Identifying Risk Factors for Subclinical Myocardial Disease in HIV Infection

确定 HIV 感染中亚临床心肌病的危险因素

• 批准号: 9330904
• 负责人: WENDY S POST
• 金额: $ 77.02万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9330904
• 关键词: Acquired Immunodeficiency Syndrome; Address; Adult; Affect; Age; Alcohol consumption; Alcohol or Other Drugs use; Alcohols; Anatomy; Angiography; Autoimmune Process; Baltimore; Biological Markers; CD4 Positive T Lymphocytes; Cardiac; Cardiomyopathies; Cardiotoxicity; Cardiovascular Diseases; Cell Count; Characteristics; Chicago; Cocaine; Cohort Studies; Coronary; Coronary Arteriosclerosis; Data; Development; Disease Outcome; Dose; Equilibrium; Etiology; Fibrosis; Frequencies; Functional disorder; Gender; Goals; HIV; HIV Infections; Heart Diseases; Heart failure; Heroin; High Prevalence; Highly Active Antiretroviral Therapy; Individual; Inflammation; Injecting drug user; Injury; Intravenous; Knowledge; Lead; Left; Left Ventricular Dysfunction; Link; Longitudinal cohort; Longitudinal cohort study; Magnetic Resonance Imaging; Measures; Mediator of activation protein; Metabolic; Myocardial Ischemia; Myocardial dysfunction; Myocardium; Participant; Periodicity; Persons; Pharmaceutical Preparations; Plasma; Populations at Risk; Prevalence; Prevention; Prevention Measures; RNA; Race; Recruitment Activity; Reporting; Risk; Risk Behaviors; Risk Factors; Sample Size; Serum; Subgroup; The Multicenter AIDS Cohort Study; United States; Ventricular; Viral; Washington; Woman; Women’s Interagency HIV Study; burden of illness; cardiovascular disorder risk; cardiovascular risk factor; cohort; coronary fibrosis; experience; high risk population; illicit drug use; immune activation; interest; intravenous drug use; men; men who have sex with men; novel; novel marker; outcome prediction; public health relevance; sex; sudden cardiac death; therapy duration

 DESCRIPTION (provided by applicant): HIV-infected (HIV+) adults are at increased risk for heart failure (HF) and sudden cardiac death (SCD) due to direct cardiotoxicity from HIV, highly active antiretroviral therapy (HAART) use, immune activation and inflammation, a high prevalence of traditional cardiovascular disease (CVD) risk factors and coronary artery disease (CAD), and substance use (including illicit drug and alcohol use). Myocardial fibrosis, assessed by cardiac MRI (CMR) or novel serum biomarkers, is strongly associated with CVD outcomes in HIV- cohorts. Other novel biomarkers of inflammation, cardiac injury and neurohormonal activation also predict outcome in HIV- cohorts and if applied to HIV+ cohorts, in combination with myocardial fibrosis measures, could provide etiologic explanations for the reported increases in HF and SCD. Only small studies of HIV+ adults have been done and suggest an increased prevalence of subclinical myocardial disease by CMR and elevated biomarkers of fibrosis and inflammation compared to HIV- individuals. None have examined etiologic relationships and small sample sizes limited assessment of mediators and confounding factors. We propose a study that will include both men and women with diverse modes of HIV acquisition and risk behaviors drawn from three long-standing, longitudinal cohort studies of demographically similar HIV+ and HIV- persons: men who have sex with men (MSM) in the Multicenter AIDS Cohort Study (MACS); women with and without intravenous drug use (IDU) in the Women's Interagency HIV Study (WIHS); and men and women with past and current IDU in the AIDS Linked to the Intravenous Experience (ALIVE) study. Each study has detailed data on risk factors for CVD. We will perform CMR to characterize subclinical myocardial disease burden and measure serum biomarkers of fibrosis, inflammation, injury and neurohormonal activation to determine if: (1) HIV+ individuals have greater myocardial disease burden than HIV- individuals, after controlling for age, sex and traditional CVD risk factors; (2) substance us and its characteristics are associated with myocardial disease burden and if greater substance use affects the association between HIV infection and myocardial disease burden; and (3) among the MACS participants who have undergone coronary CT angiography, CAD burden is associated with myocardial disease and its anatomic distribution, and whether this association differs by HIV serostatus. Overall, this study aims to investigate mechanisms that increase the risk for SCD and HF in HIV+ persons, by controlling for and identifying important confounding and modifying factors and by focusing on subclinical myocardial disease.

 描述(申请人提供)：艾滋病毒感染者(HIV+)成人心力衰竭(HF)和心脏性猝死(SCD)的风险增加，原因是艾滋病毒的直接心脏毒性、高效抗逆转录病毒疗法(HAART)的使用、免疫激活和炎症、传统心血管疾病(CVD)风险因素和冠状动脉疾病(CAD)的高度流行，以及药物使用(包括非法药物和酒精使用)。通过心脏核磁共振(CMR)或新的血清生物标记物评估的心肌纤维化与HIV队列中的心血管疾病结局密切相关。其他新的炎症、心脏损伤和神经激素激活的生物标志物也可以预测HIV阳性队列的结果，如果应用于HIV+队列，结合心肌纤维化措施，可以为已报道的HF和SCD增加提供病因学解释。仅对HIV+成人进行了小规模研究，并表明与HIV-个体相比，CMR导致亚临床心肌疾病的患病率增加，纤维化和炎症的生物标志物增加。没有人检查病因关系和小样本量，对介体和混杂因素的评估有限。我们建议进行一项研究，包括具有不同HIV感染模式和危险行为的男性和女性，这些研究来自三项长期的纵向队列研究，研究对象是人口统计学上相似的HIV+和HIV携带者：多中心艾滋病队列研究(MACS)中与男性发生过性关系的男性(MSM)；女性机构间艾滋病毒研究(WIHS)中有和没有静脉注射毒品(IDU)的女性；以及在与静脉注射经历(Alive)相关的艾滋病研究中既有和现在有静脉注射吸毒者的男性和女性。每项研究都有关于心血管疾病风险因素的详细数据。我们将进行CMR来表征亚临床心肌疾病负担，并测量纤维化、炎症、损伤和神经激素激活的血清生物标志物，以确定：(1)在控制了年龄、性别和传统的心血管疾病危险因素后，HIV阳性个体比HIV阳性个体心肌疾病负担更重；(2)物质及其特性与心肌疾病负担相关，如果更多的物质使用影响HIV感染和心肌疾病负担之间的关联；以及(3)在接受过冠状动脉CT血管成像的MACS参与者中，CAD负担与心肌疾病及其解剖分布相关，并且这种关联是否因HIV血清状态而异。总体而言，这项研究旨在通过控制和识别重要的混杂和修饰因素以及通过关注亚临床心肌疾病来研究增加HIV+人群中SCD和HF风险的机制。