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（由申请人提供）：由于 HIV 的直接心脏毒性、高效抗逆转录病毒疗法 (HAART) 的使用、免疫免疫激活，HIV 感染者 (HIV+) 成年人发生心力衰竭 (HF) 和心源性猝死 (SCD) 的风险增加炎症、传统心血管疾病 (CVD) 危险因素和冠状动脉疾病 (CAD) 的高患病率，以及通过心脏 MRI 评估的物质使用（包括非法药物和酒精使用）。 (CMR) 或新型血清生物标志物与 HIV- 队列中的 CVD 结果密切相关，其他新型炎症、心脏损伤和神经激素激活生物标志物也可以预测 HIV- 队列中的结果，如果应用于 HIV+ 队列中，则与心肌纤维化措施相结合。 ，可以为报告的 HF 和 SCD 增加提供病因学解释，仅对 HIV + 成人进行了小型研究，并表明 CMR 和升高的生物标志物导致亚临床心肌病的患病率增加。与艾滋病毒个体相比，没有人检查过病因学关系，而且样本量小，对介质和混杂因素的评估有限。我们提出一项研究，该研究将包括具有不同艾滋病毒感染模式和风险行为的男性和女性。 - 对人口统计相似的 HIV+ 和 HIV- 人群进行的长期队列纵向研究：多中心艾滋病队列研究 (MACS) 中的男男性行为者 (MSM)；妇女组中的有或没有静脉吸毒 (IDU) 的女性；机构间艾滋病毒研究 (WIHS)；以及过去和当前患有艾滋病的男性和女性静脉注射经历 (ALIVE) 研究中的每项研究都有有关 CVD 危险因素的详细数据，我们将进行 CMR 来描述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，以确定是否：（1）在控制年龄、性别和传统治疗后，HIV+个体比HIV-个体有更大的心肌疾病负担CVD 危险因素；(2) 物质及其特性与心肌疾病负担相关，以及是否更多的物质使用会影响 HIV 感染与心肌疾病负担之间的关联；(3) 在接受冠状动脉 CT 血管造影、CAD 的 MACS 参与者中；负荷与心肌疾病及其解剖分布有关，以及这种关联是否因 HIV 血清状态而异。总体而言，本研究旨在通过控制和识别来研究增加 HIV+ 人群 SCD 和 HF 风险的机制。重要的混杂因素和改变因素，并重点关注亚临床心肌疾病。