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

Mezue, Kenechukwu; Osborne, Michael T.; Abohashem, Shady; Zureigat, Hadil; Gharios, Charbel; Grewal, Simran S.; Radfar, Azar; Cardeiro, Alexander; Abbasi, Taimur; Choi, Karmel W.; Fayad, Zahi A.; Smoller, Jordan W.; Rosovsky, Rachel; Shin, Lisa M.; Pitman, Roger K.; Tawakol, Ahmed

doi:10.1016/j.jacc.2023.04.015

Cited by 25 publications

(19 citation statements)

References 28 publications

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“… 28 , 29 Recent studies point to an amygdala-vmPFC interplay for MACE prediction, with the vmPFC acting as a counter-player to the amygdala during psychological stress. 6 , 11 As such, vmPFC activation during mental stress triggers the parasympathetic system and inhibits the sympathetic system. 30 , 31 Given that the amygdala-to-vmPFC ratio might account for a potential cardioprotective effect of the vmPFC, not captured by the AmygA-to-background variable, AmygA (individually and averaged) was corrected for vmPFC activity (SUVmean) in our primary analysis (SNA [AmygA/vmPFC]).…”

Section: Methodsmentioning

confidence: 99%

“…Despite the suitability of 18 F-FDG-PET to investigate the brain–heart connection, its clinical value is unclear. Current evidence is exclusively based on U.S. 4 , 6–11 and Asian 5 , 12–14 populations, with limited information about CVD status and comorbidities. This constraint is significant given the numerous factors influencing SNA, especially in CV patients.…”

Section: Introductionmentioning

confidence: 99%

“…Besides stress-related disorders, 15 age, 16 , 17 sex, 16 obesity, diabetes, pre-existing atherosclerotic disease, or recent myocardial infarction are all linked with SNA. 14 , 17–20 Moreover, socioeconomic and lifestyle variables, including education, alcohol consumption, and physical exercise, also influence SNA, suggesting that social disparities affect health through neurobiological mechanisms 6 , 8–10 , 14 . Medications, particularly statins or anti-inflammatory drugs, negatively correlate with SNA.…”

Section: Introductionmentioning

confidence: 99%

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Imaging of the brain–heart axis: prognostic value in a European setting

Mikail,

Sager,

Gebert

et al. 2024

European Heart Journal

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Background and Aims Increasing data suggest that stress-related neural activity (SNA) is associated with subsequent major adverse cardiovascular events (MACE) and may represent a therapeutic target. Current evidence is exclusively based on populations from the U.S. and Asia where limited information about cardiovascular disease risk was available. This study sought to investigate whether SNA imaging has clinical value in a well-characterized cohort of cardiovascular patients in Europe. Methods In this single-centre study, a total of 963 patients (mean age 58.4 ± 16.1 years, 40.7% female) with known cardiovascular status, ranging from ‘at-risk’ to manifest disease, and without active cancer underwent 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography between 1 January 2005 and 31 August 2019. Stress-related neural activity was assessed with validated methods and relations between SNA and MACE (non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, and cardiovascular death) or all-cause mortality by time-to-event analysis. Results Over a maximum follow-up of 17 years, 118 individuals (12.3%) experienced MACE, and 270 (28.0%) died. In univariate analyses, SNA significantly correlated with an increased risk of MACE (sub-distribution hazard ratio 1.52, 95% CI 1.05–2.19; P = .026) or death (hazard ratio 2.49, 95% CI 1.96–3.17; P < .001). In multivariable analyses, the association between SNA imaging and MACE was lost when details of the cardiovascular status were added to the models. Conversely, the relationship between SNA imaging and all-cause mortality persisted after multivariable adjustments. Conclusions In a European patient cohort where cardiovascular status is known, SNA imaging is a robust and independent predictor of all-cause mortality, but its prognostic value for MACE is less evident. Further studies should define specific patient populations that might profit from SNA imaging.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Imaging of the brain–heart axis: prognostic value in a European setting

Mikail,

Sager,

Gebert

et al. 2024

European Heart Journal

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“…Mild to moderate alcohol consumption orchestrates various biological processes that mitigate cardiovascular risk, including beneficial regulation of lipid profiles and fibrinolysis, 20 decreased platelet aggregation, 21 improved endothelial dysfunction, 22 reduced vascular inflammation, 23 and insulin resistance. 24 Furthermore, mild to moderate alcohol consumption can play a role in lower stress-associated JAMA Network Open | Cardiology neurobiological activity, 25 a neural underpinning of atherosclerotic CVD. 26,27 These biological mechanisms of mild to moderate alcohol consumption may collaborate synergistically to reduce the risk of future CVD.…”

Section: Biological Mechanism Of Protection From Reduced Alcohol Intakementioning

confidence: 99%

Reduced Alcohol Consumption and Major Adverse Cardiovascular Events Among Individuals With Previously High Alcohol Consumption

Kang,

Lee,

Roh

et al. 2024

JAMA Netw Open

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ImportanceCardiovascular benefits of mild to moderate alcohol consumption need to be validated in the context of behavioral changes. The benefits of reduced alcohol consumption among people who drink heavily across different subtypes of cardiovascular disease (CVD) are unclear.ObjectiveTo investigate the association between reduced alcohol consumption and risk of major adverse cardiovascular events (MACEs) in individuals who drink heavily across different CVD subtypes.Design, Setting, and ParticipantsThis cohort study analyzed data from the Korean National Health Insurance Service–Health Screening database and self-reported questionnaires. The nationally representative cohort comprised Korean citizens aged 40 to 79 years who had national health insurance coverage on December 31, 2002, and were included in the 2002 to 2003 National Health Screening Program. People who drank heavily who underwent serial health examinations over 2 consecutive periods (first period: 2005-2008; second period: 2009-2012) were included and analyzed between February and May 2023. Heavy drinking was defined as more than 4 drinks (56 g) per day or more than 14 drinks (196 g) per week for males and more than 3 drinks (42 g) per day or more than 7 drinks (98 g) per week for females.ExposuresHabitual change in heavy alcohol consumption during the second health examination period. People who drank heavily at baseline were categorized into 2 groups according to changes in alcohol consumption during the second health examination period as sustained heavy drinking or reduced drinking.Main Outcomes and MeasuresThe primary outcome was the occurrence of MACEs, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death.ResultsOf the 21 011 participants with heavy alcohol consumption at baseline (18 963 males [90.3%]; mean [SD] age, 56.08 [6.16] years) included in the study, 14 220 (67.7%) sustained heavy drinking, whereas 6791 (32.2%) shifted to mild to moderate drinking. During the follow-up of 162 378 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACEs than the reduced drinking group (817 vs 675 per 100 000 person-years; log-rank P = .003). Reduced alcohol consumption was associated with a 23% lower risk of MACEs compared with sustained heavy drinking (propensity score matching hazard ratio [PSM HR], 0.77; 95% CI, 0.67-0.88). These benefits were mostly accounted for by a significant reduction in the incidence of angina (PSM HR, 0.70; 95% CI, 0.51-0.97) and ischemic stroke (PSM HR, 0.66; 95% CI, 0.51-0.86). The preventive attributes of reduced alcohol intake were consistently observed across various subgroups of participants.Conclusions and RelevanceResults of this cohort study suggest that reducing alcohol consumption is associated with a decreased risk of future CVD, with the most pronounced benefits expected for angina and ischemic stroke.

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“…Next, should such a relationship be established, mediation analyses could also identify possible downstream risk/protective factors which could be modified by other interventions. That is, alcohol may be one set of keys to these mechanisms, but other, safer keys likely exist that do not also carry adverse effects and would therefore be more appropriate for clinicians to recommend (Mezue et al., 2023). For example, if social interaction does mediate the observed benefits of low‐to‐moderate alcohol consumption against depression, clinicians could promote other interventions to improve social support as a substitute for alcohol consumption (this would also be facilitated by a greater emphasis on serving and consuming alcohol‐free beverages at pubs and clubs).…”

Section: A Roadmap For Future Researchmentioning

confidence: 99%

Is low‐level alcohol consumption really health‐protective? A critical review of approaches to promote causal inference and recent applications

Visontay,

Mewton,

Sunderland

et al. 2024

Alcohol, Clinical and Experimental Research

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Heavy and disordered alcohol consumption is a known risk factor for several health conditions and is associated with considerable disease burden. However, at low‐to‐moderate levels, evidence suggests that drinking is associated with reduced risk for certain health outcomes. Whether these findings represent genuine protective effects or mere methodological artifacts remains unclear, but has substantial consequences for policy and practice. This critical review introduces methodological advances capable of enhancing causal inference from observational research, focusing on the ‘G‐methods’ and Mendelian Randomization. We also present and evaluate recent research applying these methods and compare findings to the existing evidence base. Future directions are proposed for improving our causal understanding of the relationships between alcohol and long‐term health outcomes.

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

Cited by 25 publications

References 28 publications

Imaging of the brain–heart axis: prognostic value in a European setting

Imaging of the brain–heart axis: prognostic value in a European setting

Reduced Alcohol Consumption and Major Adverse Cardiovascular Events Among Individuals With Previously High Alcohol Consumption

Is low‐level alcohol consumption really health‐protective? A critical review of approaches to promote causal inference and recent applications

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