By Michael H. Crawford, MD
Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco
SUMMARY POINTS
- Mezue et al tested the hypothesis that light or moderate alcohol consumption (LMAC) attenuates adverse stress-related neural mechanisms after adjusting for a range of genetic, clinical, lifestyle, and socioeconomic confounders.
- Between 2010 and 2020, there were 53,064 participants in the Mass General Brigham Biobank (mean age = 60 years; 60% were women) who had filled out an optional comprehensive health behavior survey upon enrollment. This survey included questions about alcohol consumption, classified as none/minimal (0-1 drink/week), light/moderate (2-14 drinks/week), or high (more than 14 drinks/week). A cohort of 8,734 provided genetic data. Among them, 1,038 had undergone clinically indicated brain imaging for cancer surveillance or diagnosis. Those with brain tumors were excluded, leaving 713 in the brain imaging group.
- Investigators used this imaging to compare amygdala activity to the activity of the rest of the brain to determine SNA. Major adverse cardiovascular events (MACEs) were obtained from the medial records — defined as coronary revascularization, unstable angina, cerebrovascular accidents, transient ischemic attacks, peripheral vascular disease, and heart failure.
- During the median follow-up of 3.4 years, 1,914 individuals experienced a MACE, which followed a U-shaped curve in relation to alcohol consumption. The lowest rates were in the LMAC group, which did not change when adjusted for known confounders. However, LMAC was associated with a higher incidence of cancer.
- In the brain imaging group, LMAC was associated with less stress-associated neural network activity (SNA). The researchers found less SNA partially mediated the beneficial effect of LMAC on MACE rates. Among patients with a history of anxiety disorder, LMAC was associated with fewer MACEs. The authors concluded LMAC was associated with a lower risk of experiencing a MACE, which was partially related to less SNA, which is known to be associated with cardiovascular disease.
SYNOPSIS: Researchers reported consuming two to 14 alcoholic drinks per week was associated with fewer major adverse cardiovascular events, which the authors noted could be explained in part by less stress-related neural activity demonstrated on PET and CT scans.
SOURCE: 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.
What is the relationship between light or moderate alcohol consumption (LMAC) and fewer major adverse cardiovascular events (MACE)? What about among patients who abstain from alcohol and those who consume to excess? The underlying physiology is poorly understood. Investigators from the Mass General Brigham Biobank (MGBB) analyzed their database to answer these questions.
Mezue et al tested the hypothesis that LMAC attenuates adverse stress-related neural mechanisms after adjusting for a range of genetic, clinical, lifestyle, and socioeconomic confounders. Researchers assessed the effect of LMAC on resting stress-associated neural network activity (SNA) and examined whether this effect mediates the beneficial impact of LMAC on MACE. Finally, the authors evaluated whether the effect of LMAC on MACE was more pronounced among patients with chronically busier SNA, such as those with anxiety disorders.
Between 2010 and 2020, there were 53,064 participants in the MGBB (mean age = 60 years; 60% were women) who had filled out an optional comprehensive health behavior survey upon enrollment.
This survey included questions about alcohol consumption, classified as none/minimal (0-1 drink/week), light/moderate (2-14 drinks/week), or high (consuming more than 14 drinks/week). A cohort of 8,734 provided genetic data. Among them, 1,038 had undergone clinically indicated 18F-FDG-PET/CT brain imaging for cancer surveillance or diagnosis. Those with brain tumors were excluded, leaving 713 in the brain imaging group.
Investigators used this imaging to compare amygdala activity to the activity of the rest of the brain to determine SNA. MACE was obtained from the medical records — defined as coronary revascularization, unstable angina, cerebrovascular accidents, transient ischemic attacks, peripheral vascular disease, and heart failure. Most subjects were in the none/minimal (45%) or light/moderate (51%) alcohol consumption groups.
During the median follow-up of 3.4 years, 1,914 individuals experienced a MACE, which followed a U-shaped curve in relation to alcohol consumption. The lowest rates were in the LMAC group, which did not change when adjusted for known confounders (hazard ratio [HR], 0.786; 95% confidence interval [CI], 0.717-0.862). However, LMAC was associated with a higher incidence of cancer (HR, 1.23; 95% CI, 1.14-1.33; P < 0.0001).
In the brain imaging group, LMAC was associated with less SNA (odds ratio [OR], 0.192; 95% CI, 0.338-0.046; P = 0.003). The researchers found less SNA partially mediated the beneficial effect of LMAC on MACE rates (OR, 0.040; 95% CI, 0.097-0.003; P < 0.05). Also, among patients with a history of anxiety disorder, LMAC was associated with fewer MACEs (HR, 0.60; 95% CI, 0.50-0.72; P = 0.003).
The authors concluded LMAC was associated with a lower risk of experiencing a MACE, which was partially related to less SNA, which is known to be associated with cardiovascular disease. However, since LMAC raised the risk of cancer, new interventions that similarly affect SNA are needed.
COMMENTARY
What is unique about this study is the authors took advantage of clinically indicated PET brain imaging in a substantial subgroup of this huge biobank population to investigate the relationship between SNA and alcohol consumption. Interestingly, they found LMAC was associated with less SNA and that this reduction was associated with the beneficial effect on MACE rates. In addition, researchers showed that in those with a history of anxiety disorder, LMAC was associated with a greater decline in MACE rates. Thus, they concluded this reduction in SNA partially explains the observed decrease in MACE rates with LMAC.
This novel mechanistic explanation for the cardiovascular effects of LMAC is compelling and makes sense to anyone who has ever consumed an alcoholic beverage. However, the authors were careful to note their data showed an increase in cancer diagnoses with LMAC, and that higher levels of alcohol consumption slowed prefrontal and whole brain metabolic activity, which could adversely affect cognition. Again, this supports the experience of those who have drunk alcohol in excess.
Like all observational studies, unaccounted confounders might have led to biases in this analysis. Since alcohol consumption was recorded only at baseline, the authors worked with little information regarding those who were former drinkers or those who quit drinking during the study. Thus, there may have been an abstainer bias. However, a sensitivity analysis of these data failed to show this bias.
Also, the LMAC group covered a wide spectrum of alcohol consumption — between two and 14 drinks per week, which was not divided by sex. The authors could not further parse this group, which is an important weakness, since recommendations about daily alcohol consumption vary by sex.
In addition, it seems there would be a difference between two drinks per week and 14. Researchers did not collect data on different beverages (i.e., beer vs. wine vs. hard liquor) or whether patients consumed alcohol with food. Another weakness was the fact the PET data were collected from clinically indicated studies, which might not be applicable to other populations. We are left wondering if alcohol is a double-edged sword or a hatchet.
Researchers reported consuming two to 14 alcoholic drinks per week was associated with fewer major adverse cardiovascular events, which the authors noted could be explained in part by less stress-related neural activity demonstrated on PET and CT scans.
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