Cardiovascular disease risk is associated with alcohol intake in general, but variations in risk exist with levels of intake, based on data from a genetic-based assessment of more than 300,000 individuals.
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Previous studies have identified the “J-shaped model” of alcohol intake and cardiovascular disease, Kiran J. Biddinger of the Broad Institute, Cambridge, Mass., and colleagues said. The J-shaped model suggests that light alcohol intake, defined as one to two drinks per day, appears to reduce cardiovascular disease risk, while heavy alcohol intake, defined as about five drinks per day, increases cardiovascular disease risk, Mr. Biddenger said. However, most studies of the association between alcohol and cardiovascular disease risk are observational, and subject to confounders such as the impact of healthy lifestyle behaviors.
To better assess causality, the researchers used a genetics technique known as Mendelian randomization.
“Some individuals are genetically predisposed to drink more alcohol than others, based on the random allocation of alleles,” he explained. This genetic risk should not be associated with confounding variables such as vegetable consumption or physical activity.
In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the American Heart Association, the researchers analyzed genetic and lifestyle data from 371,463 participants in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom. The researchers used traditional and nonlinear genetic approaches to assess causality between alcohol consumption and cardiovascular disease.
Overall, study participants averaged 9.2 drinks per week. A total of 121,708 (32.8%) had hypertension, and 27,667 (7.5%) had coronary artery disease. The researchers found that individuals who consumed light to moderate amounts of alcohol also lived healthier lifestyles, and had a lower body mass index and higher levels of physical activity than did those who abstained from alcohol. Light to moderate drinkers also had higher vegetable consumption, lower red meat consumption, were less likely to smoke, and had higher self-reported overall health ratings, compared with abstainers.
The researchers then applied Mendelian randomization analyses, creating a genetic proxy and finding that individuals who were predisposed to drink more alcohol had a higher risk of cardiovascular disease.
Traditional and nonlinear Mendelian randomization using quadratic associations showed consistently increased risk of cardiovascular disease with increased alcohol consumption, and this risk increased dramatically for the heaviest drinkers. Compared with individuals who abstained, alcohol consumption of 7, 14, 21, and 28 drinks per week was associated, respectively, with 1.2-, 1.7-, 3.4-, and 8.9-fold odds of hypertension, and 1.2-, 2.3-, 6.2-, and 25.9-fold odds of coronary artery disease.
Notably, an increase of one standard deviation in genetic predisposition for alcohol consumption was associated with a 1.28-fold increase in hypertension, as well as significantly increased risk of coronary artery disease (odds ratio, 1.38), MI (OR, 1.37), stroke (OR, 1.26), heart failure (OR, 1.34), and atrial fibrillation (OR, 1.24).
The study findings were limited by several factors, including the inability to detect specific benefits associated with moderate alcohol consumption. However, the results suggest that, although all amounts of alcohol intake convey some increase in cardiovascular disease risk, “recommendations around alcohol use should reflect this nuanced relationship,” Mr. Biddinger said.