Research Aims to Expand Understanding of Link Between Chronic Stress and Heart Disease Among Other Age-Related Conditions

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Distinguished Professor of Epidemiology Susan Hankinson has been awarded a five-year, $4 million grant renewal by the National Institutes of Health (NIH) to advance her research into the relationship between chronic stress and an increased risk of heart disease, diabetes and other age-related conditions including Alzheimer’s.

Hankinson and co-lead investigator Laura Kubzansky, director of the Society and Health Laboratory at the Harvard T.H. Chan School of Public Health, will lead the experienced team of researchers in the largest and most diverse study of its type. Professor of Biostatistics Raji Balasubramanian is the lead biostatistician on the project.

“We were thrilled to be funded on the first competitive renewal round,” says Hankinson, a longtime senior investigator in the groundbreaking Nurses’ Health Study, one of five cohorts included in this research. “It’s not very often that happens.”

To better understand the effects of depression and anxiety – chronic stress – on future health risks, the researchers have been examining metabolites, or the products of cell metabolism, measured in blood samples using mass spectrometry-based metabolomics.

“Our overarching goal is to better understand what the metabolic consequences are of chronic stress,” Hankinson says. “And then, whether those alterations link to later chronic disease. There’s actually been remarkably few studies that have looked at links of metabolites and anxiety and depression.”

In their first round of research, Hankinson and team developed and validated a metabolomic score of chronic stress in a population of largely non-Hispanic white women, using data from the Nurses’ Health Study, the Women’s Health Initiative and the Primary Prevention of Cardiovascular Disease with a Mediterranean Diet (PREDIMED). The score was associated with a higher risk of heart disease.

Over the next five years, researchers will use cutting-edge metabolomic and biostatistical approaches to look at these known and novel biomarkers among a large, racially and ethnically diverse population, including data from the Multi-Ethnic Study of Atherosclerosis (MESA), with more than 6,800 white, African-American, Hispanic and Asian-Americans; and the Jackson Heart Study, with more than 5,300 African-American participants.

“We have a number of unidentified metabolites that were strongly related to anxiety and depression that were not included in our original score because we don’t know what they are,” Hankinson says. The team will send those metabolites to the Broad Institute of MIT and Harvard, where their collaborators will use advanced tools in an effort to identify those markers.

They hope to strengthen the chronic distress score by adding some previously unidentified metabolites strongly associated with the distress phenotype. They also will assess the score in new populations, including African-American and Hispanic men and women, and white men, optimizing the score in each population.

Next, the team will assess if the chronic distress score and its individual components are associated with diabetes and cognitive function, in addition to heart disease. The goal is to have objective and minimally invasive assessment tools – compared to subjective reports by individuals – to potentially better identify who is at risk of heart disease, diabetes and cognitive decline.

“It may also open up new avenues for prevention strategies that we don’t currently have at hand,” Hankinson says.

In addition to the lead investigators and lead statistician, the research team includes Clary Clish, senior director of the metabolomics platform at the Broad Institute; and Tianyi Huang, assistant professor of medicine at Harvard Medical School; Dr. Jerome Rotter, director of the Institute for Translational Genomics and Population Sciences at The Lundquist Institute for Biomedical Innovation; and Mario Sims, professor of social medicine, population and public health at the University of California, Riverside, and chief science officer of the Jackson Heart Study.