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

摘要：艾滋病(PWH)患者的心血管疾病(CVD)发病率高出约2.5倍 比年龄相仿的未感染艾滋病毒的成年人更多。可归因于艾滋病毒的心血管疾病风险在非洲最高。 佩戴便携式袖带24小时的动态血压(ABP)监测提供平均白天时间 和夜间血压，并检测血压日变化的异常，如 夜间无血压下降，定义为夜间血压没有通常下降10%(下降)。 与办公室血压相比，ABP更能准确地预测心血管事件。夜间血压升高和 非浸泡可能会增加PWH的心血管风险。小规模的横断面研究表明， 浸泡在PWH中更为常见，并可能与CVD有关。长期目标是减少心血管疾病 威斯康星医院的发病率和死亡率。研究目的是：1)比较不浸泡和不浸泡的时间进程 在PWH与未感染HIV的成人中导致的临床前CVD和2)以确定潜在的病理生理 可能成为未来干预目标的途径。我们建议对PWH和PWH进行一项比较队列研究 反复测量ABP、睡眠、SNS活动和临床前心血管疾病的HIV未感染成年人 在坦桑尼亚由500名PWH和500名未感染艾滋病毒的成年人组成的既定队列中进行。 目标1：确定确认的非浸泡的患病率及其与事故的关系 在接受ART治疗的500名PWH患者和500名匹配的HIV未感染患者的队列中，36个月后临床前CVD 坦桑尼亚的成年人(30岁)。ABP将在基线时进行，然后在1个月时重复。 临床前CVD将在基线以及18个月和36个月后进行量化。心血管事件的发生率也将 被监视着。我们还将检查与临床前心血管疾病相关的其他ABP异常。 目的2：确定睡眠障碍、SNS活动和非浸泡之间的时间关系 以及这是否会因艾滋病毒状况或性别而有所不同。我们将量化睡眠和SNS活动在基线和 在所有参与者18个月和36个月后。我们还将研究肾素-血管紧张素系统，胰岛素 抵抗力和慢性炎症是导致非浸泡的潜在途径。我们还将比较 PWH和未感染HIV的成人之间睡眠和SNS活动的时间趋势。 这项拟议的研究将是非洲第一个关于ABP和睡眠障碍的纵向研究，并将直接 告知针对艾滋病毒的一般指导方针。我们还将为一项机械性临床试验奠定基础，以测试 针对动脉血压异常的新的低成本策略，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.