The causal effects of alcohol-in-moderation on cardiometabolic health are continuously debated. Mendelian randomization (MR) is an established method to address causal questions in observational studies. We performed a systematic review of the current evidence from MR studies on the association between alcohol consumption and cardiometabolic diseases, all-cause mortality and cardiovascular risk factors. We performed a systematic search of the literature, including search terms on type of design and exposure. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. We additionally looked at exploration of non-linearity. We reported the direction of the studied associations. Our search yielded 24 studies that were eligible for inclusion. A full instrumental variable analysis was performed in 17 studies (71%) and 13 out of 24 studies (54%) validated all three key assumptions. Five studies (21%) assessed potential non-linearity. In general, null associations were reported for genetically predicted alcohol consumption with the primary outcomes cardiovascular disease (67%) and diabetes (75%), while the only study on all-cause mortality reported a detrimental association. Considering the heterogeneity in methodological quality of the included MR studies, it is not yet possible to draw conclusions on the causal role of moderate alcohol consumption on cardiometabolic health. As MR is a rapidly evolving field, we expect that future MR studies, especially with recent developments regarding instrument selection and non-linearity methodology, will further substantiate this discussion.

BackgroundAlcohol consumption is a frequently studied risk factor for chronic diseases, but many studies are hampered by self-report of alcohol consumption. The urinary metabolite ethyl glucuronide (EtG), reflecting alcohol consumption during the past 72 h, is a promising objective marker, but population data are lacking.ObjectiveThe objective of this study was to assess the reliability of EtG as a marker for habitual alcohol consumption compared with self-report and other biomarkers in the general population.MethodsAmong 6211 participants in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort, EtG concentrations were measured in 24-h urine samples. EtG was considered positive when concentrations were ≥100 ng/mL. Habitual alcohol consumption was self-reported by questionnaire (categories: no/almost never, 1–4 units per month, 2–7 units per week, 1–3 units per day or ≥4 units per day). Plasma HDL cholesterol concentration, erythrocyte mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltransferase (GGT) were determined as indirect biomarkers of alcohol consumption. Sensitivity, specificity, positive and negative predictive value, and proportions of agreement between reported consumption and EtG were calculated. To test the agreement of EtG concentration and alcohol consumption in categories, linear regression analysis was performed. In addition, the association between EtG concentrations and indirect biomarkers was analyzed.ResultsMean age was 53.7 y, and 52.9% of participants men. Of the self-reported abstainers, 92.3% had an EtG concentration <100 ng/mL. Sensitivity was 66.3%, positive predictive value was 96.3%, and negative predictive value was 47.4%. The proportion of positive agreement was 78.5%, and the proportion of negative agreement was 62.7%. EtG concentrations were linearly associated with higher categories of alcohol consumption (P-trend < 0.001), adjusted for age, sex, and renal function. EtG was positively related to MCV, HDL cholesterol, and GGT but not to AST and ALT concentrations.ConclusionsThis study shows that urinary EtG is in reasonable agreement with self-reported alcohol consumption and therefore can be used as an objective marker of habitual alcohol consumption in the general population.

ObjectivePeople’s socioeconomic status (SES) has a major impact on the risk of atherosclerotic cardiovascular disease (ASCVD) in primary prevention. In patients with existing ASCVD these associations are less documented. Here, we evaluate to what extent SES is still associated with patients’ risk profile in secondary prevention.MethodsBased on results from a large sample of patients with coronary heart disease from the European Action on Secondary and Primary Prevention through Intervention to Reduce Events study, the relationship between SES and cardiovascular risk was examined. A SES summary score was empirically constructed from the patients’ educational level, self-perceived income, living situation and perception of loneliness.ResultsAnalyses are based on observations in 8261 patients with coronary heart disease from 27 countries. Multivariate logistic regression analyses demonstrate that a low SES is associated (OR, 95% CI) with lifestyles such as smoking in men (1.63, 1.37 to 1.95), physical activity in men (1.51, 1.28 to 1.78) and women (1.77, 1.32 to 2.37) and obesity in men 1.28 (1.11 to 1.49) and women 1.65 (1.30 to 2.10). Patients with a low SES have more raised blood pressure in men (1.24, 1.07 to 1.43) and women (1.31, 1.03 to 1.67), used less statins and were less adherent to them. Cardiac rehabilitation programmes were less advised and attended by patients with a low SES. Access to statins in middle-income countries was suboptimal leaving about 80% of patients not reaching the low-density lipoprotein cholesterol target of <1.8 mmol/L. Patients’ socioeconomic level was also strongly associated with markers of well-being.ConclusionThese results illustrate the complexity of the associations between SES, well-being and secondary prevention in patients with ASCVD. They emphasise the need for integrating innovative policies in programmes of cardiac rehabilitation and secondary prevention.