According to a new study published in Circulation Research, children whose genetic makeup predicts high blood pressure in adulthood are more likely to survive surgery to repair a congenital heart defect.
The findings could help inform treatment strategies and improve outcomes for children undergoing congenital heart defect repair procedures, said Todd Edwards, PhD, associate professor of medicine and lead author of the study.
“There is substantial variability in outcomes after congenital heart defect repair surgery, and it’s not been clear why one patient might do well and another might not,” Edwards said. “Our study gives us a foothold – key insight into this individual variability – and an opportunity to design strategies to improve outcomes.”
Congenital heart defects (CHDs) are the most common birth defects in the United States, affecting about 40,000 babies each year, according to the Centers for Disease Control and Prevention. About half of children with coronary artery disease require surgical repairs or other procedures and are at risk for postoperative complications and death.
To explore contributors to coronary heart disease complications, Prince Kannankeril, MD, MSCI, a pediatric cardiologist at Monroe Carell Jr. Children’s Hospital in Vanderbilt, in 2007 established an ongoing cohort of patients undergoing coronary heart surgery with detailed clinical information and blood samples.
“This patient cohort is an exceptional resource nationwide,” said Edwards, a genetic epidemiologist who has partnered with Kannankeril to study genetic variation and coronary heart disease outcomes.
Edwards is also a leader in studies of genetic variation associated with a range of conditions in the Million Veteran Program (MVP), a national program to study how genes, lifestyle and military exposures affect health. and disease. Using the MVP data, Edwards and his colleagues discovered more than 200 new genetic variations associated with high blood pressure.
Scientists have been skeptical that the genetic variation linked to high blood pressure risk in adults would apply to children, Edwards said. But in 2019, a group in Germany reported that a genetic background of high blood pressure improved survival in premature infants.
“That was really interesting to us — the idea that findings in adults related to genetic determinants of a trait like blood pressure might matter in a pediatric population,” Edwards said.
Based on previous MVP results, the team developed polygenic risk scores for systolic and diastolic blood pressure: high scores predict high blood pressure. The researchers analyzed the association of blood pressure scores in the CHD cohort with death during hospital stay and with length of stay. The current study included 2,498 infants through young adults who had their first surgery for CHD at Children’s Hospital between 2007 and 2020.
Researchers found that children with high diastolic blood pressure scores had a reduced risk of in-hospital mortality and reduced time spent in intensive care and hospital after CHD repair surgery. They found that the reduction in mortality risk was related to the interaction of blood pressure variants with doses of drugs that increase blood pressure (vasopressors).
“We came up with the idea that if you were more susceptible to hypertension as an adult, you might respond better to vasopressors,” said Joseph Breeyear, graduate student and first author. “That’s exactly what we found: children with a higher load of blood pressure-raising alleles (genetic variants) needed less pharmacological help to achieve stable blood pressure.”
For children who required higher doses of vasopressors, those with high blood pressure scores had improved survival comparable to children with low blood pressure scores.
“This is a key finding from our study: For patients who are distressed after the procedure (and who require higher doses of vasopressors), this polygenic blood pressure risk score is very important,” Edwards said.
The researchers suggest that predictive models for identifying children at risk for adverse outcomes associated with coronary artery surgery could be improved by adding polygenic blood pressure risk scores.
Edwards noted that as an Army veteran himself, he is especially pleased that “veteran studies are being applied to help young children.”
In addition to Edwards, Kannankeril, and Breeyear, Vanderbilt authors of the circulation research paper include Eric Torstenson and Sara Van Driest, MD, PhD. The research was funded by the National Institutes of Health (grants HD084461, TR002244).