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

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.