We’ve known for some time that chronic stress can lead to a slew of health problems, from an increased risk of developing depression to heart disease. But new research that will be presented at the American College of Cardiology’s 65th Annual Scientific Session has managed to gain deeper insight into how stress may cause inflammation and heart problems.

Researchers used medical imaging to examine biochemical activity in the brain and how it leads to arterial inflammation, which can contribute to heart problems — including plaque buildup, heart attack, and stroke. They found that study participants who experienced high activity in areas of the brain associated with stress and fear were far more likely to have heart troubles later.

The study examined 293 patients who were on average 55 years old, and who had received a PET/CT scan between 2005 and 2008 for a cancer screening — though they had all been marked free of the disease. These same participants were also clear of heart disease at the time. The scans provided insight into brain activity, bone marrow, and arteries due to a method that made more active tissues glow brightly on the scan. The researchers divided the participants into groups based on the level of brain activity in their amygdala. High activity in the amygdala is associated with stress and fear responses.

After following up on the cardiovascular health of the participants for five years, the researchers found that those who had been placed into the high-activity amygdala group had a 14-fold higher risk of heart problems for every unit increase in brain stress activity. In addition, 35 percent of those participants experienced a cardiovascular event within the five years, compared to only 5 percent of the low-stress group.

The results are “intriguing,” Dr. Ahmed Tawakol, co-director of the cardiac MR PET CT program at Massachusetts General Hospital and an author of the study, told Medical Daily. “Our study illuminates, for the first time, a relationship between activation of neural tissues — those associated with fear and stress — and subsequent heart disease events,” Tawakol said in the statement. “There is a need to develop greater knowledge in terms of the mechanism that translates stress into cardiovascular disease risk, given the prevalence and potency of stress as a risk factor.”

It wasn’t simply high activity in the amygdala that signaled cardiovascular trouble. The researchers also found that activation of the fear center in the brain went hand-in-hand with bone marrow activation and inflammation in the arteries. Bone marrow activation refers to bone marrow producing more cells, including white blood cells called monocytes, that may contribute to inflammation. The researchers were able to measure this by the increased production of monocytes and other bone marrow-derived cells.

It’s possible that stress activity in the brain, bone marrow activation, and arterial inflammation work together to create adverse cardiovascular effects, though the current study only highlights a correlation, and not necessarily a causation. In order for the researchers to move forward, Tawakol notes, they would have to establish that stress indeed causes heart problems. To do that, they’d have to set up a study that involves an intervention, one that would reduce the brain’s stress or emotional response and prove whether that lowered cardiovascular events as well. Only then can they begin discussing the notion of treating stress by targeting the stress response in the brain.

“If we find that treating stress in one way or another results in a reduction in heart disease, then we’re going to venture towards diagnosing and intervene,” Tawakol told Medical Daily. “Certainly we want to test the hypothesis that there are coping methods for stress that reduce stimulation of the [stress] system and reduce cardiovascular risk.”

Being prescribed medications or undergoing therapy may be one way of preventing future heart problems if the researchers do end up proving the causation. And reducing stress may be just as important as quitting smoking or monitoring your diabetes.

“Over the past several years, it’s become clear that stress is not only a result of adversity but may itself also be an important cause of disease,” Tawakol said in the press release. “The risks of heart disease linked to stress is on par with that for smoking, high blood pressure, high cholesterol and diabetes, yet relatively little is done to address this risk compared to other risk factors. We are hopeful studies like this bring us closer to understand how stress may lead to heart disease.”

Source: Ishai A, Tawakol A, et al. Greater Activity of the Brain’s Emotional Stress Center Associates With Arterial Inflammation and Predicts Subsequent CVD Events. American College of Cardiology , 2016.