Predicting Early Cardiovascular Risk among HIV-Infected and Uninfected Kenyan Adults

摘要 尽管艾滋病毒在撒哈拉以南非洲的高流行率，心血管疾病（CVD）是主要原因 的发病率和死亡率。在资源丰富的国家，CVD的预测指标已经确立， 这些危险因素是否与撒哈拉以南非洲的CVD密切相关尚不清楚。 来自美国和欧洲的越来越多的证据表明，艾滋病毒本身可能是心血管疾病的一个危险因素， 联合用药的副作用，炎症和免疫激活，但如何艾滋病毒疾病和 在肯尼亚和其他艾滋病流行普遍的国家，治疗对心血管疾病风险的影响研究得较少。 本提案的总体目标是确定传统和非传统风险因素的普遍性， 肯尼亚西部艾滋病毒感染者和未感染者的心血管疾病代谢风险因素包括 高脂血症、葡萄糖耐受不良和肥胖症，当它们一起定义代谢综合征时 在高收入国家，与心肌梗死和中风相关的代谢综合征（MetS）。这将是 第一个目标的焦点。在第二个目标中，我们确定慢性炎症的患病率和预测因素， 和免疫激活，比较艾滋病毒感染者和未感染者之间的危险因素流行率， 高HIV RNA水平、抗逆转录病毒药物的使用和其他HIV特异性风险因素在HIV感染者中的作用 艾滋病。在我们的第三个目标中，我们使用高密度脂蛋白来确定这些肯尼亚成年人中亚临床动脉粥样硬化的发生率。 分辨率超声测量颈动脉内膜中层厚度（C-IMT）。我们的多学科团队来自 华盛顿大学、内罗毕大学、肯雅塔国立医院和肯尼亚卫生部 卫生部将对600名参与者进行这项横断面研究，其中300人将感染艾滋病毒， 在肯尼亚，超过10%的成年人感染了艾滋病毒。我们将利用30年的经验， 在肯尼亚进行研究和培训，并在基苏穆地区医院进行了10年的研究， 本研究的目的是通过对周围社区的调查，发现有CVD危险因素和C-反应异常的中青年人， IMT。将从艾滋病毒诊所招募30岁以上的艾滋病毒感染者和未感染者 在自愿艾滋病毒检测点，并通过与合作伙伴的外联活动。在一次随访中，一次访谈， 将进行抽血和颈动脉超声检查;将在当地研究实验室进行检测 （葡萄糖、脂质）和UW（白细胞介素-6，高敏C反应蛋白）。这个探索性的R21应用程序是 创新地使用新技术评估感染和未感染艾滋病毒的肯尼亚人的C-IMT。奠定了 坚实的基础，扩大我们建立的研究基础设施，研究CVD和非 通过显著提高我们对亚临床动脉粥样硬化的理解， 艾滋病毒、代谢危险因素、炎症和免疫激活可调节风险。这些数据将至关重要 开发有针对性的、可行的干预试验，在未来十年内在撒哈拉以南非洲地区防治心血管疾病。

ABSTRACT Despite the high prevalence of HIV in sub-Saharan Africa, cardiovascular disease (CVD) is the leading cause of morbidity and mortality in this region. Predictors of CVD are well-established in resource-rich countries, but whether these same risk factors are strongly associated with CVD in sub-Saharan Africa is not known. Growing evidence from the US and Europe suggests that HIV itself may be a risk factor for CVD, through a combination of medication side effects, inflammation and immune activation, but how HIV disease and treatment impacts CVD risk in Kenya and other countries with generalized HIV epidemics is less well studied. The overall goal of this proposal is to determine the prevalence of traditional and non-traditional risk factors for CVD in HIV-infected and uninfected men and women in western Kenya. Metabolic risk factors include hyperlipidemia, glucose intolerance and obesity, which when taken together define a metabolic syndrome (MetS) that has been associated with myocardial infarction and stroke in high-income countries. This will be the focus of the first aim. In the second aim, we determine prevalence and predictors of chronic inflammation and immune activation, comparing risk factor prevalence among HIV-infected and uninfected and defining contributions of high HIV RNA levels, antiretroviral use, and other HIV-specific risk factors among those with HIV. In our third aim, we define rates of subclinical atherosclerosis among these Kenyan adults using high resolution ultrasound to measure carotid intima media thickness (C-IMT). Our multidisciplinary team from the University of Washington (UW), University of Nairobi, Kenyatta National Hospital and the Kenya Ministry of Health will conduct this cross-sectional study of 600 participants, 300 of whom will be HIV-infected, in a part of Kenya where >10% of the adult population is infected with HIV. We will leverage 30 years of experience doing research and training in Kenya, and 10 years implementing studies in the Kisumu District Hospital and surrounding community, to identify young and middle aged individuals with CVD risk factors and abnormal C- IMT. HIV-infected men and women >30 years old will be recruited from HIV clinics and uninfected participants at voluntary HIV testing sites and through outreach to partners. During a single follow-up visit, an interview, blood draw, and carotid ultrasound will be performed; assays will be conducted at a local research laboratory (glucose, lipids) and UW (Interleukin-6, highly sensitive C-reactive protein). This exploratory R21 application is innovative in its use of new technologies to assess C-IMT in HIV-infected and uninfected Kenyans. It will lay a solid foundation for expanding our established research infrastructure into research on CVD and non- communicable diseases by significantly advancing our understanding of subclinical atherosclerosis and how risk is modulated by HIV, metabolic risk factors, inflammation and immune activation. These data will be critical to developing targeted, feasible intervention trials to combat CVD in sub-Saharan Africa over the next decade.