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：
8115839
负责人：
MATTHEW S FREIBERG
金额：
$ 98.61万
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 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8115839
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 abstracting 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

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)

描述（由申请人提供）：在使用人口控制的研究中，艾滋病毒感染与心血管疾病 (CVD) 风险增加有关。然而，这种风险的部分原因可能是艾滋病毒或其治疗以外的因素，包括较高的吸烟率、酗酒、使用可卡因、丙型肝炎感染和肾脏疾病。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，因为脂质异常在开始联合抗逆转录病毒治疗 (CART) 后突然发生，并且由于 HIV 和 HCV 的炎症作用、酒精和血管痉挛的毒性作用由于可卡因。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 的退伍军人和 3240 名年龄/种族/地点匹配的未感染 HIV 的对照者。我们与国际公认的 CVD 专家合作，建议通过判定的 CVD 终点以及 CVD 风险的生物标志物和测量来补充该队列中可用的丰富临床数据，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、心脏健康以及与血栓形成和纤溶相关的改变。有了这些丰富的数据，我们将能够确定：1) HIV 感染是否是 CVD 终点的独立危险因素，以及 HCV、物质使用和 CART 是否会改变 HIV 和 CVD 终点之间的关联，2) CVD 风险的生物标志物和衡量标准HIV 感染者和 CART 不依从者中，CVD 风险的生物标志物和测量值在 HCV 感染者和物质使用者中增加。重要的是，我们将根据 CART 依从性和竞争风险进行调整，因为 HIV 感染者的死亡率要高得多。大量、特征明确、年龄较大、以少数族裔为主的患者样本、出色的纵向随访、HCV 和物质使用的高患病率、全面的药房数据以及已建立的全面电子病历访问权限是该应用程序的重要优势。 VACS 团队强大的 CVD 专业知识、成熟的分析和指导技能，以及包含一位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 感染者和未感染者的 CVD 结果和机制的理解。心血管疾病（CVD）是人类免疫缺陷病毒（HIV）感染者的一个重要健康问题。 CVD 风险是否与 HIV 病毒、HIV 治疗或与 HIV 相关的健康问题有关尚不清楚。与未感染 HIV 的人相比，HIV 感染者吸烟、酗酒、吸食可卡因和丙型肝炎的比例更高。因此，比较 HIV 感染者与未感染 HIV 的人的 CVD 发生率非常重要。行为和人口统计上相似。该提案将提高我们对艾滋病毒感染者的心血管疾病风险的了解。（摘要完）