Childhood Risk Factors Predict Adult Cardiovascular Events

New research from physicians at Cincinnati Children’s is gaining international attention as it highlights ways to impact preventive care for two types of pediatric heart health: childhood risk factors that lead to adult heart events and stopping the progression of latent rheumatic heart disease with secondary antibiotics.

Both studies were published in the New England Journal of Medicine in 2022 and also recognized among Cincinnati Children’s top research publications of the year.

• Elaine Urbina, MD, MS; Jessica Woo, PhD; and Nanhua Zhang, PhD, contributed to “Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events,” published in May 2022.
• Andrea Beaton, MD, is the lead author on “Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease,” published in January 2022.

Each project creates opportunities for impactful future population health approaches to these pediatric heart conditions.

Proof: Childhood Cardiovascular Risk Factors Tied to Adult Cardiovascular Events

For the first time, scientific data show that cardiovascular risk factors in childhood, such as high blood pressure, high cholesterol and obesity, are directly linked to heart events in midlife, Urbina says.

The conclusion is the result of decades of work by a Cincinnati Children’s team and collaboration among multiple researchers associated with the International Childhood Cardiovascular Cohort Consortium.

“No one has actually followed people for 40 years to prove the association,” Urbina says. “It has always been assumed, but now we have the proof.”

The consortium includes seven cohorts in the United States, Finland and Australia that started following children in the 1970s and 1980s. The cohorts tracked each participant’s:

• Body mass index
• Systolic blood pressure
• Total cholesterol level
• Triglyceride level
• Youth smoking

All risk factor data were harmonized and combined into one database. A combined risk factor z-score was created for the childhood risk factors. A similar risk score was created for adult cardiovascular disease risk factors.

Participants, now in their 40s and 50s, were contacted to ascertain when and whether they experienced a hard cardiovascular event. Cardiologists, cardiovascular physicians, epidemiologists, neurologists and other specialists investigated the lifetime medical records of participants who experienced a fatal or non-fatal cardiovascular disease event.

“The risk factors in childhood predicted what can happen in adulthood,” Urbina says.

Findings show that even children with blood pressure, cholesterol or weight in the high to normal range—at levels pediatricians currently do not consider clinically dangerous—are more likely to have a cardiovascular disease event in midlife.

“We want pediatricians to understand the importance of following the screening guidelines we have,” Urbina says. “The data confirms the assumption of risk.”

Going forward, Urbina hopes to see more public health approaches to prevent cardiovascular disease, including lifestyle modifications like better school lunches, safe places to play outside, and improved insurance coverage for obesity treatments.

The study was funded by the National Institutes of Health. Learn more in our Research Annual Report.

Preventing, Reducing Cardiac Damage from Rheumatic Heart Disease

Cincinnati Children’s Andrea Beaton, MD, has studied rheumatic heart disease (RHD) for years. This is an acquired condition that damages the valves of the heart. It is caused by rheumatic fever, which occurs after an untreated strep infection. The illness is most common in school-age children living in crowded, high-poverty areas with limited access to healthcare and hygiene.

RHD affects 40.5 million people worldwide. There are about 306,000 deaths from RHD each year. This study is the first of its kind for RHD in more than 60 years.

A decade ago, physicians found that echocardiograms could spot children at the very early stages of RHD, with evidence of valvular damage, Beaton says. But what was not known was if we should be screening. “Could we prevent disease progression and improve outcomes?”

She spent the summer of 2018 in Uganda, working with volunteers from all over the world to screen 100,000 children for signs of valve damage from RHD. After the screenings, 900 children were enrolled in the trial.

Beaton and colleagues from Cincinnati Children’s led this international collaboration, bringing together researchers from RHD groups on six continents.

“The success of this trial was in large part due to deep community engagement, before, during and after the trial,” Beaton says.

Children were seen every 28 days, most at Saturday play and support groups close to their home villages. Half received penicillin, and half did not. Every child was assigned a social worker who formed deep bonds with the family. This ensured children consistently received antibiotic injections. The study reported a 99% adherence rate and a 97% retention rate.

The study found that among children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at two years.

“The penicillin injections had a powerful protective effect; more than we thought they would,” Beaton says.

Researchers also learned that:

• The number of children with latent rheumatic heart disease who need to receive prophylaxis to prevent one child from progression was 13.
• Half of the children had a normal echocardiogram at end of study.
• 8% of children in the control group children showed disease progression at two years.

Beaton hopes future research moves the RHD community closer to population-based screening and initiation of prophylaxis.

In August 2022, Beaton was awarded an $8 million grant from the Leducq Foundation for her proposal to establish an “Acute Rheumatic Fever Diagnosis Collaborative Network.”

Improved diagnostic tests for rheumatic fever are important in low-resource settings where 85% of children with rheumatic heart disease are diagnosed only after the disease has advanced. At this stage, medications are ineffective and surgical intervention—if available—is less likely to succeed.

In addition, Beaton’s colleague Sarah de Loizaga, MD, received an award from the Thrasher Research Fund to do a follow-up study investigating how to translate the clinical trial strategies into Uganda’s public health system.

The trial study was sponsored by the Children's National Research Institute and funded by the Thrasher Research Fund, the University of Cape Town, the Uganda Heart Institute and others.

(Published December 2022)

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