Cardiovascular Disease Mechanisms in HIV Infected and Uninfected Veterans

描述(由申请人提供)： 在使用人群对照的研究中，艾滋病毒感染与心血管疾病(CVD)风险增加有关。然而，这种风险可能部分是由艾滋病毒或其治疗以外的因素解释的，包括吸烟、酗酒、使用可卡因、丙型肝炎感染和肾脏疾病的比率较高。同样重要的是，艾滋病毒携带者的心血管疾病的主要机制可能与未感染的人不同，因为血脂异常是在联合抗逆转录病毒疗法(CART)开始之后突然发生的，而且由于艾滋病毒和丙型肝炎病毒的炎症效应、酒精的毒性效应和可卡因引起的血管痉挛。退伍军人老龄化队列研究(VICS)是一项正在进行的多中心前瞻性研究，涉及3227名感染艾滋病毒的退伍军人和3240名年龄/种族/地点匹配的艾滋病毒未感染对照人员。我们与国际公认的心血管疾病专家合作，建议用已判定的心血管疾病终点、生物标志物和心血管风险指标和指标来补充这一队列中现有的丰富临床数据，包括：血脂异常、胰岛素抵抗、炎症标志物、心脏结构和功能异常、身体成分变化、亚临床动脉粥样硬化、心脏健康状况以及与血栓形成和纤溶相关的变化。有了这些丰富的数据，我们将处于独特的地位，以确定是否：1)艾滋病毒感染是心血管疾病终点的独立风险因素，以及丙型肝炎病毒、药物使用和CART是否改变艾滋病毒和心血管疾病终点之间的关联；2)在艾滋病毒感染和CART未坚持的人中，心血管疾病风险的生物标志物和测量方法增加；以及3)在丙型肝炎病毒感染和药物使用的人中，心血管疾病风险的生物标志物和测量方法增加。重要的是，我们将根据购物车的坚持和竞争风险进行调整，因为艾滋病毒感染者的死亡率要高得多。大量、特征良好、年龄较大、以少数族裔为主的患者样本，具有出色的纵向随访和较高的丙型肝炎病毒和药物使用流行率，全面的药房数据，以及建立对全面电子医疗记录的访问，是该应用程序的重要杠杆优势。VAS团队强大的心血管疾病专业知识、成熟的分析和指导技能，以及包含一名有前途的新调查员的多PI计划，确保这项建议将有效地促进我们对艾滋病毒感染者和未感染者中心血管疾病结果和机制的理解。心血管疾病(CVD)是人类免疫缺陷病毒(HIV)感染者的重要健康问题。心血管疾病的风险是否与艾滋病毒、艾滋病毒的治疗或与艾滋病毒有关的健康问题有关尚不清楚。与未感染艾滋病毒的人相比，艾滋病毒感染者吸烟、酗酒、使用可卡因和丙型肝炎的比率更高。因此，重要的是将艾滋病毒感染者和行为和人口统计相似的未感染者的心血管疾病发生率进行比较。这项建议将提高我们对艾滋病毒感染者心血管疾病风险的了解。(摘要结束)

DESCRIPTION (provided by applicant): In studies using population controls, HIV infection has been associated with increased risk of cardiovascular disease (CVD). However, this risk may be partially explained by factors other than HIV or its treatment including higher rates of smoking, alcohol abuse, cocaine use, hepatitis C infection and renal disease. Equally important, major mechanisms of CVD among those with HIV likely differ from those without infection because lipid abnormalities occur abruptly--after initiation of combination antiretroviral therapy (CART), and because of inflammatory effects of HIV and HCV, toxic effects of alcohol and vasospasm due to cocaine. The Veterans Aging Cohort Study (VACS) is an ongoing, multicenter, prospective study of 3227 veterans with HIV infection and 3240 age/race/site matched HIV uninfected controls. Teamed with internationally recognized experts in CVD, we propose to supplement the rich clinical data available in this cohort with adjudicated CVD endpoints, and biomarkers and measures of CVD risk including: dyslipidemia, insulin resistance , markers of inflammation, cardiac structural and functional abnormalities, body composition changes, subclinical atherosclerosis, cardiac fitness, and alterations associated with thrombogenesis and fibrinolysis. With these enriched data we will be uniquely positioned to determine whether: 1) HIV infection is an independent risk factor for CVD endpoints and whether HCV, substance use and CART modify the association between HIV and CVD endpoints, 2) biomarkers and measures of CVD risk are increased among those with HIV infection and CART nonadherence, and 3) biomarkers and measures of CVD risk are increased among those with HCV infection and substance use. Importantly, we will adjust for both CART adherence and competing risk, since HIV infected individuals have a substantially higher mortality rate. The large, well characterized, older, predominantly minority patient sample with excellent longitudinal follow up and high prevalence of HCV and substance use, comprehensive pharmacy data, and established access to comprehensive electronic medical records are important leveraged strengths of this application. The strong CVD expertise, established analytic and mentoring skills of the VACS team, and a multi-PI plan incorporating a promising new investigator ensure that this proposal will effectively advance our understanding of CVD outcomes and mechanisms among HIV infected and uninfected individuals. Cardiovascular disease (CVD) is an important health problem among people infected with Human Immunodeficiency Virus (HIV). Whether CVD risk is associated with the HIV virus, treatment for HIV or health problems associated with HIV is not known. Compared with people who are not infected with HIV, HIV infected people have higher rates of smoking, alcohol abuse, cocaine use, and hepatitis C. Thus it is important to compare rates of CVD among those with HIV infection to those without HIV infection who are behaviorally and demographically similar. This proposal will improve our understanding of CVD risk among people infected with HIV. (End of Abstract)