Pericardial fat, inflammation, and structural heart disease in HIV

HIV 患者的心包脂肪、炎症和结构性心脏病

• 批准号: 8837686
• 负责人: Chris Todd Longenecker
• 金额: $ 15.59万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8837686
• 关键词: AIDS clinical trial group; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adipose tissue; Africa South of the Sahara; Age; Alcohol dependence; Anti-Retroviral Agents; Area; Atherosclerosis; Biological Markers; Blood Vessels; Calcium; Cardiac; Cardiology; Cardiomyopathies; Cardiovascular system; Chromium; Chronic; Clinical; Clinical Research; Comorbidity; Coronary; Coronary heart disease; Cross-Sectional Studies; Development; Dyslipidemias; Echocardiography; Ensure; Fatty acid glycerol esters; Functional disorder; Funding; Future; Gender; General Population; Geographic Locations; Goals; HIV; HIV Infections; Health; Heart Diseases; Heart failure; Immune; Immunology; Inflammation; Inflammatory; Insulin Resistance; Investigation; Journals; Lead; Left; Left Ventricular Mass; Left ventricular structure; Lipoatrophy; Longitudinal Studies; Measures; Medicine; Mentors; Mentorship; Micronutrients; Myocardial; Myocardial Infarction; Myocarditis; Observational Study; Ohio; Patients; Pericardial body location; Phenotype; Population; Population Control; Positioning Attribute; Prevention strategy; Publishing; Regimen; Renal function; Research; Research Design; Research Personnel; Residual state; Resources; Risk; Risk Reduction; Scanning; Science; Selenium; Site; Smoking; Solid; Strategic Planning; Stress; Stroke; Testing; Time; Training; Uganda; United States; United States Department of Veterans Affairs; Universities; University Hospitals; Ventricular; Veterans; Visceral; attenuation; cardiometabolic risk; cardiovascular imaging; clinical care; cohort; design; experience; high risk; imaging biomarker; immune activation; inflammatory marker; insight; non-invasive imaging; novel; programs; statistics; working group

DESCRIPTION (provided by applicant): Patients with chronic HIV-infection are at increased risk for atherosclerotic vascular disease including myocardial infarction and stroke compared to HIV-uninfected control populations. Adipose tissue dysfunction-including visceral and pericardial lipohypertrophy-may be an important contributor of risk. Compared to what is known about vascular risk, less is known about intrinsic myocardial disease or risk of heart failure in the current era of effective combination ART. The ability of imaging and biomarkers to identify early structural heart disease and prognosticate heart failure risk is an area of intense investigation i the general population, but has been scarcely investigated in the HIV-infected population. Furthermore, the impact of non-AIDS comorbidities may be greater in sub-Saharan Africa, though few studies of CVD have been conducted in patients on ART in this setting. The overall objective of this proposed K23 research plan is to use biomarkers and non-invasive imaging to identify HIV-infected patients with early structural heart disease and to understand the mechanisms of these changes, so that risk-reduction therapies can be appropriately targeted and novel preventive strategies may be developed in the future. This project aims to develop a novel "pericardial fat score" that will predict cardiometabolic risk in a 3 year longitudinal cohor of 360 patients in an AIDS Clinical Trials Group study. In a cross-sectional study of 300 subjects, we will investigate whether pericardial fat is altered in HIV-infected subjects compared to age-, gender-, and smoking-matched HIV uninfected controls in Cleveland, Ohio and Kampala, Uganda. We will additionally investigate whether pericardial fat and mean attenuation correlate with biomarkers of inflammation and cardiac stress or sensitive measures of left ventricular (LV) systolic and diastolic function. These studies will provide a comprehensive view of how adipose tissue, inflammation, immune activation, and biomarkers of cardiac stress relate to early structural heart disease among HIV- infected subjects on ART in the United States and sub-Saharan Africa. These cohorts will be followed in future longitudinal studies of cardiac function and incident heart failure risk in HIV. The PI, Dr. Longenecker, is an exceptional candidate who is seeking to become an internationally recognized clinician-investigator in the field of cardiovascular complications of HIV/AIDS. He has a solid track record of publishing in top-tier HIV/AIDS and cardiovascular journals with his current and prior research mentors. He also has four years of experience conducting clinical research in Uganda. As a cardiologist with a focus in non-invasive cardiovascular imaging, he is uniquely positioned to contribute to the research goals outlined in the NHLBI's AIDS Working Group strategic plan (September 2012). Dr. Longenecker has strong institutional support from Case Western Reserve University and the Division of Cardiovascular Medicine at University Hospitals. He will have guaranteed 75% protected research time and access to a wealth of campus resources that will ensure a successful transition to independently funded investigator. His robust training plan includes: 1) high quality mentorship from his primary mentor, Dr. Grace McComsey, as well as three cardiology co-mentors, a biostatistician, and a group of collaborators; 2) coursework in fundamental immunology with a focus on chronic HIV infection; 2) intensive training in clinical research design and statistics; 3) experience in multi-site interdisciplinary team science; and 4) Field experience in integrating clinical care and research programs.

描述（由申请人提供）：与HIV未感染的对照组相比，患有慢性HIV感染的患者患动脉粥样硬化血管疾病的风险增加了，包括心肌梗塞和中风。脂肪组织功能障碍 - 包括内脏和心包脂肪动物肉芽脂性 - 可能是风险的重要贡献者。与对血管风险的了解相比，对当前有效组合艺术时代的内在心肌疾病或心力衰竭的风险知之甚少。成像和生物标志物鉴定早期结构性心脏病和预后心力衰竭风险的能力是对普通人群进行严格调查的领域，但在HIV感染的人群中几乎没有得到研究。此外，撒哈拉以南非洲的非AIDS合并症的影响可能会更大，尽管在这种情况下，很少对患者对CVD进行研究。该提出的K23研究计划的总体目标是使用生物标志物和非侵入性成像来鉴定感染早期结构性心脏病的HIV感染患者，并了解这些变化的机制，以便可以适当地靶向风险降低疗法，并在将来开发新的预防策略。该项目旨在开发一种新颖的“心包脂肪评分”，该项目将在AIDS临床试验小组研究中预测360名患者的3年纵向副代谢风险。在对300名受试者的横断面研究中，我们将研究与年龄，性别和吸烟的HIV未感染的对照组相比，艾滋病，俄亥俄州，俄亥俄州和乌干达坎帕拉的年龄，性别和吸烟的HIV未感染的对照组是否改变了心包脂肪。我们还将研究心包脂肪和平均衰减是否与炎症和心脏应激的生物标志物相关，或者是左心室（LV）收缩压和舒张功能的敏感度量。这些研究将提供有关脂肪组织，炎症，免疫激活和心脏应激生物标志物与美国和撒哈拉以南非洲艾滋病感染受试者之间早期结构性心脏病的关系。这些队列将在未来的心脏功能和艾滋病毒事件心力衰竭风险的纵向研究中遵循。 PI Longenecker博士是一位出色的候选人，他正在寻求成为艾滋病毒/艾滋病心血管并发症领域的国际认可的临床医生评估者。他在高级艾滋病毒/艾滋病和心血管期刊上的出版记录具有稳固的记录，并具有目前的研究导师。他在乌干达也有四年的临床研究经验。作为一名心脏病专家，重点是非侵入性心血管成像，他在NHLBI的艾滋病工作组战略计划（2012年9月）中擅长为研究目标做出贡献。 Longenecker博士在Case Western Reserve大学和大学医院的心血管医学系获得了强有力的机构支持。他将保证75％的保护时间并获得大量校园资源，以确保成功过渡到独立资助的调查员。他的强大培训计划包括：1）他的主要导师Grace McComsey博士以及三位心脏病学系，一个生物统计学家和一组合作者的高质量指导； 2）基本免疫学课程，重点是慢性艾​​滋病毒感染； 2）临床研究设计和统计的深入培训； 3）多站点跨学科团队科学经验； 4）在整合临床护理和研究计划方面的现场经验。