Disturbed sleep and cardiovascular outcomes in World Trade Center Responders

世贸中心急救人员的睡眠障碍和心血管结果

• 批准号: 10749277
• 负责人: INDU A AYAPPA
• 金额: $ 50万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10749277
• 关键词: Disturbed; sleep; cardiovascular; outcomes; World

PROJECT SUMMARY Poor sleep quality is a very common symptom in the WTC General responder cohort (WTCGRC). Comorbid conditions including obstructive sleep apnea (OSA) can contribute to poor sleep quality and daytime sleepiness and may affect cardiovascular health similar to the general population. The consequences of untreated OSA include disturbed sleep, excessive daytime sleepiness, and an increased risk for major adverse cardiovascular events (MACE). In OSA patients, plasma biomarkers associated with MACE such as highly sensitive C-reactive protein (hs-CRP) are elevated. We have previously shown in the WTC-CHEST study (NCT01466218) that presence or high risk of OSA is associated with elevated levels of hs-CRP. In the current proposal, we will evaluate whether CV risk in these WTC-CHEST OSA subjects is similar to the general population, and if hs-CRP is a predictor of MACE. Three distinct clinical phenotypes of OSA have been described: 1) a sleepy phenotype (2) a disturbed sleep phenotype and 3) a minimally symptomatic phenotype. WTCGRC with OSA has almost a 50% prevalence of the disturbed sleep phenotype in contrast to other populations with OSA, where the sleepy phenotype is predominant. The pathophysiology of OSA is complex and multifactorial and has been described using polysomnographically (PSG) determined endotypic traits: impaired upper airway anatomy, low arousal threshold, high ventilatory loop gain and altered neuro-muscular control of upper airway muscles. Our preliminary data shows that unlike in other populations, low arousal threshold endotype is the primary physiological endotype that leads to OSA. However, the relationship between endotypes and clinical phenotypes are unknown. In this proposal, we will determine whether the low arousal threshold physiological endotype is associated with the “Disturbed Sleep” clinical phenotype. We will also examine the association between a recently developed PSG index, the odds ratio product (ORP-9) that measures excessive overnight wakefulness and physiological endotypes and clinical phenotypes as a biomarker of disturbed sleep. There have been no studies determining the association of clinical phenotypes of OSA and plasma hs- CRP. Therefore, the third aim of this proposal will determine whether the “Disturbed Sleep” clinical phenotype of OSA in the WTCGRC is associated with increases in plasma hs-CRP. Finally, we will determine the relationship of hs-CRP with poor sleep quality in subjects without OSA but with other comorbidities in the WTCGRC. The studies proposed in this project will significantly advance our understanding of the consequences of poor sleep in the WTCGRC and will inform future screening recommendations for these participants.

项目概要 睡眠质量差是 WTC 一般反应者队列 (WTCGRC) 中非常常见的症​​状。 阻塞性睡眠呼吸暂停 (OSA) 等共病可能导致睡眠质量和白天不佳 与一般人群相似，嗜睡可能会影响心血管健康。 未经治疗的 OSA 包括睡眠不安、白天过度嗜睡以及严重不良反应的风险增加 心血管事件 (MACE) 在 OSA 患者中，与 MACE 相关的血浆生物标志物例如高度升高。 我们之前在 WTC-CHEST 研究中表明，敏感 C 反应蛋白 (hs-CRP) 会升高。 (NCT01466218) 目前，OSA 的存在或高风险与 hs-CRP 水平升高有关。 提案中，我们将评估这些 WTC-CHEST OSA 受试者的 CV 风险是否与一般受试者相似 人群，以及 hs-CRP 是否是 MACE 的预测因子。 已经描述了 OSA 的三种不同的临床表型：1) 困倦表型 (2) 心烦意乱 睡眠表型和 3) 伴有 OSA 的轻微症状表型的患病率几乎为 50%。 与其他患有 OSA 的人群相比，睡眠障碍的表型有所不同，其中困倦的表型是 占主导地位。 OSA 的病理生理学是复杂且多因素的，已被描述为 多导睡眠图 (PSG) 确定的内型特征：上呼吸道解剖结构受损、觉醒阈值低、 我们的初步数据显示，通气环路增益较高，神经肌肉控制也发生了改变。 表明与其他人群不同，低唤醒阈值内型是主要的生理内型 然而，内型和临床表型之间的关系尚不清楚。 建议，我们将确定低唤醒阈值生理内型是否与 我们还将研究最近开发的“睡眠障碍”临床表型之间的关联。 PSG 指数，即衡量夜间过度清醒和生理状况的比值比产品 (ORP-9) 内型和临床表型作为睡眠障碍的生物标志物。 尚无研究确定 OSA 临床表型与血浆 hs- 之间的关联 因此，该提案的第三个目标将决定“睡眠障碍”是否临床。 WTCGRC 中 OSA 的表型与血浆 hs-CRP 的增加有关。 确定 hs-CRP 与无 OSA 但患有其他合并症的受试者睡眠质量差之间的关系 WTCGRC 中提出的研究将极大地增进我们对这一问题的理解。 WTCGRC 睡眠不良的后果，并将为未来的筛查建议提供依据 参与者。