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

摘要 尽管撒哈拉以南非洲的艾滋病毒感染率很高，但心血管疾病(CVD)是主要原因 这一地区的发病率和死亡率。在资源丰富的国家，心血管疾病的预测因素是成立的，但 这些同样的风险因素是否与撒哈拉以南非洲的心血管疾病密切相关尚不清楚。 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风险因素，通过 药物副作用、炎症和免疫激活的组合，但艾滋病毒疾病和 治疗对肯尼亚和其他普遍存在艾滋病毒流行的国家的心血管疾病风险的影响研究较少。 这项建议的总体目标是确定传统和非传统风险因素在 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、糖耐量低减和肥胖，综合起来就是代谢综合征 (METS)与高收入国家的心肌梗死和中风有关。这将是 第一个目标的重点。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，比较感染艾滋病毒和未感染艾滋病毒的风险因素患病率，并确定 高HIV RNA水平、抗逆转录病毒使用和其他HIV特异性风险因素对患有 爱滋病毒。在我们的第三个目标中，我们使用HIGH来定义这些肯尼亚成年人的亚临床动脉粥样硬化率。 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(UW)、内罗毕大学、肯雅塔国家医院和肯尼亚卫生部 卫生组织将对600名参与者进行这项横断面研究，其中300人将是艾滋病毒感染者，这是 肯尼亚有10%的成年人口感染了艾滋病毒。我们将利用30年的经验来做 在肯尼亚的研究和培训，以及在基苏木地区医院和 以确定有心血管疾病危险因素和C-反应蛋白异常的中青年个体。 IMT.将从艾滋病毒诊所和未感染的参与者中招募30岁的艾滋病毒感染男性和女性 在自愿艾滋病毒检测地点，并通过与合作伙伴进行外联。在一次后续访问，一次采访中， 将进行抽血和颈动脉超声检查；检测将在当地研究实验室进行 (葡萄糖、血脂)和UW(白介素6，高敏C反应蛋白)。这个探索性的R21应用程序是 在使用新技术评估感染艾滋病毒和未感染艾滋病毒的肯尼亚人的C-IMT方面具有创新性。它将为我们奠定一个 为将我们现有的研究基础扩展到心血管疾病和非 通过显著提高我们对亚临床动脉粥样硬化的理解以及如何 风险受艾滋病毒、代谢风险因素、炎症和免疫激活的调节。这些数据将非常关键 开发有针对性的、可行的干预试验，以在未来十年在撒哈拉以南非洲抗击心血管疾病。

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.