A1 Refereed original research article in a scientific journal
The association of childhood HDL cholesterol with atherosclerotic cardiovascular disease events in adults: findings from the International Childhood Cardiovascular Cohort Consortium
Authors: Wang, Jing; Kartiosuo, Noora; Raitakari, Olli T.; Viikari, Jorma; Juonala, Markus; Bazzano, Lydia A.; Sinaiko, Alan R.; Steinberger, Julia; Daniels, Stephen R.; Venn, Alison J.; Magnussen, Costan; Woo, Jessica G.; Ramakrishnan, Rema; Urbina, Elaine M.; Kahonen, Mika; Jacobs, David R.; Dwyer, Terence
Publisher: Oxford University Press (OUP)
Publishing place: OXFORD
Publication year: 2025
Journal: European Journal of Preventive Cardiology
Journal name in source: European Journal of Preventive Cardiology
Journal acronym: EUR J PREV CARDIOL
Number of pages: 10
ISSN: 2047-4873
eISSN: 2047-4881
DOI: https://doi.org/10.1093/eurjpc/zwaf117
Web address : https://doi.org/10.1093/eurjpc/zwaf117
Aims: The role of adult HDL-C in atherosclerotic cardiovascular disease (ASCVD) faces challenges from Mendelian randomisations and drug trials. However, the association between childhood HDL-C and its changes and adult ASCVD remains undefined. This study aimed to determine this association.
Methods: Participants: Children in the International Childhood Cardiovascular Cohort (i3C) Consortium with childhood HDL-C and adult ASCVD follow-up. Age- and sex-standardized HDL-C z-scores were calculated for childhood (3-19 years), early childhood (3-11 years), and adolescence (12-19 years); Low HDL-C defined as <1.03mmol/L; Participants classified as consistently normal, low-to-normal, normal-to-low, and consistently low based on HDL-C status at early childhood and adolescence. ASCVD events: Identified using self-reports adjudicated by medical records or death registries. Analysis: Cox proportional hazards models quantified the associations between childhood HDL-C and adult ASCVD.
Results: The study included 38,589 participants (49.7% males, mean age in 2016: 46.4 years) with 779 ASCVD and 784 imputed ASCVD events. After adjusting for sex, cohort, age and HDL-C measurement year, higher HDL-C z-scores in childhood, early childhood and adolescence were associated with lower adult ASCVD risk (HRs: 0.81-0.82), with the lowest risk at HDL-C >1.50mmol/L. Normal-to-low (HR 1.38, 95%CI 1.04-1.82) and consistently low (HR 1.94, 95%CI 1.45-2.63) childhood HDL-C increased adult ASCVD risk compared to consistently normal HDL-C. Adjusting for BMI and triglycerides weakened these associations.
Conclusions: Childhood and adolescent HDL-C were prospectively and inversely associated with adult ASCVD, suggesting that low HDL-C could be a risk maker of adult ASCVD. Future replications, mechanistic studies and Mendelian randomisations on childhood HDL-C may clarify its causal effects on adult ASCVD.
Funding information in the publication:
This work was supported by National Institutes of Health R01 HL121230. Historical funding for each of the cohorts can be found in Supplementary material online, Table S10in the Supplementary material online, Appendix:
Bogalusa Heart Study R01 AG016592 and R03 AG060619; R21/R33 AG057983
Childhood Determinants of Adult Health (CDAH) Commonwealth Department of Sport, Recreation and Tourism; the Commonwealth Department of Health; the Commonwealth Schools Commission; the National Heart Foundation; the National Health and Medical Research Council (grants 211316, 544923, 1128373); the Tasmanian Community Fund; Veolia Environmental Services; and the Mostyn Family Foundation
Minneapolis Cohorts R01 HL19877, R01 HL34659, R01 HL52851, and R01 DK072124; K23 HL04000; Vikings Children’s Fund; and a Department of Pediatrics Legacy Grant
Muscatine Study SCOR HL14230 and SCOR HL44546; M01-FR59 and RR-00059 from the General Clinical Research Centers Program; the Lipid Research Clinics Program (NIH-NHLBI-N01-HV-2-2913-L); the Juvenile Hypertension Program HL35600; R01s HL20124, R01 HD13374, R01 HL48050, R01 HL54730, R01 HL61857 and R01 HD29569; Iowa Heart Association grants 74-G-28 and 75-G-76; the Muscatine Rotary; the Muscatine Health Support Foundation; and the Roy J. Carver Charitable Trust, Muscatine, IA
NHLBI Growth and Health Study (NGHS) NHLBI contract N01-HC055025; U01 HL48941; R01 HL52911; R01 HL66430; and R21/R33 AG057983
Princeton Lipid Research Study (PLRS) NHLBI contract N01-HV022914L; R01 HL33973; R01 GM28719; R01 HL62394; American Heart Association 9750129N; R21 DK085363; and R21/R33 AG057983.
Cardiovascular Risk in Young Finns Study Academy of Finland: grants 117787 (Gendi), and 41071 (Skidi); Turku University Hospitals (grant X51001);
Academy of Finland (grants 255381, 256474, 283115, 302382, 319060, 320297, 314389 (TERVA), 322098, 286284, 134309 (EYE), 126925, 121584, 124282, 129378 (SALVE), 117797 (GENDI), and 141071 (SKIDI); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospital grants (government funding to University Hospitals); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research ; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Aune Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); and Tampere University Hospital Supporting Foundation and Finnish Society of Clinical Chemistry.
