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Novel Pathway for Translating Emotional Stress Into Physical Heart Disease

In This Article

  • A team of clinicians has found a novel pathway linking psychosocial stress to heart disease
  • Research has shown that chronic emotional stress is associated with disease, but it was not clear how stress from external circumstances translates into physical events in the body that lead to disease
  • This study finds that brain activity in the amygdala predicts subsequent heart attacks and stroke.

A team of clinicians led by Ahmed A. Tawakol, MD, co-director, Cardiac MR PET CT Program, has found a novel pathway linking psychosocial stress to heart disease. Published in the The Lancet, this study finds that brain activity in the amygdala predicts subsequent heart attacks and stroke.

Research has shown that chronic emotional stress is associated with disease. But it was not clear until this study how stress from external circumstances translates into physical events in the body that lead to disease.

“With the amygdala as an entry point, we show for the first time in humans that stress prompts an increase in bone marrow activity and inflammation in blood vessels. This then sets the stage for cardiovascular disease to develop,” explains Dr. Tawakol, who specializes in clinical and research cardiovascular imaging.

A Stress Translation Pathway

The findings are the result of the largest-ever longitudinal study comparing brain imaging of resting amygdalar activity and disease outcomes. The study followed a cohort of 293 people (median age=55) over four years. None had been diagnosed with heart disease or had active cancer at the outset.

In collaboration with researchers from Icahn School of Medicine at Mount Sinai, Tufts University and Weil Cornell Medical College, the team used Positron Emission Tomography (PET) imaging and linked imaging data with CV disease characteristics.

Researchers found for the first time, a series of events that have only been described before in animal studies, that stress triggers an increase in bone marrow activity, elevated arterial inflammation and circulating inflammatory markers—conditions that can predispose a person to a CV event. The researchers additionally asked two key questions that had never been addressed before in humans or in animas: 1) what part of the brain participates in this process, and 2) does activation of this system culminate in clinical disease events.

Brain Imaging, Bone Marrow, Inflammation

Researchers were surprised to find not just an association between brain imaging, bone marrow response and artery wall inflammation—but by the strength of the association. A mediation path analysis was conducted to further define roles and relationships of variables. “Through that analytical approach,” Dr. Tawakol says, “we could demonstrate that the path of a CV event included a pathway through the brain, the bone marrow and to the artery wall. That gives us a biological system: a pathway that is evidence-based—not just a concept—and against which we can design interventions.”

The team is looking at several other diseases in terms of this newly defined stress-to-disease pathway, as well as the fundamental drivers of stress.

Stress Revisited and Redefined

By finding a physical pathway, physicians are now renewing their emphasis on the role of stress in health and disease. In his own practice and personal health care, Dr. Tawakol focuses more effort on stress control through well-known stress-reduction techniques including exercise and mindfulness practices.

“Now with myself and my patients, I look at stress in medical terms—like an objective risk factor similar to LDL,” says Tawakol. “If a patient has a high burden of chronic stress, there is a possibility that reducing his or her perception of that stress might lower the risk of heart disease.” Dr. Tawakol noted however that “Large scale clinical trials still need to be performed to prove that stress reduction beneficially impacts heart disease.”

These new results are so exciting, he says, because they suggest many new promising leads to improving care for many conditions.

“There is a lot left to learn on disentangling these new pathways, on discovering the genetic underpinnings and many other aspects of stress that will have powerful and practical value to how well we can help patients take care of their health.”

Learn more about the Cardiac MR PET CT Program at Mass General Hospital

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A statistical review of imaging and cardiovascular event data at Mass General finds amygdalar activity to be significantly associated with cardiovascular disease risk.