HIV Infection, Cocaine Use and Coronary Artery Disease in HIV+ African Americans

描述(由申请人提供)：在美国，非洲裔美国人(AA)不仅在受艾滋病毒/艾滋病和可卡因成瘾影响的人中比例过高，而且在与艾滋病毒感染、抗逆转录病毒治疗(ART)和可卡因使用相关的冠状动脉疾病(CAD)患者中也是如此。根据我们的初步研究，在HIV感染的无血管症状的AA中，冠状动脉斑块/狭窄的出现率高得令人不安(27%)。在那些长期使用ART或长期吸食可卡因的人中，这一比例甚至更高。因此，评估由钙化斑块和非钙化斑块引起的冠状动脉斑块和冠状动脉管腔阻塞在参与人群中的患病率和发生率，以及在HIV感染的无血管症状的AAS中检查冠状动脉斑块和冠脉管腔阻塞的危险因素是至关重要的。此外，由于目前对HIV感染者早期CAD发生的机制了解有限，因此我们提出了一项活体机制研究，利用内皮功能障碍标志物和最先进的成像技术来量化冠状动脉内皮功能障碍--动脉粥样硬化的最早阶段。拟议的具体目标是(1)评估代谢和人体测量异常、冠状动脉斑块、显著冠状动脉狭窄和左心室(LV)功能障碍的患病率和发生率；(2)检查HIV感染的严重程度(以HIV病毒载量和CD4最低值衡量)对显著冠状动脉狭窄、冠状动脉斑块、斑块成分和LV功能障碍的存在和发展的影响；(3)检查长期ART(所有类别)，特别是基于PI的ART对显著冠状动脉狭窄、冠状动脉斑块、斑块组成和LV功能障碍的存在和发展的影响；(4)研究可卡因的使用如何改变不同类别的ART对严重冠状动脉狭窄、斑块、斑块成分和左心功能不全的存在和发展的影响；(5)纵向研究有冠状动脉斑块和显著冠状动脉狭窄的HIV感染的AA发生心血管事件的危险因素；(6)通过内皮衍生标志物测量HIV感染、ART的使用和可卡因对内皮功能障碍的直接影响和机制；以及(7)通过使用N-13-氨PET/CT成像，评估HIV感染、抗逆转录病毒治疗和可卡因使用对冠状动脉内皮功能障碍的直接影响和机制。本研究可为了解早产儿冠心病的发病机制提供重要信息，并使HIV感染者预防/干预冠心病的研究取得突破性进展，并将科学发现转化为临床应用。公共卫生相关性：这项研究将调查感染艾滋病毒的非裔美国人心脏病发病率高的原因。这项研究可以为了解过早心脏病的机制提供关键信息，并导致在预防/干预艾滋病毒感染者心脏病的研究方面取得突破，并将科学发现转化为临床应用。

DESCRIPTION (provided by applicant): African Americans (AAs) in the US are greatly over-represented not only among persons affected by HIV/AIDS and cocaine addiction, but also among persons affected by coronary artery disease (CAD) associated with HIV infection, antiretroviral therapy (ART), and cocaine use. According to our preliminary study, the rate of presence of coronary plaques/stenosis was disturbingly high in HIV-infected cardiovascularly asymptomatic AAs (27%). The rate was even higher in those who were long-term ART users or long-term cocaine users. Thus, it is critical to estimate the prevalence and incidence of coronary plaques and coronary luminal obstruction caused by both calcified and noncalcified plaques in that participating population and to examine the risk factors for coronary plaques and coronary luminal obstruction in HIV-infected cardiovascularly asymptomatic AAs. Also, since there is only a limited understanding of the mechanisms involved in the development of premature CAD in HIV-infected persons, a mechanistic study in vivo is proposed with the use of endothelial dysfunction markers and the most advanced imaging technologies to quantify coronary endothelial dysfunction - the earliest stage of atherosclerosis. The proposed specific aims are (1) To estimate the prevalence and incidence of metabolic and anthropometric abnormalities, coronary plaques, significant coronary stenoses, and left ventricular (LV) dysfunction; (2) To examine the effects of the severity of HIV infection, as measured by HIV viral load and CD4 nadir, on the presence and development of significant coronary stenoses, coronary plaques, plaque composition, and LV dysfunction; (3) To examine the effects of long-term ART (all classes), especially PI-based ART, on the presence and development of significant coronary stenoses, coronary plaques, plaque composition, and LV dysfunction; (4) To examine how cocaine use modifies the effects of the various classes of ART on the presence and development of significant coronary stenoses, coronary plaques, plaque composition, and LV dysfunction; (5) To longitudinally examine the risk factors for cardiovascular events in HIV-infected AAs with coronary plaques and significant coronary stenoses; (6) To investigate the direct effects and mechanisms of HIV infection, ART use, and cocaine use on endothelial dysfunction, as measured by endothelium-derived markers; and (7) To assess the direct effects and mechanisms of HIV infection, ART use, and cocaine use on coronary endothelial dysfunction, as measured with the use of N-13-ammonia PET/CT imaging. This study could provide critical information for understanding the mechanisms of premature CAD and lead to a breakthrough in research on prevention/intervention of CAD in HIV-infected persons and to translation of scientific discoveries into clinical applications. PUBLIC HEALTH RELEVANCE: This study will investigate why HIV-infected African Americans have high rates of heart disease. The study could provide critical information for understanding the mechanisms of premature heart disease and lead to a breakthrough in research on prevention/intervention of heart disease in HIV-infected persons and to translation of scientific discoveries into clinical applications.