Endothelial Dysfunction and the RV in the Multi-Ethnic Study of Atherosclerosis

描述（由申请人提供）：肺动脉高压是由多种心肺疾病引起的肺动脉压升高。肺动脉高压引起的右心室负荷长期增加可导致右心室肥厚并最终导致右心室衰竭。虽然全身性高血压和随后的左心室肥厚的重要性是非常明确的，但相比之下，我们对肺动脉高压对左心室的影响的了解是微不足道的。这种知识上的差距首先是由于对右心室和肺血管系统进行准确和无创评估的难度较大。此外，由于对问题认识不足和诊断困难，肺动脉高压患者就诊时往往伴有晚期右心室结构改变和严重的右心室衰竭。由于肺动脉高压和右心室衰竭的发病率和死亡率正在增加，特别是在少数民族和老年人中，这种知识差距是最令人担忧的。内皮功能障碍包括高凝性和炎症的主要成分，见于肺动脉高压和心室衰竭。针对内皮细胞的医学治疗实际上已经被发现可以恢复抗血栓特性，减少炎症，减轻症状，并延长某些形式的肺动脉高压的生存期。然而，内皮功能障碍与亚临床肺血管疾病和右心室衰竭的关系尚未得到充分研究。动脉粥样硬化多民族研究（MESA）是nhlbi赞助的一项为期10年的前瞻性队列研究，纳入6814例基线时无临床心血管疾病的少数民族患者。在2000-2001年期间，5099名MESA参与者接受了基线心脏MRI检查以及多种其他措施和静脉切开术。2006-2007年，随机抽取1720名患者进行心脏MRI检查。我们建议通过读取4200个可解释基线和1000个随访心脏mri的RV测量值，并评估内皮功能的生物标志物，来研究肺血管内皮功能和RV功能之间的关系。我们的目的是：1)根据性别、种族和民族建立MESA中右心室质量、右心室体积和右心室射血分数的标准值和指标；2)确定血浆测量，如血管性血友病因子、可溶性血栓调节蛋白、c反应蛋白、白细胞介素-6和纤维蛋白原，是否与右心室质量和右心室射血分数相关；3)确定基线时血浆内皮功能障碍测量是否能预测随访时右心室质量和右心室射血分数的变化。本研究将重点关注肺血管疾病和右心室衰竭的亚临床标志物，这是影响老年人和少数民族的越来越重要的疾病。

DESCRIPTION (provided by applicant): Pulmonary hypertension is an elevation in pulmonary artery pressure which may result from a variety of heart and lung diseases. Chronically increased right ventricular (RV) afterload from pulmonary hypertension leads to RV hypertrophy and eventual RV failure. While the importance of systemic hypertension and subsequent left ventricular hypertrophy is quite well-defined, our understanding of the effects of pulmonary hypertension on the RV is infinitesimal by comparison. This gap in knowledge is firstly attributable to the greater difficulty in performing accurate and non-invasive assessments of the RV and the pulmonary vasculature. Also, patients with pulmonary hypertension usually present to medical attention with advanced RV structural changes and severe RV failure due to under-recognition of the problem and difficulty in diagnosis. This knowledge gap is most concerning since the morbidity and mortality attributable to pulmonary hypertension and RV failure are increasing, especially among minority and older Americans. Endothelial dysfunction incorporates the primary components of hypercoagulability and inflammation seen in pulmonary hypertension and RV failure. Medical therapies targeted at the endothelium have actually been found to restore anti-thrombotic properties, decrease inflammation, reduce symptoms, and prolong survival in certain forms of pulmonary hypertension. However, the relationship of endothelial dysfunction to subclinical pulmonary vascular disease and RV failure is not well-studied. The Multi-Ethnic Study of Atherosclerosis (MESA) is an NHLBI-sponsored, ten-year, prospective cohort study of 6814 patients with strong minority representation without clinical cardiovascular disease at baseline. In 2000-2001, 5099 MESA participants underwent baseline cardiac MRI in addition to multiple other measures and phlebotomy. In 2006-2007, a random sample of 1720 patients is slated to undergo repeat cardiac MRI. We propose to study the relationship between pulmonary vascular endothelial function and RV function by reading the RV measures for 4200 interpretable baseline and 1000 follow-up cardiac MRIs and assessing biomarkers of endothelial function. We aim to 1) establish normative values and indices of RV mass, RV volumes, and RV ejection fraction in MESA by gender, race, and ethnicity, 2) to determine whether plasma measures, such as von Willebrand factor, soluble thrombomodulin, C-reactive protein, interleukin-6, and fibrinogen, are associated with RV mass and RV ejection fraction, and 3) to determine whether plasma measures of endothelial dysfunction at baseline predict change in RV mass and RV ejection fraction at follow-up. This study will focus on subclinical markers of pulmonary vascular disease and RV failure, which are increasingly important diseases impacting on older and minority Americans.