Cardiovascular Disease Mechanisms in HIV Infected and Uninfected Veterans

感染艾滋病毒和未感染艾滋病毒的退伍军人的心血管疾病机制

基本信息

批准号：
8322045
负责人：
CHUNG-CHOU Ho CHANG
金额：
$ 105.71万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-25 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8322045
关键词：
Abbreviations Abdomen Acquired Immunodeficiency Syndrome Adherence Adipose tissue Adult Adverse event Aftercare Age Aging Alberta province Alcohol abuse Alcohol consumption Alcohol or Other Drugs use Alcohols Arbitration Area Atherosclerosis Biological Markers Blood Blood Banks Blood Pressure Body Composition Body mass index C-reactive protein CD4 Lymphocyte Count Calcium Cardiac Cardiology Cardiovascular Diseases Cardiovascular system Caring Central obesity Cholesterol Clinical Clinical Data Clinical Trials Coagulation Process Cocaine Cohort Studies Comorbidity Computerized Medical Record Congestive Heart Failure Coronary artery Coronary heart disease Data Data Collection Development Disease Disease Outcome Dyslipidemias Echocardiography Education Electrocardiogram Electron Beam Electron Beam Tomography Enrollment Ensure Epidemiology Etiology Event Exercise Fibrinolysis Functional disorder Future Genetic HIV HIV Envelope Protein gp120 Health Health Surveys Health behavior Hepatitis C Hepatitis C virus High Density Lipoproteins High Prevalence Human ICD-9 Immunologic Deficiency Syndromes In Vitro Individual Infection Inflammation Inflammatory Inflammatory Response Insulin Resistance International Classification of Diseases Justice Kidney Diseases Laboratories Left Left Ventricular Ejection Fraction Left Ventricular Hypertrophy Left ventricular structure Lipids Lipoproteins Low-Density Lipoproteins Lung diseases Measures Medical Medical center Mentors Metabolic Minority Modeling Myocardial Infarction Myocardium National Heart, Lung, and Blood Institute Observational Study Opportunistic Infections Outcome Participant Patients Pericardial body location Pharmaceutical Preparations Pharmacy facility Physical Function Plant Leaves Platelet aggregation Population Population Control Positioning Attribute Prevalence Preventive Prospective Studies Protease Inhibitor Proteins Protocols documentation Pulmonary Hypertension Race Radiology Specialty Regimen Research Personnel Retroviridae Reverse Transcriptase Inhibitors Risk Risk Factors Role Sampling Site Smoke Smoking Smooth Muscle Myocytes Structure Substance abuse problem Testing Thromboplastin Thrombosis Tissues Toxic effect Vasospasm Ventricular Veterans Viral Load result Virus Virus Diseases Visceral Women&apos s Health Work X-Ray Computed Tomography adjudicate alcohol use disorder antiretroviral therapy aortic valve cardiovascular disorder risk cocaine use cofactor cohort cytokine design drinking experience fasting glucose fitness follow-up improved inflammatory marker medication compliance mortality non-nucleoside reverse transcriptase inhibitors programs prospective skills subcutaneous symposium therapy adherence treatment planning

项目摘要

ABSTRACT 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 recogized 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.

抽象的在使用人口控制的研究中，艾滋病毒感染与心血管疾病风险增加有关疾病（CVD）。然而，这种风险的部分原因可能是 HIV 或其治疗以外的因素包括吸烟、酗酒、使用可卡因、丙型肝炎感染和肾脏疾病的比例较高。同样重要的是，HIV 感染者的 CVD 主要机制可能与未感染者不同，因为脂质异常突然发生——在开始联合抗逆转录病毒治疗（CART）后，并且由于 HIV 和 HCV 的炎症作用、酒精的毒性作用和可卡因引起的血管痉挛。退伍军人老龄化队列研究 (VACS) 是一项持续进行的多中心前瞻性研究，研究对象为 3227 名感染 HIV 的退伍军人以及 3240 名年龄/种族/地点匹配的 HIV 未感染对照。与国际知名专家合作 CVD，我们建议用裁定的 CVD 终点来补充该队列中可用的丰富临床数据， CVD 风险的生物标志物和测量方法，包括：血脂异常、胰岛素抵抗、炎症、心脏结构和功能异常、身体成分变化、亚临床动脉粥样硬化、心脏健康以及与血栓形成和纤维蛋白溶解相关的改变。有了这些通过丰富的数据，我们将具有独特的优势来确定：1) HIV 感染是否是一种独立风险 CVD 终点因素以及 HCV、物质使用和 CART 是否会改变 HIV 之间的关联和 CVD 终点，2) HIV 感染者中 CVD 风险的生物标志物和测量指标增加和 CART 不依从性，以及 3) HCV 患者的生物标志物和 CVD 风险指标增加感染和物质使用。重要的是，我们将根据 CART 依从性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。规模大、特征鲜明、年代久远、主要是少数患者样本，具有出色的纵向随访和 HCV 患病率高的特点物质使用、综合药房数据以及建立综合电子医疗的访问权限记录是该应用程序的重要优势。强大的 CVD 专业知识、成熟的分析能力 VACS 团队的指导技能，以及包含有前途的新研究者的多 PI 计划，确保该提案将有效增进我们对 HIV 人群 CVD 结局和机制的理解感染者和未感染者。