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

肺动脉高压是肺动脉压力升高，其可由多种原因引起。 心脏和肺部疾病。肺动脉高压导致的右心室（RV）后负荷慢性增加 埃兹导致右心室肥大并最终导致右心室衰竭。虽然全身性高血压的重要性， 随后的左心室肥厚是相当明确的，我们对肺动脉高压的影响的理解是， 相比之下，右心室的高血压是微不足道的。这种知识差距首先是由于 对RV和肺部进行准确和无创评估的难度更大 脉管系统此外，肺动脉高压患者通常会出现晚期肺动脉高压， 由于对问题认识不足和难以解决， 诊断.这一知识差距最令人关切，因为疾病的发病率和死亡率 肺动脉高压和右心室衰竭正在增加，特别是在少数民族和老年美国人中。 内皮功能障碍包括高凝状态和炎症的主要成分， 肺动脉高压和右心室衰竭针对内皮细胞的医学疗法实际上 发现恢复抗血栓形成特性，减少炎症，减轻症状，延长生存期 在某些形式的肺动脉高压。然而，内皮功能障碍与 亚临床肺血管疾病和右心室衰竭的研究尚不充分。 多种族动脉粥样硬化研究（梅萨）是一项由NHLBI赞助的为期10年的前瞻性队列研究 6814例基线时无临床心血管疾病的少数民族患者的研究。 在2000-2001年，5099名梅萨参与者接受了基线心脏MRI检查，此外还接受了多项其他检查。 措施和放血。在2006-2007年，随机抽取1720名患者， 心脏核磁共振成像我们建议研究肺血管内皮功能与RV的关系 通过阅读4200个可解释基线和1000个随访心脏MRI的RV测量值， 评估内皮功能的生物标志物。 我们的目标是：1）建立正常值和指标的RV质量，RV体积，和RV射血分数， 根据性别、人种和种族进行梅萨，2）以确定是否血浆测量，如von Willebrand 因子、可溶性血栓调节蛋白、C-反应蛋白、白细胞介素-6和纤维蛋白原与RV相关 质量和RV射血分数，以及3）确定是否血浆测量内皮功能障碍， 基线预测随访时RV质量和RV射血分数的变化。 本研究将重点关注肺血管疾病和RV衰竭的亚临床标志物， 影响美国老年人和少数民族的日益严重的疾病。

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 eads 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 are 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.