| Abstrakt: |
Background:Depression and anxiety disorders are linked with a greater risk of major adverse cardiac events (MACE) via unclear mechanisms. Since heightened stress-related neural activity (SNA) associates with a greater risk of MACE, we hypothesized that the link between depression/anxiety disorders and MACE is in part mediated by increased SNA.Methods:Data were obtained from subjects in the Mass General Brigham Biobank (N=118 871). A subset (N=1520) underwent clinical 18F-fluorodeoxyglucose positron emission tomography imaging. Stress-related neural activity (SNA) was determined as the ratio of amygdalar to regulatory (ventromedial prefrontal cortex) activity. MACE (i.e., myocardial infarction, stroke, and heart failure), depression, and anxiety disorders were defined by the International Classification of Disease codes.Results:The median age was 59 years [interquartile range (IQR) 28]; 56.2% were female. MACE occurred in 4149 subjects (4.3%) over a median follow up of 3.3 years (IQR 2.9). Depression and anxiety independently predicted incident MACE (HR [95% CI]: 1.415 [1.323-1.513], p=5.696 x 10-24and 1.515 [1.418-1.618], p=4.548 x 10-35, respectively, adjusted for cardiovascular risk factors). In the 1520 subjects with brain imaging, depression and anxiety associated with higher SNA (standardized ß [95% CI]: 0.151 [0.048-0.254], p=0.004 and 0.123 [0.022-0.225], p=0.01, respectively, adjusted for age and sex). Further, SNA associated with MACE (OR [95% CI]: 1.295 [1.163-1.443], p=3 x 10-6). Using path analysis, increased SNA mediated the effect of both depression and anxiety on MACE (log OR [95% CI]: 0.036 [0.009-0.072], p<0.05 and 0.030 [0.005-0.063], p<0.05, respectively).Conclusion:Depression and anxiety disorders associate with greater MACE risk via a mechanism that includes heightened stress-related neural activity. Future studies should evaluate the impact of therapies on this neural pathway and downstream MACE. |
