Amygdalar Activity Independently Predicts Cardiovascular Events

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Chronic stress identified as risk factor for cardiovascular disease.
Chronic stress identified as risk factor for cardiovascular disease.

Findings reported in The Lancet show that amygdalar activity — a marker of psychological stress — is an independent predictor of cardiovascular disease (CVD).1

The risk of CVD associated with chronic emotional stress is similar to that of established risk factors such as hypertension, smoking, hyperlipidemia, and diabetes.2 However, the mechanisms underlying this link are unclear.

Activation of the brain's salience network, including the amygdala, results in “hormonal, autonomic, and behavioral changes typically associated with fear and stress,” and “the amygdala's efferent projections to the brainstem participate in the sympathetic responses to stress,” the authors wrote. While previous findings show elevated amygdalar reactivity in people with atherosclerosis, no studies have demonstrated whether it predisposes to CVD development.3

The present research examined the connection between CV events and resting metabolic activity of the amygdala in patients who underwent PET/CT imaging at Massachusetts General Hospital. The investigation consisted of 2 complementary imaging studies: one was a longitudinal study (n=293) of correlations between amygdalar activity, arterial inflammation, and CVD events, while the other was a small (n=13) cross-sectional study exploring links between perceived stress (per the Perceived Stress Scale [PSS-10]), amygdalar activity, and arterial inflammation. Two cardiologists assessed CVD events based on clinical records.

The longitudinal results show that CVD events occurred in 22 patients during a median follow-up period of 3.7 years. An association was found between amygdalar activity and increased bone marrow activity (r=0.47; P <.0001), arterial inflammation (r=0.49; P <.0001), and CVD event risk (standardized hazard ratio: 1.59; 95% CI, 1.27-1.98; P <.0001). The results further show that the amygdala-CVD relationship was significantly mediated by arterial inflammation, which was mediated by increased bone marrow activity.

The cross-sectional study revealed a significant association between amygdalar activity and arterial inflammation (r=0.70; P =.0083). Additionally, perceived stress was found to be linked with amygdalar activity (r=0.56; P =.0485), arterial inflammation (r=0.59; P =.0345), and C-reactive protein (r=0.83; P =.0210).

Taken together, these findings illuminate potential mechanisms driving the stress-CVD link and “raise the possibility that alleviation of psychosocial stress could produce benefits that extend beyond an improved sense of psychological well-being, by improving the atherosclerotic milieu,” the authors noted. “Eventually, chronic stress could be treated as an important risk factor for CVD,” with screening and management approached similarly to other risk factors for CVD disease.

Disclosures: Dr Tawakol reports receiving grants from Genentech and Takeda as well as personal fees from Takeda, Actelion, AstraZeneca, and Amgen. Dr Hoffmann reports receiving grants from Kowa Company and Heartflow. Dr Murrough reports receiving a grant from Avanir Pharmaceuticals and Otsuka as well as personal fees from Janssen Research and Development, ProPhase, Genentech, and Impel Neuropharma.


  1. Tawakol A, Ishai A, Takx RAP, et al. Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study [Published online January 11, 2017]. Lancet. doi:10.1016/S0140-6736(16)31714-7
  2. Rosengren A, Hawken S, Ôunpuu S, et al; for the INTERHEART Investigators. Association of psychosocial risk factors with risk of acute myocardial infarction in 11 119 cases and 13 648 controls from 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:953-962.
  3. Gianaros PJ, Hariri AR, Sheu LK, Muldoon MF, Sutton-Tyrrell K, Manuck SB. Preclinical atherosclerosis covaries with individual differences in reactivity and functional connectivity of the amygdala. Biol Psychiatry. 2009;65: 943-950.
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