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Amygdalar Activity Can Predict Cardiovascular Disease Risk

Key findings

  • Statistical analyses of correlated imaging scans and cardiovascular event data shows amygdalar activity significantly associated with arterial inflammation, increased bone-marrow activity and risk of cardiovascular disease events
  • Patients with higher resting amygdalar activity experienced a cardiovascular event sooner than those with lower resting activity

A brain image analysis of healthy patients found amygdalar activity to be predictive of CV event risk. Published in the Lancet in this first study of its kind, Massachusetts General Hospital researchers, including Ahmed Tawakol, MD, co-director, Cardiac MR PET CT Program, calculated that each standard deviation of amygdalar signal corresponded to a one to six time increase in risk of a cardiovascular event.

Activity in the amygdala, the brain’s stress responding region, was significantly associated with arterial inflammation and, in turn, CV events. This association was independent of other factors including Framingham risk scores and any atherosclerosis. The researchers did not find similar activity in other cerebral or cerebellar brain structures or extra-cranial tissue.

The researchers connected the level of amygdalar activity to the timing of a CV event. Subjects with higher resting amygdalar activity experienced an event sooner than those with lower resting activity. In a longitudinal imaging review from January 1, 2005 to December 31, 2008, researchers observed the uptake of 18F-fluorodexoyglucose (18F-FDG) on PET/CT images for 293 patients who were free of known cardiac or cancerous disease. Two mutually blinded researchers adjudicated, using clinical records, statistical analyses based on 22 patients who experienced CV events during three-to-seven-years of follow-up.

The Framingham Heart Study was used to define these events that included:

  • Eight myocardial infarctions
  • Three unstable anginas
  • Two cases of peripheral arterial disease
  • Six strokes
  • One heart failure
  • Two onsets of angina

A cross-sectional review of patients who underwent psychometric analysis (n=13), which included Cox models and hazard ratios, log-rank tests and mediation path analysis, found amygdalar activity to be significantly associated with increased bone-marrow activity (r=0·47; p<0·0001), arterial inflammation (r=0·49; p<0·0001) and CV disease event risk (standardized hazard ratio 1·59, 95% CI 1·27–1·98; p<0·0001).

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). In fact, amygdalar activity mediated most of the relationship between perceived stress and arterial inflammation (p<0.05).

Following a serial two-mediator analysis, more details were examined on the amygdalar activity pathway. For example, bone marrow activity accounted for 46% of the relationship between arterial inflammation and amygdalar activity, and arterial inflammation accounted for 39% of the total effect between amygdalar activity and cardiovascular disease events. When bone marrow activity was excluded, amygdala activity still led to increased arterial inflammation, which then led to cardiovascular events.

Researchers concluded amygdala activity also includes arterial inflammation and cardiovascular events via a route other than bone-marrow activity, and that amygdalar activity also leads to cardiovascular events by different means than arterial inflammation. These findings open the discussion for possible amygdalar interventions, whether through drugs or stress modification, to reduce the likelihood of a CV event.

46%
of the relationship between amygdalar activity and arterial inflammation was mediated by bone marrow activity

39%
of the relationship between amygdalar activity and CV disease events was mediated by arterial inflammation

Learn more about Mass General's Cardiac MR PET CT Program

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