EVOLUTION OF CARDIOVASCULAR RISK WITH NORMAL AGING

说明(申请人提供)：心血管(C-V)系统是受衰老过程影响最大的重要器官系统。就动脉和心脏结构/功能(C-V指数)而言，C-V老化的自然历史是由内在(生物)老化效应和从生命早期开始的C-V危险因素负担之间的复杂相互作用所支配的。这项续订申请侧重于社区黑白中年队列中与C-V老化相关的病理生物学特征，从童年开始就进行了30多年的跟踪调查。其具体目的是：1)继续监测C-V指数在年龄、C-V危险因素变量负担、C-V风险和寿命的家族特征方面的进展；2)确定C-V指数变化与染色体端粒动力学确定的生物衰老之间的关系；3)检查出生体重对儿童以来C-V危险因素变量负担和C-V指数不利变化率的影响。前一批赠款期间正在进行的研究队列(队列I，n=1,200)和10年前作为儿童接受检查的另外一个队列(队列II，n=1,200)可用于实现这些目标。除了端粒动力学、出生体重和亚临床C-V指数，还将收集与C-V老化相关的选定关键变量的数据，特别是包括炎症和氧化应激在内的代谢综合征的风险变量。2)C-V风险因素变量，包括肥胖测量、血压、脂蛋白变量、血糖、胰岛素和氧化应激参数；以及3)端粒长度。此外，队列I将获得出生体重、脂联素、胰岛素样生长因子-I和结合蛋白、同型半胱氨酸、纤维蛋白原、纤溶酶原激活物抑制物-I、C反应蛋白、白细胞介素6和细胞间黏附分子-1的数据；队列I将获得儿童到成年的端粒损失率以及C-V风险和寿命的家族特征。博加卢萨心脏研究的广泛系列数据库提供了独特而有价值的资源。这项拟议研究的结果将进一步了解C-V衰老和影响青年到中年混血人群衰老的易感因素。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，以缓和影响早产C-V发病率和死亡率的介体。

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.