Novel Mechanisms Driving Excess Atherosclerotic Cardiovascular Disease Risk in the Context of HIV: The Role of Liver Injury

HIV 背景下导致动脉粥样硬化性心血管疾病风险过高的新机制：肝损伤的作用

• 批准号: 9982396
• 负责人: Kaku So-Armah
• 金额: $ 12.96万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982396
• 关键词: Accounting; Acute myocardial infarction; Aging; Alcohol abuse; Alcohols; Atherosclerosis; Automobile Driving; Award; B-Lymphocyte Subsets; Basic Science; Behavioral; Big Data Methods; Biological Markers; Biometry; Biostatistical Methods; Blood coagulation; Calibration; Cardiac; Cardiovascular Diseases; Caring; Cause of Death; Cirrhosis; Clinical; Clinical Data; Clinical Sciences; Coagulation Process; Code; Cohort Studies; Collaborations; Collection; Conflict (Psychology); Data; Data Analyses; Data Element; Data Set; Diagnosis; Discrimination; Disease; Disease Progression; Doctor of Philosophy; Dyslipidemias; Electronic Health Record; Epidemiology; Event; Fibrosis; Funding; HIV; HIV Infections; HIV/HCV; Heart Diseases; Hepatitis C; Hepatitis C co-infection; Hepatology; Hypertension; Immune Tolerance; Inflammation; Insulin Resistance; Ischemic Stroke; K-Series Research Career Programs; Knowledge; Link; Lipids; Lipoproteins; Liver; Liver Fibrosis; Liver diseases; Longitudinal Surveys; Longitudinal observational study; Measures; Mediating; Medicare; Mentors; Mentorship; Metabolic; Metabolism; Methods; Molecular; Myocardial Infarction; National Heart, Lung, and Blood Institute; National Institute on Alcohol Abuse and Alcoholism; Natural Immunity; Outcome; Pathology; Pathway interactions; Play; Population; Population Sciences; Public Health; Publications; Recording of previous events; Research Personnel; Risk; Risk Factors; Role; Rotation; Sampling; Severities; Smoking; Source; Structure; T-Lymphocyte; Testing; Training; Veterans; Work; adaptive immunity; atherosclerosis risk; cardiovascular disorder epidemiology; cardiovascular disorder risk; cohort; comorbidity; comparison group; coronary artery calcium; design; epidemiology study; experience; glucose metabolism; heart disease risk; improved; indexing; innovation; laboratory experience; lipid metabolism; liver injury; longitudinal analysis; microbial; monocyte; multidisciplinary; novel; tool; virtual

Project Summary Human immunodeficiency virus (HIV) infected (HIV+) people have up to 50% excess risk of atherosclerotic cardiovascular disease (ASCVD, i.e. acute myocardial infarction, ischemic stroke) compared to uninfected people. This excess ASCVD risk is not explained by traditional cardiovascular disease (CVD) risk factors (e.g. smoking, hypertension). Liver disease is common among HIV+ people, and the liver regulates immuno- metabolic processes associated with atherosclerosis (e.g. inflammation, dyslipidemia and microbial translocation). Whether liver injury is in the causal pathway between HIV and incident ASCVD is unknown. The objective of this application is to understand whether liver injury contributes to the excess risk of ASCVD among HIV+ compared to uninfected people. The knowledge gained will be used to assess ways to improve existing ASCVD risk prediction tools in HIV+ populations. For these objectives, we will leverage existing NHLBI/NIAAA-funded cohorts to: 1) assess whether liver injury mediates the relationship between HIV infection and excess ASCVD risk; 2) investigate associations between liver injury and biomarkers of a) subclinical CVD, b) immuno-metabolism by HIV status; and 3) assess whether accounting for liver injury improves ASCVD risk prediction in HIV. If liver injury explains some of the excess ASCVD risk observed among HIV+ people, this would have important implications: It would reveal a novel, preventable, potentially reversible ASCVD risk factor (liver injury) that results in worse clinical outcomes for HIV+ compared to uninfected people. Two innovations in this study are: 1) the use of existing data from the Veteran's Aging Cohort Study (VACS), a large (N~150,000), national sample of HIV+ and uninfected Veterans with a rich collection of longitudinal clinical data; and 2) a causal inference strategy combining epidemiological studies of clinical ASCVD events, mechanistic studies of subclinical atherosclerosis risk and ASCVD risk prediction. Dr. So-Armah has a PhD in Epidemiology, experience designing and conducting biostatistical analyses, and a strong publication and collaboration record in the field of HIV, comorbid diseases and CVD. To successfully complete this career development award, he will pursue further didactic, experiential (clinical rotations), and professional training. With the activities proposed in this application, he will transition to an independent investigator, with expertise in novel potential mechanisms of CVD (e.g. liver injury), in the setting of HIV. He will be able to combine 1) population and clinical science, 2) understanding of pathology at the molecular level, 3) causal inference epidemiology and biostatistics methods, and 4) big data analytics to answer questions of public health importance in HIV and CVD. This inter-disciplinary K01 application is supported by a multi- disciplinary mentorship team that has a history of successful collaboration and expertise spanning HIV, hepatology, CVD, causal inference, longitudinal data analysis, and population, clinical and basic sciences.

项目摘要 感染的人类免疫缺陷病毒（HIV）患者患动脉粥样硬化的风险高达50％ 与未感染 人们。传统的心血管疾病（CVD）风险因素（例如， 吸烟，高血压）。肝病在艾滋病毒+人中很常见，肝脏调节免疫 与动脉粥样硬化相关的代谢过程（例如炎症，血脂异常和微生物 易位）。肝损伤是否在HIV和入射ASCVD之间的因果途径中尚不清楚。这 该应用的目的是了解肝损伤是否有助于ASCVD的过剩风险 与未感染的人相比，在艾滋病毒+中。获得的知识将用于评估改进的方法 HIV+人群中的现有ASCVD风险预测工具。对于这些目标，我们将利用现有的 NHLBI/NIAAA资助的队列：1）评估肝损伤是否介导HIV之间的关系 感染和ASCVD过多的风险； 2）研究肝损伤与A的生物标志物之间的关联） 亚临床CVD，b）艾滋病毒状况的免疫代谢； 3）评估是否考虑肝损伤 改善HIV中ASCVD风险预测。如果肝损伤解释了观察到的一些多余的ASCVD风险 在艾滋病毒+人中，这将具有重要的含义：它将揭示出一种小说，可预防的，潜在的 可逆的ASCVD危险因素（肝损伤），与HIV+相比，HIV+的临床结果较差 未感染的人。这项研究中的两项创新是：1）使用退伍军人衰老中的现有数据 队列研究（VACS），大型（N〜150,000），全国艾滋病毒+样本和未感染的退伍军人 纵向临床数据的收集； 2）结合流行病学研究的因果推理策略 临床ASCVD事件，亚临床动脉粥样硬化风险的机理研究和ASCVD风险预测。博士 So-Armah拥有流行病学博士学位，设计和进行生物统计分析的经验以及A 在艾滋病毒，合并症和CVD领域的强大出版和协作记录。成功 填写这个职业发展奖，他将寻求进一步的教学，体验式（临床轮换）和 专业培训。随着本申​​请中提出的活动，他将过渡到独立 研究人员在HIV的情况下具有CVD的新型潜在机制（例如肝损伤）的专业知识。他 将能够结合1）种群和临床科学，2）对分子水平的病理的理解， 3）因果推理流行病学和生物统计学方法，以及4）大数据分析回答问题 公共卫生在HIV和CVD中的重要性。该跨学科的K01申请得到了多种多样的支持 纪律指导团队具有成功的合作和专业知识的历史，跨越了艾滋病毒 肝病学，CVD，因果推断，纵向数据分析以及人群，临床和基本科学。

项目成果

HIV and Cardiovascular Disease: Update on Clinical Events, Special Populations, and Novel Biomarkers.

• DOI: 10.1007/s11904-018-0400-5
• 发表时间: 2018-06
• 期刊: Current HIV/AIDS reports
• 影响因子: 4.6
• 作者: So-Armah K;Freiberg MS
• 通讯作者: Freiberg MS

HIV and cardiovascular disease.

• DOI: 10.1016/s2352-3018(20)30036-9
• 发表时间: 2020-04
• 期刊: LANCET HIV
• 影响因子: 16.1
• 作者: So-Armah, Kaku;Benjamin, Laura A.;Bloomfield, Gerald S.;Feinstein, Matthew J.;Hsue, Priscilla;Njuguna, Benson;Freiberg, Matthew S.
• 通讯作者: Freiberg, Matthew S.