Five childhood risk factors that predict stroke and heart attacks in adulthood have been identified after being tracked for up to half a century in the world’s largest international prospective cardiovascular disease study, with some children as young as five showing signs of fatty deposits in their arteries.
The study, conducted by the International Childhood Cardiovascular Consortium (i3C) including researchers from Australia’s Murdoch Children Research Institute (MCRI), found body mass index, blood pressure, cholesterol, triglycerides (a type of fat found in blood) and youth smoking, particularly in combination in early childhood, were clinically linked with cardiovascular events, from as early as 40-years-old.
Senior study author Murdoch Children’s Professor Terence Dwyer said: “Despite the effect medical and surgical care has had on treating heart disease, the major impact will depend on effective preventive strategies. This study confirms that prevention should begin in childhood.
“Longitudinal studies like these have been hampered by a lack of inclusion of comprehensive childhood data around body measurements, blood pressure and blood lipids and a failure to follow-up at ages when cardiovascular disease becomes common.
“Studying early life influences on disease has always been put in the too hard basket. But researchers in i3C took up this challenge because we knew the potential benefits to human health at the end could be very substantial.”
The study involved 38 589 participants from Australia, Finland and the US, who were followed from age 3-19 years for 35-50 years.
Dwyer said the research found the five risk factors, individually or in combination, present in childhood were predictors of fatal and non-fatal cardiovascular events.
The results, published in the New England Journal of Medicine, showed that risk for adult cardiovascular events were seen in more than half of the children studied, with some whose risk was nine times as much as those with below average risk factors.
“While this evidence had not been available previously, the findings were not entirely surprising as it had been known for some time that children as young as five already showed early signs of fatty deposits in arteries. This new evidence justified a greater emphasis on programmes to prevent the development of these risk factors in children. Clinicians and public health professionals should now start to focus on how this might best be achieved.
“While interventions in adulthood like improving diet, quitting smoking, being more active, and taking appropriate medications to reduce risk factors are helpful, it is likely that there is much more that can be done during childhood and adolescence to reduce lifetime risk of cardiovascular disease.”
Study details
Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events
David Jacobs, Jessica Woo, Alan Sinaiko, Stephen Daniels, Johanna Ikonen, Markus Juonala, Noora Kartiosuo, Terho Lehtimäki, Costan Magnussen, Jorma Viikari, Nanhua Zhang, Lydia Bazzano, Trudy Burns, Ronald Prineas, Julia Steinberger, Elaine Urbina, Alison Venn, Olli Raitakari, Terence Dwyer.
Published in New England Journal of Medicine on 19 May 2022.
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.
NEJM article – Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events (Open access)
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