Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events

David R. Jacobs, Jessica G. Woo, Alan R. Sinaiko, Stephen R. Daniels, Johanna Ikonen, Markus Juonala, Noora Kartiosuo, Terho Lehtimäki, Costan G. Magnussen, Jorma S.A. Viikari, Nanhua Zhang, Lydia A. Bazzano, Trudy L. Burns, Ronald J. Prineas, Julia Steinberger, Elaine M. Urbina, Alison J. Venn, Olli T. Raitakari, Terence Dwyer

Research output: Contribution to journalArticlepeer-review

244 Scopus citations


BACKGROUND: Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear.

METHODS: In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohort (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression.

RESULTS: In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events.

CONCLUSIONS: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.).

Original languageEnglish (US)
Pages (from-to)1877-1888
Number of pages12
JournalNew England Journal of Medicine
Issue number20
StatePublished - May 19 2022

Bibliographical note

Funding Information:
Supported by a grant (NIH HL121230) from the National Institutes of Health. Historical funding sources for cohorts in the i3C Consortium are listed in Table S31.

Publisher Copyright:
Copyright © 2022 Massachusetts Medical Society.


  • Adolescent
  • Adult
  • Cardiovascular Diseases/epidemiology
  • Child
  • Child, Preschool
  • Cholesterol
  • Female
  • Heart Disease Risk Factors
  • Humans
  • Male
  • Prospective Studies
  • Risk Factors
  • Young Adult

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


Dive into the research topics of 'Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events'. Together they form a unique fingerprint.

Cite this