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

描述（由申请人提供）：本研究计划的主要目的是确定儿童期心血管（CV）危险因素（人体测量、血脂、血压）水平与成年期CV发病率和死亡率之间关系的本质。NHLBI儿童CV风险降低倡议指出，缺乏将儿童CV风险因素水平与成年CV终点联系起来的纵向研究是一个需要跨越的主要临床研究空白。这项研究将通过汇集来自七项主要美国和国际纵向队列研究参与者的数据来缩小这一差距，这些研究始于20世纪70年代和80年代。这些研究都测量了儿童时期详细的心血管危险因素，并有儿童期和成年期的随访数据。自2009年以来，他们作为国际儿童心血管队列（i3C）联盟一直在合作，有一个行政组织，定期组织和数据共享会议，以及15份联合出版物。本研究的具体目标1是定位美国nih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）的儿童参与者；确定事件CV终点（冠心病、心肌梗死、心力衰竭、外周动脉疾病和中风），使用经医疗记录验证的自我报告发病率；并使用国家死亡指数识别死者，并判定死亡参与者的死因。在目标2中，这些数据将用于解决以下假设：1)不良的儿童/青少年（3-19岁）CV危险因素水平（BMI、总胆固醇、LDL胆固醇、HDL胆固醇、甘油三酯、BP）与成年期CV终点发生率增加有关；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CV风险评分比任何个体危险因素更能预测成人CV终点。个体危险因素或CV危险评分与成人CV终点的关系随着年龄的增加而增强，从儿童期（3-11岁）到青春期（11-19岁）。目的3将评估心血管风险评分轨迹与成人心血管终点的关联，重点关注儿童/青少年（假设4）和儿童/青少年与成年（假设5）之间的轨迹。本研究的创新之处在于，它首次汇集了一个足够规模的队列（预计招募22,883人），有儿童危险因素测量，随访时间（40年），可以对发生CV事件的年龄的参与者进行随访。因此，它将为儿童时期的危险因素如何导致成人心脏代谢疾病提供新的见解。

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.