EVOLUTION OF CARDIOVASCULAR RISK WITH NORMAL AGING

正常衰老过程中心血管风险的演变

• 批准号: 7119557
• 负责人: GERALD Sanders BERENSON
• 金额: $ 77.55万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7119557
• 关键词: African American; aging; biomarker; blood chemistry; cardiovascular disorder epidemiology; cardiovascular disorder risk; cardiovascular function; caucasian American; clinical research; family genetics; gender difference; genetic markers; human birth weight; human subject; inflammation; longitudinal human study; metabolic syndrome; obesity; oxidative stress; pathologic process; racial /ethnic difference; restriction fragment length polymorphism; telomere; ultrasound blood flow measurement

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.

描述（由申请人提供）：心血管（C-V）系统是受衰老过程影响最大的重要器官系统。在动脉和心脏结构/功能（C-V指数）方面，C-V老化的自然史受内在（生物学）老化效应和生命早期开始的C-V风险因素负担之间复杂相互作用的影响。这项更新申请的重点是与C-V老化相关的病理生物学特征，该特征在一个以社区为基础的、黑白相间的中年队列中进行了30多年的随访，从儿童时期开始。其具体目标是：1）继续监测C-V指数随实际年龄、C-V危险因素变量的负担以及C-V风险和寿命的家族特征的进展; 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）研究出生体重对儿童期以来C-V危险因素变量负担的影响以及C-V指标的不良变化率。正在进行的研究队列（队列I，n= 1，200）和10年前作为儿童检查的另一个队列（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指数外，还将收集与C-V老化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。将检查两个队列的1）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的C-V指数; 2）C-V风险因素变量，包括肥胖测量、血压、脂蛋白变量、葡萄糖、胰岛素和氧化应激参数;和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-I和结合蛋白、同型半胱氨酸、纤维蛋白原、纤溶酶原激活物-I、C-反应蛋白、白细胞介素-6和细胞间粘附分子-1的数据;在队列I1中获得从儿童期到成年期的端粒磨损率以及C-V风险和长寿的家族特征。博加卢萨心脏研究的广泛的系列数据库提供了独特而有价值的资源。拟议研究的结果将进一步了解C-V老化和影响年轻到中年人口的双种族老化的诱发因素。 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，以调节影响过早C-V发病率和死亡率的介质。