Childhood CV Risk and Adult CVD Outcomes: an International Long-term Follow-up

描述(由申请人提供)：本研究提案的主要目的是确定儿童心血管危险因素(人体测量学、血脂、血压)水平与成年心血管发病率和死亡率之间的关系的性质。NHLBI儿科心血管风险降低倡议指出，缺乏将儿童心血管风险因素水平与成年后心血管终点联系起来的纵向研究是需要跨越的主要临床研究差距。这项研究将通过汇集始于20世纪70年代和80年代的七项主要的美国和国际纵向队列研究的参与者数据来缩小这一差距。这些研究都衡量了儿童时期详细的简历风险因素，并有跨越童年和成年的后续数据。自2009年以来，他们一直作为国际儿童心血管队列(I3C)联盟与一个行政组织合作，定期举行组织和数据共享会议，并出版15份联合出版物。这项研究的具体目标1是定位美国国立卫生研究院资助的五项纵向研究(BHS、MUSC、PFS、MCCS和NGHS)和两项国际研究(YFS和CDAH)的童年参与者；使用经医疗记录裁决证实的自我报告发病率确定事件心血管终点(冠心病、心肌梗死、心力衰竭、外周动脉疾病和中风)；并使用国家死亡指数确定已故参与者的死亡原因。在目标2中，这些数据将被用来解决以下假设：1)不利的儿童/青少年(3-19岁)心血管危险因素水平(BMI、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯、BP)与成年后心血管终点的发生率增加有关。2)加权儿童/青少年危险因素(BMI、BP、血脂、年龄、性别和种族/民族)的心血管危险分数比任何个人风险因素更能预测成人心血管终点。从儿童期(3~11岁)到青春期(11~19岁)，个体危险因素或心血管危险评分与成人心血管终点的关系随着年龄的增长而增强。目的3将评估成人心血管终点的心血管风险评分轨迹的相关性，重点放在儿童/青春期(假设4)和儿童/青春期与成年之间(假设5)的轨迹。本建议的创新之处在于，它第一次汇集了一个足够大的队列(22,883名预期招募人员)，并对儿童风险因素进行了衡量，而且后续行动的持续时间(40年)将使参与者能够在个人简历事件发生时对参与者进行跟踪。因此，它将为儿童风险因素如何导致成人心脏代谢性疾病提供新的见解。

DESCRIPTION (provided by applicant): The primary objective of this research proposal is to determine the nature of relationships between levels of cardiovascular (CV) risk factors (anthropometrics, lipids, blood pressure) in childhood and CV morbidity and mortality in adulthood. The NHLBI Pediatric CV Risk Reduction Initiative noted that the lack of longitudinal studies linking CV risk factor levels in children to CV endpoints in adulthood is a major clinical research gap that needs to be spanned. This research will close that gap by pooling data on participants from seven major U.S. and international longitudinal cohort studies that were initiated in the 1970s and 1980s. These studies all have measured detailed CV risk factors in childhood, and have follow-up data spanning childhood and adulthood. They have been collaborating since 2009 as the International Childhood Cardiovascular Cohort (i3C) Consortium, with an administrative organization, regular organizational and data sharing meetings, and fifteen joint publications. Specific Aim 1 of this study is to locate the childhood participants of five NIH-funded longitudinal studies in the U.S. (BHS, MUSC, PFS, MCCS, and NGHS) and two international studies (YFS and CDAH); identify incident CV endpoints (coronary heart disease, myocardial infarction, heart failure, peripheral artery disease, and stroke) using self-reported morbidity validated by adjudication of medical records; and identify decedents using the National Death Index and adjudicate cause of death for deceased participants. In Aim 2, these data will be used to address the hypotheses that: 1) Adverse childhood/adolescent (age 3-19) CV risk factor levels (BMI, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, BP) are related to increased incidence of CV endpoints in adulthood.; 2) A CV risk score weighting childhood/adolescent risk factors (BMI, BP, lipids, age, sex and race/ethnicity) is a stronger predictor of adult CV endpoints than any individual risk factor.; and 3) The relationship of individual risk factors or CV risk score with adult CV endpoints becomes stronger with increasing age from childhood (age 3-11) to adolescence (age 11-19). Aim 3 will evaluate the association of CV risk score trajectories on adult CV endpoints, focusing on trajectories during childhood/adolescence (hypothesis 4) and between childhood/adolescence and adulthood (hypothesis 5). The present proposal is innovative in that it assembles, for the first time, a cohort of sufficient size (22,883 anticipated recruitment), with childhood risk factor measurements, and with a duration of follow-up (40 years) that will enable follow-up of participants at ages when CV events occur. It will, therefore, provide novel insights into how childhood risk factors contribute to adult cardiometabolic disease.