PET/CT shows how stress in the brain today manifests as cardiovascular problems tomorrow

The connection between chronic emotional stress and subsequent cardiovascular disease has long been substantiated on mostly circumstantial evidence. Now it’s been empirically established with imaging: A new study has put pictures to the heretofore unseen brain mechanism behind the mind/body double trouble.  

Published online Jan. 12 in The Lancet and lead-authored by Ahmed Tawakol, MD, of Harvard, the PET/CT-based study shows that observable metabolic activity in the amygdala—one of the brain’s “emotional epicenters”—correlates with increased bone-marrow activity and arterial inflammation.

Tawakol and colleagues longitudinally studied 293 patients, median age 55, who had no known cardiovascular disease or active cancer disorders and who underwent ¹⁸FDG PET/CT at Massachusetts General Hospital from 2005 through 2008. They assessed amygdalar activity, bone-marrow activity and arterial inflammation.

In a separate cross-sectional study, they analyzed the links between perceived stress, amygdalar activity, arterial inflammation and C-reactive protein (which indicates general levels of inflammation in the body).

Mutually blinded radiologists and cardiologists reviewed the images and adjudicated cardiovascular disease events.

Of the 293 patients, 22 had a cardiovascular disease event during median follow-up of 3.7 years.  

Tawakol and team report that amygdalar activity was associated with increased bone-marrow activity (p<0.0001), arterial inflammation (p<0.0001) and risk of cardiovascular disease events (p<0.0001)—a finding that remained significant after multivariate adjustments.

“The association between amygdalar activity and cardiovascular disease events seemed to be mediated by increased bone-marrow activity and arterial inflammation in series,” the authors write.

Meanwhile, in the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation (p=0.0083), and perceived stress was associated with amygdalar activity (p=0.0485), arterial inflammation (p=0.0345), and C-reactive protein (p=0.0210).

The authors note several limitations in their study, including the participant-selection process. The patients were identified from a database of 6,088 individuals who had undergone ¹⁸FDG PET/CT for particular clinical indications—mainly cancer screening—which may limit the generalizability of our findings.

However, Tawakol and co-authors note, the association between amygdalar activity and cardiovascular disease events remained robust in the subgroup of patients who did not have a history of cancer, suggesting that this potential confounder is not responsible for the main observations of the present study.

“Our study shows, for the first time, a relation between neural tissue activity and subsequent cardiovascular events and suggests that the brain’s salience network, bone marrow and arterial inflammation together form an axis that could accelerate the development of cardiovascular disease,” Tawakol et al. write in their discussion. “Furthermore, our findings raise the possibility that efforts to attenuate psychosocial stress could produce benefits that extend beyond an improved sense of psychological wellbeing, and could beneficially impact the atherosclerotic milieu.”