HIV-associated Myocardial Diastolic Dysfunction: A Prospective Cohort Study

项目摘要/摘要 候选人：贾斯汀·金格里博士拥有内科董事会认证，并拥有心血管方面的博士学位 生理学和免疫学。在过去的四年里，他在坦桑尼亚接受了全球卫生研究员的培训， 与坦桑尼亚科学家开展合作，培训当地研究团队，并撰写了六本出版物。 Kingery博士的工作重点是单核细胞在心肌功能障碍中的作用以及心肌梗死的流行病学 这两个问题构成了拟议的研究培训的基础。 职业发展规划：金格里博士的长期目标是成为一名独立的内科科学家 致力于预防和治疗艾滋病毒感染者心血管疾病的临床研究 病人。K23奖项的目标包括：1)通过以下途径获得临床流行病学专业知识 在Fitzgerald，Kapiga和Devereux博士的指导下，临床队列的课程和招生工作。 2)在马丁·威尔斯博士的指导下，通过开设课程和分析自己的数据来提高生物统计学技能。 3)通过课程增加对艾滋病毒病毒学、免疫学和艾滋病毒引起的炎症的了解， 会议，并在菲茨杰拉德、卡皮加和科雷茨基博士的指导下进行研究。4)过渡到 独立的以病人为中心的调查员，并通过在威尔·康奈尔大学的课程学习加强领导技能 关于赠款撰写的医学，导师工作坊，以及在赠款第四年提交R01申请。 环境：拟议的研究和培训将在威尔·布甘多医学院艾滋病毒研究中心进行 诊所(坦桑尼亚)、姆万扎干预试验股(坦桑尼亚)和威尔·康奈尔医学(美国)。这个 这些机构之间的合作伙伴关系为以下基础设施提供了独特的协作环境 包括大型临床研究和转化性研究。这些机构致力于金格里博士的职业生涯。 研究：这项拟议的研究建立在金格里博士先前在坦桑尼亚所做工作的基础上。在目标1中，他将进行 一项前瞻性队列研究，以确定500人中舒张期功能不全的发生率和预测因素 坦桑尼亚感染艾滋病毒的成年人和500名未感染艾滋病毒的成年人。他假设新发病的发病率 在感染艾滋病毒的成年人中，舒张期功能障碍的≥将是未感染艾滋病毒的对照组的2倍 先于先天免疫因子Sst2升高。他还将确定传统风险的贡献 因素(年龄、高血压、肥胖症和糖尿病)和艾滋病毒特异性因素(抗逆转录病毒药物、 计数和病毒载量)。在目标2中，他将在目标1队列中进行嵌套病例对照研究 确定外周血单核细胞表型和事件之间的时间关系 四组各25人的HIV感染和未感染的成年人的舒张期功能障碍 没有舒张期功能障碍。他假设外周血交替激活的比率 在感染艾滋病毒的成年人中，单核细胞/经典激活单核细胞的≥将增加2.5倍 AAM/CAM比值升高将先于并预测发生的舒张期功能障碍。

PROJECT SUMMARY / ABSTRACT Candidate: Dr. Justin Kingery is board certified in Internal Medicine and holds a PhD in cardiovascular physiology and immunology. Training in Tanzania as a global health fellow for the past four years, he has developed collaborations with Tanzanian scientists, trained a local study team, and authored six publications. Dr. Kingery’s work has focused on the role of monocytes in myocardial dysfunction and the epidemiology of HIV-associated heart disease in Tanzania, both of which form the basis for the proposed research training. Career Development Plan: Dr. Kingery’s long-term goal is to become an independent physician scientist dedicated to clinical research in the prevention and treatment of cardiovascular disease in HIV-infected patients. Objectives during this K23 award include: 1) to gain expertise in clinical epidemiology through coursework and enrollment of a clinical cohort under the mentorship of Drs. Fitzgerald, Kapiga and Devereux. 2) To increase biostatistics skills through courses and analysis of his own data mentored by Dr. Martin Wells. 3) To increase understanding of HIV virology, immunology, and HIV-induced inflammation through courses, conferences, and mentored research under Drs. Fitzgerald, Kapiga and Koretzky. 4) To transition to an independent patient-oriented investigator and strengthen leadership skills through coursework at Weill Cornell Medicine on grant writing, workshops on mentorship and submission of a R01 application in grant Year 4. Environment: The proposed research and training will take place at the Weill Bugando School of Medicine HIV Clinic (Tanzania), the Mwanza Intervention Trials Unit (Tanzania) and Weill Cornell Medicine (USA). The partnership between these institutions provides a unique collaborative environment with the infrastructure for both large clinical studies and translational research. These institutions are committed Dr. Kingery’s career. Research: The proposed research builds upon Dr. Kingery’s prior work in Tanzania. In Aim 1, he will conduct a prospective cohort study to determine the incidence and predictors of diastolic dysfunction in 500 HIV-infected and 500 uninfected adults in Tanzania. He hypothesize that the incidence of new-onset diastolic dysfunction will be ≥ 2-times higher in HIV-infected adults than in HIV-uninfected controls and preceded by elevated innate immune factor sST2. He will also determine the contributions of traditional risk factors (age, hypertension, obesity, and diabetes) and HIV-specific factors (antiretroviral drugs, nadir CD4 count, and viral loads). In Aim 2, he will conduct a nested case control study within the Aim 1 cohort to determine the temporal relationship between peripheral blood monocyte phenotype and incident diastolic dysfunction in four groups of 25 each of HIV-infected and uninfected adults with and without diastolic dysfunction. He hypothesize that the ratio of peripheral blood alternatively activated monocytes (AAM)/classically activated monocytes (CAM) will be ≥ 2.5 times higher in HIV-infected adults and that an increased AAM/CAM ratio will precede and predict incident diastolic dysfunction.