It's official: Weight, blood pressure, and other traditional cardiovascular (CV) risk factors in early childhood do link to cardiac events and deaths in older age, longitudinal cohort data proved.
As interpolated from surrogate markers and biostatistical wrangling, hard evidence from 38,589 people followed in seven cohorts from the U.S., Finland, and Australia, showed that average risk children had more events in adulthood than those with the lowest combined risk factor z scores (≥0 vs less than -0.5).
Each 1 point increase in the combined risk factor z score was associated with a 2.71- to 3.54-fold higher likelihood of death from CV events in adulthood, depending on adjustment methods, reported Jessica G. Woo, PhD, of the Cincinnati Children's Hospital Medical Center, at the American College of Cardiology meeting, held virtually and in Washington. Findings were simultaneously published in the (NEJM).
For individual risk factors measured at ages 3 to 19 years (mean 11.8 years), each 1 point increase in z score was associated with the following hazard ratios for dying from a CV event by the mean adult follow-up age of 31:
- For total cholesterol: 1.30 (95% CI 1.14-1.47)
- For BMI: 1.44 (95% CI 1.33-1.57)
- For systolic blood pressure: 1.34 (95% CI 1.19-1.50)
- For triglycerides: 1.50 (95% CI 1.33-1.70)
- For smoking: 1.61 (95% CI 1.21-2.13)
The findings mark the "coming of age" of robust clinical cohorts that provide the "direct evidence that CV risk factors in childhood are linked to hard CV disease (CVD) outcomes in adulthood" that has been so "elusive," stated NEJM deputy editor Julie Ingelfinger, MD, of Mass General Hospital for Children in Boston.
"If CV risk factors can be identified early in life, we as clinicians have opportunities to address health issues early and might uncouple risk from an inexorable march toward CVD and death," she wrote in an accompanying editorial. "We have been waiting for hard data showing that risk factors seen in childhood forecast future disease, and now we have a good start concerning CVD."
In the International Childhood Cardiovascular Cohorts (i3C) Consortium Outcomes Study of participants that enrolled in the 1970s to 1990s, the average combined-risk z score was 0.16, and 59.9% came in at 0 or greater, corresponding to the risk-factor level of an average child.
"None of the interaction terms of childhood age group (3 to 11 years vs 12 to 19 years), race, or sex were notable," the researchers wrote. "The childhood risk score was also positively associated with total mortality."
The study accrued 319 fatal CV events in the population, occurring at a median age of 47.
One limitation was that Black participants accounted for just 15% of the study population, which along with the few Latinx and Asian participants, raises some question of generalizability, Ingelfinger pointed out.
"Whereas the findings for fatal CV events were clear, with vital status or cause of death having been verified in 96% of all the participants, nonfatal CV events posed a problem, because 46% of the sample could not be contacted," she added.
Disclosures
The trial was funded by the NIH.
Woo disclosed relationships with the National Heart, Lung, and Blood Institute, the National Institute of Nursing Research, and the NIH.
Ingelfinger disclosed relationships with Springer and St. Martin's Press.
Primary Source
New England Journal of Medicine
Jacobs DR, et al "Childhood cardiovascular risk factors and Adult cardiovascular events" N Engl J Med 2022; DOI: 10.1056/NEJMoa2109191.
Secondary Source
New England Journal of Medicine
Ingelfinger JR "Childhood risk factors and prediction of adult cardiovascular end points" N Engl J Med 2022; DOI: 10.1056/NEJMe2203743.