Study of Cardiac Mechanics in Systemic Hypertension

描述（由申请人提供）：尽管知道高血压是心力衰竭的主要危险因素，但尚不清楚为什么有些高血压患者会发展为心力衰竭综合征，而另一些人则不会。由于心脏力学异常发生在从高血压到心力衰竭的过程中，了解高血压中心脏力学异常的决定因素是一个关键的未满足的需求。敏感的超声心动图指标（心肌组织速度、应变和无创压力-容积分析）可以在大型流行病学研究中提供对心脏力学的深入了解。我们建议在高血压遗传流行病学网络（HyperGEN）家庭血压项目（FBPP）研究中使用最先进的斑点跟踪分析来量化心脏力学。通过一项基于人群的流行病学研究，我们的目的是：(1)确定高血压患者心脏力学异常的获得性危险因素；(2)确定非裔美国人和白人心脏收缩和舒张力学的遗传性；(3)在青年人冠状动脉风险发展（CARDIA）研究和huterite家族健康研究中，通过与复制的全基因组关联研究，确定与异常心脏力学相关的新基因位点。我们预计本研究的结果将：(1)为高血压患者心脏力学异常发展的危险因素提供更好的理解；(2)在了解高血压、肥厚和心力衰竭之间转变的分子途径方面取得突破。

DESCRIPTION (provided by applicant): Despite knowledge that hypertension is a major risk factor for heart failure, it is unclear why some individuals with hypertension develop the heart failure syndrome while others do not. Since abnormalities in cardiac mechanics occur during the progression from hypertension to heart failure, understanding the determinants of abnormal cardiac mechanics in hypertension is a critical unmet need. Sensitive echocardiographic indices (myocardial tissue velocities, strain, and non-invasive pressure-volume analysis) can provide insight into cardiac mechanics in large epidemiologic studies. We propose to use state-of-the-art speckle tracking analysis to quantify cardiac mechanics in the Hypertension Genetic Epidemiology Network (HyperGEN) Study of the Family Blood Pressure Program (FBPP). By studying cardiac mechanics in a population-based epidemiologic study, we aim to: (1) determine the acquired risk factors for abnormal cardiac mechanics in hypertension; (2) determine heritability of systolic and diastolic cardiac mechanics in African Americans and whites; and (3) identify novel genetic loci associated with abnormal cardiac mechanics in a genome-wide association study with replication in the Coronary Artery Risk Development in Young Adults (CARDIA) Study and the Hutterite Family Health Study. We anticipate that results from this study will: (1) provide greater understanding of risk factors for the development of abnormal cardiac mechanics in hypertension; and (2) lead to a breakthrough in the understanding of the molecular pathways which dictate the transition between hypertension, hypertrophy, and heart failure.