Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events

David R Jacobs Jr; 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

doi:10.1056/NEJMoa2109191

Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events

N Engl J Med. 2022 May 19;386(20):1877-1888. doi: 10.1056/NEJMoa2109191. Epub 2022 Apr 4.

Authors

David R Jacobs Jr¹, Jessica G Woo¹, Alan R Sinaiko¹, Stephen R Daniels¹, Johanna Ikonen¹, Markus Juonala¹, Noora Kartiosuo¹, Terho Lehtimäki¹, Costan G Magnussen¹, Jorma S A Viikari¹, Nanhua Zhang¹, Lydia A Bazzano¹, Trudy L Burns¹, Ronald J Prineas¹, Julia Steinberger¹, Elaine M Urbina¹, Alison J Venn¹, Olli T Raitakari¹, Terence Dwyer¹

Affiliation

¹ From the Division of Epidemiology and Community Health, School of Public Health (D.R.J.), and the Department of Pediatrics, University of Minnesota Medical School (A.R.S., J.S.), University of Minnesota, Minneapolis; the Division of Biostatistics and Epidemiology (J.G.W., N.Z.), and the Heart Institute (E.M.U.), Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati College of Medicine (J.G.W., N.Z., E.M.U.) - both in Cincinnati; the Department of Pediatrics, University of Colorado School of Medicine, and Anschutz Medical Campus, Children's Hospital Colorado - both in Aurora (S.R.D.); the Center for Population Health Research (J.I., N.K., C.G.M., O.T.R.), the Research Center of Applied and Preventive Cardiovascular Medicine (J.I., N.K., C.G.M., O.T.R.), and the Departments of Medicine (M.J., J.S.A.V.) and Mathematics and Statistics (N.K.), University of Turku, and the Center for Population Health Research (J.I., N.K., C.G.M., O.T.R.), the Division of Medicine (M.J., J.S.A.V.), and the Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Turku, and the Department of Clinical Chemistry, Fimlab Laboratories, and the Finnish Cardiovascular Research Center, and the Faculty of Medicine and Health Technology, Tampere University, Tampere (T.L.) - all in Finland; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS (C.G.M., A.J.V., T.D.), and the Heart Research Group, Murdoch Children's Research Institute, Melbourne, VIC (T.D.) - both in Australia; the School of Public Health and Tropical Medicine, Tulane University, New Orleans (L.A.B.); the Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (T.L.B.); the Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC (R.J.P.); and the Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom (T.D.).

Abstract

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.).

Publication types

Research Support, N.I.H., Extramural

MeSH terms

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

Substances

Cholesterol

Grants and funding

R01 HL121230/HL/NHLBI NIH HHS/United States