Chronic Renal Insufficiency and Silent Progression of Aortic Stenosis (CRISP-AS)

慢性肾功能不全和无症状进展的主动脉瓣狭窄 (CRISP-AS)

基本信息

批准号：
10718275
负责人：
Jordan Blair Strom
金额：
$ 87.14万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10718275
关键词：
Address Adult Age Albuminuria Aorta Aortic Valve Stenosis Atherosclerosis Atherosclerosis Risk in Communities Atrial Fibrillation Biological Biological Markers Biological Models Blood Pressure Blood Vessels Calcium Cardiovascular Diseases Cardiovascular system Cessation of life Chest Chronic Kidney Failure Chronic Kidney Insufficiency Clinical Clinical Data Cohort Studies Communities Data Development Diabetes Mellitus Dialysis patients Dialysis procedure Disease Echocardiography Effectiveness Enrollment Etiology Fibrinogen Funding General Population Goals Heart Heart Valve Diseases Heart failure Image Individual Interleukin-6 Kidney Diseases Knowledge Link Lipoprotein (a)Measures Medical Modeling Myocardial Infarction National Heart, Lung, and Blood Institute National Institute of Diabetes and Digestive and Kidney Diseases Observational Study Obstruction Operative Surgical Procedures Outcome Participant Patients Perioperative Peripheral arterial disease Phenotype Physiologic pulse Physiology Population Prosthesis Race Renal function Reporting Research Risk Risk Factors Serum Severities Severity of illness Stroke TNF gene Testing Tobacco smoking behavior Transforming Growth Factor beta Visit adjudication aged alpha-Fetoproteins aortic valve aortic valve replacement calcification cardiovascular risk factor clinical risk cohort comparative coronary calcium scoring glomerular filtration hemodynamics human old age (65+)improved inorganic phosphate insight inter-individual variation mortality risk novel population based pre-clinical premature prevent prospective risk prediction sex

项目摘要

PROJECT SUMMARY Aortic stenosis (AS), is common and progression to symptomatic, severe AS is universally fatal without treatment with aortic valve replacement (AVR), though only 1/3 of individuals receive AVR, due in part to concerns about high perioperative risk and rapid valvular calcification/degeneration. Despite more than half a century of research on this topic, comparatively little is known about risk factors for hemodynamic progression of AS and there are no medical therapies of proven benefit for slowing or preventing AS progression. In this setting, chronic kidney disease (CKD) represents an attractive model to study AS progression due to rapid and premature valvular calcification, yielding mechanistic insights that could be applied to non-CKD population. This proposal leverages the unique and granular phenotyping of participants in the Chronic Renal Insufficiency Cohort (CRIC) and Atherosclerosis Risk in Communities (ARIC) Studies. CRIC is a large, multicenter, prospective, well-phenotyped observational study, begun in 2003 and funded by NIDDK, enrolling adults (aged 21-74) with varying severity of CKD, with a goal to examine progression of cardiovascular disease amongst CKD patients. A total of 3,552 CRIC participants had comprehensive transthoracic echocardiograms (TTEs) at years 1, 4, and 7 post-enrollment and upon initiation of dialysis, making it the only prospective population-based cohort enrolling a large number of adults with CKD with serial TTEs, and thus uniquely allows us to test several important biologic hypotheses in Aims 1-3 (to be additionally tested in individuals without CKD who received TTEs in visits 5 [2011-2013] and 7 [2018-2019] of the Atherosclerosis Risk in Communities [ARIC] Study in Aim 4). Preliminary data from CRIC indicate that progression of aortic peak velocity was greater than the general population but lower than prior estimates in the dialysis population. As this measure is only one of several AS severity measures and is influenced by transvalvular flow, we propose to review existing CRIC TTE images (7,317 TTEs) to calculate all AS severity parameters, and then analyze existing and newly measured data to address several questions. In Aim 1, we will evaluate if AS progression in CKD varies according to two measures of kidney function (estimated glomerular filtration and albuminuria) and quantify the inter-individual variability in AS progression rate. In Aim 2, we will identify clinical and biomarker risk factors that associate with progression of AS, and whether these associations vary by kidney function. In Aim 3, we will determine the relationship between rapid AS progression in CKD and adverse cardiovascular outcomes, and whether this varies by kidney function. In Aim 4, in the ARIC cohort, we will examine if similar clinical and biomarker risk factors identify an analogous risk of AS progression in a cohort without CKD. Doing so, we will leverage the unique physiology of CKD to improve understanding of AS progression, providing biologic insights into the mechanisms of progression of this serious and important valvular disease.

项目摘要主动脉狭窄（AS）是常见的，并且进展为症状，严重，普遍致命而没有治疗主动脉瓣置换术（AVR），尽管只有1/3个人会收到AVR，部分原因是对高围手术期风险和快速瓣膜钙化/变性。尽管半个多世纪关于此主题的研究，关于血液动力学进展的风险因素的了解相对较少而且，没有医疗疗法可以放缓或阻止进展。在这种环境，慢性肾脏疾病（CKD）代表了一个有吸引力的模型，可以随着快速而进行研究和过早的瓣膜钙化，产生可以应用于非CKD种群的机械见解。该提案利用参与者在慢性肾功能不全中的独特和颗粒状表型社区（ARIC）研究中的队列（CRIC）和动脉粥样硬化风险。 Cric是一个大型的多中心，前瞻性，良好的观察性研究，始于2003年，由NIDDK资助，招募成人（老年人） 21-74）具有不同严重性的CKD，目的是检查CKD中心血管疾病的进展患者。总共有3,552名CRIC参与者在年份具有全面的经胸膜超声心动图（TTE） 1、4和7的注册后并在开始透析后，使其成为唯一的前瞻性基于人群的前瞻性队列将大量的成年人与串行TTE一起招募，因此允许我们进行测试目标1-3中的几种重要生物学假设（还需要在没有CKD的个体中进行测试在访问中获得TTE的5 [2011-2013]和7 [2018-2019]的动脉粥样硬化风险 [ARIC]在AIM 4中进行研究。来自CRIC的初步数据表明，主动脉峰速度的进展更大比普通人群，但低于透析人群中的先前估计。因为这个措施只是一项在几种严重程度措施中，受跨性流动的影响，我们建议审查现有的CRIC TTE图像（7,317 ttes）以计算所有严重性参数，然后分析现有和新的测量数据以解决几个问题。在AIM 1中，我们将评估随着CKD的进展是否有所不同根据肾功能的两种措施（估计的肾小球过滤和蛋白尿），并量化 AS进展率的个体间变异性。在AIM 2中，我们将确定临床和生物标志物风险因素与AS的进展以及这些关联是否因肾功能而变化。在AIM 3中，我们将确定随着CKD的进展和不良心血管结局的进展，快速之间的关系，以及这是否因肾功能而异。在AIM 4中，在ARIC队列中，我们将检查是否相似生物标志物危险因素确定了没有CKD的队列中AS进展的类似风险。这样做，我们会利用CKD的独特生理学来提高对AS进展的理解，提供生物学深入了解这种严重而重要的瓣膜疾病进展的机制。