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：
8334808
负责人：
MATTHEW S FREIBERG
金额：
$ 27.47万
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/8334808
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）：在使用人群控制的研究中，HIV感染与心血管疾病（CVD）的风险增加有关。但是，这种风险可能部分由艾滋病毒以外的其他因素或其治疗方法来解释，包括较高的吸烟率，酗酒，可卡因使用，乙型肝炎感染和肾脏疾病。同样重要的是，在艾滋病毒患者中，CVD的主要机制可能与没有感染的人不同，因为脂质异常突然发生 - 在启动抗逆转录病毒疗法（CART）之后，HIV和HCV的炎症作用，艾滋病毒和HCV的炎症作用，由于癌和癌的毒性作用。退伍军人老化队列研究（VACS）是一项持续的，多中心的前瞻性研究，对3227名患有HIV感染的退伍军人和3240岁的年龄/种族/部位匹配的HIV未感染的对照。 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血栓形成和纤维蛋白溶解。 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使用物质。重要的是，由于艾滋病毒感染的个体的死亡率较高，因此我们将针对卡车依从性和竞争风险进行调整。较大的，良好的，较老的，主要是少数族裔患者样本，具有出色的纵向随访，HCV和药物使用，综合药房数据以及已建立的综合电子病历的访问是该应用程序的重要杠杆优势。强大的CVD专业知识，建立了VACS团队的分析和指导技能，以及纳入有前途的新研究人员的多PI计划确保该建议将有效地提高我们对受HIV感染和未感染的人中CVD结果和机制的理解。心血管疾病（CVD）是感染人类免疫缺陷病毒（HIV）的人的重要健康问题。 CVD风险是否与HIV病毒相关，HIV治疗或与HIV相关的健康问题尚不清楚。与未感染艾滋病毒的人相比，受艾滋病毒感染的人的吸烟，酗酒，可卡因使用和丙型肝炎的发生率更高。因此，与患有艾滋病毒感染感染的患者与没有行为上和人口统计学相似的艾滋病毒感染的患者中的CVD率更重要。该提案将提高我们对感染艾滋病毒的人的CVD风险的理解。（抽象的结尾）