Exploring the Link Between Childhood Adversity and Adult Heart Disease

Children’s of Alabama researchers are using an NIH grant to study the link between childhood adversity and adult heart disease.

Children’s of Alabama pediatric nephrologist Michael Seifert, M.D., and cardiorenal physiologist Jennifer Pollock, Ph.D., have received a five-year, National Institutes of Health-funded grant to explore the link between stressful childhood experiences and increased risk for cardiovascular disease in adulthood.

“We’re trying to study how exposure to early life stress (ELS) starts to have an effect in childhood on your cardiovascular system,” Seifert said. ELS includes adverse experiences such as physical and emotional abuse or neglect before age 18.

Studies over the last 20 years have linked ELS to adult-onset heart disease and other poor health outcomes like diabetes, mental illness, cancer and high-risk health behaviors. “But despite that, we still know relatively little about the mechanisms connecting the two,” Seifert said.

Seifert and Pollock will test their central hypothesis: ELS causes immune cell activation and inflammation, leading to vascular dysfunction and increasing the risk for hypertension and cardiovascular disease (CVD) later in life.

The investigators will follow a group of 300 adolescents from racially diverse backgrounds to identify critical clinical features and molecular pathways in ELS-associated CVD risk. Early research shows that this population has increased vascular stiffness and ambulatory diastolic blood pressure as well as pro-inflammatory metabolite and gene methylation patterns in plasma and circulating monocytes, respectively.

Seifert and Pollock will use comprehensive profiling to measure vascular stiffness and blood pressure and analyze the metabolome and epigenome—chemical signatures in blood and genes. The goal is to identify inflammatory and molecular pathways linked to cardiovascular changes. The grant also includes two basic science studies that will further inform the clinical trial and a similar study in young adults who had early-life stress exposure.

While it might seem counterintuitive to have nephrology specialists working on a cardiovascular health study, the two are closely linked. “We expect the same things increasing cardiovascular risk probably also increase chronic kidney disease risk,” Seifert said. “There is a lot of cross-talk between the cardiovascular system and the kidneys.” Findings may reveal new therapeutic targets. “This study has important translational potential,” Seifert said. “If we identify something in adolescence that’s driving this, maybe we can mitigate some effects of early-life stress.”