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：
8852691
负责人：
Corrilynn Olesky Hileman
金额：
$ 13.4万
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 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8852691
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 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 Myocarditis 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 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 intimal medial thickening mortality multidisciplinary oxidation prospective protective effect research study rosuvastatin sex

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）：这个为期五年的职业发展奖的总体目标是 1.) 通过高级教学课程、结构化指导和临床研究的开展/分析，使候选人能够作为独立临床研究人员实现职业发展； 2.) 更好地将维生素 D 状态定义为 HIV 相关心血管疾病 (CVD) 的调节因素，并确定维生素 D 状态是否会改变瑞舒伐他汀对 HIV 相关 CVD 风险的影响。感染艾滋病毒的成年人比一般人群患心血管疾病的风险更高。维生素 D 缺乏在 HIV 患者中很常见，似乎在一般人群的全身炎症和 CVD 中发挥着关键作用，但在 HIV 患者中尚未得到充分研究。改变 HIV 中 CVD 风险的策略为初级疾病预防提供了机会，这是治疗既定疾病的重要公共卫生替代方案，与 NHLBI“促进心脏病的预防和治疗并增强健康水平”的使命密切相关。所有人的生活，以便他们能够活得更长久、更充实。”候选人将进行两项独立但互补的研究，一项是双向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正在进行的研究中。候选提案的具体目标是： 1.) 评估维生素 D 状态随时间的推移对 HIV 感染成人在开始抗逆转录病毒治疗 (ART) 之前和之后以及治疗期间颈动脉内膜中层厚度 (cIMT) 进展和促炎生物标志物的影响。年龄、性别和种族匹配的未感染艾滋病毒的成年人； 2.) 评估瑞舒伐他汀对稳定 ART 中 HIV 感染成人维生素 D 水平的影响； 3.) 确定维生素 D 状态是否会改变瑞舒伐他汀对接受稳定 ART 治疗的 HIV 感染成人的 CVD 替代标志物、促炎生物标志物和胆固醇水平的影响。终点将包括已确定的 CVD 替代标志物，即通过超声测量的 cIMT、通过 CT 扫描测量的冠状动脉钙评分、通过超声测量的血流介导的肱动脉扩张，以及炎症、内皮活化、凝血和氧化的几个重要生物标志物。统计分析将包括多重线性回归和混合效应建模。候选人将接受由 Grace McComsey 博士领导的多学科团队的指导，Grace McComsey 博士是国际公认的 HIV 相关代谢并发症（包括心血管疾病）临床研究员。该候选人通过获得流行病学硕士学位以及迄今为止专注于艾滋病毒相关心血管疾病领域的研究项目和降低这一风险的目标，表现出了对临床研究职业的奉献精神。该职业发展奖将为候选人提供独立研究生涯的基础，致力于更好地了解 HIV 相关 CVD 的病理生理学并降低其后续发病率和死亡率。