Enhancing cardiovascular risk estimation in individuals aging with HIV/HCV co-infection

加强对艾滋病毒/丙肝病毒合并感染的老年个体的心血管风险评估

• 批准号: 10613780
• 负责人: Virginia Athena Triant
• 金额: $ 41.83万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10613780
• 关键词: AIDS/HIV problem; Administrative Supplement; Affect; Age; Aging; Calibration; Cardiovascular Diseases; Chronic; Clinical; Data; Discrimination; Disease; Grant; HIV; HIV/HCV; Hepatitis C; Hepatitis C co-infection; Hepatitis C virus; Immune; Individual; Inflammation; Inflammatory; Modeling; Persons; Population; Prevention; Research; Research Infrastructure; Risk; Risk Factors; U-Series Cooperative Agreements; United States National Institutes of Health; cardiometabolic risk; cardiovascular disorder risk; cardiovascular risk factor; clinically relevant; co-infection; cohort; improved; interest; model development; parent grant; prevent; public health priorities; response; risk prediction; risk prediction model

This administrative supplement to parent grant R01 AG062393 is submitted for consideration in response to NOT-AG-22-014, Notice of Special Interest: Administrative Supplements for HIV/AIDS and Aging Research and PA-20-272, Administrative Supplements to Existing NIH Grants and Cooperative Agreements. The prevention and management of chronic noncommunicable diseases such as cardiovascular disease (CVD) is a priority for the aging HIV population. Traditional CVD risk factors do not fully explain the increased CVD risk observed among people living with HIV (PWH), and HIV-related inflammation and immune dysregulation are thought to drive excess risk. Indeed, established CVD risk prediction functions have been demonstrated to underestimate risk in HIV. The mechanism of CVD risk in PWH is further complicated in the setting of co-infection with Hepatitis C virus (HCV), which affects cardiometabolic risk factors and confers an inflammatory state. The aims of the parent grant are to investigate the association of HCV with CVD risk among PWH. Completed analyses from Aim 1 of the parent grant indicate that HCV modifies the increasing risk of AMI with age, with a greater AMI risk per ten-year increase in age for PWH with HCV versus those without HCV. In this supplement application, we propose to use these findings to inform new analyses that extend the CVD risk prediction analyses in Aim 3 of the parent grant. The proposed supplement will employ data from the NA-ACCORD cohort and leverage existing research infrastructure to investigate the synergistic impact of HCV infection and age on CVD risk prediction in PWH, with the objective of developing a new risk prediction model for individuals living with HIV and HCV. The findings will answer critical and clinically relevant questions through the following Aims: Specific Aim 1: Assess the synergistic effect of HCV and age on CVD risk prediction in PWH. We will incorporate an interaction term for HCV and age into established CVD risk prediction functions, assessing whether inclusion of the interaction term improves the accuracy of models compared to established risk prediction functions and to a function with HCV alone among a cohort of PWH. The accuracy of newly- developed risk prediction models will be assessed via discrimination and calibration. Specific Aim 2: Develop a tailored CVD risk prediction model for PWH with HCV co-infection. We will incorporate HCV-related variables into established CVD risk prediction functions in a cohort of PWH with HCV. Traditional CVD risk factors and HIV-related factors will also be considered in model development. The accuracy of the new risk prediction function will be assessed and compared with models generated in Aim 1 with the objective of developing an optimal risk prediction function for HIV/HCV co-infected individuals.

对父母赠款R01 AG062393的这种行政补充提交了审议 NOT-AG-22-014，特别兴趣通知：艾滋病毒/艾滋病和老龄化研究的行政补品 和PA-20-272，为现有NIH赠款和合作协议的行政补充。 慢性非传染性疾病（例如心血管疾病）的预防和管理 （CVD）是艾滋病毒衰老人群的优先事项。传统的CVD风险因素无法完全解释增加 在艾滋病毒（PWH）患者中观察到的CVD风险以及与HIV相关的炎症和免疫 人们认为失调会导致多余的风险。确实，已建立的CVD风险预测功能已经 被证明低估了艾滋病毒的风险。 PWH中CVD风险的机制在 与丙型肝炎病毒（HCV）共同感染，该病毒影响心脏代谢危险因素并赋予 炎症状态。父母赠款的目的是调查HCV与CVD风险的关联 在PWH中。来自父母赠款的AIM 1完成的分析表明，HCV会修改增加 随着年龄的增长，AMI的风险，与HCV相比 没有HCV。在此补充申请中，我们建议使用这些发现来告知新分析 在父母赠款的AIM 3中扩展CVD风险预测分析。拟议的补充剂将雇用 来自NA-Accord队列的数据并利用现有的研究基础设施来研究 HCV感染和年龄对PWH中CVD风险预测的协同影响，目的是 为艾滋病毒和HCV患者开发新的风险预测模型。调查结果会 通过以下目的回答关键和临床相关问题： 具体目标1：评估HCV和年龄对PWH中CVD风险预测的协同作用。我们将 将HCV和年龄的交互项纳入已建立的CVD风险预测功能，评估 与已建立风险相比，包含交互项是否可以提高模型的准确性 预测功能和单独使用HCV的功能在PWH队列中。新近的准确性 开发的风险预测模型将通过歧视和校准进行评估。 特定目标2：通过HCV共感染为PWH开发量身定制的CVD风险预测模型。我们将 将与HCV相关的变量合并到与HCV的PWH队列中已建立的CVD风险预测函数中。 传统的CVD风险因素和与HIV相关的因素也将在模型开发中考虑。这 将评估新风险预测功能的准确性，并将其与AIM 1中产生的模型进行比较 目的是为HIV/HCV共感染的个体开发最佳风险预测功能。