Alcohol, Other Drugs, and Health: Current Evidence May–June 2019 Journal Club Alcohol, Other Drugs, and Health: Current Evidence May–June 2019 www.aodhealth.org

Millwood IY, et al. Lancet. 2019;393(10183):1831–1842. Featured Article Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China Millwood IY, et al. Lancet. 2019;393(10183):1831–1842. www.aodhealth.org

Study Objective “To assess the relationships between cardiovascular risk and genotype-predicted mean alcohol intake in men.” www.aodhealth.org

Study Design Prospective study of 512,715 adults in China, followed for 10 years. Participants were monitored for cardiovascular disease (CVD). Alcohol use was measured by self-report. Of these, 161,498 participants were genotyped for variants involved in alcohol metabolism and participated in a Mendelian randomization study. www.aodhealth.org

Assessing Validity of an Article about Prognosis Are the results valid? What are the results? How can I apply the results to patient care? Based on the Users’ Guides to the Medical Literature; for more information, see the following: http://www.cche.net/usersguides/main.asp http://pubs.ama-assn.org/misc/usersguides.dtl www.aodhealth.org

Are the Results Valid? Was the sample representative? Were the subjects sufficiently homogeneous with respect to prognostic risk? Was follow-up sufficiently complete? Were objective and unbiased outcome criteria used? www.aodhealth.org

Was the sample representative? The sample was representative of the population in China. Participants came from 10 diverse areas of China. However, very few women consume alcohol in China, so findings are limited to men. www.aodhealth.org

Were the subjects sufficiently homogeneous with respect to prognostic risk? Mostly, although the authors state that alcohol use varies greatly by study area. Results were stratified by area and adjusted for age. www.aodhealth.org

Was follow-up sufficiently complete? Yes. At 10-years, only 4781 (0.9%) of participants were lost to follow-up. 44,037 (8.6%) died in that time. www.aodhealth.org

Were objective and unbiased outcome criteria used? Yes. www.aodhealth.org

What Are the Results? How likely are the outcomes over time? How precise are the estimates of likelihood? www.aodhealth.org

How likely are the outcomes over time? Conventional epidemiological analyses adjusted for demographics and smoking found “U-shaped” curves for stroke and coronary heart disease, with nadirs for people who reported drinking occasionally and those drinking 100 g ethanol in a week on average (about 7 US standard drinks). In the genotypic analyses, there was a linear association between genotype-predicted mean alcohol consumption and stroke risk (with alcohol accounting for 8% of all ischemic strokes and 16% of all intracerebral hemorrhages in men), and no association (protective or harmful) with coronary heart disease. Of note, both self-reported alcohol and genotype-predicted means were associated linearly with known alcohol effects (systolic blood pressure, HDL cholesterol, and gamma-glutamyl transferase). www.aodhealth.org

How precise are the estimates of likelihood? For stroke, genotype-predicted mean alcohol intake had a continuously positive log-linear association with risk, which was stronger for intracerebral haemorrhage (relative risk [RR] per 280 g per week 1.58, 95% CI 1.36–1.84) than for ischaemic stroke (1.27, 1.13–1.43). For myocardial infarction, genotype-predicted mean alcohol intake was not significantly associated with risk (RR per 280 g per week 0.96, 95% CI 0.78–1.18, p=0.69). Usual alcohol intake in current drinkers and genotype-predicted alcohol intake in all men had similarly strong positive associations with systolic blood pressure (each p<0.0001). www.aodhealth.org

How Can I Apply the Results to Patient Care? Were the study patients and their management similar to those in my practice? Was follow-up sufficiently long? Can I use the results in the management of patients in my practice? www.aodhealth.org

Were the study patients similar to those in my practice? The study population was large and drawn from 10 diverse areas of China. Only 2% of the women in the study consumed alcohol, compared with 33% of men. www.aodhealth.org

Was follow-up sufficiently long? Yes. www.aodhealth.org

Can I use the results in the management of patients in my practice? Yes. No study is perfect, nor can a single study answer a question definitively. But we now have several Mendelian randomization studies and several high-quality meta-analyses that have minimized confounding and biases and suggest that the previously observed associations between consumption of low amounts of alcohol and cardiovascular outcomes are not cause and effect. www.aodhealth.org