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.

Public Health Relevance

With the high number of deaths in adults from heart disease and diabetes, it is important to develop intervention strategies to reduce the risk factors causing those diseases. This study will combine information from seven large international studies that enrolled children up to 40 years ago, and determine which participants have developed heart disease in adulthood. The study aims to identify risk factors measured in children that increase their chance of developing adult heart disease, so preventive measures can be started early in life.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Jaquish, Cashell E
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Cincinnati Children's Hospital Medical Center
United States
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Li, Ying; Zhang, Tao; Han, Tianshu et al. (2018) Impact of cigarette smoking on the relationship between body mass index and insulin: Longitudinal observation from the Bogalusa Heart Study. Diabetes Obes Metab 20:1578-1584
Koskinen, Juha; Juonala, Markus; Dwyer, Terence et al. (2018) Impact of Lipid Measurements in Youth in Addition to Conventional Clinic-Based Risk Factors on Predicting Preclinical Atherosclerosis in Adulthood: International Childhood Cardiovascular Cohort Consortium. Circulation 137:1246-1255
Koskinen, Juha; Juonala, Markus; Dwyer, Terence et al. (2018) Utility of Different Blood Pressure Measurement Components in Childhood to Predict Adult Carotid Intima-Media Thickness. Hypertension :HYPERTENSIONAHA11812225
Zhang, Tao; Li, Shengxu; Bazzano, Lydia et al. (2018) Trajectories of Childhood Blood Pressure and Adult Left Ventricular Hypertrophy: The Bogalusa Heart Study. Hypertension 72:93-101
Yan, Yinkun; Zhang, Tao; Li, Shengxu et al. (2018) Black-White Difference in the Impact of Long-Term Blood Pressure From Childhood on Adult Renal Function: The Bogalusa Heart Study. Am J Hypertens 31:1300-1306
Wang, Yiping; Xiong, Xu; Bazzano, Lydia et al. (2018) Childhood cardiovascular health and subfertility: the Bogalusa Heart Study. Pediatr Res :
Harville, Emily W; Chen, Wei; Guralnik, Jack et al. (2018) Reproductive history and physical functioning in midlife: The Bogalusa Heart Study. Maturitas 109:26-31
Sinaiko, Alan R; Jacobs Jr, David R; Woo, Jessica G et al. (2018) The International Childhood Cardiovascular Cohort (i3C) consortium outcomes study of childhood cardiovascular risk factors and adult cardiovascular morbidity and mortality: Design and recruitment. Contemp Clin Trials 69:55-64
Koskinen, Juha; Magnussen, Costan G; Sinaiko, Alan et al. (2017) Childhood Age and Associations Between Childhood Metabolic Syndrome and Adult Risk for Metabolic Syndrome, Type 2 Diabetes Mellitus and Carotid Intima Media Thickness: The International Childhood Cardiovascular Cohort Consortium. J Am Heart Assoc 6:
Zhang, Huijie; Zhang, Tao; Li, Shengxu et al. (2017) Long-Term Excessive Body Weight and Adult Left Ventricular Hypertrophy Are Linked Through Later-Life Body Size and Blood Pressure: The Bogalusa Heart Study. Circ Res 120:1614-1621

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