Study of Cardiac Mechanics in Systemic Hypertension

描述(申请人提供)：尽管知道高血压是心力衰竭的一个主要风险因素，但尚不清楚为什么一些高血压患者会患上心力衰竭综合症，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发展过程中，了解高血压心脏力学异常的决定因素是一个关键的未得到满足的需要。在大型流行病学研究中，敏感的超声心动图指标(心肌组织速度、应变和无创压力-容量分析)可以提供对心脏力学的洞察。我们建议在高血压遗传流行病学网络(HyperGEN)的家庭血压计划(FBPP)研究中使用最先进的斑点跟踪分析来量化心脏力学。通过在人群流行病学研究中研究心脏力学，我们的目标是：(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的收缩和舒张期心脏力学的遗传度；以及(3)在全基因组研究中确定与异常心脏力学相关的新基因位点，并在青年冠状动脉风险发展(CARDIA)研究和Hutterite家庭健康研究中重复进行。我们预计，这项研究的结果将：(1)为高血压异常心脏力学的发展提供更多的危险因素；以及(2)导致对决定高血压、肥厚和心力衰竭之间过渡的分子途径的理解的突破。 公共卫生相关性：高血压是心力衰竭最常见的危险因素，高血压和心力衰竭都是主要的公共卫生问题，会导致相当大的发病率和死亡率。因此，重要的是要更好地理解为什么一些高血压患者会患上心力衰竭，而另一些人则不会。由于高血压时心脏力学异常会导致心力衰竭综合征，因此，在这项流行病学研究中，确定与心脏力学异常相关的获得性和遗传性因素将为高血压心力衰竭的发病机制提供新的见解，并最终可能为高血压心脏病的预防和治疗找到新的治疗靶点。

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. PUBLIC HEALTH RELEVANCE: Hypertension is the most common risk factor for heart failure, and both hypertension and heart failure are major public health problems which cause substantial morbidity and mortality. It is therefore important to improve understanding of why some individuals with hypertension develop heart failure while others do not. Since abnormal cardiac mechanics in hypertension lead to the heart failure syndrome, determining the acquired and genetic factors associated with abnormal cardiac mechanics in this epidemiologic study will provide novel insights into the pathogenesis of heart failure in hypertension and may ultimately identify novel therapeutic targets for the prevention and treatment of hypertensive heart disease.