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

预测感染艾滋病毒和未感染艾滋病毒的肯尼亚成年人的早期心血管风险

• 批准号: 9231919
• 负责人: CAREY FARQUHAR
• 金额: $ 17.34万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9231919
• 关键词: AIDS/HIV problem; Address; Adopted; Adult; Adverse effects; Africa; Africa South of the Sahara; African; Age; Alcohol consumption; Anti-Retroviral Agents; Atherosclerosis; Bacterial Infections; Biological Assay; Blood; Blood Glucose; Blood Pressure; C-reactive protein; Cardiovascular Diseases; Central obesity; Cessation of life; Chronic; Clinic; Clinical; Collaborations; Combination Medication; Communicable Diseases; Communities; Complex; Country; Cross-Sectional Studies; Data; Development; Disease; District Hospitals; Dyslipidemias; Endocrine; Epidemic; Epidemiology; Europe; Exposure to; Fasting; Foundations; Future; Glucose; Glucose Intolerance; Goals; Guidelines; HIV; HIV Infections; Health; Helminths; High Prevalence; Hospitals; Human immunodeficiency virus test; Hyperlipidemia; Hypertension; Immune; Income; Individual; Inflammation; Inflammatory; Insulin Resistance; Interleukin-6; International; Intervention; Intervention Trial; Interview; Kenya; Laboratory Research; Life; Lipids; Malaria; Measures; Metabolic; Metabolic Pathway; Metabolic syndrome; Modeling; Morbidity - disease rate; Myocardial Infarction; Obesity; Opportunistic Infections; Parasitic infection; Participant; Persons; Play; Policies; Population; Prevalence; Prevention program; Principal Investigator; Public Health; RNA; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Research Training; Resolution; Resources; Risk; Risk Factors; Role; Site; Smoking; Solid; Staging; Stroke; Students; Technology; Training Programs; Uganda; Ultrasonography; Universities; University Hospitals; Viremia; Visit; Washington; Woman; Work; antiretroviral therapy; base; cardiovascular disorder risk; cardiovascular risk factor; career; co-infection; cohort; combat; defined contribution; experience; follow-up; immune activation; innovation; innovative technologies; intimal medial thickening; men; middle age; mortality; multidisciplinary; new technology; outreach; prevent; programs; sex

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.

抽象的 尽管撒哈拉以南非洲地区艾滋病毒流行率很高，但心血管疾病 (CVD) 是主要原因 该地区的发病率和死亡率。 CVD 的预测在资源丰富的国家已经很成熟，但是 这些相同的危险因素是否与撒哈拉以南非洲地区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危险因素，通过 药物副作用、炎症和免疫激活的结合，但艾滋病毒疾病和 在肯尼亚和其他普遍存在艾滋病毒流行的国家，治疗对心血管疾病风险的研究还较少。 该提案的总体目标是确定传统和非传统风险因素的流行程度。 肯尼亚西部感染艾滋病毒和未感染艾滋病毒的男性和女性的心血管疾病。代谢风险因素包括 高脂血症、葡萄糖不耐受和肥胖，将它们结合起来定义为代谢综合征 （MetS）与高收入国家的心肌梗塞和中风有关。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 HIV 感染者和未感染者之间的危险因素患病率并定义 高 HIV RNA 水平、抗逆转录病毒药物的使用以及其他 HIV 特异性危险因素对艾滋病毒感染者的影响 艾滋病病毒。在我们的第三个目标中，我们使用高剂量来定义这些肯尼亚成年人的亚临床动脉粥样硬化发生率。 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 (UW)、内罗毕大学、肯雅塔国家医院和肯尼亚卫生部 卫生部门将对 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，其中一部分 肯尼亚超过 10% 的成年人口感染艾滋病毒。我们将利用 30 年的经验 在肯尼亚进行研究和培训，并在基苏木地区医院进行了 10 年的研究 周边社区，识别具有CVD危险因素和异常C-的中青年个体 IMT。将从 HIV 诊所招募 30 岁以上的 HIV 感染男性和女性以及未感染的参与者 在自愿艾滋病毒检测点以及通过与合作伙伴的外展活动。在一次后续访问、访谈中， 将进行抽血和颈动脉超声检查；化验将在当地研究实验室进行 （葡萄糖、脂质）和 UW（白细胞介素 6，高度敏感的 C 反应蛋白）。这个探索性的 R21 应用程序是 创新性地使用新技术来评估感染艾滋病毒和未感染艾滋病毒的肯尼亚人的 C-IMT。它将奠定一个 为将我们现有的研究基础设施扩展到 CVD 和非化学研究领域奠定了坚实的基础 通过显着提高我们对亚临床动脉粥样硬化及其如何发生的理解来预防传染病 风险受到艾滋病毒、代谢危险因素、炎症和免疫激活的调节。这些数据将至关重要 未来十年，开展有针对性的、可行的干预试验，以对抗撒哈拉以南非洲地区的心血管疾病。