Reversibility of Cardiovascular Injury with CPAP Use: Mechanisms Involved

使用 CPAP 治疗心血管损伤的可逆性：涉及的机制

• 批准号: 8471749
• 负责人: CLAUDIA E KORCARZ
• 金额: $ 14.54万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8471749
• 关键词: Address; Adult; Affect; Age; Apnea; Blood Pressure; Blood Vessels; Blood flow; Body Weight Changes; Cardiac; Cardiovascular Diseases; Centenarian; Chronic; Confounding Factors (Epidemiology); Continuous Positive Airway Pressure; Coronary; Coronary Arteriosclerosis; Coronary artery; Country; Diagnosis; Diastolic blood pressure; Early Diagnosis; Endothelin-1; Endothelium; Epidemic; Ethnic Origin; Event; Excess Mortality; Exposure to; Female; Functional disorder; Goals; Grant; High Prevalence; Hour; Hypertension; Hypoxia; Image; Individual; Inflammatory; Laboratories; Lead; Link; Measures; Mediating; Obesity; Obstructive Sleep Apnea; Odds Ratio; Oxidative Stress; Patients; Peripheral; Peripheral Resistance; Physiologic pulse; Physiological; Prevalence; Race; Regulation; Reperfusion Therapy; Reporting; Research; Research Personnel; Research Project Grants; Research Proposals; Research Training; Risk; Risk Factors; Severities; Sleep Disorders; Study Subject; Suggestion; Testing; Time; Training; Vasodilation; Wakefulness; Withdrawal; arterial stiffness; base; brachial artery; cardiovascular disorder risk; cardiovascular injury; career; design; experience; human old age (65+); improved; improved functioning; indexing; male; middle age; mortality; multimodality; patient oriented research; pressure; public health relevance; research study; response; sex; vasoconstriction

DESCRIPTION (provided by applicant): The prevalence of Obstructive Sleep Apnea (OSA) in middle-aged adults is at least 4% in males and 2% in females and will probably increase with the obesity epidemic in this country. Individuals with OSA are at increased risk for fatal and non-fatal cardiovascular disease (CVD) events. Treatment with continuous positive airway pressure (CPAP) may reduce CVD risk; however, the mechanisms, time course, and durability of its benefit are not known. These are especially important issues since patients with OSA often are not compliant or are intermittently compliant with CPAP therapy. This research proposal describes our plans to evaluate the time course and magnitude of the effects of CPAP therapy on two measures of arterial function, namely arterial stiffness and endothelium-dependent vasodilation. This study has four specific aims that address four inter- related hypotheses: To determine if (i) CPAP therapy reduces carotid-to-femoral pulse wave velocity, a marker of aortic stiffness, (ii) CPAP therapy improves flow-mediated vasodilation of the brachial artery, a marker of endothelial function, (iii) the time course of changes in arterial function observed with CPAP therapy and their duration after cessation of therapy, and (iv) if coronary artery flow regulation observed in patients with OSA improves after CPAP therapy. Multimodality non-invasive cardiac and vascular imaging will be used to prospectively investigate these aims in 130 CPAP-naive adults (21-45 years old) with moderate to severe OSA, before starting CPAP therapy, after 4 and 12 weeks, and then 712 days after withdrawal. This study will have adequate power to adjust for possible confounders such as degree of obesity, sleepiness, sex, race, and CPAP compliance. This training grant and research study will provide the applicant with training and research experiences to permit her to become an independent investigator that designs and conducts rigorous patient- oriented research projects related to sleep disorders and CVD. Dr. Korcarz's long-term career goal is to be an independent investigator that performs cutting edge physiological research related to sleep disorders and cardiovascular disease risk.

描述(由申请人提供)： 阻塞性睡眠呼吸暂停(OSA)在中年人中的患病率男性至少为4%，女性为2%，而且随着肥胖在这个国家的流行，OSA的患病率可能会增加。OSA患者发生致命性和非致命性心血管疾病(CVD)事件的风险增加。持续气道正压(CPAP)治疗可能会降低心血管疾病的风险；然而，其益处的机制、时程和持久性尚不清楚。这些都是特别重要的问题，因为阻塞性睡眠呼吸暂停综合征患者经常不依从或间歇性地依从性接受CPAP治疗。这项研究计划评估CPAP治疗对动脉功能的两项指标，即动脉僵硬和内皮依赖性血管扩张的影响的时间进程和程度。这项研究有四个具体目标，旨在解决四个相互关联的假设：确定(I)CPAP治疗是否降低颈动脉到股动脉的脉搏波速度，(Ii)CPAP治疗改善血流介导的臂动脉血管扩张，(Iii)CPAP治疗观察到的动脉功能变化的时间进程及其停止治疗后的持续时间，以及(Iv)CPAP治疗后观察到的OSA患者的冠状动脉血流调节是否改善。在CPAP治疗前、治疗后4周、12周、停药后712天，对130例未经CPAP治疗的中重度阻塞性睡眠呼吸暂停患者(21~45岁)进行多模式无创性心脏血管成像前瞻性研究。这项研究将有足够的能力调整可能的混杂因素，如肥胖程度、嗜睡、性别、种族和CPAP依从性。这项培训资助和研究研究将为申请者提供培训和研究经验，使她能够成为一名独立调查员，设计和实施与睡眠障碍和心血管疾病有关的严格的以患者为中心的研究项目。科尔卡兹博士的长期职业目标是成为一名独立研究员，进行与睡眠障碍和心血管疾病风险相关的尖端生理学研究。