Endogenous Cardiac Glycosides in AASK

描述(申请人提供)：慢性肾脏疾病(CKD)在美国估计有1900万成年人受到影响，并与心血管疾病(CVD)和死亡率的风险增加有关。这种风险增加的部分原因是几种心血管危险因素的患病率上升，包括高血压、左心室肥厚(LVH)和心力衰竭，随着肾功能下降，这些因素的患病率和严重性都会增加。非裔美国人患有高血压和慢性肾脏病的比例更高，与白人相比，他们患上与肾功能障碍相关的心血管疾病的风险可能更高。CKD患者特别容易患上“尿毒症心肌病”，这种疾病的特征是左心室肥厚、舒张期功能障碍和氧化应激，这会显著增加心血管疾病的风险。然而，CKD导致这些变化的机制在很大程度上是未知的。最近发现了一类新的内源性激素，包括哇巴因和华蟾素。这些激素在慢性肾脏病患者中显著升高，并可能通过几种不同的途径对心血管系统产生影响。我们假设这些激素在从慢性肾脏疾病到左心室肥厚、心力衰竭和随后的心血管疾病的过程中发挥核心作用。我们计划在参加非裔美国人肾脏疾病和高血压研究(AASK)队列研究的参与者中研究这些相关性。AASK的队列研究招募了患有高血压肾病的非裔美国人。参与者接受了多次临床访问、组织多普勒超声心动图和240小时动态血压监测。我们建议在随机抽样的255名AASK患者中检测内源性哇巴因和马利诺蟾毒配基，并将这些测量与肾功能指标(估计的肾小球滤过率、蛋白尿)、昼夜血压、NT-proBNP、心肌肌钙蛋白I以及左心室几何和功能联系起来。这一领域的进一步研究有可能确定新的预后和治疗目标，以减少这一高危人群心血管疾病的发病率上升。公共卫生相关性：我们希望了解两种强心激素在慢性肾脏疾病患者心血管疾病的发生中所起的作用。这些信息可能有助于确定治疗或预防的目标，以降低慢性肾脏疾病患者心血管疾病的高风险。

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) affects an estimated 19 million adults in the US and is associated with an elevated risk of cardiovascular disease (CVD) and mortality. This increased risk is partially explained by an elevated prevalence of several CVD risk factors, including hypertension, left ventricular hypertrophy (LVH) and heart failure, which increase in prevalence and severity as kidney function declines. African Americans are disproportionately afflicted with hypertension and CKD, and may be at higher risk of CVD associated with kidney dysfunction than are whites. Individuals with CKD are particularly susceptible to developing "uremic cardiomyopathy," a condition characterized by LVH, diastolic dysfunction and oxidative stress, which impart a significant increase in CVD risk. The mechanisms through which CKD causes these changes, however, are largely unknown. A new class of endogenous hormones, including ouabain and marinobufagenin, has recently been characterized. These hormones are significantly higher in persons with CKD, and may have effects on the cardiovascular system through several different pathways. We hypothesize that these hormones play a central role in the pathway leading from chronic kidney disease to LVH, heart failure and subsequent cardiovascular disease. We plan to study these associations in participants enrolled in the African American Study of Kidney Disease and Hypertension (AASK) Cohort Study. The AASK Cohort Study enrolled African Americans with hypertensive kidney disease. Participants underwent numerous clinic visits, tissue Doppler echocardiography, and 240hour ambulatory blood pressure monitoring. We propose to measure endogenous ouabain and marinobufagenin in a random sample of 255 AASK participants and coorelate these measures with markers of kidney function (estimated glomerular filtration rate, albuminuria), daytime and nighttime blood pressure, NT-proBNP, cardiac troponins I, and left ventricular geometry and function. Further research in this area has the potential to identify new targets for prognosis and treatment to reduce the elevated incidence of cardiovascular disease in this high-risk population. PUBLIC HEALTH RELEVANCE: We hope to learn what role two cardiotonic hormones play in the development of cardiovascular disease among individuals with chronic kidney disease. This information may help identify targets for treatment or prevention to reduce the high risk of cardiovascular disease in patients with chronic kidney disease.