Cumulative Alcohol Consumption Research Articles

Screening for depression and anxiety in lung cancer patients: A real-world study using GAD-7 and HADS.

The psychological well-being of lung cancer patients is critical in-patient care but frequently overlooked. This study, employing a cross-sectional, questionnaire-based design, aimed to elucidate the prevalence of depressive and anxiety symptoms among lung cancer patients and identify associated risk factors. Participants' demographic, medical history, disease stage, and pathology were systematically collected. Psychological assessment was conducted using the general anxiety disorder-7 (GAD-7), patient health questionnaire-9 (PHQ-9), and hospital anxiety and depression scale (HADS). Statistical analyses were performed using SPSS software (version 25.0). Out of 294 distributed questionnaires, 247 lung cancer patients were included in the final analysis, with an average completion time of 9.08 min. Notably, 32.4% exhibited depressive symptoms, while 30% displayed signs of anxiety. A significant correlation was found between both depressive and anxiety symptoms and a history of tobacco and alcohol consumption. Specifically, increased nicotine dependence and greater cumulative tobacco use were linked to higher rates of depressive symptoms, whereas cumulative alcohol consumption was associated with increased risks of anxiety symptoms. The study affirms the feasibility of GAD-7, PHQ-9, and HADS as screening tools for depressive and anxiety symptoms in lung cancer patients. It further highlights tobacco and alcohol consumption as significant risk factors for poor psychological health in this population.

Circulating metabolites may illustrate relationship of alcohol consumption with cardiovascular disease

BackgroundMetabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD.MethodsCumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine, and liquor on average of 19 years in 2428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women). We used linear mixed models to investigate the associations of alcohol consumption with 211 log-transformed plasma metabolites, adjusting for age, sex, batch, smoking, diet, physical activity, BMI, and familial relationship. Cox models were used to test the association of alcohol-related metabolite scores with fatal and nonfatal incident CVD (myocardial infarction, coronary heart disease, stroke, and heart failure).ResultsWe identified 60 metabolites associated with cumulative average alcohol consumption (p < 0.05/211 ≈ 0.00024). For example, 1 g/day increase of alcohol consumption was associated with higher levels of cholesteryl esters (e.g., CE 16:1, beta = 0.023 ± 0.002, p = 6.3e − 45) and phosphatidylcholine (e.g., PC 32:1, beta = 0.021 ± 0.002, p = 3.1e − 38). Survival analysis identified that 10 alcohol-associated metabolites were also associated with a differential CVD risk after adjusting for age, sex, and batch. Further, we built two alcohol consumption weighted metabolite scores using these 10 metabolites and showed that, with adjustment age, sex, batch, and common CVD risk factors, the two scores had comparable but opposite associations with incident CVD, hazard ratio 1.11 (95% CI = [1.02, 1.21], p = 0.02) vs 0.88 (95% CI = [0.78, 0.98], p = 0.02).ConclusionsWe identified 60 long-term alcohol consumption-associated metabolites. The association analysis with incident CVD suggests a complex metabolic basis between alcohol consumption and CVD.

Patients hospitalized with alcohol-related liver disease and prior bariatric surgery are more prone to develop acute-on-chronic liver failure.

Patients with a history of bariatric surgery (BS) are susceptible to developing alcohol use disorder. We and others have previously shown that these patients can develop severe alcohol-related liver disease (ARLD). Our aim was to describe the demographics, co-morbidities and mortality of a hospitalized population diagnosed with alcohol-related liver disease, in relation to BS. We included 299 patients hospitalized with ARLD at the Ghent University Hospital between 1 January 2018 and 31 December 2022. Clinical, biochemical and outcome data were retrospectively retrieved from the most recent hospitalization. Statistical analysis was performed using the t test, Mann-Whitney U and χ2 tests. Thirteen per cent (39/299) of patients admitted with ARLD had a history of bariatric surgery, of whom 25 (64.1%) had undergone Roux-en-Y gastric bypass. Patients with a history of BS were predominantly female (76.9%), in contrast to the non-BS population (29.2%) (p < .0001), and despite being significantly younger (p < .0001) and had a similar survival (61.5% vs. 58.1%). Bariatric surgery and older age at diagnosis were both significantly associated with poorer transplant-free survival. The cause of death was acute-on-chronic liver failure in 73.3% of BS patients, compared to only 19.2% of those without a history of BS (p < .0001). The weekly amount of alcohol consumed (p = .012) and duration of use (p < .0001) were significantly lower/shorter in the BS population. BS patients hospitalized with ARLD are predominantly younger women with a lower cumulative alcohol consumption compared to those without prior BS. BS impacted transplant-free survival, with ACLF as the predominant cause of death in these patients.

Development and validation of an LC-MS/MS method to quantify the alcohol biomarker phosphatidylethanol 16:0/18:1 in dried blood spots for clinical research purposes

Phosphatidylethanol (PEth) is a group of phospholipids detectable in red blood cells exclusively following ethanol consumption. The primary PEth analog, PEth 16:0/18:1, has an extended half-life in red cells, providing a long window of detection and tremendous potential for the quantification of cumulative alcohol consumption. We developed and validated an LC/MS-MS method to quantify PEth 16:0/18:1 in dried blood spots (DBS) for clinical research purposes. Method development and validation followed FDA guidance but expanded on prior published methods through the evaluation of additional DBS-specific factors such as sample hematocrit, punch location, and spot volume. This method was applied to the quantification of PEth in participant samples.

Alcohol consumption and epigenetic age acceleration in young adults.

Alcohol is a widely consumed substance in the United States, however its effect on aging remains understudied. In this study of young adults, we examined whether cumulative alcohol consumption, i.e., alcohol years of beer, liquor, wine, and total alcohol, and recent binge drinking, were associated with four measures of age-related epigenetic changes via blood DNA methylation. A random subset of study participants in the Coronary Artery Risk Development in Young Adults Study underwent DNA methylation profiling using the Illumina MethylationEPIC Beadchip. Participants with alcohol consumption and methylation data at examination years 15 (n = 1,030) and 20 (n = 945) were included. Liquor and total alcohol consumption were associated with a 0.31-year (P = 0.002) and a 0.12-year (P = 0.013) greater GrimAge acceleration (GAA) per additional five alcohol years, while beer and wine consumption observed marginal (P = 0.075) and no associations (P = 0.359) with GAA, respectively. Any recent binge drinking and the number of days of binge drinking were associated with a 1.38-year (P < 0.001) and a 0.15-year (P < 0.001) higher GAA, respectively. We observed statistical interactions between cumulative beer (P < 0.001) and total alcohol (P = 0.004) consumption with chronological age, with younger participants exhibiting a higher average in GAA compared to older participants. No associations were observed with the other measures of epigenetic aging. These results suggest cumulative liquor and total alcohol consumption and recent binge drinking may alter age-related epigenetic changes as captured by GAA. With the increasing aging population and widespread consumption of alcohol, these findings may have potential implications for lifestyle modification to promote healthy aging.

Relationship between alcohol consumption and dementia with Mendelian randomization approaches among older adults in the United States

AbstractBackgroundPrior research is mixed concerning the association between alcohol consumption, a modifiable factor, and dementia. Genetic causal inference approaches may help elucidate the relationship between alcohol consumption and dementia.MethodWe performed a two‐sample Mendelian randomization study using harmonized, genome‐wide significant (p‐value&lt;10−8), and independent (r2&lt;.001) single nucleotide polymorphisms’ (SNPs) summary statistics from the largest publicly available meta‐analyses of genome‐wide association studies of weekly alcohol consumption (Liu et al., 2019, n = 941,280) and late onset Alzheimer’s disease (Kunkle et al., 2019, n = 21,982 cases, 41,944 controls). Next, in the 2012 wave of the United States Health and Retirement Study (HRS), we employed individual polygenic scores of alcohol consumption via one‐sample Mendelian randomization. Polygenic scores were calculated and standardized within genetic ancestry across 1,399,824 SNPs overlapping Liu et al. without HRS and 23andMe samples (n = 522,159). G‐estimation provided odds ratios (ORs) of the relationship between a standard deviation increase in genetic risk of alcohol consumption and dementia and cognitive impairment without dementia compared to normal cognition in models stratified by genetic ancestry.ResultOf 99 SNPs associated with weekly alcoholic drink consumption and 71 SNPs associated with late onset Alzheimer’s disease, 59 overlapping and harmonized SNPs met instrument selection criteria. We did not observe evidence of a relationship between alcohol consumption and late‐onset Alzheimer’s disease using the inverse variance weighted two‐sample Mendelian randomization estimator (OR = 1.15, 95% confidence interval (CI):[0.78, 1.72]), nor with complementary estimators. In HRS, Mendelian randomization revealed no relationship between cumulative genetic alcohol consumption risk and cognitive impairment without dementia (African ancestry sample (n = 2,402, OR = 0.86, 95% CI:[0.47, 1.58]); European ancestry sample (n = 9,576, OR = 0.96, 95% CI:[0.86, 1.07])) and dementia in the African ancestry sample (n = 1,908, OR = 0.50, 95% CI:[0.13, 2.00]). Alcohol consumption genetic risk was inversely associated with dementia in the European ancestry sample (n = 8,518, OR = 0.77, 95% CI:[0.62, 0.95]).ConclusionOur results largely suggest there is no causal relationship between alcohol consumption and dementia. The protective association observed between alcohol consumption and dementia among those of European ancestry in an aging American cohort may be due to genetic pleiotropy and/or selection bias in our empirical sample within the Health and Retirement Study.

Cumulative Alcohol Consumption Burden and the Risk of Stroke in Young Adults: A Nationwide Population-Based Study.

Alcohol consumption is one of the important modifiable risk factors for stroke in young adults. The association between the cumulative burden of alcohol consumption and its impact on incident stroke in young adults is unknown. We aimed to investigate the association between cumulative alcohol burden and the risk for stroke among young adults. Using data from the Korean National Health Insurance Service database, patients age between 20 and 39 years, who underwent 4 consecutive annual health examinations between 2009 and 2012, were included. The cumulative alcohol burden score of moderate-to-heavy drinking was evaluated by assigning a score of 1 for alcohol consumption ≥105 g/wk at the health examination each year and calculating the sum of 4 years (0-4). The main outcome was incident stroke and its subtypes, ischemic stroke, and hemorrhagic stroke during the follow-up period. Of 1 536 668 patients (mean age of 29.5 years, 71.5% male, and median follow-up of 6-year), 3 153 experienced an incident stroke (incidence rate, 0.37 per 1,000 person-years). After multivariable adjustment, patients with alcohol burden scores of 2, 3, and 4, who consumed more than 105 g/wk of alcohol for 2, 3, and 4 years, demonstrated significantly higher risks for stroke (hazard ratio [HR] 1.19, 95% CI 1.05-1.34 for 2; HR 1.22, 95% CI 1.09-1.38 for 3; HR 1.23, 95% CI 1.10-1.38 for 4) compared with those with a burden score of 0. This positive dose-response relationship was primarily driven by hemorrhagic rather than ischemic stroke. High alcohol burden scores (i.e., 2, 3, and 4) were significantly associated with higher risks for hemorrhagic stroke (HR 1.30, 95% CI 1.10-1.54 for 2; HR 1.42, 95% CI 1.21-1.67 for 3; HR 1.36, 95% CI 1.16-1.59 for 4) compared with a burden score of 0. Young adults who engaged in moderate-to-heavy drinking demonstrated a higher risk for incident stroke, especially hemorrhagic stroke. Reducing alcohol consumption should be emphasized in young adults with heavy drinking habits as part of any stroke prevention strategy.

Habitual Alcohol Intake and Risk of Atrial Fibrillation in Young Adults in Korea

Guidelines recommend that all risk factors for early-onset atrial fibrillation, including lifestyle factors, be proactively managed, considering the poor prognosis of the disease. Not much is known about the association of cumulative alcohol intake with the risk of atrial fibrillation in young adults aged 20 to 39 years, especially among heavy drinkers. To explore the association of alcohol consumption with the risk of incident atrial fibrillation in young adults. Using the National Health Insurance Service database, a nationwide population-based cohort study of adults aged 20 to 39 years without prior atrial fibrillation who underwent 4 serial annual health examinations between 2009 and 2012 was conducted. The cumulative alcohol consumption burden over 4 years was calculated by assigning 1 point to more than moderate drinking (≥105 g of alcohol per week) each year. Additionally, a semiquantitative cumulative burden was calculated by assigning 0, 1, 2, and 3 points to non, mild (<105 g per week), moderate (105-210 g per week), and heavy (≥210 g per week) drinking, respectively. Data were analyzed from May to June 2021. Amount of alcohol intake in 4 years. The primary outcome was incident atrial fibrillation during the follow-up period. A total of 1 537 836 participants (mean [SD] age 29.5 [4.1] years, 1 100 099 [71.5%] male) were included in the final analysis. According to the 4-year cumulative burden of alcohol consumption stratified by moderate to heavy drinking, 889 382 participants (57.8%) were in the burden 0 group, 203 374 participants (13.2%) in the burden 1 group, 148 087 participants (9.6%) in the burden 2 group, 144 023 participants (9.4%) in the burden 3 group, and 152 970 participants (9.9%) in the burden 4 group. During a median (IQR) follow-up of 6.13 (4.59-6.48) years, atrial fibrillation was newly diagnosed in 3066 participants (0.36 per 1000 person-years). Participants with a cumulative burden of 4 points who continued more than moderate drinking for 4 years showed a 25% higher risk of atrial fibrillation compared with 0-point participants who kept non-to-mild drinking over 4 years (adjusted HR, 1.25; 95% CI, 1.12-1.40). In a semiquantitative analysis, participants who sustained heavy drinking for 4 consecutive years were associated with a 47% higher atrial fibrillation risk than those who remained nondrinkers over 4 years (aHR, 1.47, CI 1.18-1.83). Persistent moderate to heavy drinking and higher cumulative alcohol consumption burden might increase the risk of atrial fibrillation even in young adults aged 20 to 39 years.

Association of drinking behaviors with TXNIP DNA methylation levels in leukocytes among the general Japanese population

ABSTRACT Background: Thioredoxin-interacting protein (TXNIP) controls the cellular redox balance by binding to and inhibiting the expression and function of thioredoxin. DNA methylation of the TXNIP gene is involved in the regulation of TXNIP mRNA expression. Changes in TXNIP DNA methylation levels are associated with the development of various diseases such as type 2 diabetes mellitus (T2DM). However, few studies have focused on the influence of lifestyle factors such as alcohol intake on TXNIP DNA methylation. Objectives: This research examines the association of drinking behaviors with TXNIP DNA methylation levels in the general Japanese population. Methods: We conducted a cross-sectional study of 404 subjects (176 males and 228 females) who were divided into non-, moderate and heavy drinkers based on self-reported drinking behaviors. TXNIP DNA methylation levels in leukocytes were determined using a pyrosequencing assay. Results: The mean TXNIP DNA methylation level in heavy drinkers (74.2%) was significantly lower than that in non- and moderate drinkers (non: 77.7%, p < .001; moderate: 76.6%, p = .011). Multivariable linear regression analysis showed that log-transformed values of daily (b = −1.34; p < .001) and cumulative (b = −1.06; p = .001) alcohol consumption were associated with decreased TXNIP DNA methylation levels. Conclusion: TXNIP DNA methylation levels in heavy drinkers was lower than in non- and- moderate drinkers. Decreased TXNIP DNA methylation level increases the expression of TXNIP and elevates the risk of developing of diseases such as T2DM. Therefore, decreasing alcohol use in heavy drinkers may lessen the likelihood of some alcohol-related illnesses moderated through TXNIP DNA methylation.

Associations of delay discounting and drinking trajectories from ages 14 to 22.

While drinking alcohol, one must choose between the immediate rewarding effects and the delayed reward of a healthier lifestyle. Individuals differ in their devaluation of a delayed reward based on the time required to receive it, i.e., delay discounting (DD). Previous studies have shown that adolescents discount more steeply than adults and that steeper DD is associated with heavier alcohol use in both groups. In a large-scale longitudinal study, we investigated whether higher rates of DD are an antecedent or a consequence of alcohol use during adolescent development. As part of the IMAGEN project, 2220 adolescents completed the Monetary Choice Questionnaire as a DD measure, the Alcohol Use Disorders Identification Test, and the Timeline Follow Back interview at ages 14, 16, 18, and 22. Bivariate latent growth curve models were applied to investigate the relationship between DD and drinking. To explore the consequences of drinking, we computed the cumulative alcohol consumption and correlated it with the development of discounting. A subsample of 221 participants completed an intertemporal choice task (iTeCh) during functional magnetic resonance imaging at ages 14, 16, and 18. Repeated-measures ANOVA was used to differentiate between high-risk and low-risk drinkers on the development of neural processing during intertemporal choices. Overall, high rates of DD at age 14 predicted a greater increase in drinking over 8years. In contrast, on average, moderate alcohol use did not affect DD from ages 14 to 22. Of note, we found indicators for less brain activity in top-down control areas during intertemporal choices in the participants who drank more. Steep DD was shown to be a predictor rather than a consequence of alcohol use in low-level drinking adolescents. Important considerations for future longitudinal studies are the sampling strategies to be used and the reliability of the assessments.

Abstract P180: Relative Contributions Of Six Lifestyle Components To Epigenetic Aging In The Coronary Artery Risk Development In Young Adults (CARDIA) Study

Background: DNA methylation-based epigenetic age acceleration (EAA) is associated with age-related health outcomes including cardiovascular disease. Since DNA methylation is modifiable by external stimuli, including lifestyle components, interventions for healthier lifestyles could contribute to decreased risk of health conditions related to epigenetic changes including EAA. In consideration of public health intervention, it is also important to identify which lifestyle components have the greatest impact on EAA. Here, we assessed the relative contributions of lifestyle components to EAA, as well as their collective association. Methods: We included 744 participants (391 men and 353 women) from the Coronary Artery Risk Development in Young Adults (CARDIA) study with DNA methylation information at Y20 (2005-2006, mean age 45.9). Six lifestyle components at Y20 were included in the analysis: cumulative smoking, cumulative alcohol consumption, education, diet, sleep, and physical activity. We used quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods to assess the relative contribution of each lifestyle component to EAA. We also assessed overall association of the six lifestyle components as a combination with EAA. Finally, we performed stratified analyses by participants’ smoking history, race, and sex. Results: Cumulative smoking showed the greatest positive contribution to EAA in total participants. Healthy diet and education years showed inverse contributions to EAA. We observed a non-linear pattern in the contribution of cumulative alcohol consumption to EAA. We observed positive associations between the collective lifestyle components and greater EAA. While cumulative smoking was the greatest contributor across sex and race subgroups, the relative contributions of other components varied by subgroups. Conclusion: Cumulative smoking, cumulative alcohol consumption, diet, and education showed the highest contributions in our study. Higher amounts of smoking and alcohol consumption were likely to contribute to greater EAA, whereas healthier diet and achieved education were likely to contribute to lesser EAA. Identifying pertinent lifestyle components in a context of collective lifestyle components can provide a direction for intervention strategies, and suggests which components should be the primary focus for promoting younger EAA.

Abstract P3-12-19: Associations of alcohol consumption with benign breast tissue composition

Abstract Objectives: Alcohol is a known breast cancer risk factor and it is also associated with increased mammographic breast density, a well-established, strong breast cancer risk factor. Despite some evidence on the associations of alcohol use with tissue composition on mammograms, no studies have examined these associations using direct measurement of tissue composition in normal breast tissue of cancer-free women. We investigated the associations of recent and cumulative average alcohol use with percentage of epithelium, stroma, fibroglandular (epithelium+stroma), and fat tissue in benign breast biopsy samples. Methods: This study included 859 cancer-free women with biopsy-confirmed benign breast disease (BBD) within the Nurses’ Health Study and Nurses’ Health Study II cohorts. Percentage of each tissue type was measured on whole section images with a deep-learning technique. All tissue measures were log-transformed. The data on alcohol use was obtained from semi-quantitative food frequency questionnaires. Information on other covariates was collected on initial questionnaire and updated biennially thereafter. We examined associations for recent (at the time of biopsy) and cumulative average alcohol use (from all questionnaire preceding the biopsy), both of which were modeled as a continuous (g/day) and categorical (using various approaches: 0, 0-&amp;lt;5, and ≥5 g/day; non-drinkers, &amp;lt;11 g/day [&amp;lt;1 drink/day], 11-&amp;lt;22g/day [1-&amp;lt;2 drinks/day], and ≥ 22 g/day [≥2 dinks/day]; and quartiles based on the distribution in the study sample). Generalized linear regression was used to examine the associations of alcohol with % of tissue types, while adjusting for known breast cancer risk factors and BBD subtype. Results: In this study of 859 cancer-free women, 260 (30.3%) had non-proliferative disease, 485 (56.5%) had proliferative disease without atypia, and 114 (13.3%) had atypical hyperplasia, consistent with previously reported distributions of these BBD subtypes. In our study, 30.3% of women consumed ≥5 g/day of alcohol at the time of biopsy and 18.1% consumed ≥11 g (≥1 drinks) of alcohol per day. The average % of epithelium, stroma, and fat in our study was 9.0% (range 0.7-52.2%), 72.4% (range 23.6-99.0%), and 18.6% (range 0-71.3%), respectively. Both recent and cumulative alcohol use were inversely associated with % of stroma and fibroglandular tissue; these associations were most pronounced for recent use of ≥22 g (≥2 drinks) per day (stroma: β=-0.08, 95% Confidence Interval [CI] -0.13;-0.03; fibroglandular: β=-0.09, 95% CI -0.13;-0.04) and cumulative average use of ≥22 g (≥2 drinks) per day (stroma β=-0.08, 95% CI -0.13;-0.02; fibroglandular: β=-0.09, 95% CI -0.14;-0.04). Recent and cumulative average use of ≥22 g/day were also positively associated with % of fat (β=0.30, 95% CI 0.03; 0.57 for recent and β=0.32, 95% CI 0.04; 0.61 for cumulative average). In stratified analysis by menopausal status, recent and cumulative average alcohol use were inversely associated with % of stroma and fibroglandular tissue and positively associated with % of fat in postmenopausal women. The strongest associations were observed for recent alcohol use of ≥22 g/day (stroma: β=-0.12, 95% CI -0.21;-0.04; fat: β=0.67, 95% CI 0.23;1.12; fibroglandular: β=-0.15, 95% CI -0.23;-0.07) and cumulative average use of ≥22 g/day (stroma β=-0.14, 95% CI -0.23;-0.04; fat: β=0.53, 95% CI 0.03;1.03; fibroglandular: β=-0.16, 95% CI -0.25;-0.07). We found no associations of alcohol use with any of the tissue measures in premenopausal women. Conclusion: Our findings suggest that both recent and cumulative average alcohol consumption are associated with smaller proportion of stroma and fibroglandular tissue and a greater proportion of fat in postmenopausal women. Future studies are warranted to confirm our findings and to elucidate the underlying biological mechanisms. Citation Format: Lusine Yaghjyan, Rebecca Austin-Datta, Yujing J Heng, Gabrielle Baker, Bernard Rosner, Rulla Tamimi. Associations of alcohol consumption with benign breast tissue composition [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-19.

Alcohol consumption and the risk of gastric intestinal metaplasia in a U.S. Veterans population.

Chronic alcohol use is a risk factor for non-cardia gastric adenocarcinoma. However, it is less well understood whether alcohol use is a risk factor for premalignant mucosal changes, namely gastric intestinal metaplasia. We examined the association between various parameters of alcohol use and risk of gastric intestinal metaplasia. We used data from 2084 participants (including 403 with gastric intestinal metaplasia) recruited between February 2008-August 2013 into a cross-sectional study at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas. All participants underwent a study upper endoscopy with systematic gastric mapping biopsies. Cases had intestinal metaplasia on any non-cardia gastric biopsy. Participants self-reported lifetime history of alcohol consumption, along with other lifestyle risk factors, through a study survey. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for categories of average alcohol consumption using multivariable logistic regression, and restricted cubic spline regression to explore the potential shape of a dose-response relationship. Compared to lifelong non-drinkers, individuals who consumed on average ≥28 drinks per week had no elevated risk for gastric intestinal metaplasia (adjusted OR, 1.27; 95% CI, 0.74-2.19). Based on a spline regression curve and its 95% CI, there was also no demonstrable association between cumulative lifetime alcohol consumption and risk of gastric intestinal metaplasia. Similarly, we found no association between beverage type (beer, wine, liquor/spirits) and risk for gastric intestinal metaplasia. Neither amount of alcohol consumed nor specific beverage type was associated with risk of gastric intestinal metaplasia.

692Association of drinking habits with TXNIP DNA methylation levels in leukocytes among general Japanese population

Abstract Background Thioredoxin-interacting protein (TXNIP) inhibits the activity of thioredoxin (TXN), leading to increased oxidative stress. Expression of the TXNIP gene is regulated by DNA methylation. However, no study has reported the influence of lifestyle factors on TXNIP DNA methylation. Our goal was to determine the association between drinking habits and TXNIP DNA methylation levels in the general Japanese population. Methods We conducted a cross-sectional study of 404 subjects (176 males and 228 females) participating in a health examination. Subjects were divided into non-, moderate (male: 1-39g; female: 1-19g ethanol/day) and heavy (male: ≥40g; female: ≥20g ethanol/day) drinkers based on self-reported drinking habits. We used a pyrosequencing assay to determine TXNIP DNA methylation levels in leukocytes. Results Among men, the mean TXNIP DNA methylation level in heavy drinkers (73.2%) was significantly lower than that in non- and moderate drinkers (non: 76.7%, p&amp;lt;0.001; moderate: 75.8%, p=0.024). In multiple linear regression analysis adjusted for confounding factors, TXNIP DNA methylation levels showed significant negative association with alcohol consumption per day and cumulative alcohol consumption in male current drinkers. Conclusions We found that heavy drinkers had TXNIP DNA hypomethylation compared to non- and moderate drinkers in men. Moreover, alcohol consumptions were also negatively associated with TXNIP DNA methylation levels in male current drinkers. Key messages Heavy drinkers had decreased levels of TXNIP DNA methylation compared to non- and moderate drinkers in men.

The longitudinal associations between trajectory of and quantity of alcohol consumption and subsequent changes in blood pressure levels among non-hypertensive adults.

Given the dynamic characteristic of an individual's drinking behaviours, comprehensive consideration of alcohol consumption variation using repeated measures may improve insight into the nature of its association with blood pressure (BP) change. We examined the association between longitudinal alcohol consumption (trajectory and quantity) and changes in BP and pulse pressure (PP) among Korean aged ≥ 40 years living in rural areas. Totally, 1682 hypertension-free participants who completed all three health examinations (median, 5·3 years) were included. All three visits were used to determine the cumulative trajectory of and quantity of alcohol consumption and the latest two visits and the last visit were used for the recent trajectory and the most recent quantity of alcohol consumption, respectively. Changes in BP and PP from the baseline to the third visit were used as outcome. In men, ≥30 ml/d cumulative average alcohol consumption was associated with the greatest increase in systolic BP (SBP) in both baseline outcome-unadjusted (2·9 mmHg, P = 0·032) and -adjusted models (3·6 mmHg, P = 0·001), and the given association for the most recent alcohol consumption was observed in the baseline outcome-adjusted model (3·9 mmHg, P = 0·003). For PP, similar associations were observed only in the baseline outcome-adjusted model. No meaningful associations in diastolic BP in men and any BP or PP in women existed. The quantity of alcohol consumption rather than the trajectory may be significantly related to raised SBP, and a possible short-term influence of the most recent alcohol consumption may exist when baseline SBP is adjusted in men.

Associations between daily alcohol consumption and systemic lupus erythematosus-related cytokines and chemokines among US female nurses without SLE.

Moderate alcohol consumption has been associated with decreased systemic lupus erythematosus risk, but the biologic basis for this association is unknown. We aimed to determine whether moderate alcohol consumption was associated with lower concentrations of systemic lupus erythematosus-associated chemokines/cytokines in an ongoing cohort of female nurses without systemic lupus erythematosus, and whether the association was modified by the presence of systemic lupus erythematosus-related autoantibodies. About 25% of participants from the Nurses' Health Study (n = 121,700 women) and Nurses' Health Study 2 (n = 116,429) donated a blood sample; of these, 1177 women were without systemic lupus erythematosus at time of donation. Cumulative average and current (within 4 years) intakes of beer, wine or liquor were assessed from pre-blood draw questionnaires. Chemokine/cytokine concentrations (stem cell factor, B-lymphocyte stimulator, interferon-inducible protein-10, interferon-alpha, interleukin-10) and antibodies against dsDNA and extractable nuclear antigens were obtained using enzyme-linked immunosorbent assays. Antinuclear antibodies were detected by indirect immunofluorescence on HEp-2 cells. At blood draw, the women's mean age was 56 years and 22% were antinuclear antibody positive; 36% were African-American. About half (46%) reported consuming 0-5 g/day of alcohol. Stem cell factor levels were 0.5% lower (p < 0.0001) for every gram per day increase in cumulative average alcohol consumption. Women who consumed >5 g/day had mean stem cell factor levels 7% lower (p = 0.002) than non-drinkers. Other cytokines were not significantly associated with alcohol intake. Autoantibody status did not modify observed associations. In this study of female nurses, moderate alcohol consumption was associated with lower stem cell factor levels, suggesting a plausible mechanism through which alcohol may lower systemic lupus erythematosus risk might be by decreasing circulating stem cell factor.

Cumulative alcohol consumption and stroke risk in men.

Views on the relationship between alcohol consumption and stroke risk remain controversial. Moreover, data on cumulative alcohol intake are limited. We examined the potential impact of cumulative alcohol consumption on the risk of total stroke and its subtypes in men. This prospective study included 23,433 men from the Kailuan Study. Cumulative alcohol consumption was taken as the primary exposure by calculating self-reported alcohol consumption from three consecutive examinations (in 2006, 2008, and 2010). The first occurrence of stroke was confirmed by reviewing medical records from 2010 to 2016. We used Cox proportional hazards regression to analyze the data. During the 5.9 ± 0.8years of follow-up, 678 total strokes were identified, including 595 ischemic stroke (IS), 90 intracerebral hemorrhage and 19 subarachnoid hemorrhage cases. The adjusted hazard ratios (95% confidence intervals) of total stroke for light, moderate and heavy cumulative alcohol consumption were 1.23 (1.01-1.51), 1.49 (1.13-1.97), and 1.50 (1.21-1.86), respectively, compared with those of nondrinkers. The results were similar for IS. Cumulative alcohol consumption was not associated with intracerebral hemorrhage risk (hazard ratio 1.46; 95% confidence interval, 0.74-2.08). Cumulative alcohol consumption is an independent risk factor of total stroke and IS in men in a community-based cohort. Even light alcohol intake increases the risk of total stroke and IS.

Association Between Alcohol Intake and Cardiac Remodeling

BackgroundAlcohol-induced cardiotoxicity is incompletely understood. Specifically, the long-term impact of alcohol use on ventricular remodeling or dysfunction, its modulators, and effect thresholds among young adults remain controversial. ObjectivesThe authors sought to evaluate a potential relationship between alcohol intake and cardiac remodeling, assessed by echocardiography, over 20 years of follow-up. MethodsAmong the CARDIA (Coronary Artery Risk Development in Young Adults) study cohort, the authors studied all subjects without baseline heart disorders who provided adequate information on their drinking habits and underwent echocardiographic evaluation at years 5 and 25 of the study. The echocardiographic outcomes were left ventricular (LV) ejection fraction, indexed LV end-diastolic volume and LV mass, and left atrial diameter. Participants were grouped according to their weighted-average weekly drinking habits. An additional analysis used the estimated cumulative alcohol consumption. Regression models and multivariable fractional polynomials were used to evaluate the association between alcohol consumption and the outcomes. ResultsAmong the 2,368 participants, alcohol consumption was an independent predictor of higher indexed LV mass (p = 0.014) and indexed LV end-diastolic volume (p = 0.037), regardless of sex. No significant relationship between alcohol intake and LV ejection fraction was found. Drinking predominantly wine was associated with less cardiac remodeling and there was a nonsignificant trend for a harmful effect of binge drinking. ConclusionsAfter 20 years of follow-up, alcohol intake was associated with adverse cardiac remodeling, although it was not related with LV systolic dysfunction in this initially healthy young cohort. Our results also suggest that drinking predominantly wine associates with less deleterious findings in cardiac structure.

Women and alcoholic liver disease - warning of a silent danger.

Alcohol use and 'social' drinking are increasing among the young and particularly in women. However, gender equity does not extend to the risk of alcohol-associated liver disease and alcoholic hepatitis, which are increased and often caused by as little as half as much cumulative alcohol consumption in women compared with men.

Influence of Alcohol Consumption on the Risk of Systemic Lupus Erythematosus Among Women in the Nurses' Health Study Cohorts.

Moderate alcohol consumption has antiinflammatory properties and is associated with reduced cardiovascular disease and rheumatoid arthritis risks. We investigated the association between alcohol consumption and systemic lupus erythematosus (SLE) risk among women followed in the Nurses' Health Study (NHS) cohorts. We conducted a prospective cohort analysis among 204,055 women in NHS (1980-2012) and NHSII (1989-2011) who were free of connective tissue disease and provided alcohol information at baseline. Alcohol consumption was assessed using a semiquantitative food frequency questionnaire every 2-4 years. We validated incident SLE through medical record review after self-report. Cox proportional hazards models estimated hazard ratios (HRs) for SLE based on cumulative average alcohol intake, adjusting for potential confounders. Results were meta-analyzed using DerSimonian and Laird random-effects models. We further investigated SLE risk associated with wine, beer, and liquor intake. We identified 125 incident SLE cases in NHS and 119 in NHSII. Mean ± SD age at SLE diagnosis was 55.8 ± 9.5 years in NHS and 43.4 ± 7.7 years in NHSII. Compared to no alcohol intake, the meta-analyzed multivariable HR for cumulative alcohol consumption ≥5 gm/day was 0.61 (95% confidence interval [95% CI] 0.41-0.89). When limiting alcohol exposure to >4 years prior to SLE diagnosis, the multivariable HR was similar: 0.61 (95% CI 0.41-0.91). Women who drank ≥2 servings/week of wine had significantly decreased SLE risk (HR 0.65, 95% CI 0.45-0.96) compared to women who did not drink wine. In these large prospective cohorts, we demonstrated an inverse association between moderate alcohol consumption (≥5 grams or 0.5 drink/day) and SLE risk in women.