Risk factors for cardiovascular-kidney-metabolic disease can be identified in young children

Risk factors for cardiovascular-kidney-metabolic disease, a health condition made up of heart disease, kidney disease, diabetes, and obesity, can be identified in children as young as 8, UTHealth Houston researchers discovered. 

Using a group of 273 children who participate in the Border Health Research Cohort within the Border Health Research Center at UTHealth Houston School of Public Health in Brownsville, researchers analyzed 5,000 proteins and identified six “signatures” of proteins that significantly influence the risk of developing cardiovascular-kidney-metabolic disease in adulthood. The same protein signature was present in 685 adults from the same community who were at high risk of irreversible cardiovascular-kidney-metabolic disease, according to the team. 

The research was published today in Nature Metabolism and led by first author Heather Highland, PhD, assistant professor of epidemiology at the School of Public Health. 

“Understanding the development of cardiovascular-kidney-metabolic disease across the lifecourse is critical,” Highland said. “Proteins circulating in the blood can serve as markers of nascent pathologies across the body. These early markers can help identify people at greater risk for increased monitoring and potentially early intervention.” 

To confirm the findings, the team assessed the association of their protein signatures with disease outcomes in more than 28,000 adults participating in the UK Biobank, a large-scale prospective study of more than 500,000 people living in the UK. Individuals in the UK Biobank who had the similar protein signatures were at a higher risk of having a heart attack or other poor health outcomes associated with cardiovascular-kidney-metabolic disease, according to the team. 

Importantly, the team also compared their findings to the results of GLP-1 drug trials and found the majority of the proteins in the signatures that place individuals at high risk of irreversible cardiovascular-kidney-metabolic disease were reversible in adults taking GLP-1 drugs. 

“This association is really one of the most exciting messages, because those proteins that predict the risk of cardiometabolic diseases all moved in a healthy direction after these adults took GLP-1. This makes this a modifiable risk state rather than a fixed marker of fate,” said corresponding author Kari North, PhD, director of the Border Health Research Center and professor at the School of Public Health. “Childhood is the time that we really need to start intervening because it’s reversible.” 

Many of the children who participated in the study already had phenotypes, or physical traits, associated with cardiovascular-kidney-metabolic disease, including obesity, liver function, cholesterol levels, and insulin resistance. However, many of the blood tests performed by the team are not typical of what a child would receive at an annual doctor’s visit. 

The findings support the importance of early intervention and a move toward precision medicine, the team said. 

“The dysregulation of the proteins that influence risk of heart attack later in life, if we can reverse them in childhood,  then we can really make a huge dent in the cardiovascular disease burden that we see in adult populations around the world today,” North said. “ We need to do better screening in children, and if we see children who are at an elevated risk, the time to act is now.”

Senior authors Joseph McCormick, MD, professor of epidemiology and James H. Steele, DVM, Professor at the School of Public Health, and Susan Fisher-Hoch, MD, professor of epidemiology at the School of Public Health, are co-founders of the Cameron County portion of the Border Health Research Cohort, and have overseen the population-based study since 2014. 

“The cohort provides key silent markers of chronic disease traits that are manifest in adults, including some parents of the children, with clinical disease. These children have generously participated in the study at our Clinical Research Unit in Brownsville,” McCormick said. 

Fisher-Hoch also credited the staff and the wider Brownsville community with making the research possible. 

Nearly 20 staff, recruited from the same community and provided appropriate skills, did the hard work of conducting the detailed study of the children in our clinical research unit and laboratory. The community-based team is immensely proud of the contribution of their efforts to human health.”

Susan Fisher-Hoch, MD, professor of epidemiology, School of Public Health, UTHealth Houston

Additional authors from UTHealth Houston include: Victoria Buchanan, PhD; Mohammad Y. Anwar, PhD; Absalon Gutierrez, MD; Miryoung Lee, PhD; and Kristin L. Young, PhD.

Authors from Vanderbilt University include: Joshua Landman, PhD; Andrew Perry, MD; Quanhu Sheng, PhD; Anna Lorenz, MS; Shilin Zhao, PhD; Wanying Zhu, MS; Elizabeth G. Frankel, BS; Rashedeh Roshani, MS; Alyssa Scartozzi, PhD; Eric H. Farber-Eger, MS; Ash Breidenbach, PhD; Ting-Chen Wang, BS; Jaclyn Tamaroff, MD; Lauren E. Petty, PhD; Alexander S. Petty, BS; Benjamin Lippi, BS; Quinn Wells, MD; Kahraman Tanriverdi, PhD; Jane E. Freedman, MD; Eric R. Gamazon, PhD; Jennifer E. Below, PhD; and Ravi V. Shah, MD. 

Authors from the University of North Carolina at Chapel Hill include: Annie G. Howard, PhD; Xinruo Zhang, PhD; Alexandra B. Palmer, MD, PhD; Jessica K. Sprinkles, PhD; Christine A. Ballard, MS; Mariaelisa Graff, PhD; Katie A. Meyer, ScD; and Penny Gordon-Larsen, PhD. 

Additional authors include: Matthew Nayor, MD, of Boston University; Lindsay Fernandez-Rhodes, PhD; and Mohanraj Krishnan, PhD, of Pennsylvania State University; and Hung-Hsin Chen of the Institute of Biomedical Sciences in Taiwan.