Alcohol consumption and subclinical and clinical coronary heart disease: a Mendelian randomization analysis

Abstract

Abstract Aims The potential effect of alcohol consumption on coronary heart disease (CHD) remains unclear. We used the variant rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) as an instrument to investigate the causal role of alcohol intake in subclinical and clinical CHD. Methods We conducted two Mendelian randomization studies: a cross-sectional study of coronary artery calcification (CAC) on computed tomography of 1029 healthy men (mean age, 63.8 years) and a case–control study of 421 men with CHD [acute coronary syndrome (ACS) or stable angina pectoris] who underwent coronary revascularization and 842 age-matched male controls. Results In the CAC study, medians (25%tiles, 75%tiles) of alcohol consumption by ALDH2-rs671 *2 homozygotes [n = 86 (8.4%)], *1*2 heterozygotes [n = 397 (38.5%)], and *1 homozygotes [n = 546 (53.1%)] were 0.0 (0.0, 0.0), 28.0 (0.0, 129.0), and 224.0 (84.0, 350.0) g/week, respectively. In age-adjusted Poisson regression with robust error variance, compared with *2 homozygotes, relative risks for prevalent CAC score >0, ≥100, and ≥300 in *1 homozygotes were 1.29 (95% confidence interval, 1.06–1.57), 1.76 (1.05–2.96), and 1.81 (0.80–4.09), respectively. In age-adjusted ordinal logistic regression for CAC distributions, we observed higher odds among *1 homozygotes [odds ratio, 2.19 (1.39–3.46)] and even among *1*2 heterozygotes [1.77 (1.11–2.82)] compared with *2 homozygotes. In the case–control study, conditional logistic regression revealed lower prevalence of *1 homozygotes among men with CHD [odds ratio, 0.54 (0.35–0.82)], especially ACS [0.46 (0.27–0.77)], than controls. Conclusion Our findings indicate a positive association of alcohol consumption with CAC burden but an inverse association with clinical CHD, especially ACS.