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

Stress-Associated Neurobiological Pathway Linking Socioeconomic Disparities to Cardiovascular Disease.

Author information

1
Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: atawakol@mgh.harvard.edu.
2
Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
3
Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nuclear Medicine, the First Hospital of China Medical University, Heping District, Shenyang, China.
4
Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
5
Department of Psychology, Tufts University, Medford, Massachusetts.
6
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
7
Clinical Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
8
Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
9
Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
10
Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
11
Cardiology Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
12
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
13
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Abstract

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

PMID:
31248544
PMCID:
PMC6767929
[Available on 2020-07-02]
DOI:
10.1016/j.jacc.2019.04.042

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