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Neuroimmune Pathway Linked to Socioeconomic Status and CVD Outcomes

Key findings

  • Among 509 patients who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography, lower socioeconomic status was associated with higher metabolic activity in the amygdala, an indicator of stress-associated neural activity
  • Lower socioeconomic status was linked to the incidence of major cardiac events (MACE) via a stress-associated pathway that includes higher amygdalar activity, bone marrow activity and arterial inflammation
  • This study sets the stage for testing new interventions that might reduce the incidence of MACE

Cardiovascular disease (CVD) outcomes are known to be influenced by measures of socioeconomic status, such as income and neighborhood environmental factors. The disparities are large and are not adequately explained by differences in CVD risk factors, access to quality care and health behaviors.

In previous research published in The LancetAhmed Tawakol, MD, co-director of the Cardiac MR PET CT Program in the Cardiology Division at Massachusetts General Hospital, Katrina Armstrong, MD, chair of the Department of Medicine, and colleagues found that amygdalar activity robustly predicted the risk for, and timing of, subsequent CVD. Furthermore, they determined that amygdalar activity was associated with an increased risk of CVD through heightened leukopoiesis and arterial inflammation.

In a new study, Dr. Tawakol, Dr. Armstrong and colleagues demonstrated that lower socioeconomic status is linked to higher amygdalar activity, which in-turn independently associates with a higher risk of major adverse cardiac events (MACE) via a pathway involving hightened leukopoiesis and arterial inflammation in series. The findings are published in the Journal of the American College of Cardiology.

Study Participants

The researchers retrospectively studied 509 adults older than 30 who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography at Mass General (primarily for cancer surveillance) between 2005 and 2008. All of them had imaging data available on metabolic activity in the arterial wall (a measure of atherosclerotic inflammation) and in the bone marrow (a measure of leukopoiesis).

A subset of 289 patients also had data available on metabolic activity in the amygdala (AmygA, a measure of stress-associated neural activity). At the time of imaging, patients had to be free of known CVD and inflammatory or autoimmune diseases. They were subsequently followed for the development of CVD.

Socioeconomic Status, AmygA and Arterial Inflammation

Neighborhood median income was negatively associated with resting AmygA, leukopoietic activity and arterial inflammation after adjustments for confounders.

Socioeconomic Status and MACE

  • During a median follow-up period of four years, 40 patients experienced at least one MACE
  • Neighborhood median income was negatively associated with MACE and the neighborhood crime rate was positively associated
  • After adjustment for CVD risk factors, there remained an approximately six-fold higher risk of MACE in patients in the lowest (vs. highest) quartile of neighborhood income
  • After adjustment for health care access (insurance status and whether patients had to travel from another state for care at Mass General), there remained an approximately four-fold higher risk of MACE in patients in the lowest (vs. highest) quartile of neighborhood income

AmygA and MACE Among Patients with Lower Socioeconomic Status

  • AmygA remained strongly predictive of MACE after adjustment for socioeconomic status (HR, 1.44; 95% CI, 1.14–1.83; P = .003)
  • AmygA remained predictive of MACE within the subset of patients living in neighborhoods with high socioeconomic stress (lowest tertile of neighborhood household income or highest tertile of crime rate)

MACE and Amygdalar–Hematopoietic–Arterial Inflammatory Activity

  • AmygA was associated with both leukopoietic tissue activity and arterial inflammation after adjustment for CVD risk factors and neighborhood income
  • MACE was associated with AmygA (HR, 1.423; 95% CI, 1.088–1.860; P = .010), leukopoietic tissue activity (HR, 2.196; 95% CI, 1.400–3.445; P = .001) and arterial inflammation (HR, 1.819; 95% CI, 1.399–2.366; P < .001) after adjustment for CVD risk factors and neighborhood income

Mediation Analysis

When considered together, two serial biologic pathways accounted for 28% of the total effect of socioeconomic status on the risk of MACE:

  • Lower socioeconomic status to increased­ AmygA to increased leukopoietic tissue activity to increased arterial inflammation to increased MACE (standardized log odds ratio, −0.0137; 95% CI, −0.0570 to −0.0003; P < .05)
  • Lower socioeconomic status to increased AmygA to increased arterial inflammation to increased MACE (standardized log odds ratio, −0.0137; 95% CI, −0.0546 to −0.0001; P < .05)

Applying the Findings

Lower income, higher crime rates and other adverse socioeconomic factors are notoriously difficult to remedy, but several components of the amygdalar-leukopoietic-arterial pathway may be amenable to interventions for preventing MACE:

  • The use of drugs to reduce arterial inflammation (e.g., anti-inflammatories or statins)
  • The use of drugs to inhibit the release of proinflammatory cells from the bone marrow in response to stress (e.g., beta-adrenoreceptor antagonists)
  • Amelioration of the neural response to low socioeconomic status, for example through stress reduction techniques, physical activity or novel drugs that target the amygdala or other stress-related brain regions

The researchers caution that the statistically significant mediation analyses do not prove causation between the biological pathways and MACE, but a causal interpretation of the findings is supported by prior observations in animal models.

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Related topics


A statistical review of imaging and cardiovascular event data at Mass General finds amygdalar activity to be significantly associated with cardiovascular disease risk.


Ahmed Tawakol, MD, co-director of the Cardiac MR PET CT Program, discusses the link between stress and atherosclerotic disease, and his team’s work using multimodality imaging to better understand that risk.