Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2025 Jan:276:114277.
doi: 10.1016/j.jpeds.2024.114277. Epub 2024 Sep 2.

A Clinical Tool to Relate Youth Risk Factors to Adult Cardiovascular Events and Type 2 Diabetes: The International Childhood Cardiovascular Cohort Consortium

Jessica Haley  1 , Jessica G Woo  2 , David R Jacobs Jr  3 , Lydia Bazzano  4 , Stephen Daniels  5 , Terry Dwyer  6 , Markus Juonala  7 , Olli Raitakari  8 , Alan Sinaiko  9 , Julia Steinberger  9 , Alison Venn  10 , Kara M Whitaker  11 , Elaine M Urbina  12
Affiliations
Observational Study

A Clinical Tool to Relate Youth Risk Factors to Adult Cardiovascular Events and Type 2 Diabetes: The International Childhood Cardiovascular Cohort Consortium

Jessica Haley et al. J Pediatr. 2025 Jan.

Erratum in

Abstract

Objective: To translate data relating childhood cardiovascular (CV) risk factors and adult CV disease and type 2 diabetes mellitus (T2DM) to clinically actionable values.

Study design: This was a prospective observational study (n = 38 589) in the International Childhood Cardiovascular Cohort Consortium. Children at age 3 through 19 years were enrolled in the 1970s and 1980s and followed for more than 30 years. Five childhood CV risk factors (smoking, body mass index [BMI], systolic blood pressure, triglycerides, and total cholesterol) were related to adult CV events. Secondary analyses in a subset included low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glucose, and insulin level. Age- and sex-specific z scores were calculated for each risk factor, and a combined-risk z score was calculated by averaging z scores for the 5 key CV risk factors. Risk factor z scores were back-transformed to natural units for clinical interpretation, with hazard ratios for adult CV events presented in color-coded tables (green: no increased risk; orange: 1.4 to <2.0-fold increased risk; red: at least doubling of risk). Risk levels for development of adult T2DM on the basis of BMI, glucose, and insulin were similarly calculated and presented.

Results: Increased risk for CV events was observed at levels lower than currently defined abnormal clinical thresholds except for TC. Doubling of risk was observed at high normal levels just below the clinical cut point for abnormality. Risk for adult T2DM began at levels of BMI and glucose currently considered normal.

Conclusions: On the basis of data showing significant relationships between childhood CV risk factors and adult CV events and T2DM, this study shows that risk in childhood begins below levels currently considered normal.

Keywords: cardiovascular disease; diabetes; pediatric; prevention; preventive cardiology.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest Supported by a grant from the National Institutes of Health (NIH) (HL121230). Historical funding sources for cohorts in the International Childhood Cardiovascular Cohort (i3C) Consortium are listed in our previous publication.(5) J.W., D.J., L.B., T.D., M.J., O.R., A.S., J.S., A.V., and E.U. received grant funding for this project from the NIH. E.U. also received grant funding from DSMB Astellas Pharma, and Honorarium Targus Medical Inc. The other authors have no disclosures or relationships with industry to report.

Figures

Figure 1:
Figure 1:
Categories of risk for adult CV events by childhood CV risk factor levels across pediatric ages. Sex-averaged values of CV risk factors presented by i3C z-score category. A) BMI (kg/m2), B) BMI CDC Percentile, C) Total Cholesterol (mg/dL), D) Triglycerides (mg/dL), E) SBP CPG Percentile, and F) LDL Cholesterol (mg/dL). Risk for adult CV events is indicated by green (low risk), orange (significant hazard ratio (HR) 1.4 to <2), and red (significant HR≥2). Dotted lines on the graph are category separators, solid white lines are the currently accepted clinical cut-points (Supplemental Table 1)–. HR for categories so defined is indicated to the right of each graph. Data adapted from Jacobs et al
Figure 1:
Figure 1:
Categories of risk for adult CV events by childhood CV risk factor levels across pediatric ages. Sex-averaged values of CV risk factors presented by i3C z-score category. A) BMI (kg/m2), B) BMI CDC Percentile, C) Total Cholesterol (mg/dL), D) Triglycerides (mg/dL), E) SBP CPG Percentile, and F) LDL Cholesterol (mg/dL). Risk for adult CV events is indicated by green (low risk), orange (significant hazard ratio (HR) 1.4 to <2), and red (significant HR≥2). Dotted lines on the graph are category separators, solid white lines are the currently accepted clinical cut-points (Supplemental Table 1)–. HR for categories so defined is indicated to the right of each graph. Data adapted from Jacobs et al
Figure 1:
Figure 1:
Categories of risk for adult CV events by childhood CV risk factor levels across pediatric ages. Sex-averaged values of CV risk factors presented by i3C z-score category. A) BMI (kg/m2), B) BMI CDC Percentile, C) Total Cholesterol (mg/dL), D) Triglycerides (mg/dL), E) SBP CPG Percentile, and F) LDL Cholesterol (mg/dL). Risk for adult CV events is indicated by green (low risk), orange (significant hazard ratio (HR) 1.4 to <2), and red (significant HR≥2). Dotted lines on the graph are category separators, solid white lines are the currently accepted clinical cut-points (Supplemental Table 1)–. HR for categories so defined is indicated to the right of each graph. Data adapted from Jacobs et al
Figure 1:
Figure 1:
Categories of risk for adult CV events by childhood CV risk factor levels across pediatric ages. Sex-averaged values of CV risk factors presented by i3C z-score category. A) BMI (kg/m2), B) BMI CDC Percentile, C) Total Cholesterol (mg/dL), D) Triglycerides (mg/dL), E) SBP CPG Percentile, and F) LDL Cholesterol (mg/dL). Risk for adult CV events is indicated by green (low risk), orange (significant hazard ratio (HR) 1.4 to <2), and red (significant HR≥2). Dotted lines on the graph are category separators, solid white lines are the currently accepted clinical cut-points (Supplemental Table 1)–. HR for categories so defined is indicated to the right of each graph. Data adapted from Jacobs et al
Figure 1:
Figure 1:
Categories of risk for adult CV events by childhood CV risk factor levels across pediatric ages. Sex-averaged values of CV risk factors presented by i3C z-score category. A) BMI (kg/m2), B) BMI CDC Percentile, C) Total Cholesterol (mg/dL), D) Triglycerides (mg/dL), E) SBP CPG Percentile, and F) LDL Cholesterol (mg/dL). Risk for adult CV events is indicated by green (low risk), orange (significant hazard ratio (HR) 1.4 to <2), and red (significant HR≥2). Dotted lines on the graph are category separators, solid white lines are the currently accepted clinical cut-points (Supplemental Table 1)–. HR for categories so defined is indicated to the right of each graph. Data adapted from Jacobs et al
Figure 1:
Figure 1:
Categories of risk for adult CV events by childhood CV risk factor levels across pediatric ages. Sex-averaged values of CV risk factors presented by i3C z-score category. A) BMI (kg/m2), B) BMI CDC Percentile, C) Total Cholesterol (mg/dL), D) Triglycerides (mg/dL), E) SBP CPG Percentile, and F) LDL Cholesterol (mg/dL). Risk for adult CV events is indicated by green (low risk), orange (significant hazard ratio (HR) 1.4 to <2), and red (significant HR≥2). Dotted lines on the graph are category separators, solid white lines are the currently accepted clinical cut-points (Supplemental Table 1)–. HR for categories so defined is indicated to the right of each graph. Data adapted from Jacobs et al
See this image and copyright information in PMC

References

    1. Woo JG, Zhang N, Fenchel M, Jacobs DR Jr., Hu T, Urbina EM, Burns TL, Raitakari O, Steinberger J, Bazzano L, Prineas RJ, Jaquish C, Juonala M, Ryder JR, Daniels SR, Sinaiko A, Dwyer T and Venn A Prediction of adult class II/III obesity from childhood BMI: the i3C consortium. Int J Obes (Lond). 2020;44:1164–1172. - PMC - PubMed
    1. Urbina EM, Khoury PR, Bazzano L, Burns TL, Daniels S, Dwyer T, Hu T, Jacobs DR Jr., Juonala M, Prineas R, Raitakari O, Steinberger J, Venn A, Woo JG and Sinaiko A. Relation of Blood Pressure in Childhood to Self-Reported Hypertension in Adulthood. Hypertension. 2019;73:1224–1230. - PMC - PubMed
    1. Nuotio J, Pitkanen N, Magnussen CG, Buscot MJ, Venalainen MS, Elo LL, Jokinen E, Laitinen T, Taittonen L, Hutri-Kahonen N, Lyytikainen LP, Lehtimaki T, Viikari JS, Juonala M and Raitakari OT. Prediction of Adult Dyslipidemia Using Genetic and Childhood Clinical Risk Factors: The Cardiovascular Risk in Young Finns Study. Circ Cardiovasc Genet 2017;10. - PubMed
    1. Ryder JR, Xu P, Inge TH, Xie C, Jenkins TM, Hur C, Lee M, Choi J, Michalsky MP, Kelly AS and Urbina EM. Thirty-Year Risk of Cardiovascular Disease Events in Adolescents with Severe Obesity. Obesity (Silver Spring). 2020;28:616–623. - PMC - PubMed
    1. Jacobs DR Jr., Woo JG, Sinaiko AR, Daniels SR, Ikonen J, Juonala M, Kartiosuo N, Lehtimaki T, Magnussen CG, Viikari JSA, Zhang N, Bazzano LA, Burns TL, Prineas RJ, Steinberger J, Urbina EM, Venn AJ, Raitakari OT and Dwyer T Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events. N Engl J Med 2022;386:1877–1888. - PMC - PubMed

Publication types

LinkOut - more resources