Physicians' Academy for Cardiovascular Education

Amygdalar activity in response to stress predicts development of subsequent CV events

Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study

Literature - Tawakol A, Ishai A, Takx RAP, et al., - The Lancet. Published January 11, 2017. DOI:

Main results


This is the first study in humans that demonstrates that resting metabolic activity within the amygdala, an important component in the brain’s network involved in stress, predicts the development of CVD, independent of traditional CV risk factors. Amygdalar activity, which was associated with perceived stress in the cross-sectional study, correlated with increased haemopoietic activity and increased arterial inflammation in the longitudinal study.

Thus, these findings suggest that the amygdala may be a key structure in the pathway that links stress to CV events, and upregulation of haemopoietic tissue activity and increased atherosclerotic inflammation also seem implicated in this neural-haemopoietic-arterial axis.

Editorial comment

Bot and Kuiper [9] note in their editorial comment that, although the statistical mediation analyses that showed that bone-marrow activity, followed by vascular inflammation, significantly mediated the relation between amygdalar activity and the incidence of CV events, these analyses do not provide evidence of causality. The data are, however, in line with data from an animal study in which stress induced an inflammatory response via activation of the bone marrow.

Also the data of the perceived stress study are in line with data of other cohorts of patients with post-traumatic stress disorder (PTSD), depression and other disease associated with chronic stress, in which associations between stress and CRP concentrations were described. Indeed, these individuals with high perceived stress levels appear to be at higher risk of having a CVD event.

According to Bot and Kuiper, the study of Tawakol justifies further larger and longer studies into the CV risk in patients with PTSD. Analysis of interleukin-6, which is often increased in stress, in addition to CRP might shed more light on the underlying inflammatory mechanisms. Of note, the association between the incidence of amygdalar activity and CVD remained after correction for history of depression or anxiety, suggesting that the data are also applicable to individuals without a history of psychological disorders. “Together, these clinical data establish a connection between stress and cardiovascular disease, thus identifying chronic stress as a true risk factor for acute cardiovascular syndromes, which could, given the increasing number of individuals with chronic stress, be included in risk assessments of cardiovascular disease in daily clinical practice.”


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