Exploring Causal Associations Between Alcohol and Coronary Heart Disease Risk Factors: Findings From a Mendelian Randomization Study in the Copenhagen General Population Study

Study Questions:

Is alcohol associated with coronary heart disease risk factors?

Methods:

Data from the Copenhagen General Population Study were used for the present analysis. This study is a large general population cohort study that aims to eventually recruit 100,000 participants and collect genotypic and phenotypic data of relevance to a wide range of health-related problems. Individuals are randomly selected from the national Danish Civil Registration System and have to be ages 20 years or older and a resident in greater Copenhagen; they also have to be white and of Danish decent. Recruitment began in 2003 and is still ongoing. Variants in ADH1B and ADH1C genes were used as instrumental variables to estimate the causal effect of long-term alcohol consumption on body mass index (BMI), blood pressure (BP), lipids, fibrinogen, and glucose. Alcohol intake was reported as weekly consumption of beer in bottles and standard glasses of wine and spirits; each of these in Denmark contains the equivalent of approximately 12 g of pure alcohol. The ADH1B (rs1229984, Arg47His in exon 3) and ADH1C (rs698, Ile349Val in exon 8) genotypes were identified by TaqMan assays.

Results:

A total of 54,604 Danes (mean age 56 years) were included in this analysis. Overall, 10% of the population reported drinking no alcohol and 9% reported drinking 25 or more drinks per week. Drinking differed by gender, with 13% of women reporting no consumption and 3% reporting 25 or more drinks per week, compared with 6% of men reporting no consumption and 17% reporting 25 or more drinks per week (p < 0.0001). Both confounder-adjusted multivariable and instrumental variable analyses suggested that greater alcohol consumption among those who drank any alcohol resulted in a higher BP. The mean difference in systolic BP per doubling of alcohol consumption among drinkers was 0.76 mm Hg (95% confidence interval, 0.63-0.90) from multivariable analyses and 0.94 mm Hg (23.03-4.69) from instrumental variable analyses (p value for difference in these results = 0.95). Alcohol was positively associated with high-density lipoprotein (HDL) cholesterol in the multivariable analyses (4.9% [4.7-5.1]) and appeared stronger than in the instrumental variable analyses (1.5% [24.5-7.4]). A weak inverse association with fibrinogen was also noted in the multivariable analysis (22.0% [22.1-21.8]), which was not present in the instrumental variable analyses [0.6% (23.8-5.0)]. A weak inverse association of alcohol with BMI was observed (20.13 kg/m2 [20.16-20.10]) in multivariable analyses, with a strong positive association of alcohol with BMI (1.37 kg/m2 [0.59-2.15]) in instrumental variables analyses. A weak inverse association of alcohol with BMI was observed for triglycerides (20.4% [20.7-0.4]) in multivariable analyses, which was in contrast to the strong inverse association in instrumental variable analyses (214.9% [225.6-24.3]). Alcohol was not associated with non-HDL cholesterol or glucose.

Conclusions:

The authors concluded that long-term alcohol consumption had adverse effects on blood pressure and BMI, in addition to a novel observation of improvement in triglyceride levels.

Perspective:

Prior epidemiologic studies have suggested a beneficial association between moderate alcohol intake and heart disease risk, often thought to be mediated through HDL cholesterol. The data presented in this study suggest otherwise. As the authors suggest, further investigation is warranted.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism, Nonstatins

Keywords: Cholesterol, Body Mass Index, Biological Markers, Denmark, Beer, Coronary Disease, Blood Pressure, Genotype, Triglycerides, Wine


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