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Has the mechanism for the CV benefits of light-to-moderate alcohol consumption been found?

Light-to-moderate alcohol consumption reduces the risk of major adverse cardiovascular events, but could this be linked to a reduction in stress-related activity in the brain? Clinical writer Rod Tucker investigates.

It was Oscar Wilde who coined the phrase ‘Everything in moderation, including moderation’, and so it is with drinking alcohol. After all, it seems there are apparent benefits from light-to-moderate drinking, as revealed in a 2011 systematic review of 84 studies.

The researchers concluded that light-to-moderate alcohol consumption, which is defined as one to two drinks per day, is associated with a reduced risk of multiple cardiovascular outcomes.

Furthermore, being more specific, a recent systematic review, found that wine consumption lowered the risk of death by 27%. Unfortunately, since the amount of wine consumed was not always reported, there remains some uncertainty over exactly how much wine needs to be drunk to achieve this benefit.

Whether the UK Government is unaware of this research, or simply chooses to ignore it, is unclear, and the advice is to not regularly drink more than 14 units of alcohol per week – one unit being equivalent to only half a small glass of wine, half a pint of beer or one standard measure of spirits. It also says: ‘there is no definitively “safe“ lower limit – no level of regular alcohol consumption improves health.’

If the scientific evidence, rather than the UK Government, is correct, and light-to-moderate drinking does actually have a cardiovascular benefit, what is the underlying mechanism responsible for this effect?

Alcohol and the brain

There’s no doubt that drinking too much is bad for the brain, causing the tissue to contract and destroying brain cells. Alcohol also seems to attenuate functional connectivity between the amygdala and the right orbitofrontal cortex. This finding suggests that alcohol may impair the perception of social threat signals and could contribute to the harm during intoxication.

Nonetheless, the amygdala also plays a role in other brain functions, and there is evidence of heightened neural activity in the amygdala in response to stress. This effect increases inflammation and could serve as a precursor to conditions such as cardiovascular disease.

While it is clear that alcohol has an effect on the brain, it may be possible that light-to-moderate intake confers a cardiovascular benefit by reducing this stress-related neural network activity (SNA) pathway. But this requires further analysis of recent research findings.

Alcohol intake and MACE

In a recent and intriguing study, published in the Journal of the American College of Cardiology, researchers wondered just that: is the link between light-to-moderate alcohol intake and a reduction on major adverse cardiovascular events (MACE) mediated by a lowering SNA?

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The team used 18F-fluorodeoxyglucose positron emission tomography to assess SNA in a group of patients. They categorised the participants‘ alcohol intake as none or minimal (less than one drink per week), light to moderate (one to 14 drinks per week) or high (more than 14 drinks per week).

The working hypothesis of the team was that higher levels of SNA would be linked to greater incidence of MACE. If this could be shown, then the converse must also be true.

The team had access to data on 53,064 participants and were able to follow them for nearly three and a half years. During this time, 1,914 individuals experienced a MACE.

MACE risk and anxiety

The hypothesis was correct. Higher SNA did indeed predict greater MACE and, interestingly, was also associated with measures of atherosclerosis upon imaging.

After adjustments for known cardiovascular risk factors, the researchers found that light-to-moderate alcohol intake was associated with a 21% lower risk of experiencing MACE when compared to those who were minimal drinkers (hazard ratio, HR = 0.79, 95% CI 0.72 – 0.86, p < 0.0001).

It was also apparent from the imaging data that light to moderate alcohol consumption, again in comparison to minimal drinkers, was significantly associated with decreased SNA (p = 0.010), even after adjusting for various lifestyle and socioeconomic factors that could have affected the result (p = 0.034).

But, if light drinking reduced a stress-related pathway in the brain linked to inflammation, would the effect on MACE be magnified in those with existing stress or anxiety? In other words, would the effects of light to moderate drinking have a greater calming effect – and ultimately a lower incidence of MACE – in those who were already anxious.

This too was found to be true. The 10-year risk of MACE was estimated to be 22% lower in those without prior stress but reduced by 40% lower in those who reported pre-existing anxiety.

Should HCPs change their advice on drinking?

It would be a risky strategy to advise patients to take up drinking alcohol, because there is no guarantee that everyone would be able to restrict their intake. Moreover, it would be remiss to not mention the study also found that light drinking led to a 23% higher risk of cancer.

On balance, therefore, it seems that light drinking probably confers cardiovascular health benefits, but these certainly have to be weighed against the increased malignancy risk.

Perhaps we should all embrace Wilde’s aphorism ‘everything in moderation’, because, in reality, there are few things in life that are completely risk-free.

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