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。由于大多数新的HF诊断发生在75岁以上的成人中，HF现在被认为是一种生命过程疾病。从逻辑上讲，一个人的HF风险增加应该表现为随着时间的推移可以跟踪的进行性心脏异常，与年龄增长和累积风险暴露有关。然而，传统的成像方法在区分或多或少可能发展为临床HF的个体方面能力有限。我们和其他人已经表明，先进的超声测量心脏微观结构可以可靠地量化组织水平的变化，在细胞和细胞外组成的心肌，包括纤维化。基于我们先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HF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在生命过程中发生的心脏微结构的变化，并导致HF的发展和相关的不良后果。具体而言，我们将研究：（1）心脏微结构变化与衰老的自然史和相关性，（2）心脏微结构的进行性改变在多大程度上特别易患HF，以及（3）心脏微结构作为生活在社区的人群中HF谱不良结局风险的预后标志物的潜在效用。拟议研究的总体贡献预计将包括：全面了解心脏微结构在从风险因素到HF结局发作的进展过程中如何改变;以及评估一种基于成像的心脏微结构新指标，该指标可作为预测HF风险个体的广泛可及且具有成本效益的工具。这些贡献将是重要的，因为它们将为制定有针对性的干预措施奠定基础，以减少HF相关的发病率和死亡率在整个人口。

 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.