Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk

Kenechukwu Mezue; Michael T Osborne; Shady Abohashem; Hadil Zureigat; Charbel Gharios; Simran S Grewal; Azar Radfar; Alexander Cardeiro; Taimur Abbasi; Karmel W Choi; Zahi A Fayad; Jordan W Smoller; Rachel Rosovsky; Lisa Shin; Roger Pitman; Ahmed Tawakol

doi:10.1016/j.jacc.2023.04.015

Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk

J Am Coll Cardiol. 2023 Jun 20;81(24):2315-2325. doi: 10.1016/j.jacc.2023.04.015.

Authors

Affiliations

¹ Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
² Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
³ Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁴ Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁵ Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Center for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁶ BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁷ Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
⁸ Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁹ Department of Psychology, Tufts University, Medford, Massachusetts, USA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
¹⁰ Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
¹¹ Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. Electronic address: atawakol@mgh.harvard.edu.

PMID: 37316112
PMCID: PMC10333800 (available on 2024-06-20)
DOI: 10.1016/j.jacc.2023.04.015

Abstract

Background: Chronic stress associates with major adverse cardiovascular events (MACE) via increased stress-related neural network activity (SNA). Light/moderate alcohol consumption (AC_l/m) has been linked to lower MACE risk, but the mechanisms are unclear.

Objectives: The purpose of this study was to evaluate whether the association between AC_l/m and MACE is mediated by decreased SNA.

Methods: Individuals enrolled in the Mass General Brigham Biobank who completed a health behavior survey were studied. A subset underwent ¹⁸F-fluorodeoxyglucose positron emission tomography, enabling assessment of SNA. Alcohol consumption was classified as none/minimal, light/moderate, or high (<1, 1-14, or >14 drinks/week, respectively).

Results: Of 53,064 participants (median age 60 years, 60% women), 23,920 had no/minimal alcohol consumption and 27,053 AC_l/m. Over a median follow-up of 3.4 years, 1,914 experienced MACE. AC_l/m (vs none/minimal) associated with lower MACE risk (HR: 0.786; 95% CI: 0.717-0.862; P < 0.0001) after adjusting for cardiovascular risk factors. In 713 participants with brain imaging, AC_l/m (vs none/minimal) associated with decreased SNA (standardized beta -0.192; 95% CI: -0.338 to -0.046; P = 0.01). Lower SNA partially mediated the beneficial effect of AC_l/m on MACE (log OR: -0.040; 95% CI: -0.097 to -0.003; P < 0.05). Further, AC_l/m associated with larger decreases in MACE risk among individuals with (vs without) prior anxiety (HR: 0.60 [95% CI: 0.50-0.72] vs 0.78 [95% CI: 0.73-0.80]; P interaction = 0.003).

Conclusions: AC_l/m associates with reduced MACE risk, in part, by lowering activity of a stress-related brain network known for its association with cardiovascular disease. Given alcohol's potential health detriments, new interventions with similar effects on SNA are needed.

Keywords: alcohol consumption; amygdala; brain; cardiovascular disease; chronic stress; stress-associated neural network activity.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Cardiovascular Diseases* / epidemiology
Cardiovascular Diseases* / etiology
Ethanol
Female
Heart Disease Risk Factors
Humans
Male
Middle Aged
Neural Networks, Computer
Risk Factors

Substances

Ethanol

Abstract

Publication types

MeSH terms

Substances

Grants and funding