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

描述（由申请人提供）：美国的非裔美国人（AA）不仅在受艾滋病毒/艾滋病和可卡因成瘾影响的人群中比例过高，而且在受与艾滋病毒感染、抗逆转录病毒治疗相关的冠状动脉疾病（CAD）影响的人群中比例也过高。（ART）和可卡因使用。根据我们的初步研究，在HIV感染的心血管无症状性AA中，冠状动脉斑块/狭窄的存在率高得令人不安（27%）。在那些长期使用抗逆转录病毒疗法或长期使用可卡因的人中，这一比例甚至更高。因此，在参与人群中评估钙化和非钙化斑块引起的冠状动脉斑块和冠状动脉管腔阻塞的患病率和发生率，并检查HIV感染的心血管无症状性AA中冠状动脉斑块和冠状动脉管腔阻塞的危险因素至关重要。此外，由于对HIV感染者中过早CAD发展所涉及的机制只有有限的了解，因此提出了使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）的体内机制研究。提出的具体目标是（1）估计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）检测HIV感染的严重程度（通过HIV病毒载量和CD 4最低值测量）对显著冠状动脉狭窄、冠状动脉斑块、斑块组成、（3）观察长期ART的疗效（所有类别），尤其是基于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各种ART对严重冠状动脉狭窄、冠状动脉斑块、（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的心血管事件的危险因素;（6）研究HIV感染、ART使用和可卡因使用对内皮功能障碍的直接影响和机制，通过内皮衍生标记物测量;以及（7）通过使用N-13-氨PET/CT成像评估HIV感染、ART使用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。这项研究可以为了解早发CAD的机制提供关键信息，并导致艾滋病毒感染者CAD预防/干预研究的突破，并将科学发现转化为临床应用。公共卫生相关性：这项研究将调查为什么艾滋病毒感染的非洲裔美国人有心脏病的高发病率。这项研究可为了解早发性心脏病的机制提供关键信息，并导致艾滋病毒感染者心脏病预防/干预研究的突破，以及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.