New findings suggest the benefit of light or moderate alcohol consumption on cardiovascular disease (CVD) risk is due to its ability to ease stress-related neural network activity. However, the researchers added that alcohol consumption’s link to malignancy and other potentially harmful effects mean this intervention is a less-than-perfect solution. “The current study provides novel insights into a mechanism by which light/moderate alcohol may reduce CVD,” says the study, which was published Monday online and in the June 20 issue of the Journal of the American College of Cardiology. “This effect on SNA [stress-associated neural network activity] appears to be driven by decreased activity of the amygdala rather than by enhanced activity of the regulatory vmPFC [ventromedial prefrontal cortex],” the authors added. Further findings reveal that the beneficial impact of light or moderate alcohol intake on major adverse cardiovascular events (MACE) in the study population was nearly twice as great among individuals with anxiety compared to those without) anxiety. Population from Mass General Brigham (MGB) Biobank Researchers from the Yale School of Medicine, Massachusetts General Hospital and Harvard Medical School identified 53,064 individuals enrolled in the Mass General Brigham (MGB) Biobank. The subjects’ median age was 60 years (interquartile range [IQR]: 47 to 73 years), and 31,762 (59.9%) were women. These participants were asked to complete an optional comprehensive health behavior survey that included a question on alcohol intake during the year before enrollment. Alcohol consumption was classified for both men and women as none/minimal (<1 drink/week), light/moderate (1 to 14 drinks/week), and high (>14 drinks/week). Among a subset of 8,734 individuals who provided genetic data, the team identified 1,038 participants who underwent clinically indicated 18F-fluorodeoxyglucose positron emission tomography /computed tomography for cancer surveillance or diagnosis. Regional brain activity was also measured and evaluated from these images. To adjust for possible genetic influences on the relationship between light or moderate alcohol use and brain activity, the team leveraged genomic analysis that was performed on the subset of patients who provided genetic data. Results of the study Results revealed that out of the 53,064 study subjects, 23,920 had <1 drink/week (none/minimal intake), 27,053 had 1 to 14 drinks/week (light/moderate intake), and 2,091 subjects had >14 drinks/week (high intake). Notably, the high alcohol consumption group represented 3.9% of the clinical cohort and 5.4% of the imaging cohort, and thus, 2,091 participants were excluded. Over a median follow-up of 3.4 years, 1,914 experienced MACE with light or moderate alcohol consumption . Compared with none/minimal consumption, light or moderate alcohol consumption was associated with lower MACE risk (hazard ratio [HR]: 0.786; 95% confidence interval [CI]: 0.717-0.862; P < 0.0001) after adjusting for cardiovascular risk factors. In 713 participants with brain imaging, light or moderate alcohol consumption was associated with decreased SNA compared to none/minimal consumption (standardized beta -0.192; 95% CI: -0.338 to -0.046; P=0.01). Lower SNA partially mediated the beneficial effect of light or moderate alcohol consumption on MACE (log odds ratio: -0.040; 95% CI: -0.097 to -0.003; P<0.05). Further, light or moderate alcohol consumption was associated with larger decreases in MACE risk among individuals with prior anxiety compared to those 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). Reduction in amygdalar activity Light or moderate alcohol consumption “was found to associate with a substantial reduction in amygdalar activity relative to vmPFC activity, resulting in overall reductions in SNA,” said the authors, led by Kenechukwu Mezue, MD, from the Yale School of Medicine in New Haven, Connecticut, and Michael T. Osborne, MD, from Massachusetts General Hospital and Harvard Medical School in Boston. “This finding is important, given the established association between heightened SNA and downstream CVD, and partially explains the protective effect of light/moderate alcohol (vs none/minimal) on CVD risk in this population,” the authors wrote. Commenting that light or moderate alcohol consumption was associated with reduced leukopoietic activity and high-sensitivity C-reactive protein, the team suggested that light or moderate alcohol consumption may reduce MACE through down-regulation of a neural-leukopoietic-arterial axis that otherwise potentiates CVD. The research team also highlighted the potential adverse impacts that light or moderate alcohol consumption could have on other noncardiac disease processes such as malignancy and dependence/abuse. “With higher intakes of alcohol, we observed decreases in prefrontal and whole brain activity,” the team commented. “Such findings may be associated with adverse cognitive health. Ultimately, an intervention that acts similarly on SNA without alcohol’s potential detrimental effects would be a far more attractive therapeutic option.” Anti-inflammatory properties of resveratrol and flavonoid The comments were echoed in an accompanying editorial, co-authored by Giovanni de Gaetano, MD, PhD, and Simona Costanzo, PhD, both from the IRCCS NEUROMED in Pozzilli, Italy, and Augusto Di Castelnuovo, PhD from the Mediterranea Cardiocentro in Naples, Italy. “It is important to underline that excessive or irregular (binge) alcohol consumption has detrimental effects on brain health and increases the risk of cognitive impairment and dementia,” they said. “We wish to insist that individuals consuming alcohol do not exceed the recommended daily dose limits suggested in many countries and that no abstainer should start to drink, even in moderation, solely for the purpose of improving his/her health outcomes,” they wrote. The editorialists also put forward the benefits of the antioxidant and anti-inflammatory properties of certain compounds found in alcoholic beverages, especially in wine, such as resveratrol and flavonoid. These compounds have been shown, in experimental systems, to protect against oxidative stress and inflammation, which can contribute to neuronal damage and cognitive decline. “Although not a randomized clinical trial, the study uses a different original approach to further support many previous observational studies showing that light/moderate alcohol consumption reduces the global risk of cardiovascular disease,” they concluded. Sources: Mezue K, Osborne MT, Abohashem S, et al. Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk. J Am Coll Cardiol. 2023;81:2315–2325. De Gaetano G, Costanzo S, Di Castelnuovo A. Alcohol and Neural Network Activity: A New Link Between Alcohol in Moderation and Cardiovascular Health? J Am Coll Cardiol. 2023;81:2326–2327. Image Credit: Africa Studio – stock.adobe.com