A Chinese genetic epidemiological analyses revealed that alcohol intake uniformly increases blood pressure (BP) and stroke, indicating that the apparently protective effects of moderate alcohol intake against stroke suggested by conventional epidemiological analyses are largely non-causal. The study enrolled 512 715 adults between June 25, 2004, and July 15, 2008, from ten areas of China, and followed them for about 10 years (until Jan 1, 2017). 161 498 participants were genotyped for two variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984. Adjusted Cox regression was used to obtain the relative risks (RR) associating disease incidence with self-reported drinking patterns (conventional epidemiology) or with genotype-predicted mean male alcohol intake (genetic epidemiology—i.e., Mendelian randomization), with stratification by study area. 33% (69 897/210 205) of men reported drinking alcohol in most weeks, mainly as spirits, compared with only 2% (6245/302 510) of women. Among men, conventional epidemiology showed that self-reported alcohol intake had U-shaped associations with the incidence of ischemic stroke (n=14 930), intracerebral hemorrhage (n=3496), and acute myocardial infarction (MI, n=2958); men who reported drinking about 100 g of alcohol per week (1 to 2 drinks per day) had lower risks of all three diseases than non-drinkers or heavier drinkers. In contrast, genotype-predicted mean alcohol intake had a continuously positive log-linear association with stroke risk, which was stronger for intracerebral hemorrhage (RR per 280 g per week 1·58) than for ischemic stroke (1·27), although genotype-predicted mean male alcohol intake varied widely (from 4 to 256 g per week—ie, near 0 to about 4 drinks per day). However, genotype-predicted mean alcohol intake was not significantly associated with MI risk. Usual alcohol intake in current drinkers and genotype-predicted alcohol intake in all men had similarly strong positive associations with systolic BP. Among women, few drank and the studied genotypes did not predict high mean alcohol intake and were not positively associated with BP, stroke, or MI, suggesting that the genotypic findings among men were mediated chiefly by alcohol rather than by any other (i.e., pleiotropic) effects of genotype. The findings suggest that alcohol consumption increases BP and stroke risk, and that the apparently protective effects of moderate alcohol intake against stroke may have reflected biases of reverse causation or confounding. Source: https://www.thelancet.com/
