Evaluation of HIV-associated Cardiac Dysfunction in Women

女性 HIV 相关心脏功能障碍的评估

• 批准号: 9250013
• 负责人: JORGE R KIZER
• 金额: $ 81.71万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9250013
• 关键词: Acquired Immunodeficiency Syndrome; Address; Age; Anti-Retroviral Agents; Autoimmunity; Behavioral; Biological Markers; Brain natriuretic peptide; CD4 Lymphocyte Count; Cardiac; Cardiomyopathies; Cardiovascular system; Carotid Atherosclerotic Disease; Cells; Chronic; Complement; Control Groups; Coronary heart disease; Data; Depressed mood; Detection; Development; Dilated Cardiomyopathy; Disease; Echocardiography; Elderly; Enrollment; Evaluation; Event; Fibrosis; Follow-Up Studies; Fostering; Functional disorder; Gadolinium; HIV; HIV Infections; Health; Heart Diseases; Heart failure; Impairment; Individual; Infarction; Inflammation; Interleukin-6; Knowledge; Lead; Left; Left Ventricular Dysfunction; Left Ventricular Ejection Fraction; Left Ventricular Function; Left Ventricular Mass; Left ventricular structure; Life Expectancy; Link; Lipids; Magnetic Resonance; Magnetic Resonance Spectroscopy; Measures; Mechanics; Mediating; Metabolic; Modernization; Myocardial; Myocardial dysfunction; N-terminal; Nonesterified Fatty Acids; Participant; Patients; Pharmaceutical Preparations; Plasma; Population; Prevalence; Prevention; Prospective cohort; Protease Inhibitor; RNA; Risk Factors; Role; Site; Stress; Techniques; Tenofovir; Tissues; Triglycerides; Troponin I; Ultrasonography; Ventricular; Viral; Visit; Woman; Women’s Interagency HIV Study; antiretroviral therapy; assault; circulating biomarkers; cohort; coronary fibrosis; diabetic cardiomyopathy; disorder risk; extracellular; follow-up; healthy volunteer; heart dimension/size; imaging study; improved; indexing; interstitial; mortality; novel; pathogen; prevent; prognostic; public health relevance; secondary analysis; success

 DESCRIPTION (provided by applicant): The advent of combination antiretroviral therapy (cART) has led to marked decreases in AIDS- related mortality in people with HIV infection. Although this has been accompanied by reduction of severe dilated cardiomyopathy associated with late-stage HIV, echocardiographic studies of HIV-infected cohorts in the cART era have highlighted pronounced increases in the prevalence of milder forms of LV systolic dysfunction and, particularly, diastolic dysfunction. Given the young age of such cohorts, and the advancing age of people living with HIV, these echo findings herald a potential upsurge of HF in this population. Moreover, novel cardiac magnetic resonance (CMR) techniques have shown interstitial fibrosis and intramyocardial triglyceride (TG) content to be increased in the setting f cardiovascular and metabolic risk factors, and to correlate with impaired LV function. Such risk factors are well-known to be associated with HIV and its treatment, and modest-sized CMR studies of HIV-infected patients have recently demonstrated increased myocardial fibrosis and TG content, along with depressed myocardial mechanics. Like the majority of available echo studies, these CMR studies did not focus on women, and are limited both by inclusion of healthy volunteers as controls, and by lack of detailed longitudinal assessment of HIV-related factors or treatment. Meanwhile, the development of speckle-tracking echo assessment of myocardial deformation now permits more accurate evaluation of subclinical cardiac dysfunction using a widely applicable non-invasive technique. We propose to leverage the largest and longest prospective cohort of HIV-infected and well-matched uninfected women, the Women's Interagency HIV Study, to build on our previous echo study among Bronx and Brooklyn participants, and perform repeat echoes approximately 12 years later. This will allow the first long-term longitudinal assessment of LV dysfunction in HIV-infected and uninfected women, and a well-sized evaluation of myocardial deformation in such individuals. This will be complemented by CMR assessment of interstitial fibrosis and myocardial TG content, as well as infarct. Using repeated measures of HIV-specific exposures and ART, and added biomarkers of cardiac stress, inflammation and lipid dysregulation, this proposal stands to provide important new knowledge concerning the role of HIV infection and related factors in subclinical myocardial dysfunction and disease. In so doing, the proposed project will identify strategies and future research to avert the potential rise in symptomatic HF that threatens the HIV-infected population in the cART era.

 描述（由适用提供）：抗逆转录病毒疗法（CART）的冒险导致HIV感染患者的艾滋病死亡率显着下降。尽管这是通过减少与晚期HIV相关的严重扩张心肌病来实现的，但在购物车时代，对HIV感染的队列的超声心动图研究突显了Miller形式的LV系统功能障碍的患病率的明显增加，尤其是解答功能障碍。鉴于这种队列的年龄和艾滋病毒感染者的发展年龄，这些回声的发现预示了该人群的HF潜在增长。此外，新颖的心脏磁共振（CMR）技术显示了间隙纤维化和心脏内甘油三酸酯（TG）含量在f心血管和代谢风险因素中增加，并与LV功能受损相关。众所周知，危险因素与HIV及其治疗有关，艾滋病毒感染患者的适度CMR研究最近证明心肌纤维化和TG含量增加，以及抑郁的心肌力学。像大多数可用的ECHO研究一样，这些CMR研究也不关注女性，并且由于将健康的志愿者包括作为对照而受到限制，并且缺乏对HIV相关因素或治疗的详细纵向评估。同时，斑点跟踪的回声评估心肌变形现在可以使用更广泛的适用非侵入性技术对亚临床心脏功能障碍进行更准确的评估。我们建议利用艾滋病毒感染且匹配良好的未感染的妇女（妇女的机构艾滋病毒研究）的最大，最长的前瞻性人群，以基于我们先前在布朗克斯和布鲁克林参与者中的回声研究，并在大约12年后进行重复回声。这将允许对艾滋病毒感染和未感染的妇女的LV功能障碍进行首次长期纵向评估，并对此类个体的心肌变形进行大尺寸的评估。这将通过CMR评估间质纤维化和心肌TG含量以及梗塞来完成。该建议使用重复测量HIV特异性暴露和ART，并增加了心脏应激，感染和脂质失调的生物标志物，该建议将提供有关HIV感染和相关因素在亚临床心肌功能障碍和疾病中的作用的重要新知识。在这样做的过程中，拟议的项目将确定策略和未来的研究，以避免有症状的HF的潜在增加，从而威胁到购物车时代的HIV感染人群。