Cardiac Microstructure and Heart Failure Risk in the Community

 描述(由申请人提供)：心力衰竭(HF)仍然是美国发病率和死亡率的主要原因。随着大多数新的心力衰竭诊断发生在75岁以上的成年人，心力衰竭现在被认为是一种生命过程疾病。从逻辑上讲，一个人患心力衰竭的风险增加应该表现为随着年龄的增长和累积的风险暴露，可以随着时间的推移而跟踪的渐进性心脏异常。然而，传统的成像方法在区分或多或少可能发展为临床心衰的个体方面的能力有限。我们和其他人已经证明，先进的心脏微结构超声测量可以可靠地量化心肌细胞和细胞外成分的组织水平变化，包括纤维化。根据我们以前的工作和初步数据，我们假设心脏微结构随时间的变化受到累积暴露于危险因素的影响，心脏微结构变化的不同模式可以区分心力衰竭风险较高或较低的个体。因此，我们建议使用一种新的超声方法来研究心脏微结构在生命过程中发生的变化，并导致心力衰竭的发展和相关的不良后果。具体地说，我们将调查：(1)心脏微结构的变化与年龄的自然历史和相关性，(2)心脏微结构的渐进性变化在多大程度上易患心衰，以及(3)心脏微结构作为预测社区居民各种心力衰竭预后风险的潜在用途。预计这项拟议研究的总体贡献将包括：全面了解心脏微结构在从危险因素到心力衰竭结果开始的过程中是如何改变的；以及评估一种新的基于成像的心脏微结构测量方法，该方法可以作为一种广泛使用的、具有成本效益的工具来预测高危个体的心力衰竭。这些贡献将是重大的，因为它们将为制定有针对性的干预措施奠定基础，以减少一般人口中与心力衰竭相关的发病率和死亡率。

 DESCRIPTION (provided by applicant): Heart failure (HF) remains a leading cause of morbidity and mortality in the United States. With the majority of new HF diagnoses occurring in adults over age 75 years, HF is now recognized as a life course disease. It logically follows that a person's increasing risk for HF should manifest with progressive cardiac abnormalities that can be tracked over time, in relation to advancing age and cumulative risk exposures. However, conventional imaging methods have limited ability to discriminate between individuals more or less likely to develop clinical HF. We and others have shown that advanced ultrasonic measures of cardiac microstructure can reliably quantify tissue-level alterations in the cellular and extracellular composition of the myocardium, including fibrosis. Based on our prior work and preliminary data, we hypothesize that changes in cardiac microstructure over time are influenced by cumulative exposure to risk factors and that distinct patterns of change in cardiac microstructure can differentiate individuals at greater or lesser risk for HF. Therefore, we propose to use a novel ultrasonic method to study the changes in cardiac microstructure that occur over the life course and leading up to the development of HF and related adverse outcomes. Specifically, we will investigate: (1) the natural history and correlates of change in cardiac microstructure with aging, (2) the extent to which progressive alterations in cardiac microstructure predispose specifically to HF, and (3) the potential utility of cardiac microstructure to serve as a prognostic marker of risk for adverse outcomes across the spectrum of HF among persons living in the community. The overall contribution of the proposed research is expected to include: a comprehensive understanding of how cardiac microstructure is altered during the progression from risk factors to the onset of HF outcomes; and evaluation of a novel imaging-based measure of cardiac microstructure that could serve as a widely-accessible and cost-effective tool for predicting HF in individuals at risk. These contributions will be significant because they will lay groundwork for developing targeted interventions to reduce HF related morbidity and mortality in the population at large.