Activation of Brain’s Stress Center May Spur Inflammation, Cardiovascular Events

A new imaging study is offering information about a potential mechanism to explain the established link between emotional stress and cardiovascular events. Greater activity in the amygdala—the brain’s stress center—is associated with elevated bone marrow activity, arterial inflammation, and risk of subsequent cardiovascular disease events, researchers say.

This represents the first time a relationship between activation of neural tissues and future heart disease events has been identified, according to Ahmed Tawakol, MD (Massachusetts General Hospital, Boston, MA), who reported the findings to the press ahead of their formal release at the upcoming American College of Cardiology meeting in Chicago, IL.

It may be that stress centers in the brain, bone marrow, and arterial inflammation may all be part of a system that precipitates cardiovascular events, he said on a conference call with reporters.

“This finding . . . highlights a potential pathway for further study and potential intervention,” Tawakol said. “Future studies should identify ways to interrupt this mechanism in order to reduce the burden of stress-associated cardiovascular disease.”

The study included 293 patients without known cardiovascular disease who underwent whole-body positron emission tomography (PET)/CT imaging for cancer screening at Mass General between 2005 and 2008 and were found to not have active cancer. Amygdala activity was measured using the target-to-background ratio, which assesses the absolute activity in that area of the brain corrected for background brain activity. Fear, posttraumatic stress disorder, and anxiety have been shown to increase activity in the amygdala.

PET/CT imaging was also used to look for atherosclerotic inflammation and bone marrow activation.

Through median follow-up of 3.8 years, there were 22 individuals with 38 cardiovascular disease events. The event rate was greater in patients with higher versus lower baseline amygdala activation (roughly 40% vs 5%; P < 0.001).

Various amygdala activity measures predicted cardiovascular disease events “rather robustly,” Tawakol said. The relationship was consistent when looking only at MACE as an endpoint, when excluding patients with prior cancer, and when adjusting for known cardiovascular risk factors.

Also, as suggested by prior animal studies, amygdala activity was associated with bone marrow activation and arterial inflammation.

Managing Stress in the Clinic

Tawakol noted that the magnitude of the relationship between psychosocial stress and cardiovascular disease is similar to the strength of links between cardiovascular risk and smoking, dyslipidemia, hypertension, and diabetes.

“Yet we tend not to do so much about it in terms of management of our patients with cardiovascular disease,” he said.

Although the current study does not inform potential interventions, Tawakol said he could envision a time when patients would receive assessments of stress levels in addition to the typical evaluations of cardiovascular risk factors.

Patients with high levels of stress could then possibly be managed with behavioral or pharmacologic approaches, he said, noting that meditation and mindfulness are known to modulate amygdala activity and that animal studies have provided some evidence that medications could interrupt the pathway observed in the current study.

However, he said, it will take further prospective research to determine which interventions might be effective.

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