HIV, Sleep, Nocturnal Non-dipping, and Cardiovascular Disease: a Tanzanian Cohort

摘要：HIV感染者（PWH）的心血管疾病（CVD）发病率高出约2.5倍 比同龄的未感染艾滋病毒的成年人要多。艾滋病毒引起的CVD风险在非洲最高。 使用便携式袖带进行24小时动态血压（ABP）监测， 和夜间血压，并检测血压昼夜变化中的异常， 夜间非下降，其定义为夜间血压没有超过10%的正常下降（下降）。 ABP比诊室血压更准确地预测CVD事件。夜间血压升高， 非浸渍可能导致PWH中CVD风险过高。小规模的横断面研究表明， 浸渍在PWH中更常见，并且可能与CVD相关。长期目标是减少CVD 威尔斯亲王医院的发病率及死亡率。研究目的是：1）比较非浸渍的时间过程， PWH与未感染HIV的成人相比，导致临床前CVD; 2）确定潜在的病理生理学 这可能是未来干预的目标。我们提出了一个比较队列研究的PWH和 重复测量ABP、睡眠、SNS活动和临床前CVD的未感染HIV的成年人， 在坦桑尼亚的500名PWH和500名未感染HIV的成年人中进行。 目的1：确定确认的非浸渍的患病率及其与事件的关联 500例接受稳定ART治疗的PWH患者和500例匹配的HIV未感染者队列中36个月后的临床前CVD 坦桑尼亚的成年人（年龄>30岁）。将在基线时进行ABP，然后在1个月时重复进行。 将在基线以及18个月和36个月后定量临床前CVD。CVD事件的发生率也将 监测。我们还将研究其他ABP异常与临床前CVD的关系。 目的2：确定睡眠障碍，SNS活动和非浸渍之间的时间关系 以及这是否因艾滋病毒感染状况或性别而异。我们将在基线时量化睡眠和SNS活动， 18和36个月后，所有参与者。我们还将研究肾素-血管紧张素系统，胰岛素 抵抗和慢性炎症作为导致非浸渍的潜在途径。我们还将比较 PWH和未感染艾滋病毒的成年人之间睡眠和社交网络活动的时间趋势。 这项拟议的研究将是非洲第一项关于ABP和睡眠障碍的纵向研究， 为艾滋病毒的具体和一般准则提供信息。我们还将为一项机械临床试验奠定基础， 一种新的，低成本的策略，针对ABP异常，以预防PWH中的CVD。

ABSTRACT: The incidence of cardiovascular disease (CVD) in people with HIV (PWH) is ~2.5-fold higher than among HIV-uninfected adults of similar age. HIV-attributable CVD risk is highest in Africa. Ambulatory blood pressure (ABP) monitoring with a portable cuff worn for 24 hours provides mean daytime and nighttime blood pressures and detects abnormalities in the diurnal variation of blood pressure such as nocturnal non-dipping, which is defined by the absence of the 10% usual fall (dip) in blood pressure at night. ABP more accurately predicts CVD events than office blood pressure. Elevated nighttime blood pressure and non-dipping may contribute to the excess CVD risk in PWH. Small, cross-sectional studies suggest that non- dipping is more common in PWH and may be associated with CVD. The long-term goal is to reduce CVD morbidity and mortality in PWH. The study objectives are to 1) compare the time course of non-dipping and resulting preclinical CVD in PWH vs. HIV-uninfected adults and 2) to identify potential pathophysiologic pathways that could be targets for future intervention. We propose a comparative cohort study of PWH and HIV-uninfected adults with repeated measures of ABP, sleep, SNS activity and preclinical CVD to be conducted in an established cohort of 500 PWH and 500 HIV-uninfected adults in Tanzania. Aim 1: To determine the prevalence of confirmed non-dipping and its association with incident preclinical CVD after 36 months in a cohort of 500 PWH on stable ART and 500 matched HIV-uninfected adults (age >30 years) in Tanzania. ABP will be performed at baseline and then repeated at 1 month. Preclinical CVD will be quantified at baseline and after 18 and 36 months. Incidence of CVD events will also be monitored. We will also examine other ABP abnormalities in relationship to preclinical CVD. Aim 2: To determine the temporal relationship between sleep disorders, SNS activity and non-dipping and whether this differs by HIV status or gender. We will quantify sleep and SNS activity at baseline and after 18 and 36 months on all participants. We will also investigate the renin-angiotensin system, insulin resistance and chronic inflammation as potential pathways leading to non-dipping. We will also compare temporal trends in sleep and SNS activity between PWH and HIV-uninfected adults. The proposed research will be the first longitudinal study of ABP and sleep disorders in Africa and will directly inform HIV-specific and general guidelines. We will also lay groundwork for a mechanistic clinical trial to test a novel, low-cost strategy targeting ABP abnormalities to prevent CVD in PWH.