Epidemiologic Evidence Does Not Support Protective Effects of Alcohol for Stroke

In contrast to findings using conventional epidemiology, genetic epidemiology found that alcohol intake is associated with uniform increases in blood pressure and stroke, according to a study published in The Lancet.

For this study, researchers examined the relationships between alcohol intake and cardiovascular risk in east Asia, where 2 common genetic variants (ADH1B-rs1229984 and ALDH2-rs671) cause large absolute differences in patterns of alcohol consumption. The study focused on men and researchers compared those findings with women, few of whom drink.

The study analyzed China Kadoorie Biobank data on 512,715 adults from 10 areas of China who were enrolled between June 2004 and July 2008 and were followed for approximately 10 years (until 2017). Only 161,498 of the total participants were genotyped for the 2 common variants that alter the metabolism of alcohol in the east Asian population.

Adjusted Cox regression was used to determine the relative risks that link cardiovascular disease incidence with self-reported patterns of drinking (conventional epidemiology) or mean male alcohol intake as predicted by genotype (genetic epidemiology, ie, Mendelian randomization).

Only 2% of women (6245/302,510) reported drinking alcohol (primarily spirits) most weeks, compared with 33% of men (69,897/210,205). For men, analysis using conventional epidemiology showed U-shaped associations between self-reported alcohol consumption and the incidence of acute myocardial infarction (n=2958), intracerebral hemorrhage (n=3496), and ischemic stroke (n=14,930).

Men reporting an intake of approximately 100g of alcohol/week (1 to 2 drinks/day) had lower risks of all 3 diseases than both non-drinkers and heavier drinkers. However, although the mean male alcohol intake predicted by genotype varied from 4 to 256 g/week, the analysis did not find any U-shaped associations between intake and cardiovascular risk.

A continuously positive log-linear association was found between genotype-predicted intake and stroke risk, with relative risk (RR) being stronger for intracerebral hemorrhage than ischemic stroke (RR for 280 g per week, 1.58; 95% CI, 1.36–1.84; P <.0001; and RR, 1.27; 95% CI, 1.13–1.43; P =.0001, respectively).

Genotype-predicted alcohol consumption was not significantly associated with risk for myocardial infarction (RR, 0.96; 95% CI, 0.78–1.18; P =.69). Usual alcohol intake and genotype-predicted intake each had a similarly strong positive association with increased systolic blood pressure (P <.0001 for both).

Few women in the study drank, the genotypes did not predict high mean alcohol intake, and alcohol consumption among women was not positively associated with stroke, myocardial infarction, or blood pressure.

“The genetic epidemiological analyses in this large study do not support the apparently protective effects against stroke of moderate drinking when compared with no drinking that are suggested by conventional epidemiological analyses,” the study researchers concluded.

Reference

Millwood IY, Walters RG, Mei XW, et al. Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China [published online April 4, 2019]. The Lancet. doi: 10.1016/S0140-6736(18)32214-1