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.

提交本母公司补助金R 01 AG 062393的行政补充申请，以供审议， NOT-AG-22-014，特别关注通知：HIV/AIDS和衰老研究的行政补充 和PA-20-272，对现有NIH赠款和合作协议的行政补充。 预防和管理心血管疾病等慢性非传染性疾病 (CVD)是老龄化艾滋病毒感染者的优先事项。传统的心血管疾病危险因素不能完全解释增加的 在艾滋病毒感染者（PWH）中观察到的心血管疾病风险，以及艾滋病毒相关的炎症和免疫反应。 监管失调被认为会导致过度风险。事实上，已建立的CVD风险预测功能已被 低估了感染艾滋病的风险。PWH中心血管疾病风险的机制进一步复杂化， 合并感染丙型肝炎病毒（HCV），影响心脏代谢危险因素，并赋予 炎症状态父母补助金的目的是调查HCV与CVD风险的关系 在PWH。对父母补助金目标1的完整分析表明，HCV改变了父母补助金增加的趋势。 AMI的风险随年龄增长而增加，与年龄每增加10岁的PWH伴HCV患者相比， 没有HCV。在本补充申请中，我们建议使用这些发现来通知新的分析， 扩大父母补助金目标3中的心血管疾病风险预测分析。拟议的补充将雇用 来自NA-ACCORD队列的数据，并利用现有的研究基础设施来调查 HCV感染和年龄对PWH CVD风险预测的协同影响，目的是 为HIV和HCV感染者开发新的风险预测模型。其成果将 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 CVD风险预测的协同作用。我们将 将HCV和年龄的相互作用项纳入已建立的CVD风险预测函数，评估 与已建立的风险相比，纳入交互作用项是否提高了模型的准确性 预测功能，并与PWH队列中单独使用HCV的功能相关。新的准确性- 将通过区分和校准来评估开发的风险预测模型。 具体目标2：为PWH合并HCV感染开发定制的CVD风险预测模型。我们将 将HCV相关变量纳入已建立的患有HCV的PWH队列中的CVD风险预测函数。 在模型开发中还将考虑传统的CVD风险因素和HIV相关因素。的 将评估新风险预测功能的准确性，并与目标1中生成的模型进行比较 其目的是为HIV/HCV共感染个体开发最佳风险预测函数。