Stress-Associated Neurobiological Pathway Linking Socioeconomic Disparities to Cardiovascular Disease

J Am Coll Cardiol. 2019 Jul 2;73(25):3243-3255. doi: 10.1016/j.jacc.2019.04.042.


Background: Lower socioeconomic status (SES) associates with a higher risk of major adverse cardiac events (MACE) via mechanisms that are not well understood.

Objectives: Because psychosocial stress is more prevalent among those with low SES, this study tested the hypothesis that stress-associated neurobiological pathways involving up-regulated inflammation in part mediate the link between lower SES and MACE.

Methods: A total of 509 individuals, median age 55 years (interquartile range: 45 to 66 years), underwent clinically indicated whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging and met pre-defined inclusion criteria, including absence of known cardiovascular disease or active cancer. Baseline hematopoietic tissue activity, arterial inflammation, and in a subset of 289, resting amygdalar metabolism (a measure of stress-associated neural activity) were quantified using validated 18F-fluorodeoxyglucose positron emission tomography/computed tomography methods. SES was captured by neighborhood SES factors (e.g., median household income and crime). MACE within 5 years of imaging was adjudicated.

Results: Over a median 4.0 years, 40 individuals experienced MACE. Baseline income inversely associated with amygdalar activity (standardized β: -0.157 [95% confidence interval (CI): -0.266 to -0.041]; p = 0.007) and arterial inflammation (β: -0.10 [95% CI: -0.18 to -0.14]; p = 0.022). Further, income associated with subsequent MACE (standardized hazard ratio: 0.67 [95% CI: 0.47 to 0.96]; p = 0.029) after multivariable adjustments. Mediation analysis demonstrated that the path of: ↓ neighborhood income to ↑ amygdalar activity to ↑ bone marrow activity to ↑ arterial inflammation to ↑ MACE was significant (β: -0.01 [95% CI: -0.06 to -0.001]; p < 0.05).

Conclusions: Lower SES: 1) associates with higher amygdalar activity; and 2) independently predicts MACE via a serial pathway that includes higher amygdalar activity, bone marrow activity, and arterial inflammation. These findings illuminate a stress-associated neurobiological mechanism by which SES disparities may potentiate adverse health outcomes.

Keywords: cardiovascular disease; neurobiology; positron emission tomography; socioeconomic disparities; stress.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amygdala / diagnostic imaging
  • Amygdala / physiopathology*
  • Arteritis / diagnostic imaging
  • Arteritis / etiology*
  • Arteritis / psychology
  • Female
  • Fluorodeoxyglucose F18
  • Heart Diseases / etiology*
  • Heart Diseases / psychology
  • Hematopoiesis
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Positron Emission Tomography Computed Tomography
  • Retrospective Studies
  • Social Class*
  • Stress, Psychological / complications*
  • Stress, Psychological / diagnostic imaging
  • Stress, Psychological / physiopathology


  • Fluorodeoxyglucose F18