Endogenous Cardiac Glycosides in AASK

AASK 中的内源性强心苷

• 批准号: 8404072
• 负责人: Brad C Astor
• 金额: $ 8.85万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-14 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8404072
• 关键词: Endogenous; Cardiac; Glycosides; AASK

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.

描述（由申请人提供）：慢性肾脏疾病（CKD）在美国影响约1900万成年人，并与心血管疾病（CVD）和死亡率的风险升高相关。这种增加的风险部分可以解释为几种心血管疾病危险因素的患病率升高，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程度都会增加。非裔美国人患高血压和慢性肾病的比例过高，与白人相比，患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”，这是一种以LVH、舒张功能障碍和氧化应激为特征的疾病，会显著增加心血管疾病的风险。然而，CKD引起这些变化的机制在很大程度上是未知的。一类新的内源性激素，包括哇巴因和马里诺bufagenin，最近已被表征。这些激素在CKD患者中明显升高，并且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LVH、心力衰竭和随后的心血管疾病的途径中发挥核心作用。我们计划在参加非裔美国人肾病和高血压研究（AASK）队列研究的参与者中研究这些关联。AASK队列研究招募了患有高血压肾病的非裔美国人。参与者接受了多次门诊就诊、组织多普勒超声心动图检查和240小时动态血压监测。我们建议在255名AASK参与者的随机样本中测量内源性瓦巴因和马里诺bufagenin，并将这些测量与肾功能标志物（估计肾小球滤过率、蛋白尿）、白昼夜血压、NT-proBNP、心脏肌钙蛋白I和左心室几何形状和功能相关联。在这一领域的进一步研究有可能确定预后和治疗的新靶点，以降低这一高危人群心血管疾病的发病率升高。公共卫生相关性：我们希望了解两种促心激素在慢性肾脏疾病患者心血管疾病发展中的作用。这一信息可能有助于确定治疗或预防目标，以降低慢性肾病患者心血管疾病的高风险。