Transition from Risk Factors to Early HF: Prevalence, Pathogenesis, and Phenomics

从危险因素到早期心力衰竭的转变：患病率、发病机制和表型组学

• 批准号: 9115219
• 负责人: Alain Gerald Bertoni
• 金额: $ 190.02万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9115219
• 关键词: Address; Adult; Affect; Age; Air Pollution; Ancillary Study; Anthropometry; Atherosclerosis; Big Data; Biological Markers; Blood Pressure; Blood Vessels; Cardiac; Cardiac Output; Cardiopulmonary; Cardiovascular system; Chronic Kidney Failure; Clinical; Clinical Trials; Code; Communities; Coronary; Coronary Arteriosclerosis; Coupling; Data; Development; Diabetes Mellitus; Diet; Dyspnea; EFRAC; Early Diagnosis; Echocardiography; Elderly; Electrocardiogram; Epidemiologic Studies; Epidemiology; Ethnic Origin; Exercise stress test; Fatigue; Functional disorder; Future; Galectin 3; Gender; General Population; Goals; Health; Heart; Heart Atrium; Heart failure; Hospitalization; Hypertension; ICD-9; Image; Incidence; Individual; Laboratories; Lead; Left; Machine Learning; Magnetic Resonance Imaging; Measures; Mechanics; Mediating; Methods; Myocardial; Myocardial Infarction; Obesity; Outcome; Outpatients; Participant; Pathogenesis; Patients; Phenotype; Physical activity; Physiological; Population; Prevalence; Prevention; Prevention strategy; Public Health; Race; Recruitment Activity; Renal function; Rest; Risk; Risk Factors; Sampling; Spirometry; Staging; Stress; Structure; Surveys; Symptoms; Syndrome; Techniques; Testing; Time; Tissues; Ultrasonography; Validation; Ventricular; Walking; Weight; aged; arterial stiffness; arterial tonometry; base; brachial artery; clinical Diagnosis; cohort; design; endothelial dysfunction; epidemiology study; ethnic diversity; exercise intolerance; fasting glucose; fitness; functional status; high risk; indexing; novel; novel marker; phenomics; population based; pressure; screening; statistics; trend

 DESCRIPTION (provided by applicant): Heart failure (HF) is a major public health problem: it affects >6 million people in the U.S., it is the #1 cause of hospitalization and readmission in older adults, and 5-year survival after HF hospitalization is a dismal 35%, regardless of underlying ejection fraction (EF). These statistics highlight the urgent need for prevention of HF and better understanding of how and why HF develops in high-risk individuals. However, a critical limitation of prior population-based studies is the ascertainment of incident HF based on hospitalizations for HF and/or signs of overt volume overload. Many older individuals may suffer from early HF: breathlessness, fatigue, and exercise intolerance (without overt volume overload) due to underlying cardiac structure/function abnormalities, typically with a preserved EF (i.e. early HFpEF). Thus, the current epidemiology of HF is most likely missing a major form of prevalent HF. In this ancillary study of the Multi-Ethnic Study of Atherosclerosis (MESA, Year-15 Exam, n=3500), we will define early HF in a contemporary, multi-ethnic, elderly cohort; we will utilize cutting- edge indices of cardiac mechanics and ventricular-arterial interactions, including Lagrangian strain and time- varying pressure-stress analyses; and we will perform novel phenomics analyses to better characterize the interplay of risk factors and cardiac structure/function abnormalities (i.e., multi-dimensional phenotypic signatures) as they relate to early and overt HF. The aims of our study are to: (1) determine the prevalence of early HF using a combination of validated symptom surveys, 6-minute walk test, NTproBNP, and echocardiography, with validation using cardiopulmonary exercise testing (CPEX); (2) better understand the pathophysiology of early HF, particularly HFpEF; and (3) delineate the key phenotypic signatures associated with early and overt HF. The proposed exam will include anthropometry, blood pressure, symptom surveys, functional status (6-minute walk test), physical activity, laboratory measures (NTproBNP, fasting glucose, renal function), and comprehensive echocardiography (with tissue Doppler and speckle-tracking at rest and during physiologic maneuvers) in all participants. In sub-samples we will also measure arterial tonometry, novel biomarkers, and fitness (CPEX). We will utilize the wealth of data collected during the 5 prior MESA exams to perform longitudinal analyses (including latent class trajectory and statistical learning analyses) to determine the extent to which risk factors are associated with early HF, particularly early HFpEF. By the end of our 4-year study, we will accomplish the following key goals, each of which will have a lasting impact on the field of HF: (1) we will establish the prevalence of early HF in the community; (2) we will have a standardized method for the screening/diagnosis of early HFpEF, validated by CPEX, and readily applicable to the clinical setting; (3) we will define novel mechanisms by which risk factors, alone and in combination, relate to abnormalities in cardiac mechanics and ventricular-arterial coupling in the general population; and (4) we will have defined phenotypic signatures of HF development that will inform future clinical trials for HF prevention and treatment.

 简介(由申请人提供)：心力衰竭(HF)是一个主要的公共卫生问题：在美国，它影响着600万人，它是老年人住院和再入院的头号原因，无论潜在的射血分数(EF)如何，心力衰竭住院后的5年存活率都是令人沮丧的35%。这些统计数据突出表明迫切需要预防心力衰竭，并更好地了解心力衰竭是如何以及为什么在高危人群中发展的。然而，先前基于人群的研究的一个关键限制是根据因心力衰竭住院和/或明显的容量超负荷的迹象来确定发生心力衰竭的情况。由于潜在的心脏结构/功能异常，许多老年人可能患有早期心衰：呼吸困难、疲劳和运动不耐受(没有明显的容量超负荷)，通常伴有保留的EF(即早期HFpEF)。因此，目前的HF流行病学很可能遗漏了流行的一种主要形式的HF。在这项动脉粥样硬化的多种族研究(MESA，15年检查，n=3500)的辅助研究中，我们将在当代、多种族、老年队列中定义早期心力衰竭；我们将利用心脏力学和心室-动脉相互作用的尖端指数，包括 拉格朗日应变和时变压力-应力分析；我们将进行新的表型分析，以更好地表征风险因素和心脏结构/功能异常(即多维表型特征)之间的相互作用，因为它们与早期和显性心衰有关。我们研究的目的是：(1)结合症状调查、6分钟步行试验、NTproBNP和超声心动图，结合心肺运动试验(CPEX)来确定早期心衰的患病率；(2)更好地了解早期心衰的病理生理学，特别是HFpEF；以及(3)描述与早期和显性心衰相关的关键表型特征。拟议的检查将包括所有参与者的人体测量、血压、症状调查、功能状态(6分钟步行试验)、体力活动、实验室测量(NTproBNP、空腹血糖、肾功能)以及全面的超声心动图(静息和生理动作时具有组织多普勒和斑点跟踪)。在子样本中，我们还将测量动脉血压计、新的生物标志物和适合度(CPEX)。我们将利用在之前的5次MESA考试中收集的丰富数据进行纵向分析(包括潜在的班级轨迹和统计学习分析)，以确定风险因素与早期HF，特别是早期HFpEF的关联程度。在我们为期4年的研究结束时，我们将实现以下关键目标，每个目标都将对心力衰竭领域产生持久的影响：(1)我们将建立社区早期心力衰竭的流行率；(2)我们将有一种标准化的方法筛查/诊断早期HFpEF，该方法经CPEX验证，并易于应用于临床；(3)我们将定义危险因素单独或联合与普通人群心脏力学异常和室动脉偶联相关的新机制；以及(4)我们将定义心力衰竭发展的表型特征，这将为未来的心力衰竭预防和治疗临床试验提供信息。