Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study. Issue 10071 (25th February 2017)

• Record Type: Journal Article
• Authors: Tawakol, Ahmed; Ishai, Amorina; Takx, Richard AP; Figueroa, Amparo L; Ali, Abdelrahman; Kaiser, Yannick; Truong, Quynh A; Solomon, Chloe JE; Calcagno, Claudia; Mani, Venkatesh; Tang, Cheuk Y; Mulder, Willem JM; Murrough, James W; Hoffmann, Udo; Nahrendorf, Matthias; Shin, Lisa M; Fayad, Zahi A; Pitman, Roger K
• Is Part Of: Lancet. Volume 389:Issue 10071(2017)
• Page Start: 834
• Page End: 845
• Publication Date: 2017-02-25
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Medicine; Electronic journals; Periodicals; 610.5
• DOI: 10.1016/S0140-6736(16)31714-7
• Languages: English
• ISSNs: 0140-6736

Abstract

Summary: 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 18 F-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.