Exploring causal associations between alcohol and coronary heart disease risk factors: findings from a Mendelian randomization study in the Copenhagen General Population Study

TLDR: The results show adverse effects of long-term alcohol consumption on body mass index (BMI), blood pressure, lipids, fibrinogen, and glucose and novel evidence for a potentially beneficial effect on triglyceride levels, which needs further replication.

Abstract: Aims To explore the causal effect of long-term alcohol consumption on coronary heart disease risk factors. Methods and results We used variants in ADH1B and ADH1C genes as instrumental variables (IV) to estimate the causal effect of long-term alcohol consumption on body mass index (BMI), blood pressure (BP), lipids, fibrinogen, and glucose. Analyses were undertaken in 54 604 Danes (mean age 56 years). Both confounder-adjusted multivariable and IV analyses suggested that a greater alcohol consumption among those who drank any alcohol resulted in a higher BP [mean difference in SBP per doubling of alcohol consumption among drinkers: 0.76 mmHg (95% CI: 0.63, 0.90) from multivariable analyses and 0.94 mmHg (−3.03, 4.69) from IV analyses; P -value for difference in these results = 0.95]. The positive association of alcohol with HDLc in the multivariable analyses [4.9% (4.7, 5.1)] appeared stronger than in the IV analyses [1.5% (−4.5, 7.4)], and the weak inverse association with fibrinogen in the multivariable analysis [−2.0% (−2.1, −1.8)] was not present in the IV analyses [0.6% (−3.8, 5.0)], but statistically the results for both of these could not be reliably distinguished from each other ( P -values 0.21 and 0.32, respectively). The weak inverse association of alcohol with BMI [−0.13 kg/m2 (−0.16, −0.10)] and with triglycerides [−0.4% (−0.7, 0.4)] in multivariable analyses were in contrast to the strong positive association of alcohol with BMI [1.37 kg/m2 (0.59, 2.15)] and the strong inverse association with triglycerides [−14.9% (−25.6, −4.3)] in IV analyses; P = 0.006 and 0.01, respectively, for difference between the two. Alcohol was not associated with non-HDLc or glucose. Conclusion Our results show adverse effects of long-term alcohol consumption on BP and BMI. We also found novel evidence for a potentially beneficial effect on triglyceride levels, which needs further replication.