Etiology of Sleep Apnea-Related Hyperaldosteronism

睡眠呼吸暂停相关醛固酮增多症的病因学

• 批准号: 6719702
• 负责人: DAVID A CALHOUN
• 金额: $ 28.84万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-15 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6719702
• 关键词: aldosterone; angiotensin /renin /aldosterone hypertension; clinical research; disease /disorder etiology; electrocardiography; human subject; human therapy evaluation; hyperaldosteronism; oxygen consumption; polysomnography; respiratory therapy; sleep apnea; urinalysis

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) and hypertension are highly associated, particularly among subjects with resistant hypertension. The mechanism, however, by which the two disorders are related, remains obscure. In evaluating subjects with resistant hypertension, we observed that a large percentage subjects diagnosed with primary hyperaldosteronism (PA) were also being diagnosed with OSA. To further examine this relationship, we prospectively determined plasma renin activity and 24-hr urine aldosterone excretion in 114 subjects with resistant hypertension. In addition, subjects completed the Berlin Questionnaire, a validated instrument for identifying subjects at high risk of having OSA. Subjects at high risk of having OSA had lower plasma renin activity, significantly greater 24-hr urinary aldosterone excretion and were 2 times more likely to have been diagnosed with PA than subjects at low-risk of having OSA. Based on the strength of these results, the overall goal of the current proposal is to test the hypothesis that OSA contributes to the development of resistant hypertension by inducing hyperaldosteronism. Specific Aim 1: To test the hypothesis that aldosterone excretion and obstructive sleep apnea (OSA) are positively related in subjects with resistant hypertension, we will a) correlate 24-hr urinary aldosterone excretion, respiratory disturbance index and nocturnal oxygen saturation as determined during full-night polysomnographic evaluation in 190 consecutive subjects referred to UAB for resistant hypertension; and b) compare the prevalence of OSA in hypertensive subjects with confirmed primary hyperaldosteronism (PA) versus non-PA control subjects. Specific Aim 2: To test the hypothesis that obstructive sleep apnea stimulates aldosterone excretion, we will determine the effects of chronic OSA therapy (i.e., continuous positive airway pressure) on 24-hr urinary aldosterone excretion and known and proposed stimuli of aldosterone excretion (renin, ACTH, atrial natriuretic peptide, norepinephrine and endothelin-1) in 120 consecutive hypertensive subjects with newly diagnosed OSA. Subjects found not to have OSA will serve as controls.

描述（由申请人提供）：阻塞性睡眠呼吸暂停（OSA）和高血压高度相关，尤其是在具有抗高血压的受试者中。 然而，两种疾病相关的机制仍然晦涩难懂。 在评估具有耐药性高血压的受试者时，我们观察到，诊断为原发性甲状腺醛固醇（PA）的大部分受试者也被诊断出患有OSA。 为了进一步研究这种关系，我们前瞻性地确定了114名患有耐药性高血压的受试者中的血浆肾素活性和24小时尿醛酮的排泄。 此外，受试者还完成了柏林问卷，这是一种经过验证的工具，用于识别具有OSA高风险的受试者。 OSA高风险的受试者的血浆肾素活性较低，24小时的尿醛酮排泄明显高，被诊断为PA的可能性要高出2倍，是OSA低风险的受试者的2倍。 基于这些结果的强度，当前提案的总体目标是检验OSA通过诱导高醛溶剂促进耐药性高血压的假设。 Specific Aim 1: To test the hypothesis that aldosterone excretion and obstructive sleep apnea (OSA) are positively related in subjects with resistant hypertension, we will a) correlate 24-hr urinary aldosterone excretion, respiratory disturbance index and nocturnal oxygen saturation as determined during full-night polysomnographic evaluation in 190 consecutive subjects referred to UAB for resistant hypertension; b）将高血压受试者中OSA与确认的原发性甲醛体主义（PA）与非PA对照受试者进行比较。 Specific Aim 2: To test the hypothesis that obstructive sleep apnea stimulates aldosterone excretion, we will determine the effects of chronic OSA therapy (i.e., continuous positive airway pressure) on 24-hr urinary aldosterone excretion and known and proposed stimuli of aldosterone excretion (renin, ACTH, atrial natriuretic peptide, norepinephrine and endothelin-1)连续120名具有新诊断的OSA的高血压受试者。 发现没有OSA的受试者将用作控制。