Sleep Restriction and Augmented Vascular Risk in Prehypertension

睡眠限制与高血压前期血管风险增加

• 批准号: 9052213
• 负责人: Virend K Somers
• 金额: $ 59.56万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9052213
• 关键词: Acclimatization; Address; Adipocytes; Adipose tissue; Adult; Affect; American; Area; Attenuated; Biopsy; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Chronic; Collaborations; Comorbidity; Complement; Coronary Arteriosclerosis; Cross-Over Studies; Data; Development; Epidemic; Etiology; Evaluation; Experimental Models; General Population; Goals; Health; Heart Diseases; Hour; Human; Hygiene; Hypertension; Individual; Inflammation; Intervention; Link; Measures; Mediator of activation protein; Modeling; Molecular; Monitor; Patients; Physiological; Polysomnography; Population; Preventive service; Public Health; Randomized; Reporting; Research; Risk; Risk Factors; Role; Sleep; Sleep Deprivation; Study Subject; System; Tissues; Vascular Diseases; Vascular Endothelial Cell; Wakefulness; base; cardiovascular risk factor; endothelial dysfunction; experience; high risk; mortality; novel; prehypertension; programs; relating to nervous system; research study; young adult

DESCRIPTION (provided by applicant): Voluntary sleep restriction is common; 30% of the US adult population reports <6 h of sleep per night, and those who do are 24% more likely to have cardiovascular disease and have twice the risk of hypertension. Sleep deprivation may be one of the commonest preventable cardiovascular risk factors. Prehypertension is also highly prevalent, affecting >25% of adults, and this population is at particularly high risk of developing frank hypertension and cardiovascular disease. The comorbidity of inadequate sleep and prehypertension is likely to be very common, with implications for frank hypertension and cardiovascular complications. No definitive experimental studies in humans show whether partial sleep deprivation indeed results in impaired cardiovascular function, nor are there conclusive experiments addressing the underlying physiologic and molecular mechanisms that may be involved, especially with regard to any changes in blood pressure. We propose to conduct a randomized, cross-over study in individuals with prehypertension, incorporating a 3-day acclimation period with 9 nights of sleep restricted to 4 hours per night. These data will be compared to a control/normal sleep sequence. Subjects will complete both sleep restriction and control sequences, separated by a 3-month washout period. Thus, each subject will serve as his or her own control in an experiment that closely matches real-world sleep restriction. We will combine this robust model with a state-of-the-art sleep monitoring system that provides continuous and accurate sleep/wake data in an unobtrusive way. We are currently using this model of sleep restriction in successful ongoing studies and have several decades of experience in conducting human studies of cardiovascular physiology. Comprehensive serial physiologic data will be complemented by detailed translational molecular studies of microvessels and adipocytes obtained by tissue biopsy before and after sleep restriction. Upon completion of these studies we will be able to ascertain: 1. The effects of sleep restriction on blood pressure throughout the entire 24-hour period 2. The effects of sleep restriction on neural circulatory control 3. The effects of sleep restriction on vascular function 4. The effects of slep restriction on systemic and adipose tissue inflammation Important strengths of this application include our compelling preliminary data, the ability to accomplish the specific aims while minimizing potential confounders, our focus on a group at high risk of developing frank hypertension and cardiovascular disease, the integration of widely accepted surrogates of cardiovascular risk with mechanistic molecular studies at the level of the vascular endothelial cell and the adipocyte, and a statistical plan that will provide a rich summary of the effects of sleep restriction on the four specific aims. Our long-term goal is to identify the fundamental biologic mechanisms that link sleep restriction to cardiovascular disease so as to define targets for interventions directed at reducing cardiovascular risk.

描述（由申请人提供）：自愿睡眠限制很常见；美国成人人群中有30％的报告每晚睡眠不足6小时，患有心血管疾病的可能性高24％，并且具有高血压风险的两倍。睡眠剥夺可能是最常见的可预防的心血管危险因素之一。预期前的高度也很普遍，影响> 25％的成年人，并且该人群的发展尤其高 坦率的高血压和心血管疾病。睡眠不足和预付液的合并症可能非常普遍，这对坦率的高血压和心血管并发症有影响。 在人类中没有明确的实验研究表明，部分睡眠剥夺是否确实会导致心血管功能受损，也没有确定的实验来解决可能涉及的潜在生理和分子机制，尤其是在血压变化方面。我们建议对具有预付液的个体进行随机，交叉研究，并结合了为期3天的适应期，睡眠9晚限制为每晚4个小时。这些数据将与对照/正常睡眠序列进行比较。受试者将完成睡眠限制和控制序列，分别为3个月的洗涤期。因此，在与现实世界中的睡眠限制相匹配的实验中，每个主题都将作为他或她自己的控制。我们将将这种强大的模型与最先进的睡眠监控系统相结合，该系统以不引人注目的方式提供连续，准确的睡眠/唤醒数据。我们目前正在成功进行的研究中使用这种睡眠限制模型，并且在进行人类心血管生理学研究方面拥有数十年的经验。全面的串行生理数据将通过在睡眠限制前后通过组织活检获得的微血管和脂肪细胞的详细翻译分子研究来补充。这些研究完成后，我们将能够确定：1。整个24小时期间睡眠限制对血压的影响2。限制睡眠对神经循环控制的影响3.睡眠限制对血管功能的影响4。slep限制对系统性和脂肪组织炎症的影响，包括我们在我们的启发方面的重要范围，使我们的启发性范围包括在我们的范围内完成的范围，使我们的启动范围的特定范围启动，使得启动启动的范围，使得启动的能力，使得启动启动的范围。一群人患有坦率的高血压和心血管疾病的群体，在血管内皮细胞和脂肪细胞水平上，广泛接受的心血管风险替代物与机械分子研究的整合，以及统计计划，该计划将提供对四个特定特定目标的睡眠效果的丰富摘要。我们的长期目标是确定将睡眠限制与心血管疾病联系起来的基本生物学机制，以定义针对降低心血管风险的干预措施的目标。

项目成果

High-normal blood pressure is associated with increased resting sympathetic activity but normal responses to stress tests.

• DOI: 10.3109/08037051.2012.759689
• 发表时间: 2013-06
• 期刊: Blood pressure
• 影响因子: 1.8
• 作者: Hering D;Kara T;Kucharska W;Somers VK;Narkiewicz K
• 通讯作者: Narkiewicz K

Sleep Duration and Cardiovascular Disease Risk: Epidemiologic and Experimental Evidence.

• DOI: 10.1016/j.jsmc.2015.10.007
• 发表时间: 2016-03
• 期刊: Sleep medicine clinics
• 影响因子: 2.8
• 作者: Covassin N;Singh P
• 通讯作者: Singh P