CHILDHOOD PREDICTOR OF ADULT CORONARY ARTERY DISEASE

成人冠状动脉疾病的儿童期预测因素

• 批准号: 2205189
• 负责人: GERALD Sanders BERENSON
• 金额: $ 33.84万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2205189
• 关键词: African American; adipose tissue; adolescence (12-20); blood lipoprotein; blood lipoprotein metabolism; body regions; cardiovascular disorder diagnosis; child (0-11); cholesterol; computer data analysis; coronary disorder; disease /disorder proneness /risk; early diagnosis; family genetics; gender difference; high density lipoproteins; human subject; lipid peroxides; longitudinal human study; low density lipoprotein; prognosis; racial /ethnic difference; statistics /biometry; triglycerides; very low density lipoprotein

Advances toward improving cardiovascular health lie in the recognition that pathogenesis of atherosclerosis begins in childhood. The aim of this research is to identify childhood markers or traits for adult coronary artery disease (CAD). Given the familial nature of atherosclerosis, essential hypertension, and diabetes mellitus, the research is based on hypotheses that children of coronary-prone parents show early evidence of abnormalities in parameters related to atherogenesis and thrombogenesis, and that childhood predictors of CAD risk may vary between blacks and whites, and may even be influenced by gender differences of adult heart disease. These hypotheses will be tested in a total biracial community of Bogalusa, Louisiana, taking advantage of the resources and an extensive data base of the ongoing Bogalusa Heart Study program. Longitudinal changes in lipoprotein profiles and other risk factor variables during childhood and adolescence in offspring of parents with clinically proven CAD in comparison to matched group of offspring of parents unaffected by CAD will be determined by a retrospective data analysis. A unique data set of a cohort of about 2,000 young adults aged 18 to 31 years with a 15 year data span of cardiovascular risk factors including lipoproteins is available for this purpose. A second study will use reported family histories of CAD from two cross-sectional surveys (1987-88 and 1992-94 each including over 3,500 children, ages 5-17 years). This involves selection of black and white families (N = 50 each) that have at least one parent (aged 30 to 55 years) with clinically validated CAD. Appropriately matched control families with no family history of the disease will be studied as well. Parents will be given a regular cardiovascular risk factor examination. Children (aged 8 to 19 years, N = 250-300) of these case-control families will be studied in depth including an oral fat load test to evaluate the post-prandial triglyceride-rich lipoprotein metabolism. Data will be obtained on 1) anthropometric variables related to body fat distribution, 2) serum lipoprotein variables (total cholesterol, triglycerides, VLDL-C, LDL-C, HDL2-C, HDL3-C, HDL-apoE, LpA- l, LpA-l:All, apoA-l, apoB, LDL-apoB, apoE, HDL-apoE, and LDL lipid peroxides) and related candidate genes (Lp(a), apo(a) phenotypes, and apoE phenotypes), and 3) other variables related to atherosclerosis and thrombosis (glucose, insulin, thromboxane, prostacycline, von Willebrand factor antigen, fibrinogen, fibrin degradation products, homocysteine, and uric acid). The study of heritability and penetrance by linkage of relevant candidate gene markers in multiple generations of these index families remains a long-term objective. White blood cells from children and parents will be collected and stored for this purpose. Understanding childhood predictors of adult CAD in a biracial population can lead to more rational programs for health promotion and disease prevention.

改善心血管健康的进展在于认识到 动脉粥样硬化的发病机制始于儿童期。此举的目的 研究的目的是确定成人冠状动脉的儿童标记或特征 动脉疾病（CAD）。鉴于动脉粥样硬化的家族性， 原发性高血压和糖尿病，该研究基于 假设父母有冠心病倾向的孩子表现出早期证据 与动脉粥样硬化和血栓形成相关的参数异常， 儿童时期 CAD 风险的预测因素在黑人和黑人之间可能有所不同 白人，甚至可能受到成人内心性别差异的影响 疾病。这些假设将在一个由混血儿组成的社区中得到检验 路易斯安那州博加卢萨，利用资源和广泛的 正在进行的 Bogalusa 心脏研究计划的数据库。纵向 脂蛋白谱和其他危险因素变量的变化 父母子女的童年和青春期经临床证明 CAD 与未受影响的父母的后代的匹配组进行比较 CAD 将通过回顾性数据分析来确定。独特的数据集 大约 2,000 名 18 至 31 岁的年轻人组成的队列，其中 15 岁 包括脂蛋白在内的心血管危险因素的数据跨度为 可用于此目的。第二项研究将使用报告的家庭 两次横断面调查（1987-88 年和 1992-94 年）的 CAD 历史 每个项目包括 3,500 多名 5 至 17 岁的儿童）。这涉及到 选择至少有一个黑人和白人家庭（每个家庭 N = 50） 父母（年龄 30 至 55 岁）患有经临床验证的 CAD。适当地 没有该疾病家族史的匹配对照家庭将 也研究过。家长将定期接受心血管风险监测 因素检验。其中儿童（8 至 19 岁，N = 250-300） 将深入研究病例对照家庭，包括口腔脂肪负荷 测试评估餐后富含甘油三酯的脂蛋白 代谢。将获得以下方面的数据：1) 相关的人体测量变量 体脂肪分布，2) 血清脂蛋白变量（总 胆固醇、甘油三酯、VLDL-C、LDL-C、HDL2-C、HDL3-C、HDL-apoE、LpA- l、LpA-l：全部、apoA-l、apoB、LDL-apoB、apoE、HDL-apoE 和 LDL 脂质 过氧化物）和相关候选基因（Lp(a)、apo(a) 表型和 apoE 表型），以及3）与动脉粥样硬化相关的其他变量和 血栓（葡萄糖、胰岛素、血栓素、前列环素、血管性血友病 因子抗原、纤维蛋白原、纤维蛋白降解产物、同型半胱氨酸和 尿酸）。通过连锁研究遗传力和外显率 这些指数的多代中的相关候选基因标记 家庭仍然是一个长期目标。儿童白细胞 为此目的，父母将被收集和存储。理解 混血儿人群中成人 CAD 的儿童期预测因素可能导致 更合理的健康促进和疾病预防计划。