Moderate alcohol intake associates with a decreased risk of venous thrombosis: mediation through decreased stress-associated brain activity
Authors: Mezue K , Osborne M T , Abbasi T , Zureigat H , Abohashem S , Gharios C , Akuffo E , Cardeiro A , Pitman R , Shin L , Jaffer F , Rosovsky R , Tawakol A 
Published: October 2021

Abstract

Background
Prior studies suggest that moderate alcohol intake may associate with a lower incidence of deep venous thrombosis (DVT). However, it is unclear if this association persists after robust adjustment for confounders. Moreover, the mechanisms mediating this potential benefit are unclear. Prior studies show that chronic stress promotes stress-related neural activity (amygdalar activity: AmygA), which in turn triggers inflammation and elevates thrombosis risk. Since moderate alcohol intake decreases AmygA, we hypothesize that this neural effect of alcohol may partially mediate its beneficial impact on DVT risk.

Purpose
To evaluate whether the association between moderate alcohol intake and decreased DVT risk: A) persists after robustly accounting for potential confounders and B) is mediated by reductions in stress-related neural activity.

Methods
Data were obtained from the Mass General Brigham Biobank, which included detailed health, lifestyle, and follow-up outcomes information on 53 059 adult participants. Alcohol intake was classified as low (&lt;1 drink/week), moderate (1–14 drinks/week), or high (&gt;14 drinks/week). A subset of 656 study subjects underwent clinical 18F-fluorodeoxyglucose positron emission tomography imaging from which AmygA was measured as the ratio of amygdalar to regulatory (ventromedial pre-frontal cortex) activity. Individuals on anticoagulant therapies for atrial fibrillation prior to enrolment and/or imaging were excluded. Cox analysis were performed wherein patients who developed DVT prior to Biobank enrolment (1064 subjects) were excluded. Mediation analysis was used to examine the role of AmygA in mediating the link between alcohol intake and DVT.

Results
The median age of the study population was 59 years [interquartile range (IQR) 26] and 51.9% were female. DVT occurred in 573 participants (1.2%) over a median follow up period of 3.4 years (IQR 2.9). Cox regression analysis showed that moderate alcohol intake was associated with lower incident DVT rates after controlling for confounders (hazard ratio [95% confidence intervals (CI)] 0.773 [0.644,0.929], p=0.006, Table 1). In the subset of participants who underwent brain imaging, moderate alcohol intake associated with decreased AmygA activity (standardized β [95% CI]: −0.218 [−0.370, −0.065], p=0.005). Further, AmygA associated with DVT (odds ratio (OR) [95% CI]: 1.374 [1.089, 1.734], p=0.007). Path analysis demonstrated that decreased AmgyA mediated the salutary effect of moderate alcohol on DVT (log OR [95% CI]: −0.0635 [−0.1383, −0.0078], p&lt;0.05, Figure 1).

Conclusion
Moderate alcohol intake is associated with a decreased risk of DVT via a mechanism that may involve a reduction in stress-related neurobiological activity. Alternative therapies targeting this neural pathway should be identified with the goal of reducing the burden of DVT.

Funding Acknowledgement
Type of funding sources: None.