Cardiac Microstructure and Heart Failure Risk in the Community

 描述（由申请人提供）：心力衰竭（HF）仍然是美国发病和死亡的主要原因。由于大多数新诊断的心力衰竭发生在 75 岁以上的成年人中，心力衰竭现已被认为是一种终生疾病。从逻辑上讲，一个人心力衰竭风险的增加应该表现为进行性心脏异常，这些异常可以随着时间的推移进行跟踪，与年龄的增长和累积的风险暴露相关。然而，传统成像方法区分更有可能或不太可能发生临床心力衰竭的个体的能力有限。我们和其他人已经证明，心脏微观结构的先进超声测量可以可靠地量化心肌细胞和细胞外组成的组织水平变化，包括纤维化。根据我们之前的工作和初步数据，我们假设心脏微观结构随时间的变化受到累积暴露于危险因素的影响，并且心脏微观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颖的超声方法来研究生命过程中发生的心脏微观结构的变化，并导致心力衰竭的发生和相关不良后果。具体来说，我们将研究：（1）心脏微观结构变化与衰老的自然史和相关性，（2）心脏微观结构的渐进性改变在多大程度上特别容易诱发心力衰竭，以及（3）心脏微观结构作为社区居民心力衰竭不良后果风险预后标志的潜在效用。拟议研究的总体贡献预计包括： 全面了解心脏微观结构在从危险因素到心力衰竭结果发生的过程中如何改变；评估一种基于成像的新型心脏微观结构测量方法，该方法可以作为一种广泛使用且具有成本效益的工具来预测高危个体的心力衰竭。这些贡献将是意义重大的，因为它们将为制定有针对性的干预措施奠定基础，以减少广大人群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.