Vascular Health and Risk Factors in Children with Down Syndrome

摘要： 背景：与老龄化相关的心血管(CV)疾病的风险正在增加 唐氏综合症(DS)患者的寿命更长。在儿童中诊断的心血管疾病危险因素可追溯到成年期和 导致痴呆症和心脏病发作。因为许多心血管疾病风险因素是可以改变的，然而，在早期 治疗可以延缓或预防成人疾病。血管健康的亚临床变化可以使用 血管研究，包括脉搏波速度(PWV)、颈动脉内膜中层厚度(CIMT)和颈动脉 膨胀性(CD)。每一项指标都与未来的血管疾病风险有关。成人中的数据 DS显示心血管疾病风险因素概况和血管研究结果与个人的结果不同 没有DS。在患有DS的儿童中，心血管疾病危险因素数据有限，很少有研究评估其影响 心血管疾病危险因素对血管健康的影响。我们的目标是确定心血管疾病危险因素的患病率。 并评价其对动脉粥样硬化早期血管标志物的影响。 研究设计和方法：我们建议对心血管疾病的危险因素及其影响因素进行横断面评估。 在儿科心脏网络内的3个中心对DS儿童血管健康的影响 (PHN)。具体目的1：评估DS儿童心血管疾病的危险因素。我们将描述常见的简历 DS儿童的疾病危险因素包括人体测量、临床危险因素(饮食、活动； 吸烟；高血压；先天性心脏病、睡眠呼吸暂停、癌症病史； 早期心血管疾病)和血清危险因素(空腹血脂、胰岛素、血糖、 糖化血红蛋白(Hb、AIC、C反应蛋白)与DS患儿的关系。我们将把这些数据与已公布的国家标准进行比较 没有DS的儿童。具体目标2：确定心血管疾病危险因素和标记物之间的关联 DS儿童早期动脉粥样硬化的危险因素。我们将对DS儿童进行PWV、CIMT和CD研究 并将这些数据与没有DS的儿童的现有数据进行比较。我们将使用特定目标1的调查结果来 进行多变量分析以确定血管疾病危险因素组合的影响 这是DS儿童血管研究中独有的。 职业发展计划：KL2职业发展奖将解决我目前 研究能力：1)提高对简历风险因素、预测模型的理解和评估能力； 结果测量，包括在干预试验中使用的那些；2)执行和解释先进的能力 血管成像研究；3)发展研究设计、统计学、流行病学和研究方面的专业知识 领导需要在患有DS的儿童中进行CV研究。这些弱点将通过使用 犹他大学稳健的KL2计划提供的资源，并通过推荐的课程和 实践培训以及与国际导师和顾问团队的互动。

ABSTRACT: Background: The risk of cardiovascular (CV) diseases associated with aging is increasing as individuals with Down syndrome (DS) are living longer. CV disease risk factors diagnosed in children track into adulthood and cause dementia and heart attacks. Because many CV disease risk factors are modifiable, however, early treatment may delay or prevent adult disease. Subclinical changes in vascular health can be measured using vascular studies, including pulse wave velocity (PWV), carotid intimal medial thickness (CIMT), and carotid distensibility (CD). Each measure has been associated with future risk of vascular disease. Data in adults with DS show CV disease risk factor profiles and vascular study results differ compared to results from individuals without DS. In children with DS, CV disease risk factor data are limited with few studies evaluating the impact of CV disease risk factors on vascular health. We aim to determine the prevalence of CV disease risk factors in children with DS and evaluate their effect on vascular markers of early atherosclerosis. Research Design and Methods: We propose a cross-sectional evaluation of CV disease risk factors and their impact on vascular health in children with DS to be performed at 3 centers within the Pediatric Heart Network (PHN). Specific Aim 1: Evaluate CV disease risk factors in children with DS. We will describe common CV disease risk factors in children with DS including anthropometric measures, clinical risk factors (diet; activity; smoke exposure; hypertension; history of congenital heart disease, sleep apnea, cancer; and family history of early CV disease), and serologic risk factors (fasting lipid profiles with sub-fractionation, insulin, glucose, hemoglobin AIc, and CRP) in children with DS. We will compare these data to published national norms of children without DS. Specific Aim 2: Determine the associations between CV disease risk factors and markers of early atherosclerosis in children with DS. We will perform PWV, CIMT, and CD studies in children with DS and compare these data to available data in children without DS. We will use findings from Specific Aim 1 to perform multivariable analysis to determine the influence of combinations of vascular disease risk factors unique to children with DS on their vascular studies. Career Development Plan: The KL2 Career Development Award will address these gaps in my current research abilities: 1) improve my understanding and ability to evaluate CV risk factors, prediction models, and outcome measures including those used in interventional trials; 2) ability to perform and interpret advanced vascular imaging studies; 3) develop the expertise in study design, statistics, epidemiology, and research leadership needed to conduct CV studies in children with DS. These weaknesses will be addressed using the resources provided by the University of Utah's robust KL2 program and through recommended courses and hands-on training as well as interactions with an international team of mentors and advisors.