Alcohol consumption in relation to cardiovascular diseases and mortality: a systematic review of Mendelian randomization studies.

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.

Adherence to Drinking Guidelines and Reasons for Alcohol Consumption Cessation in the Southern Cone of Latin America - Findings from the CESCAS Study.

Introduction: Alcohol consumption is a risk factor for morbidity and mortality globally. Consumption levels in Southern Latin America are among the highest in the world. Objectives: To describe consumption patterns and adherence to guidelines in the general adult population of Southern Latin America, as well as exploration of reasons for alcohol cessation and the advising role of the health worker in this decision. Methods: In 7,520 participants from the Centro de Excelencia en Salud Cardiovascular para el America del Sur (CESCAS) cohort, consumption patterns were described and the proportion excessive drinkers (i.e. >7 units/week for women and >14 for men or binge drinking: >4 (women) or >5 (men) units at a single occasion) was calculated. Former drinkers were asked if they had quit alcohol consumption on the advice of a health worker and/or because of health reasons. Furthermore, among former drinkers, multivariable logistic regression analysis was performed to assess which participant characteristics were independently associated with the chance of quitting consumption on a health worker's advice. Results: Mean age was 54.8 years (SD = 10.8), 42% was male. Current drinking was reported by 44.6%, excessive drinking by 8.5% of the population. In former drinkers, 23% had quit alcohol consumption because of health reasons, half of them had additionally quit on the advice of a health worker. The majority of former drinkers however had other, unknown, reasons. When alcohol cessation was based on a health worker's advice, sex, country of residence, educational status and frequency of visiting a physician were independent predictors. Conclusion: In this Southern American population-based sample, most participants adhered to the alcohol consumption guidelines. The advising role of the health worker in quitting alcohol consumption was only modest and the motivation for the majority of former drinkers remains unknown. A more detailed assessment of actual advice rates and exploration of additional reasons for alcohol cessation might be valuable for alcohol policy making.

Socioeconomic characteristics of patients with coronary heart disease in relation to their cardiovascular risk profile.

OBJECTIVE: People'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. METHODS: Based 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. RESULTS: Analyses 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. CONCLUSION: These 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.

Alcohol consumption patterns across Europe and adherence to the European guidelines in coronary patients: Findings from the ESC-EORP EUROASPIRE V survey.

BACKGROUND AND AIMS: Alcohol consumption is an important risk factor for cardiovascular morbidity and mortality worldwide. The highest levels of alcohol consumption are observed in Europe, where alcohol as contributing cause of coronary heart disease (CHD) is also most significant. We aimed to describe alcohol consumption patterns across European regions and adherence to the current guidelines in patients with a recent CHD event. METHODS: The ESC-EORP survey (EUROASPIRE V) has been conducted in 2016-2017 at 131 centers in 27 European countries in 7350 patients with a recent CHD. Median alcohol consumption, as well as the proportion of abstainers and excessive drinkers (i.e. >70 g/week for women and >140 for men, as recommended by the European guidelines on cardiovascular prevention), was calculated for each region. To assess adherence to guidelines, proportions of participants who were advised to reduce excessive alcohol consumption and participants who were incorrectly not advised were calculated per region. RESULTS: Mean age was 64 years (SD: 9.5), 75% were male. Abstention rates were 53% in males and 77% in females, whereas excessive drinking was reported by 9% and 5% of them, respectively. Overall, 57% of the participants were advised to reduce alcohol consumption. In the total population, 3% were incorrectly not advised, however, this percentage differed per region (range: 1%-9%). In regions where alcohol consumption was highest, participants were less often advised to reduce their consumption. CONCLUSION: In this EUROASPIRE V survey, the majority of CHD patients adhere to the current drinking guidelines, but substantial heterogeneity exists between European regions.

Urinary Ethyl Glucuronide as Measure of Alcohol Consumption and Risk of Cardiovascular Disease: A Population-Based Cohort Study.

Background Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease (CVD) and all-cause mortality compared with heavy drinkers and abstainers. To date, studies have relied on self-reported consumption, which may be prone to misclassification. Urinary ethyl glucuronide (EtG) is an alcohol metabolite and validated biomarker for recent alcohol consumption. We aimed to examine and compare the associations of self-reported alcohol consumption and EtG with CVD and all-cause mortality. Methods and Results In 5676 participants of the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study cohort, EtG was measured in 24-hour urine samples and alcohol consumption questionnaires were administered. Participants were followed up for occurrence of first CVD and all-cause mortality. Cox proportional hazards regression models, adjusted for age, sex, and CVD risk factors, were fitted for self-reported consumption, divided into 5 categories: abstention, 1 to 4 units/month (reference), 2 to 7 units/week, 1 to 3 units/day, and ≥4 units/day. Similar models were fitted for EtG, analyzed as both continuous and categorical variables. Follow-up times differed for CVD (8 years; 385 CVD events) and all-cause mortality (14 years; 724 deaths). For both self-reported alcohol consumption and EtG, nonsignificant trends were found toward J-shaped associations between alcohol consumption and CVD, with higher risk in the lowest (hazard ratio for abstention versus 1-4 units/month, 1.42; 95% CI, 1.02-1.98) and highest drinking categories (hazard ratio for ≥4 units/day versus 1-4 units/month, 1.11; 95% CI, 0.68-1.84). Neither self-report nor EtG was associated with all-cause mortality. Conclusions Comparable associations with CVD events and all-cause mortality were found for self-report and EtG. This argues for the validity of self-reported alcohol consumption in epidemiologic research.

Moderate and heavy alcohol consumption are prospectively associated with decreased left ventricular ejection fraction: The Hoorn Study.

BACKGROUND AND AIMS: Data on the prospective relationship of alcohol consumption at more moderate levels with systolic and diastolic function are scarce. We aimed to examine the prospective association of alcohol consumption with echocardiographic measures of cardiac structure and function, in individuals with and without type 2 diabetes (T2DM). METHODS AND RESULTS: We included 778 participants from the Hoorn Study (aged 68.4 ± 7.2 years, 49% women), a population-based prospective cohort study, oversampled for people with impaired glucose metabolism or T2DM. Self-reported alcohol consumption was collected at baseline with a validated food-frequency questionnaire and categorized into: none (0/week), light (>0-≤30 g/week), light-to-moderate (>30-≤70 g/week), moderate (>70-≤140 g/week), and heavy drinkers (>140 g/week). Echocardiography was performed at baseline (N = 778) and after 8 years follow-up (N = 404). Multiple linear regression was used to study the association between alcohol consumption and echocardiographic measures (left ventricular ejection fraction (LVEF), left atrial volume index (LAVI) and left ventricular mass index (LVMI)), adjusted for confounders. Moderate and heavy alcohol consumption were associated with a decreased LVEF of -3.91% (CI: -7.13;-0.69) for moderate and -4.77% (-8.18;-1.36) for heavy drinkers compared to light drinkers. No associations were found between alcohol consumption, LVMI and LAVI. Modified Poisson regression showed a trend that higher alcohol consumption amounts were associated with a higher risk of incident systolic dysfunction (LVEF≤50%) (P-for-trend 0.058). CONCLUSION: The findings provide longitudinal evidence that moderate and heavy alcohol consumption are associated with decreased LVEF and trend towards a higher risk of incident LV systolic dysfunction, compared to light drinkers.

Urinary Ethyl Glucuronide Can Be Used as a Biomarker of Habitual Alcohol Consumption in the General Population.

BACKGROUND: Alcohol 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. OBJECTIVE: The 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. METHODS: Among 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. RESULTS: Mean 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. CONCLUSIONS: This 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.