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Lancet. 2017 Feb 25;389(10071):834-845. doi: 10.1016/S0140-6736(16)31714-7. Epub 2017 Jan 12.

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

Author information

1
Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: atawakol@mgh.harvard.edu.
2
Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
3
Radiology Department, Weil Cornell Medical College, New York, NY, USA.
4
Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
5
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
6
Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.
7
Department of Psychology, Tufts University, Medford, MA, USA.
8
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Erratum in

Abstract

BACKGROUND:

Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic activity predicts risk of subsequent cardiovascular events.

METHODS:

Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent 18F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally. Amygdalar activity, bone-marrow activity, and arterial inflammation were assessed with validated methods. In a separate cross-sectional study we analysed the relation between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. Image analyses and cardiovascular disease event adjudication were done by mutually blinded researchers. Relations between amygdalar activity and cardiovascular disease events were assessed with Cox models, log-rank tests, and mediation (path) analyses.

FINDINGS:

293 patients (median age 55 years [IQR 45·0-65·5]) were included in the longitudinal study, 22 of whom had a cardiovascular disease event during median follow-up of 3·7 years (IQR 2·7-4·8). Amygdalar activity was associated with increased bone-marrow activity (r=0·47; p<0·0001), arterial inflammation (r=0·49; p<0·0001), and risk of cardiovascular disease events (standardised hazard ratio 1·59, 95% CI 1·27-1·98; 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. In the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation (r=0·70; p=0·0083). Perceived stress was associated with amygdalar activity (r=0·56; p=0·0485), arterial inflammation (r=0·59; p=0·0345), and C-reactive protein (r=0·83; p=0·0210).

INTERPRETATION:

In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings.

FUNDING:

None.

Comment in

PMID:
28088338
DOI:
10.1016/S0140-6736(16)31714-7
[Indexed for MEDLINE]

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