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器官系统之一。除了内在衰老之外，C-V危险因素的长期负担也是C-V结构-功能变化的基础，最终导致普通人群的发病率和死亡率。拟议的补充项目是家长赠款AG-16592“正常老龄化条件下的心血管风险演变”的延伸。研究队列包括1200名出生于1959年至1969年之间的人，他们从小就至少接受过四次博加卢萨心脏检查，现在已经进入中年。这项正在进行的研究试图描述固有的或“正常”衰老的特征，以及跟踪调查25到30年的黑人-白人人群的长期风险因素负担。从童年起就获得了一个与临床C-V风险因素和沉默的潜在C-V疾病的发展有关的广泛的数据库。该队列正在接受肥胖测量、血压、脂蛋白变量、血糖、胰岛素和非传统风险因素变量(如同型半胱氨酸和C反应蛋白)的检查。研究中的生活方式和心理社会变量包括烟酒使用、体育活动、饮食和生活改变事件。重要的是，正在测量亚临床心脏和颈动脉的结构-功能以及臂动脉和桡动脉的顺应性。此外，选择的与长寿相关的等位基因标记，如apoE，正在进行检查。这项补充研究的目的是：1)评估研究队列中老年亲属(&gt；84岁)的家族长寿特征；2)构建“健康家系树”，描述研究队列中兄弟姐妹、父母、阿姨、叔叔、祖父母的C-V疾病和危险因素，以计算“家庭风险分数”，这是一种衡量C-V疾病家族易感性的指标；3)将上述家族特征与C-V风险变量和结局(C-V结构-功能)表型以及与长寿相关的候选基因联系起来。这并没有偏离这项受资助研究的最初目标。通过利用现有的设施和工作人员，将家族特征数据纳入正在进行的研究是具有成本效益的，但重要的是，这将有助于更好地描述研究队列的特征。这些观察将对影响正常衰老中亚临床C-V结构-功能变化的易感因素提供更多的洞察。这项研究的主要优势包括混血、黑人和白人人口达到中年，以及从童年起和在相对同质的农村社区环境中获得的多重观察。了解C-V风险在正常衰老中的演变将有助于开发更合理的方案，以实现成功的衰老和C-V疾病的预防。

DESCRIPTION (provided by applicant): The cardiovascular (C-V) system is one of the organ systems most affected by the aging process. In addition to intrinsic aging, the long-term burden of C-V risk factors underlies C-V structure-function changes, which eventually lead to morbidity and mortality in the general population. The proposed supplemental project is an extension of the parent grants AG-16592 "Evolution of C-V Risk with Normal Aging". The study cohort includes 1,200 individuals born between 1959 and 1969 who were examined in the Bogalusa Heart at least four times since childhood and who are now entering middle age. The ongoing research is an attempt to characterize traits of intrinsic or "normal" aging versus the long-term risk factor burden of a black-white population being followed over 25 to 30 years. An extensive database has been obtained since childhood related to the development of clinical C-V risk factors and silent, underlying C-V disease. The cohort is being examined for obesity measures, blood pressure, lipoprotein variables, glucose, insulin, and nontraditional risk factor variables such as homocysteine and C-reactive protein. Lifestyles and psychosocial variables under study include tobacco and alcohol use, physical activity, diet, and life change events. Importantly, sub-clinical cardiac and carotid structure-function and brachial and radial artery compliance are being measured. In addition, selected longevity-associated allele markers like apoE, are being examined. The proposed research of this supplement is directed to 1) evaluate the familial longevity trait among the elderly relatives (>84 years old) of the study cohort, 2) construct a "Health Family Tree" describing reported C-V disease and risk factors on siblings, parents, aunts, uncles, and grandparents of the study cohort to compute a "Family Risk Score", a measure of familial predisposition to C-V diseases and 3) link the above familial traits with the intermediate (C-V risk variables) and outcome (C-V structure-function) phenotypes as well as longevity-related candidate genes. This is not a departure from the original aims of the funded study. Incorporation of the familial traits data into the ongoing research as proposed is cost-effective by using existing facilities, and staff, but, importantly will help better characterize the study cohort. These observations will provide additional insight into predisposing factors that influence the sub-clinical C-V structure-function changes in normal aging. The major strengths of the study include a biracial, black-white population reaching middle age along with multiple observations obtained since childhood and in a relatively homogenous setting of a rural community. Understanding the evolution of C-V risk in normal aging will aid the development of more rational programs to achieve successful aging and C-V disease prevention.