A circulating blood protein signature identified in children as young as 8 years old can detect early signs of cardiovascular-kidney-metabolic disease, according to a study published September 11 in Nature Metabolism. Researchers from Vanderbilt Health, UTHealth Houston, and the University of North Carolina at Chapel Hill found that these molecular biomarkers mirror those previously associated with irreversible cardiovascular disease in adults, opening a potential path for early precision medicine interventions.
Identifying Molecular Signatures in Pediatric Populations
The research team analyzed data from 273 children and adolescents participating in the Border Health Research Cohort in Cameron County, Texas. According to the study findings, more than a third of the young participants displayed phenotypes of cardiovascular, kidney, and metabolic disease. These physical characteristics included obesity, higher-than-normal blood pressure, prediabetic insulin resistance, and levels of lipids (fats) in the blood associated with increased risk of heart disease.
Using machine learning techniques and blood samples alongside physical measures, researchers established proteomic signatures of cardiovascular-kidney-metabolic disease (CKMD). To validate these patterns, the team compared the pediatric data against blood samples from 685 adults in the same Cameron County community and more than 28,000 adults stored in the UK Biobank.
“Childhood is not simply a precursor to adult health,” said Kari North, professor at UTHealth Houston School of Public Health and director of the Border Health Research Center. “It is where the biology of adult cardiovascular disease is already taking place.”
Potential Links to Emerging Therapeutics
The study highlights a significant overlap between the protein patterns identified in children and molecular changes in adults that respond to specific therapies. According to the researchers, levels of these disease-associated proteins in adults decline in response to treatment with semaglutide, a GLP-1 receptor agonist developed for type 2 diabetes that is now widely used for obesity and weight management.
Pediatric prescriptions for GLP-1 receptor agonists increased by nearly 600% between 2020 and 2023. Despite this surge, researchers cautioned that the benefit of such therapy must be balanced with potential risk.
Traditional efforts to address childhood obesity through promoting cardiovascular health through exercise, a healthy diet and, increasingly, weight loss drugs and surgery have yielded limited success, prompting a reevaluation of early intervention strategies. “Because many of the protein patterns we identified are potentially modifiable,” said co-corresponding author Ravi Shah, Gottlieb C. Friesinger Professor of Cardiovascular Medicine at Vanderbilt Health, “these findings suggest that the greatest opportunity to prevent heart disease may come decades before the first symptoms appear.”
Current medical guidelines for diagnosing and treating cardiovascular-kidney-metabolic disease focus on adults. Senior author Penny Gordon-Larsen, vice chancellor for research at the University of North Carolina at Chapel Hill, emphasized that “the importance of identifying early metabolic signals of the biological processes that drive CKMD cannot be overstated.”
While the authors note that additional research is required to validate these results, the identification of early proteomic signatures provides a framework for recognizing children most at risk. By detecting these pathways during childhood, clinicians may eventually utilize targeted precision medicine approaches to alter long-term cardiovascular health trajectories before irreversible damage occurs.
Related reading