EVOLUTION OF CARDIOVASCULAR RISK WITH NORMAL AGING

描述（申请人提供）：心血管（C-V）系统是最受衰老影响的重要器官系统。就动脉和心脏结构/功能（C-V指数）而言，C-V衰老的自然历史是由内在（生物）衰老效应和生命早期开始的C-V危险因素负担之间的复杂相互作用决定的。这项更新应用的重点是与C-V衰老相关的病理生物学特征，在一个以社区为基础的黑人-白人中年队列中，从童年开始随访超过30年。具体目的是：1)继续监测C-V指数在实足年龄、C-V危险因素变量负担、C-V风险和寿命家族特征方面的进展；2)通过染色体端粒动力学确定C-V指数变化与生物衰老的关系；3)考察出生体重对儿童期C-V危险因素变量负担的影响及C-V指标不良变化率。为了实现这些目标，在上一个赠款期间跟踪的正在进行的研究队列（队列1，n= 1200）和10年前儿童时期检查的另一个队列（队列2，n= 1200）可用。除了端粒动力学、出生体重和亚临床C-V指数外，还将收集与C-V衰老相关的选定关键变量的数据，特别是代谢综合征的风险变量，包括炎症和氧化应激。两组患者将通过颈动脉IMT、左心室结构和功能、肱动脉顺应性和动脉脉搏波速度来检查C-V指数；2) C-V危险因素变量，包括肥胖指标、血压、脂蛋白变量、葡萄糖、胰岛素和氧化应激参数；3)端粒长度。此外，将在队列I中获得出生体重、脂联素、胰岛素样生长因子-1及结合蛋白、同型半胱氨酸、纤维蛋白原、纤溶酶原激活物抑制剂-1、c反应蛋白、白细胞介素-6和细胞间粘附分子-1的数据；队列1中儿童期至成年期端粒磨损率及C-V风险和寿命的家族特征。Bogalusa心脏研究的广泛序列数据库提供了独特而宝贵的资源。本研究的结果将进一步了解双种族中青年人群C-V老化和影响衰老的易感因素。从这项研究中得出的观察结果将有助于制定有效的预防策略，以缓和影响过早C-V发病率和死亡率的介质。

DESCRIPTION (provided by applicant): The cardiovascular (C-V) system is a vital organ system most affected by the aging process. The natural history of C-V aging in terms of arterial and cardiac structure/function (C-V indices) is governed by a complex interplay between an intrinsic (biologic) aging effect and a burden of C-V risk factors beginning early in life. This renewal application focuses on the pathobiological traits associated with C-V aging in a community-based, black-white, middle-aged cohort having been followed over 30 years beginning in childhood. The specific aims are to 1) continue monitoring the progression of C-V indices with respect to chronological age, the burden of C-V risk factor variables and familial traits of C-V risk and longevity; 2) determine the relationship between changes in C-V indices and biological aging ascertained by chromosomal telomere dynamics; 3) examine the influence of birth weight on the burden of C-V risk factor variables since childhood and the rate of adverse changes in C-V indices. The ongoing study cohort followed during the previous grant period (Cohort I, n=1,200) and an additional cohort examined as children 10 years ago (Cohort II, n=1,200) are available to achieve these aims. In addition to telomere dynamics, birth weight, and subclinical C-V indices, data on selected key variables relevant to C-V aging, in particular risk variables of metabolic syndrome including inflammation and oxidative stress will be collected. Both cohorts will be examined for 1) C-V indices by carotid IMT, left ventricular structure and function, brachial artery compliance, and arterial pulse wave velocity; 2) C-V risk factor variables comprising obesity measures, blood pressure, lipoprotein variables, glucose, insulin, and parameters of oxidative stress; and 3) telomere length. In addition, data on birth weight, adiponectin, insulin like growth factor-I and binding proteins, homocysteine, fibrinogen, plasminogen activator inhibitor-I, C-reactive protein, interleukin-6, and intercellular adhesion molecule-1 will be obtained in Cohort I; telomere attrition rate from childhood to adulthood and familial traits of C-V risk and longevity in Cohort I1. The extensive serial database of the Bogalusa Heart Study provides unique and valuable resources. Findings from the proposed research will further the understanding of C-V aging and predisposing factors that influence aging in a bi-racial young to middle age population. Observations derived from this research will help develop effective preventive strategies to temper mediators that influence premature C-V morbidity and mortality.