Even Light Drinking Ups CV Risk; Harm Rises With Higher Intakes

March 29, 2022

Even very light alcohol intake is associated with an increased risk for cardiovascular disease compared with not drinking at all, and the risk increases exponentially as alcohol intake rises, even at moderate levels, a new study shows.

"Our findings suggest that the observed benefit in individuals with light to moderate alcohol intake, which is consistently shown in epidemiological studies, is likely due to other positive lifestyle factors that are common in these individuals who drink lightly," senior author Krishna Aragam, MD, Massachusetts General Hospital, Boston, told theheart.org | Medscape Cardiology.

"Our results also showed that while all levels of alcohol were linked to increased risk of cardiovascular disease, the association was not linear. Rather, light alcohol intake was associated with rather modest risk increases, but there were exponential increases in cardiovascular risk with increasing amounts of alcohol consumption," he said.

As the risk gradient appeared to increase quite sharply even between 1 and 2 drinks per day, Aragam suggested that what might be regarded as safe levels of drinking may trend downward in the future.    

The study was published online March 25 in JAMA Network Open.

The cohort study used data from the UK Biobank, collected between 2006 and 2010 with follow-up until 2016, to assess the relationship between various levels of alcohol consumption and risk for cardiovascular disease.

Data were analyzed from 371,463 participants (mean age, 57 years; 46% men) who consumed an average of 9.2 standard drinks per week. Of these participants, 33% had hypertension, and 7.5% had coronary artery disease.

"Use of the UK biobank database gives the advantage of a large, well-phenotyped population with a lot of information on various lifestyle factors that could be potential confounders," Aragam noted. 

Results showed that well-established J- or U-shaped curves were seen for the association between alcohol consumption and both the prevalence and hazards of hypertension, coronary artery disease, myocardial infarction, stroke, heart failure, and atrial fibrillation.

However, individuals in the light and moderate consumption group had healthier lifestyle behaviors than abstainers, self-reporting better overall health and exhibiting lower rates of smoking, lower body mass index, higher physical activity, and higher vegetable intake.   

Adjustment for these lifestyle factors attenuated the cardioprotective associations with modest alcohol intake. For example, in baseline models, moderate intake was associated with significantly lower risk of hypertension and coronary artery disease, but adjustment for just six lifestyle factors rendered these results insignificant.

"Adjustments for yet unmeasured or unknown factors may further attenuate, if not eliminate, the residual, cardioprotective associations observed among light drinkers," the researchers suggest.

They also conducted genetic analyses to examine the effect of alcohol and cardiovascular disease.   

Aragam explained that previous work has shown good evidence, in individuals who choose to drink, that several relevant genetic variants predict quite accurately levels of alcohol consumption.

"Mendelian randomization using these gene variants allows for stronger inferences about potential causality than do observational studies, as they are less affected by confounding factors," he noted.

Newer techniques in Mendelian randomization in which data on several gene variants linked to alcohol consumption are combined into a score, allows for a greater understanding of the risk linked to different amount of alcohol intake, he added.

In these Mendelian randomization analyses, a 1-standard deviation increase in genetically predicted alcohol consumption was associated with 1.3-fold higher risk of hypertension (P < .001) and 1.4-fold higher risk of coronary artery disease (P = .006).

Further analyses suggested nonlinear associations between alcohol consumption and both hypertension and coronary artery disease: light alcohol intake was associated with minimal increases in cardiovascular risk, whereas heavier consumption was associated with exponential increases in risk of both clinical and subclinical cardiovascular disease.

These results were replicated in a second database of 30,716 individuals from the Mass General Brigham Biobank.

"The findings of this study suggest that the observed cardioprotective effects of light to moderate alcohol intake may be largely mediated by confounding lifestyle factors," the researchers conclude. "Genetic analyses suggest causal associations between alcohol intake and cardiovascular disease but with unequal and exponential increases in risk at greater levels of intake, which should be accounted for in health recommendations around the habitual consumption of alcohol."

What Is an Acceptable Level? 

"Specifically, our results suggest that consuming as many as 7 drinks per week is associated with relatively modest increases in cardiovascular risk," they write.

But they point out that there are unequal increases in cardiovascular risk when progressing from 0 to 7 vs 7 to 14 drinks per week in both men and women.

"Although risk thresholds are inherently somewhat subjective, these findings again bring into question whether an average consumption of 2 drinks per day (14 drinks per week) should be designated a low-risk behavior," they say.

"Furthermore, as several-fold increases in risk were observed for those consuming 21 or more drinks per week, our results emphasize the importance of aggressive efforts to reduce alcohol intake among heavy drinkers," they add.

Aragam elaborated: "Our data suggest that reducing alcohol intake will reduce cardiovascular risk in all individuals, but the extent of the relative risk reduction is quite different depending on the current levels of consumption. For the same absolute reduction in alcohol intake, the gains in terms of reduction in cardiovascular risk will be more pronounced in those who drink heavily and will be more modest in those who drink at a light level."

The results also suggest that while all levels of alcohol intake increase cardiovascular risk, there are low levels of alcohol consumption that do not carry major elevations in risk, but these are probably lower than those currently recommended, Aragam pointed out. 

"This doesn't mean that everyone has to give up drinking alcohol completely, just that you shouldn't consume with the goal of improving cardiovascular health. In fact, our analyses suggest that in an otherwise healthy person, up to 1 drink per day may not pose outsized risks," he said. "And, even in a less healthy person who might be smoking, eating poorly, and drinking up to 1 drink per day, it may be a higher priority to focus on smoking cessation and diet than cutting back further on alcohol.

"Beyond that amount, though, the jury is still out. Our models suggested marked increases in risk even between 1 and 2 drinks per day, and of course even greater risk increases beyond that. So, it's probably worth revisiting what one might consider a 'safe' amount within the moderate drinking categories. The conservative move for now might be to advise a limit of 1 drink per day," he said.   

Aragam is supported by grants from the National Institutes of Health and the American Heart Association. He reports receiving speaking fees from the Novartis Institute for Biomedical Research.

JAMA Network Open. Published online March 25, 2022. Full text

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