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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Background: Chronic stress associates with major adverse cardiovascular events (MACE) via increased stress-related neural network activity (SNA). Light/moderate alcohol consumption (ACl/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 ACl/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 ACl/m. Over a median follow-up of 3.4 years, 1,914 experienced MACE. ACl/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, ACl/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 ACl/m on MACE (log OR: −0.040; 95% CI: −0.097 to −0.003; P < 0.05). Further, ACl/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: ACl/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.

Original languageEnglish
Pages (from-to)2315-2325
Number of pages11
JournalJournal of the American College of Cardiology
Issue number24
StatePublished - 20 Jun 2023


  • alcohol consumption
  • amygdala
  • brain
  • cardiovascular disease
  • chronic stress
  • stress-associated neural network activity


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