Moderate Alcohol Tied to Lower Stress-Related Brain Activity, MACE

Marlene Busko

May 11, 2021

Previously reported benefits of alcohol intake for patients with cardiovascular disease appear to be partially mediated through modulation of stress-associated brain activity, a new study suggests.

The researchers found two J-shaped relationships: one between alcohol intake and major adverse cardiovascular events (MACE), and another between alcohol intake and stress-associated amygdalar metabolic activity, measured using 18 fluorine-fluorodeoxyglucose positron-emission tomography/CT (18F-FDG PET/CT).

Compared to those with low alcohol intake, defined as having fewer than one drink per week, or those with high alcohol intake, defined as having more than 14 drinks per week, those with moderate alcohol intake (between one and 14 drinks per week) were less likely to have MACE events, and they were also found to have less amygdalar activity on imaging.

Dr Kenechukwu Mezue

Kenechukwu Mezue, MD, a clinical and research nuclear cardiology fellow at Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, reported the findings in a press briefing and will present the study in an oral session at the upcoming American College of Cardiology 2021 Scientific Session.

" 'Association is not causation' is a mantra we learn in epidemiology," Mezue noted to | Medscape Cardiology in an email. Nevertheless, these findings present a possible mechanism for part of the cardiovascular benefit of moderate drinking, which would need to be examined in further study.

"After an analysis that robustly controlled for confounders including socioeconomic and lifestyle factors, there was a 20% reduction in MACE events for moderate alcohol intake," Mezue noted, consistent with prior research.

The current study also showed for the first time that moderate alcohol intake was associated with reduced stress-associated brain activity, which may explain some of the benefit regarding cardiovascular outcomes.

"Our study does not intend to encourage alcohol use, as alcohol intake in excess is associated with a lot of harm [including liver damage], and even moderate alcohol intake is associated with increased cancer risk and dependence," Mezue cautioned.

Rather, "we think that shining a light on this potential mechanism of reducing cardiovascular events can open doors to new therapeutics that can optimize stress reduction without the harmful effects of alcohol," he said. For example, exercise or yoga can also be prescribed to reduce stress.

Future studies with repeat brain scans and more detailed assessments of alcohol intake over time could provide further insight into the mechanism of action.

Confirms Previous Studies

"This study confirmed previous studies that show that moderate consumption seems to carry lower risk of cardiovascular events," said the press briefing moderator, Eugene Yang, MD, from the University of Washington, Seattle, Washington, and chair, ACC Prevention of Cardiovascular Disease Council.

"Then it goes further by looking at brain imaging," he told | Medscape Cardiology in an interview. "It gives some potential clue perhaps as to why there's a [cardiovascular] benefit to alcohol in moderation."

Study limitations, Yang observed, include that it was not powered to distinguish differences between men and women, although moderate drinking is defined as having up to seven drinks per week for women and up to 14 drinks per week for men.

Also, the individuals underwent only one scan, but brain activity is dynamic, he said.

In addition, it would have been good to have data on binge drinking (defined as having >5 drinks for men and >4 drinks for women in 2 hours), which, in a previous study, was linked to a greater risk for cardiovascular events.

He also noted that the researchers lacked information about the type of alcohol that was consumed, so they could not determine whether, for example, red wine was more beneficial.

Massachusetts General Brigham Biobank

The researchers identified 53,064 individuals in the Massachusetts General Brigham Biobank, which agreed to provide data for genetic studies. All provided self-reported information on alcohol consumption, as indicated on one survey question.

The average age of the participants was 57 years, and 60% were women.

Participants were divided into three groups on the basis of alcohol consumption. Roughly half had no or low alcohol consumption, half had moderate alcohol consumption, and only 2000 drank >14 alcoholic drinks per week.

A subset of 752 participants underwent whole-body 18F-FDG PET/CT scanning, mostly for cancer diagnosis or surveillance, during 2005 to 2020. They fasted overnight and abstained from alcohol for 12 hours before the scan.

In this subset, 220 individuals had MACE, defined as unstable angina, myocardial infarction, coronary revascularization, symptomatic peripheral artery disease, peripheral revascularizations, stroke, and transient ischemic attack.

After adjusting for age, sex, race, hypertension, diabetes, hyperlipemia, smoking, physical activity, body mass index, employment, education, income, depression, anxiety, and insomnia, moderate alcohol intake was associated with reduced risk for MACE in comparison with low/no alcohol intake (odds ratio, 0.80; P < .0001).

The researchers determined the ratio of metabolic activity in the amygdala, which is increased during stress, to that of the prefrontal cortex, which acts to modulate the activity of the amygdala.

Activity in the prefrontal cortex was similar in the three groups.

"It is important to note that chronic moderate alcohol intake did not have a general effect on the brain," Mezue said. "Rather, it reduced activity in the stress-related areas preferentially."

After adjusting for age and sex, compared to low/no alcohol intake, moderate intake was associated with decreased stress-associated neural activity (P = .018).

The researchers report no relevant financial relationships.

American College of Cardiology (ACC) 2021 Annual Scientific Session: Abstract 912-08. To be presented May 17, 2021.

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