Patterns of Cardiopulmonary health across the life course

整个生命过程中心肺健康的模式

• 批准号: 10634635
• 负责人: Sadiya Sana Khan
• 金额: $ 67.79万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10634635
• 关键词: Adult; Affect; Age; Age of Onset; Air Pollution; Ancillary Study; Biological Assay; Biological Markers; Biological Process; Black race; Cardiac; Cardiac health; Cardiopulmonary; Cardiovascular system; Cause of Death; Chronic lung disease; Clinical; Coronary Artery Risk Development in Young Adults Study; Data; Detection; Disease; EFRAC; Echocardiography; Elderly; Epidemiology; Event; Evolution; Four-dimensional; Functional disorder; Goals; Health; Health Transition; Heart; Heart Diseases; Heart failure; Image; Impairment; Individual; Inflammation; Inflammatory; Intervention; Joints; Left; Left ventricular structure; Life; Life Cycle Stages; Link; Lung; Lung diseases; Magnetic Resonance Imaging; Measures; Mechanics; Mediating; Mediator; Morbidity - disease rate; Multimodal Imaging; National Heart, Lung, and Blood Institute; Outcome Study; Participant; Pathway interactions; Pattern; Phenotype; Predisposition; Prevention; Prevention strategy; Proteomics; Public Health; Pulmonary Emphysema; Pulmonary Heart Disease; Pulmonary Hypertension; Race; Research; Respiratory Tract Infections; Risk; Risk Factors; Risk Marker; Scanning; Sex Differences; Spirometry; Strategic vision; Structure; Symptoms; Systems Biology; Testing; Time; Tobacco; Tobacco use; United States; Ventricular; Ventricular End-Diastolic Volumes; Viral Respiratory Tract Infection; Work; X-Ray Computed Tomography; advanced disease; blood-based biomarker; cardiac magnetic resonance imaging; clinically relevant; comorbidity; critical period; design; disorder prevention; health care service utilization; hemodynamics; imaging study; lung health; lung injury; middle age; mortality; multidisciplinary; novel; phenotypic data; pulmonary function; resilience; risk sharing; screening; theories; tobacco exposure; young adult

ABSTRACT Chronic lung disease and heart failure (HF) are highly prevalent, commonly co-occur, and are associated with significant morbidity and mortality. Work from our group and others has demonstrated an independent relationship between chronic lung disease and incident HF that may be driven in part by inflammation. We have also documented that even in the absence of symptomatic lung disease, impaired lung function defined by spirometry is associated with adverse cardiac remodeling on echocardiography and incident HF events. While symptomatic lung disease and HF often occur in the elderly, many younger adults have relatively asymptomatic impairment in lung health and cardiac structure and function. These subclinical cardiopulmonary abnormalities develop during the key modifiable period from young adulthood to midlife. However, data are sparse on the timing and associated mechanisms of the transition from health to disease spanning young adulthood to midlife, and related race-sex differences. Without identifying these unique patterns of change, it will not be possible to screen for subclinical changes and employ prevention strategies prior to irreversible damage in the lung and heart. This requires upstream identification at the earliest detectable change. While spirometry is the gold standard for lung disease detection, it is a relatively crude and insensitive measure of impaired lung health. In contrast, lung injury (quantified using a novel local histogram analysis developed and validated by our group) from computed tomography (CT) scans is a more sensitive and earlier indicator of impaired lung health (e.g. due to tobacco, air pollution, and respiratory viral infection). Therefore, we now propose to take advantage of the Coronary Artery Risk Development in Young Adults (CARDIA) study’s unique platform to study the temporal relationship of and mechanisms underlying the transition from lung and heart health to disease. To-date, our group has investigated the predictors and consequences of impaired lung health and HF, separately, in CARDIA. In this project, we will build upon our prior work by analyzing CT scans to determine the concurrent evolution of lung injury and adverse cardiac remodeling and identify mechanisms by assaying a multitude of blood-based biomarkers (using a multiplexed array) and performing 4-dimensional flow cardiovascular magnetic resonance imaging (cMRI). We will test the hypothesis that detailed imaging and blood-based markers can inform clinically relevant endotypes reflecting dynamic changes in lung injury and adverse cardiac remodeling during a key vulnerable period of life through the following specific aims: (1) Determine the longitudinal association between lung injury and left ventricular end-diastolic volume (LVEDV); (2) Determine the risk of subclinical and clinical HF among joint lung injury and LVEDV trajectory groups; and (3) Determine the hemodynamic mediators of the association between lung injury and adverse cardiac remodeling. This study will investigate factors associated with transitions from cardiopulmonary health to disease and associated mechanisms, and in doing so, will identify screening strategies and contribute novel pathways for targeted disease interception of lung and heart disease.

抽象的 慢性肺部疾病和心力衰竭（HF）高度普遍，通常是同时发生的，并且与 显着的发病率和死亡率。我们小组和其他人的工作表现出了独立 慢性肺疾病与事件HF之间的关系可能部分由炎症驱动。我们有 还记录到，即使没有症状性肺病，肺功能受损 肺活量测定法与超声心动图和事件HF事件的不良心脏重塑有关。尽管 有症状的肺部病和HF通常发生在老年人中，许多年轻人患有相对无症状的年轻人 肺部健康和心脏结构和功能的损害。这些亚临床心肺异常 从成年到中年的关键可修改时期发展。但是，数据在 从健康到中年的疾病过渡到疾病的时间和相关机制， 和相关的种族性差异。如果不确定这些独特的变化模式，就不可能 在肺部发生不可逆损害之前，筛选亚临床变化和员工预防策略 心。这需要最早可检测到的上游标识。而肺活量测定法是黄金 肺部疾病检测的标准是对肺部健康受损的相对粗略和不敏感的测量。 对比，肺损伤（使用我们小组开发和验证的新型局部直方图分析进行了量子） 来自计算机断层扫描（CT）扫描是一个更敏感的肺部健康状况不佳的指标（例如 烟草，空气污染和呼吸道病毒感染）。因此，我们现在建议利用 年轻人的冠状动脉风险发展（Cardia）研究的独特平台研究临时性 从肺和心脏健康转变为疾病的过渡的关系和机制的关系。迄今为止，我们的 集团在Cardia中分别研究了肺部健康和HF受损的预测因素和后果。 在这个项目中，我们将通过分析CT扫描来确定同时发展的基础 肺损伤和不良心脏重塑，并通过分析多种血液来识别机制 生物标志物（使用多重阵列）并执行4维流量心血管磁共振 成像（CMRI）。我们将测试以下假设，即详细的成像和基于血液的标记可以在临床上告知 相关的内型反映了肺部肺损伤和不良心脏重塑的动态变化 通过以下特定目的通过以下特定目标：（1）确定纵向关联 肺部损伤和左心室末端 - 舒张体积（LVEDV）； （2）确定亚临床和临床HF的风险 在关节肺损伤和LVEDV轨迹组中； （3）确定的血流动力学介质 肺损伤和不良心脏重塑之间的关联。这项研究将研究相关的因素 通过从心肺健康到疾病和相关机制的过渡，这样做会确定 筛查策略，并为肺部疾病和心脏病的靶向疾病拦截贡献新的途径。

项目成果

The 2017 American College of Cardiology/American Heart Association Hypertension Guideline and Blood Pressure in Older Adults.

2017 年美国心脏病学会/美国心脏协会高血压指南和老年人血压。

• DOI: 10.1016/j.amepre.2023.04.011
• 发表时间: 2023
• 期刊: American journal of preventive medicine
• 影响因子: 5.5
• 作者: Wang,MichaelC;Petito,LuciaC;Pool,LindsayR;Foti,Kathryn;Juraschek,StephenP;McEvoy,JohnW;Nambi,Vijay;Carnethon,MercedesR;Michos,ErinD;Khan,SadiyaS
• 通讯作者: Khan,SadiyaS

Moving the Paradigm Forward for Prediction and Risk-Based Primary Prevention of Heart Failure in Special Populations.

推动特殊人群心力衰竭预测和基于风险的一级预防的范例。

• DOI: 10.1007/s11883-022-01009-7
• 发表时间: 2022
• 期刊: Current atherosclerosis reports
• 影响因子: 5.8
• 作者: Everitt,IanK;Trinh,KatherineV;Underberg,DanielL;Beach,Lauren;Khan,SadiyaS
• 通讯作者: Khan,SadiyaS

Cardiovascular Health in the Postpartum Period.

产后的心血管健康。

• DOI: 10.1001/jama.2023.19192
• 发表时间: 2023
• 期刊: JAMA
• 作者: Khan,SadiyaS;Grobman,WilliamA;Cameron,NatalieA
• 通讯作者: Cameron,NatalieA

Social and Psychosocial Determinants of Racial and Ethnic Differences in Cardiovascular Health in the United States Population.

美国人口心血管健康种族和民族差异的社会和心理社会决定因素。

• DOI: 10.1161/circulationaha.122.061991
• 发表时间: 2023
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Shah,NilayS;Huang,Xiaoning;Petito,LuciaC;Bancks,MichaelP;Ning,Hongyan;Cameron,NatalieA;Kershaw,KiarriN;Kandula,NamrathaR;Carnethon,MercedesR;Lloyd-Jones,DonaldM;Khan,SadiyaS
• 通讯作者: Khan,SadiyaS

Leveraging the Metabolome: Translating Social Risk Into Biological Pathways.

• DOI: 10.1161/circresaha.122.321700
• 发表时间: 2022-09-16
• 期刊: CIRCULATION RESEARCH
• 影响因子: 20.1
• 作者: Mehta, Rupal;Khan, Sadiya S.
• 通讯作者: Khan, Sadiya S.