; base; cardiovascular risk factor; comparison group; diabetes risk; effective therapy; endophenotype; experience; falls; improved; indexing; intima media; isoprostaglandin F2alpha type-III; patient population; pressure; response; urinary; vigilance; waist circumference

Obesity and obstructive sleep apnea (OSA) are independent risk factors for insulin resistance, systemic hypertension and cardiovascular disease. Both disorders are associated with increased sympathetic and inflammatory activity, and increased oxidative stress, presumed mediators of their shared clinical consequences. Due to conflicting results of previous intervention studies treating OSA patients with CPAP, we still do not know if treatment of obese OSA patients has a substantial benefit on these risk factors. In Aim 1, to determine the effects of obesity on the response to CPAP treatment in OSA patients, we will compare responses in daytime sleepiness, insulin resistance, and arterial blood pressure following CPAP treatment in obese and lean OSA patients, stratified by the amount of abdominal visceral adipose tissue, a fat depot associated with increased sympathetic activity, inflammation, and oxidative stress, and a more powerful predictor than BMI of adverse cardiovascular and metabolic outcomes. Aim 2 will determine the effect of CPAP treatment in these two groups on sympathetic activity, and inflammatory and oxidative stress biomarkers. Our overall hypothesis is that, adjusting for OSA severity and obtaining normative data from non-OSA subjects with comparable amounts of visceral adiposity (Aim 3), the two OSA groups will have comparable improvements in daytime sleepiness, but that the cardiovascular and metabolic improvements following CPAP therapy will be decreased in OSA patients with increased visceral adipose tissue. We anticipate that although there will be a greater absolute change in markers of sympathetic activity, inflammation and oxidative stress in obese compared to lean OSA patients following CPAP treatment, the levels will still be abnormally high in the obese patients resulting in the decreased improvements in insulin resistance, arterial blood pressure, and vascular health in obese versus lean OSA patients. Relevance: Obese patients are at increased risk of developing sleep apnea. Both obesity and sleep apnea are felt to increase the risk of diabetes, hypertension, and cardiovascular disease. The proposed research will begin to determine if treating obese patients with sleep apnea helps to reduce these risks. If the beneficial effects of CPAP treatment are reduced in obese compared to lean patients with sleep apnea, then treatment of sleep apnea in obese patients needs to be combined with effective management of their obesity.

肥胖和阻塞性睡眠呼吸暂停（OSA）是胰岛素抵抗、全身性和全身性疾病的独立危险因素。 高血压和心血管疾病。这两种疾病都与交感神经和 炎症活动和氧化应激增加，推测它们共同的临床 后果由于以前用CPAP治疗OSA患者的干预研究的结果相互矛盾， 我们仍然不知道肥胖OSA患者的治疗是否对这些危险因素有实质性的益处。在 目的1，确定肥胖对OSA患者CPAP治疗反应的影响，我们将 比较CPAP治疗后白天嗜睡、胰岛素抵抗和动脉血压的反应 肥胖和瘦型OSA患者的治疗，按腹部内脏脂肪组织的量分层， 与交感神经活动增加、炎症和氧化应激相关的脂肪储存，以及更多的 比BMI更强有力的心血管和代谢不良结果的预测因子。目标2将决定 CPAP治疗对两组患者交感神经活性、炎症和氧化应激的影响 生物标志物。我们的总体假设是，调整OSA的严重程度，并从 对于内脏脂肪量相当的非OSA受试者（目标3），两个OSA组将具有 白天嗜睡的改善，但心血管和代谢的改善， 在内脏脂肪组织增加的OSA患者中，CPAP治疗后的收缩压将降低。我们 预计尽管交感神经活动标记物的绝对变化会更大， 与瘦型OSA患者相比，CPAP治疗后肥胖患者的炎症和氧化应激反应， 肥胖患者的胰岛素水平仍然异常高， 肥胖与瘦型OSA患者的阻力、动脉血压和血管健康。相关性： 肥胖患者患睡眠呼吸暂停的风险增加。肥胖和睡眠呼吸暂停都被认为是 增加患糖尿病、高血压和心血管疾病的风险。拟议的研究将开始 以确定治疗患有睡眠呼吸暂停的肥胖患者是否有助于降低这些风险。如果有益的影响 的CPAP治疗减少肥胖相比，瘦患者的睡眠呼吸暂停，然后治疗 肥胖患者的睡眠呼吸暂停需要与其肥胖的有效管理相结合。