Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease
Original investigation
Key Points
Question
What is the risk of cardiovascular disease associated with different amounts of habitual alcohol consumption?
Findings
In this cohort study of 371 463 individuals, genetic evidence supported a nonlinear, consistently risk-increasing association between all amounts of alcohol consumption and both hypertension and coronary artery disease, with modest increases in risk with light alcohol intake and exponentially greater risk increases at higher levels of consumption.
Meaning
In this study, alcohol consumption at all levels was associated with increased risk of cardiovascular disease, but clinical and public health guidance around habitual alcohol use should account for the considerable differences in cardiovascular risk across different levels of alcohol consumption, even those within current guideline-recommended limits.
Abstract
Importance
Observational studies have consistently proposed cardiovascular benefits associated with light alcohol consumption, while recent genetic analyses (ie, mendelian randomization studies) have suggested a possible causal link between alcohol intake and increased risk of cardiovascular disease.
However, traditional approaches to genetic epidemiology assume a linear association and thus have not fully evaluated dose-response estimates of risk across different levels of alcohol intake.
Objectives
To assess the association of habitual alcohol intake with cardiovascular disease risk and to evaluate the direction and relative magnitude of cardiovascular risk associated with different amounts of alcohol consumption.
Design, Setting, and Participants
This cohort study used the UK Biobank (2006-2010, follow-up until 2016) to examine confounding in epidemiologic associations between alcohol intake and cardiovascular diseases. Using both traditional (ie, linear) and nonlinear mendelian randomization, potential associations between alcohol consumption and cardiovascular diseases (eg, hypertension and coronary artery disease) as well as corresponding association shapes were assessed. Data analysis was conducted from July 2019 to January 2022.
Exposures
Genetic predisposition to alcohol intake.
Main Outcomes and Measures
The association between alcohol consumption and cardiovascular diseases, including hypertension, coronary artery disease, myocardial infarction, stroke, heart failure, and atrial fibrillation.
Results
This study included 371,463 participants (mean [SD] age, 57.0 [7.9] years; 172,400 [46%] men), who consumed a mean (SD) 9.2 (10.6) standard units of alcohol per week. Overall, 121,708 participants (33%) had hypertension.
Light to moderate alcohol consumption was associated with healthier lifestyle factors, adjustment for which attenuated the cardioprotective epidemiologic associations with modest intake.
In linear mendelian randomization analyses, a 1-SD increase in genetically predicted alcohol consumption was associated with a 1.3-fold (95% CI, 1.2-1.4) higher risk of hypertension (P < .001) and 1.4-fold (95% CI, 1.1-1.8) higher risk of coronary artery disease (P = .006). Nonlinear mendelian randomization 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 the risk of both clinical and subclinical cardiovascular disease.
Conclusions and Relevance
In this cohort study, coincident, favorable lifestyle factors attenuated the observational benefits of modest alcohol intake. Genetic epidemiology suggested that alcohol consumption of all amounts was associated with increased cardiovascular risk, but marked risk differences exist across levels of intake, including those accepted by current national guidelines.
Research interpretation
Previous observational research has shown that light or low-dose alcohol use may have cardiovascular benefits. More recent genetic analyses such as Mendelian randomization studies indicate a possible causal link between alcohol intake and increased risk of cardiovascular disease.
This study aimed to answer the question of how habitual alcohol use affects cardiovascular risk and to find out the levels of cardiovascular risk associated with different amounts of alcohol consumption. The study was conducted by a team led by researchers at Massachusetts General Hospital (MGH) and the Broad Institute of MIT and Harvard.
The study participants included 371,463 adults with an average age of 57 years and average alcohol consumption of 9.2 units of alcohol per week. The participants were part of the UK Biobank which is a large-scale biomedical database and research resource containing in-depth genetic and health information.
Key findings of the study
The findings affirm that alcohol intake should not be recommended to improve cardiovascular health; rather, that reducing alcohol intake will likely reduce cardiovascular risk in all individuals, albeit to different extents based on one’s current level of consumption,” said Krishna G. Aragam, MD, MS, a cardiologist at MGH and an associate scientist at the Broad Institute and senior author of the study, as per Massachusettes General Hospital.
Krishna G. Aragam, MD, MS, associate scientist, Broad Institute
- Heavy alcohol users had the highest risk of heart disease.
- Light to low-dose alcohol users had the lowest heart disease risk, followed by people who abstained from alcohol use.
- However, the lower heart disease risk among low-dose alcohol users compared to abstainers can be attributed to other healthy lifestyle factors such as more physical activity and vegetable intake, and less smoking.
- In other words, the low-dose alcohol users in this study had overall healthier lifestyles, compared to the abstainers.
- Taking just a few of these other healthy lifestyle factors into account significantly lowered any benefit associated with alcohol consumption.
The researchers also applied Mendelian randomization which uses genetic variants to determine whether an observed link between an exposure and an outcome is consistent with a causal effect. Because the variants are distributed randomly in a population, they can serve in a study as the equivalent of randomly assigning people to abstain or to use alcohol at varying levels. Then researchers can ask if those with variants that are linked to greater alcohol consumption have more heart disease and high blood pressure than those with variants linked to lower consumption.
The study used the latest techniques of Mendelian randomization to answer whether light alcohol consumption causes a person to be protected against cardiovascular disease.
- Individuals with genetic variants that predicted higher alcohol consumption were more likely to consume greater amounts of alcohol, and more likely to have hypertension and coronary artery disease.
- There were substantial differences in cardiovascular risk across the spectrum of alcohol consumption among both men and women. The risk grew exponentially with increased consumption.
- Zero to seven alcohol units per week caused minimal increases in risk.
- Seven to 14 units per week caused a much higher risk.
- 21 units of alcohol or more led to an especially higher risk.
- The findings indicate there is a rise in cardiovascular risk even at levels deemed “low risk” by national guidelines from the U.S. Department of Agriculture (below two units per day for men and one unit per day for women).
Implications of the study findings
The study found that the relationship between alcohol intake and cardiovascular risk is not a linear one but rather an exponential one.
This means the risk of heart disease and high blood pressure started slowly as the number of alcohol units started to increase from 0, but the risk quickly increased as the number of alcohol units increased, soaring as people got into the heavy alcohol use range of 21 or more units of alcohol a week.
An additional analysis of data on 30,716 participants in the Mass General Brigham Biobank supported this finding of an exponential increase in cardiovascular risk with rising alcohol units.
This means that while reducing alcohol intake can benefit everyone even those consuming at low-dose levels, the health gains of cutting back on alcohol will be much more prominent for those consuming heavier amounts of alcohol.
Applying the study results, Dr. Krishna G. Aragam says a typical middle-aged person in the study who did not use alcohol had an estimated 9% chance of having coronary heart disease. A person who had one unit of alcohol a day had an estimated 10.5% chance. After that, though, the risk increases quickly.
Many earlier studies of alcohol use and heart health, including those showing benefits, were only observational studies. This means the subjects were followed over time to see if the amount of alcohol was linked to heart health. Such studies only find correlations and not causation.
The Mendelian randomization method is more suggestive of causality, therefore, the results carry more weight.
During the pandemic, alcohol use increased in the U.S., and alcohol-related deaths rose by 25%. Dr. Stanley L. Hazen, a cardiologist at the Cleveland Clinic, and his colleagues found that blood pressure also increased during the pandemic by nearly 3 millimeters of mercury in all 50 states. Changes in participants’ body weight did not account for this rise in blood pressure. After the findings of the above study, Dr. Hazen thinks this rise in blood pressure could be a result of rising alcohol use during the pandemic.
Sources
JAMA Network: “Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease“
Massachusettes General Hospital: “Large study challenges the theory that light alcohol consumption benefits heart health“
The New York Post: “Does Moderate Drinking Protect Your Heart? A Genetic Study Offers a New Answer.“