Vitamin D Status, Inflammation and Cardiac Risk in HIV

HIV 患者的维生素 D 状态、炎症和心脏风险

基本信息

批准号：
8466057
负责人：
Corrilynn Olesky Hileman
金额：
$ 13.37万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-22 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8466057
关键词：
25-hydroxyvitamin D 7-dehydrocholesterol Adult Affect Age Anti-Inflammatory Agents Anti-inflammatory Area Attenuated Biological Markers Blinded Blood Vessels C-reactive protein Calcium Cardiac Cardiovascular Diseases Cell Adhesion Cell Adhesion Molecules Cholesterol Clinical Clinical Research Clinical Trials Coagulation Process Cohort Studies Comorbidity Coronary artery Dedications Deficiency Diseases Disease Double-Blind Method Epidemiology Etiology F2-Isoprostanes Fibrin fragment D Foundations Functional disorder Funding Future General Population Goals Guidelines HIV Health Heart Diseases Hydroxymethylglutaryl-CoA Reductase Inhibitors Individual Inflammation Institutes Insulin Resistance Intercellular adhesion molecule 1 Interleukin-6 Investigation K-Series Research Career Programs LDL Cholesterol Lipoproteins Lead Life Link Lipids Longitudinal Studies Measures Mediating Mediator of activation protein Mentors Metabolic Metabolism Mission Modeling Morbidity - disease rate Myocardial National Heart, Lung, and Blood Institute Pathogenesis Patients Play Population Prevention Property Public Health Race Randomized Clinical Trials Reporting Research Research Personnel Research Project Grants Risk Risk Reduction Role Smooth Muscle Myocytes Structure Supplementation Surrogate Markers TNFR-Fc fusion protein Testing Thick Time Ultrasonography United States National Institutes of Health Vascular Cell Adhesion Molecule-1 Vitamin D Vitamin D Deficiency X-Ray Computed Tomography antiretroviral therapy brachial artery cardiovascular disorder prevention cardiovascular disorder risk career career development cell growth cost effective cytokine disorder prevention high risk improved insight intima media mortality multidisciplinary oxidation prospective protective effect research study rosuvastatin sex

25-hydroxyvitamin D 7-dehydrocholesterol Adult Affect Age Anti-Inflammatory Agents Anti-inflammatory Area Attenuated Biological Markers Blinded Blood Vessels C-reactive protein Calcium Cardiac Cardiovascular Diseases Cell Adhesion Cell Adhesion Molecules Cholesterol Clinical Clinical Research Clinical Trials Coagulation Process Cohort Studies Comorbidity Coronary artery Dedications Deficiency Diseases Disease Double-Blind Method Epidemiology Etiology F2-Isoprostanes Fibrin fragment D Foundations Functional disorder Funding Future General Population Goals Guidelines HIV Health Heart Diseases Hydroxymethylglutaryl-CoA Reductase Inhibitors Individual Inflammation Institutes Insulin Resistance Intercellular adhesion molecule 1 Interleukin-6 Investigation K-Series Research Career Programs LDL Cholesterol Lipoproteins Lead Life Link Lipids Longitudinal Studies Measures Mediating Mediator of activation protein Mentors Metabolic Metabolism Mission Modeling Morbidity - disease rate Myocardial National Heart, Lung, and Blood Institute Pathogenesis Patients Play Population Prevention Property Public Health Race Randomized Clinical Trials Reporting Research Research Personnel Research Project Grants Risk Risk Reduction Role Smooth Muscle Myocytes Structure Supplementation Surrogate Markers TNFR-Fc fusion protein Testing Thick Time Ultrasonography United States National Institutes of Health Vascular Cell Adhesion Molecule-1 Vitamin D Vitamin D Deficiency X-Ray Computed Tomography antiretroviral therapy brachial artery cardiovascular disorder prevention cardiovascular disorder risk career career development cell growth cost effective cytokine disorder prevention high risk improved insight intima media mortality multidisciplinary oxidation prospective protective effect research study rosuvastatin sex

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项目摘要

DESCRIPTION (provided by applicant): The overall aims of this five-year career development award are to 1.) enable the candidate's career development as an independent clinical researcher through advanced didactic coursework, structured mentoring and conduct/analysis of a clinical research study; and 2.) better define vitamin D status as a mediator of HIV-related cardiovascular disease (CVD) as well as to determine if vitamin D status changes the effect of rosuvastatin on HIV-related CVD risk. Adults living with HIV are at higher risk than the general population for CVD. Vitamin D deficiency is common in HIV, and appears to play a critical role in systemic inflammation and CVD in the general population, but is not well studied in HIV. Strategies to modify the risk of CVD in HIV present an opportunity for primary disease prevention-an important public health alternative to the treatment of established disease and closely aligned with the mission of NHLBI "to promote the prevention and treatment of heart disease and enhance the health of all individuals so that they can live longer and more fulfilling lives." The candidate will conduct two separate, but complimentary studies one ambispective, cohort study and one randomized clinical trial that will be embedded into two already funded, ongoing studies. The specific aims of the candidates proposal are: 1.) to evaluate the effect over time of vitamin D status on carotid intima media thickness (cIMT) progression and proinflammatory biomarkers in HIV- infected adults before and after initiating antiretroviral therapy (ART) and in age-, sex- and race-matched HIV- uninfected adults; 2.) to evaluate the impact over time of rosuvastatin on vitamin D levels in HIV-infected adults on stable ART; and 3.) to determine if vitamin D status modifies the effect of rosuvastatin on surrogate markers of CVD, proinflammatory biomarkers and cholesterol levels in HIV-infected adults on stable ART. Endpoints will include established surrogate markers of CVD, i.e., cIMT measured by ultrasound, coronary artery calcium score measured by CT scanning, flow mediated dilation of the brachial artery measured by ultrasound, and several important biomarkers of inflammation, endothelial activation, coagulation and oxidation. Statistical analyses will include multiple linea regression and mixed effects modeling. The candidate will be mentored by a multidisciplinary team led by Dr. Grace McComsey, an internationally-recognized clinical researcher in HIV- related metabolic complications, including cardiovascular disease. The candidate has shown a dedication to a career in clinical research through receipt of a Master's in Epidemiology and profile of research projects to date focused in the area of HIV-related CVD and targets to ameliorate this risk. This Career Development Award will provide the foundation for the candidate to pursue an independent research career dedicated to better understanding the pathophysiology of and targets to reduce subsequent morbidity and mortality associated with HIV-related CVD.

描述（由申请人提供）：这个五年职业发展奖的总体目标是1。和2.）更好地将维生素D状态定义为HIV相关心血管疾病（CVD）的介体，并确定维生素D状态是否改变了瑞明素对HIV相关CVD风险的影响。患有艾滋病毒的成年人的风险高于CVD的一般人群。维生素D缺乏症在HIV中很常见，并且在全身炎症和CVD中似乎在普通人群中起关键作用，但在HIV中没有很好地研究。改变HIV中CVD风险的策略为预防原发性疾病提供了机会 - 一种重要的公共卫生替代已建立疾病的替代方法，并与NHLBI的使命紧密地保持一致，以“促进预防和治疗心脏病的预防和治疗，并增强所有人的健康，以便他们能够生活更长的生活和更多充实的生活。”候选人将进行两项独立但免费的研究，这是一项雄心勃勃的队列研究和一项随机临床试验，该试验将嵌入两项已经资助的持续研究中。候选人提案的具体目的是：1。）评估维生素D状态的影响对颈动脉内膜媒体厚度（CIMT）的进展（CIMT）的进展和促进性生物标志物在受HIV感染的成年人中和启动抗逆转录病毒疗法（ART）以及年龄，性别和种族和种族的成年人之前和之后的成人; 2.）评估瑞明素对艾滋病毒感染的成年人对稳定艺术的维生素D水平的影响； 3.）为了确定维生素D状态是否会改变沙前生对HIV感染的成年人对稳定艺术的CVD替代标记，促炎生物标志物和胆固醇水平的影响。终点将包括CVD的已建立的替代标记，即通过超声测量的CIMT，通过CT扫描测量的冠状动脉钙评分，通过超声测量的流动动脉的流量扩张，以及几种重要的炎症生物标志物，炎症，内皮活化，凝结，凝结，凝结和氧化。统计分析将包括多个Linea回归和混合效应建模。候选人将由由国际认可的HIV与HIV相关代谢并发症（包括心血管疾病）的国际认可的临床研究者Grace McComsey博士领导的多学科团队指导。该候选人通过收到迄今为止的流行病学和研究项目的概况，迄今为止，候选人奉献了临床研究的职业，迄今为止，研究项目的概况集中在与HIV相关的CVD领域和目标上，以改善这种风险。该职业发展奖将为候选人提供基础，从而从事独立研究职业，致力于更好地了解与HIV相关CVD相关的随后的发病率和死亡率的病理生理学和目标。