Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease.

Alcohol-related liver disease (ARLD) represents a major public health burden. Identification of high-risk individuals would allow efficient targeting of public health interventions. Here, we show significant interactions between pattern of drinking, genetic predisposition (polygenic risk score, PRS) and diabetes mellitus, and risk of incident ARLD, in 312,599 actively drinking adults in UK Biobank. Binge and heavy binge drinking significantly increase the risk of alcohol-related cirrhosis (ARC), with higher genetic predisposition further amplifying the risk. Further, we demonstrate a pronounced interaction between heavy binge drinking and high PRS, resulting in a relative excess risk due to interaction (RERI) of 6.07. Diabetes consistently elevates ARC risk across all drinking and PRS categories, and showed significant interaction with both binge patterns and genetic risk. Overall, we demonstrate synergistic effects of binge drinking, genetics, and diabetes on ARC, with potential to identify high-risk individuals for targeted interventions.

A comprehensive evaluation of the longitudinal association between alcohol consumption and a measure of inflammation: Multiverse and vibration of effects analyses.

BACKGROUND: Moderate alcohol consumption appears to be associated with reduced inflammation. Determining whether this association is robust to common variations in research parameters has wide-reaching implications for our understanding of disease aetiology and public health policy. We aimed to conduct comprehensive multiverse and vibration of effects analyses evaluating the associations between alcohol consumption and a measure of inflammation. METHODS: A secondary analysis of the 1970 British Birth Cohort Study was performed, using data from 1970 through 2016. Measurements of alcohol consumption were taken in early/mid-adulthood (ages 34 and 42), and level of inflammation marker high-sensitivity C-reactive protein (hsCRP) at age 46. Multiverse analyses were applied to comparisons of low-to-moderate consumption and consumption above various international drinking guidelines with an 'abstinent' reference. Research parameters of interest related to: definitions of drinking and reference groups; alcohol consumption measurement year; outcome variable transformation; and breadth of covariate adjustment. After identifying various analytic options within these parameters and running the analysis over each unique option combination, specification curve plots, volcano plots, effect ranges, and variance decomposition metrics were used to assess consistency of results. RESULTS: A total of 3101 individuals were included in the final analyses, with primary analyses limited to those where occasional consumers served as reference. All combinations of research specifications resulted in lower levels of inflammation amongst low-to-moderate consumers compared to occasional consumers (1st percentile effect: -0.21; 99th percentile effect: -0.04). Estimates comparing above-guidelines drinking with occasional consumers were less definitive (1st percentile effect: -0.26; 99th percentile effect: 0.43). CONCLUSIONS: The association between low-to-moderate drinking and lower hsCRP levels is largely robust to common variations in researcher-defined parameters, warranting further research to establish whether this relationship is causal. The association between above-guidelines drinking and hsCRP levels is less definitive.

Changes over time in the Chronic Liver Disease risk score predict liver-related outcomes: longitudinal analysis of the Whitehall II study.

BACKGROUND AND AIMS: The Chronic Liver Disease (CLivD) risk score was recently shown to predict future advanced liver disease in the general population. We here investigated the impact of individual CLivD-score changes over time. METHODS: Participants of both phase 3 (baseline, 1991-1994) and phase 5 (follow-up, 1997-1999) examinations of the Whitehall II study were followed for liver-related outcomes (hospitalization, cancer, death) until December 2019 through linkage with electronic healthcare registers. The CLivD score, its modifiable components (alcohol use, waist-hip ratio [WHR], diabetes, and smoking), and their individual changes were studied. RESULTS: Among 6590 adults (mean age 50 years, 30% women) with a median 21-year follow-up, there were 80 liver outcomes. A rise in the CLivD score between baseline and follow-up examinations significantly increased the risk for liver-related outcomes (adjusted hazard ratio [aHR] 1.62, 95% confidence interval [CI] 1.01-2.60), more so in subjects with baseline intermediate-high CLivD scores (HR 2.4 for a CLivD-change) compared to minimal-low CLivD scores. Adverse changes over time in alcohol use and WHR, and new-onset diabetes also predicted liver outcomes. In contrast to WHR, changes in body weight (kg) showed a U-shaped association with liver outcomes. CONCLUSIONS: A change in the CLivD score over time corresponds to a true change in the risk for liver-related outcomes, suggesting the usefulness of the CLivD score for assessing response to liver-directed lifestyle interventions. Changes in WHR predicted liver outcomes better than changes in body weight or waist circumference, independent of body mass index, supporting the WHR in assessing risk for future liver disease.

Alcohol Consumption and Adiposity: A Longitudinal Analysis of 45,399 UK Biobank Participants.

The evidence on the association between alcohol consumption and adiposity is inconsistent and fragmented. We investigated the longitudinal association between alcohol consumption pattern and four different adiposity markers with repeated measures of adiposity and obesity incidence. We categorized current drinkers based on the sex-specific quartiles of their weekly alcohol consumption and the UK alcohol drinking guidelines. We used multivariable adjusted generalised linear models. With the exception of a direct association between alcohol volume and body fat percentage (BF%) in women (B = 0.42%; 95%CI: 0.04, 0.80% for women in the top quartile), we found no associations between alcohol consumption and adiposity markers for either sex. Red wine and champagne/white wine consumption were inversely associated with waist circumference (WC) for both sexes (B = -0.58 cm, 95%CI: -0.77, -0.38 cm and B= -0.49 cm, 95%CI: -0.68, -0.29 cm, respectively, for women; B = -0.28 cm, 95%CI: -0.47, -0.08 cm and B = -0.23 cm, 95%CI: -0.42, -0.04 cm, respectively, for men). Female and male spirit drinkers had higher WC than non-spirit drinkers. Alcohol consumption was associated with a lower risk of obesity incidence in women (OR:0.60, 95%CI:0.45, 0.80 for the 2nd quartile, OR:0.53, 95%CI: 0.40, 0.70 for the 3rd quartile and OR:0.61, 95%CI:0.46, 0.80 for the 4th quartile). We found limited evidence of longitudinal associations between alcohol intake and adiposity. The few statistically significant associations we observed are unlikely to be of clinical importance.

Workplace interventions for cardiovascular diseases: protocol of a systematic review and meta-analysis.

INTRODUCTION: Cardiovascular diseases (CVDs) are the number one cause of death globally, impacting on public and private sectors. Current traditional interventions to prevent CVDs are mainly provided in healthcare centres and even when they are effective, they are not enough to reduce the rising prevalence; therefore, additional strategies are needed. Evidence suggests that health interventions in the workplace supply numerous benefits improving cardiovascular risk factor profiles in individuals. Hence, the aim of this systematic review and meta-analysis is to collate the evidence from randomised controlled trials, cluster randomised trials and quasi-experimental studies of workplace interventions to determine their effectiveness in terms of improving cardiovascular risk factors and preventing CVDs. METHODS AND ANALYSIS: EMBASE, PsycINFO, PubMed, the Cochrane Central Register of Controlled Trials, LILACS, Scopus, Web of Science, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov and ProQuest Dissertations & Theses Global will be searched to include articles on workplace interventions in adults for CVDs events, cardiometabolic risk factors or behavioural risk factors. The study selection, data extraction, risk of bias and the assessment of the quality of the body of evidence will be conducted by two reviewers working in parallel and disagreements will be resolved by consensus or consultations with a third reviewer. Data synthesis will be done by meta-analysis using random-effects models when possible, otherwise the vote counting method will be applied. Statistical heterogeneity will be assessed by a χ2 test and I2 statistics. The quality of the body of evidence for each outcome will be assessed by applying the Grading of Recommendations, Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review protocol. The results of the systematic review will be published in a peer-reviewed journal and will be publicly available. PROSPERO REGISTRATION NUMBER: CRD42021276161.

Attribution of diabetes to the development of severe liver disease in the general population.

BACKGROUND AND AIMS: Diabetes is associated with advanced liver disease and predicts mortality regardless of the primary aetiology of the liver disease. Even a family history of diabetes has been linked to advanced liver fibrosis in non-alcoholic fatty liver disease (NAFLD). However, the fraction of liver-related outcomes in the general population that are attributable to diabetes remains unclear. METHODS: The population attributable fraction (PAF) of diabetes for liver disease as a time-dependent exposure was estimated in the Finnish FINRISK study (n = 28 787) and the British Whitehall II study (n = 7855). We also assessed the predictive ability of a family history of diabetes for liver-related outcomes. Incident diabetes data were from drug purchase/reimbursement and healthcare registries (FINRISK) or follow-up examinations (Whitehall II). Incident severe liver outcomes were identified through linkage with national healthcare registries. RESULTS: Diabetes was associated with a two-fold risk of liver-related outcomes in both the FINRISK (HR, 1.92; p < .001) and Whitehall II (HR, 2.37; p < .001) cohorts, and this remained significant after adjusting for multiple confounders. PAF analyses demonstrated that diabetes explained 12-14% of the risk for severe liver-related outcomes after 10 and 20 years of follow-up. Also, maternal diabetes increased the risk of liver-related outcomes in the FINRISK (HR, 1.43; p = .044) and Whitehall II (HR, 2.04; p = .051) cohorts. CONCLUSION: Approximately 12%-14% of severe liver-related outcomes are attributable to diabetes at the population level. The association between maternal diabetes and liver disease might suggest a mitochondrial genetic mechanism.

Development and validation of a model to predict incident chronic liver disease in the general population: The CLivD score.

BACKGROUND & AIMS: Current screening strategies for chronic liver disease focus on detection of subclinical advanced liver fibrosis but cannot identify those at high future risk of severe liver disease. Our aim was to develop and validate a risk prediction model for incident chronic liver disease in the general population based on widely available factors. METHODS: Multivariable Cox regression analyses were used to develop prediction models for liver-related outcomes with and without laboratory measures (Modellab and Modelnon-lab) in 25,760 individuals aged 40-70 years. Their data were sourced from the Finnish population-based health examination surveys FINRISK 1992-2012 and Health 2000 (derivation cohort). The models were externally validated in the Whitehall II (n = 5,058) and Copenhagen City Heart Study (CCHS) (n = 3,049) cohorts. RESULTS: The absolute rate of incident liver outcomes per 100,000 person-years ranged from 53 to 144. The final prediction model included age, sex, alcohol use (drinks/week), waist-hip ratio, diabetes, and smoking, and Modellab also included gamma-glutamyltransferase values. Internally validated Wolbers' C-statistics were 0.77 for Modellab and 0.75 for Modelnon-lab, while apparent 15-year AUCs were 0.84 (95% CI 0.75-0.93) and 0.82 (95% CI 0.74-0.91). The models identified a small proportion (<2%) of the population with >10% absolute 15-year risk for liver events. Of all liver events, only 10% occurred in participants in the lowest risk category. In the validation cohorts, 15-year AUCs were 0.78 (Modellab) and 0.65 (Modelnon-lab) in the CCHS cohort, and 0.78 (Modelnon-lab) in the Whitehall II cohort. CONCLUSIONS: Based on widely available risk factors, the Chronic Liver Disease (CLivD) score can be used to predict risk of future advanced liver disease in the general population. LAY SUMMARY: Liver disease often progresses silently without symptoms and thus the diagnosis is often delayed until severe complications occur and prognosis becomes poor. In order to identify individuals in the general population who have a high risk of developing severe liver disease in the future, we developed and validated a Chronic Liver Disease (CLivD) risk prediction score, based on age, sex, alcohol use, waist-hip ratio, diabetes, and smoking, with or without measurement of the liver enzyme gamma-glutamyltransferase. The CLivD score can be used as part of health counseling, and for planning further liver investigations and follow-up.

Work Exposures and Development of Cardiovascular Diseases: A Systematic Review.

INTRODUCTION: Cardiovascular diseases (CVDs) are the number one cause of death, and there is evidence that work exposures could be associated with their development. This study aimed to systematically review observational studies of adults exposed to job strain, effort-reward imbalance, long working hours, job insecurity, shift work, and occupational noise, and assess the association of those work exposures with CVDs. METHODS: The Navigation Guide framework was applied. The population were adults of working age (18-65), and cohort and case-control studies were included. The work exposures were job strain, effort-reward imbalance, long working hours, job insecurity, shift work, and occupational noise. The outcomes were cerebrovascular diseases, ischaemic heart disease, and hypertensive diseases. The selection, data extraction, risk of bias assessment, and quality assessment were carried out by two reviewers independently and disagreements were solved by a third reviewer or by consensus. The synthesis of the results was done by applying the 'vote counting based on direction' method, and the results were summarized in an effect direction plot. The strength of the evidence for every risk factor and CVD was defined by consensus. RESULTS: A total of 17 643 papers were initially identified in the literature search, but after applying the filters by title and abstract, and full text, 86 studies were finally included. From the included studies, sufficient evidence was found of the harmfulness of job strain for cerebrovascular disease and ischemic heart disease. Furthermore, there was sufficient evidence of the harmfulness of shift work for ischemic heart disease. Evidence of no relationship was found between long working hours and shift work with ischaemic heart disease and hypertensive disease, respectively. The other associations of work exposures and CVDs had limited or inadequate evidence of harmfulness. CONCLUSIONS: In this comprehensive review, there was sufficient evidence of a harmful relationship between job strain, shift work, and CVDs. For the other work exposures, more high-quality studies are needed. In order to improve current prevention strategies for CVDs, the findings of this review imply that job strain and shift work are work exposures that constitute additional risk factors that could be approached as targets for worksite interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020179972.

Alcohol intake and mortality risk of COVID-19, pneumonia, and other infectious diseases: An analysis of 437191 UK biobank participants.

This study aims to investigate the association between alcohol consumption and COVID-19, infectious diseases, and pneumonia mortality. This is a prospective analysis of 437,191 UK Biobank participants (age 56.3 years, 54% female). The main exposure was self-reported alcohol consumption. In addition to never and previous drinkers, we applied quartiles-based and UK guidelines-based criteria to divide current drinkers by weekly consumption into four groups. Outcomes included COVID-19, infectious diseases, and pneumonia mortality, obtained from the national death registries until May 2020. After an 11-year follow-up, compared to never drinkers, previous drinkers had higher mortality risks of infectious diseases and pneumonia (adjusted HR: 1.29 [95% CI 1.06-1.57] and 1.35 [1.07-1.70], respectively), but not COVID-19. There was a curvilinear association of alcohol consumption with infectious diseases and pneumonia mortality. Drinking within-guidelines (<14 UK units/wk) and amounts up to double the recommendation (14 to < 28 UK units/wk) was associated with the lowest mortality risks of infectious diseases (0.70 [0.59-0.83] and 0.70 [0.59-0.83], respectively) and pneumonia (0.71 [0.58-0.87] and 0.72 [0.58-0.88], respectively). Alcohol consumption was associated with lower risks of COVID-19 mortality (e.g., drinking within-guidelines: 0.53 [0.33-0.86]). Drinkers reporting multiples of the recommended alcohol drinking amounts did not have higher mortality risks of COVID-19 and other infectious diseases than never drinkers. Despite the well-established unfavorable effects on general health, we found no deleterious associations between alcohol consumption and the risk of infectious diseases, including COVID-19. Future research with other study designs is needed to confirm the causality.

Trajectories of alcohol consumption in relation to all-cause mortality in patients with cardiovascular disease: a 35-year prospective cohort study.

BACKGROUND AND AIMS: Research into alcohol consumption and cardiovascular disease (CVD) patients' prognosis has largely ignored the longitudinal dynamics in drinking behaviour. This study measured the association between alcohol consumption trajectories and mortality risk in CVD patients. DESIGN: Prospective cohort study. SETTING: UK-based Whitehall II Study. PARTICIPANTS: A total of 1306 participants with incident non-fatal CVD (coronary heart disease/stroke) events. MEASUREMENTS: Up to eight repeated measures of alcohol intake were available for each patient from the most recent assessment phase pre-incident CVD and all subsequent phases post-incident CVD, spanning up to three decades. Six trajectory groups of alcohol consumption were identified using group-based trajectory modelling and related to the risk of all-cause mortality, adjusting for demographics and changes in life-style and health status. FINDINGS: Three hundred and eighty deaths were recorded during a median follow-up of 5 years after patients' last alcohol assessment. Compared with patients who consistently drank moderately (≤ 14 units/week), former drinkers had a greater risk of mortality (hazard ratio = 1.74, 95% confidence interval = 1.19-2.54) after adjustment for covariates. There was no significantly increased risk of mortality in long-term abstainers, reduced moderate drinkers, stable or unstable heavy drinkers. Cross-sectional analyses based only on drinking information at patients' last assessment found no significant differences in mortality risk for abstainers, former or heavy drinkers versus moderate drinkers. CONCLUSIONS: Cardiovascular disease patients who consistently drink ≤ 14 units/week appear to have a similar risk of mortality to those who are long-term abstainers, which does not support a protective effect of moderate drinking on total mortality. Cardiovascular disease patients who stop drinking appear to have increased mortality risk compared with continuous moderate drinkers, but this may be linked to poor self-rated health before cardiovascular disease onset.

QRS micro-fragmentation as a mortality predictor.

AIMS: Fragmented QRS complex with visible notching on standard 12-lead electrocardiogram (ECG) is understood to represent depolarization abnormalities and to signify risk of cardiac events. Depolarization abnormalities with similar prognostic implications likely exist beyond visual recognition but no technology is presently suitable for quantification of such invisible ECG abnormalities. We present such a technology. METHODS AND RESULTS: A signal processing method projects all ECG leads of the QRS complex into optimized three perpendicular dimensions, reconstructs the ECG back from this three-dimensional projection, and quantifies the difference (QRS 'micro'-fragmentation, QRS-µf) between the original and reconstructed signals. QRS 'micro'-fragmentation was assessed in three different populations: cardiac patients with automatic implantable cardioverter-defibrillators, cardiac patients with severe abnormalities, and general public. The predictive value of QRS-µf for mortality was investigated both univariably and in multivariable comparisons with other risk factors including visible QRS 'macro'-fragmentation, QRS-Mf. The analysis was made in a total of 7779 subjects of whom 504 have not survived the first 5 years of follow-up. In all three populations, QRS-µf was strongly predictive of survival (P < 0.001 univariably, and P < 0.001 to P = 0.024 in multivariable regression analyses). A similar strong association with outcome was found when dichotomizing QRS-µf prospectively at 3.5%. When QRS-µf was used in multivariable analyses, QRS-Mf and QRS duration lost their predictive value. CONCLUSION: In three populations with different clinical characteristics, QRS-µf was a powerful mortality risk factor independent of several previously established risk indices. Electrophysiologic abnormalities that contribute to increased QRS-µf values are likely responsible for the predictive power of visible QRS-Mf.

Sex differences in functional limitations and the role of socioeconomic factors: a multi-cohort analysis.

BACKGROUND: Women are more likely to have functional limitations than are men, partly because of greater socioeconomic disadvantage. However, how sex differences vary by severity of functional limitations remains unclear. We examined sex differences in functional limitations, with attention to socioeconomic factors and severity of limitations. METHODS: Longitudinal data on limitations in basic activities of daily living (ADL) and instrumental activities of daily living (IADL) and mobility activities were drawn from 62 375 participants from 14 countries. For ADL, IADL, and mobility, participants were categorised based on number of limited activities (0, 1, 2, or ≥3). Sex differences in limitations in four birth cohorts (1895-1929, 1930-38, 1939-45, and 1946-60) were analysed before and after adjustment for socioeconomic factors (education and labour force status). FINDINGS: The prevalence of IADL and ADL limitations was higher in women than in men. After adjustment for socioeconomic factors, this sex difference was attenuated. The sex difference in IADL limitations at age 75 years (in the 1895-1929 cohort) was 3·7% before adjustment for socioeconomic factors (95% CI 2·6-4·7) and 1·7% (1·1-2·2) after adjustment. For ADL, the sex difference in limitations at age 75 years (in the 1895-1929 cohort) was 3·2% (2·3-4·1) before adjustment for socioeconomic factors and 1·4% (0·9-1·8) after adjustment. Sex differences in mobility limitations (16·1%, 95% CI 14·4-17·7) remained after adjustment for socioeconomic factors (14·3%, 12·7-15·9). After age 85 years, women were more likely to have three or more IADL or mobility limitations and men were more likely to have one or two limitations. INTERPRETATION: Socioeconomic factors largely explain sex differences in IADL and ADL limitations but not mobility. Sex differences in mobility limitations in midlife are important targets for future research and interventions. FUNDING: National Institute on Aging, UK National Institute for Health Research, European Commission, and US Social Security Administration.

Trajectories of alcohol consumption up to 30 years before and after the diagnosis of cardiovascular diseases: a longitudinal case-control study of 12 502 participants.

BACKGROUND: To examine the longitudinal trajectories of alcohol consumption prior to and following the diagnosis of cardiovascular diseases (CVD). METHODS: We conducted a case-control study of 2501 incident cases of angina, myocardial infarction or stroke and 10 001 matched controls without the condition. Repeated measures of alcohol were centred on the date of diagnosis, spanning up to 30 years before and after CVD onset. Mean trajectories of weekly consumption were estimated using growth curve models. RESULTS: For trajectories prior to diagnosis, mean volume of alcohol consumed among male cases increased over time, peaking at around 8 years before diagnosis at 95 (95% CI 60 to 130) g/week and declining afterwards. Trajectories following diagnosis showed mean consumption in male cases dropped from 87 (95% CI 54 to 120) g/week to 74 (95% CI 45 to 102) g/week after the date of diagnosis and then slightly rose to 78 (95% CI 40 to 116) g/week at the subsequent 3.5 years, before gradually declining to 31 (95% CI 2 to 61) g/week at 30 years after diagnosis. Mean consumption among female cases remained stable prior to diagnosis (at about 30 g/week), fell marginally to 25 (95% CI 20 to 30) g/week after the date of diagnosis and kept decreasing afterwards. Similar trajectories were obtained in cases and controls. CONCLUSIONS: This is the first attempt to show how patients with CVD change their drinking volume over such a wide time span. Future research needs to establish insight into drinking behaviour in other ways (such as frequency and context) and address the impact of changes in drinking on patients with CVD.

Association of alcohol consumption with morbidity and mortality in patients with cardiovascular disease: original data and meta-analysis of 48,423 men and women.

BACKGROUND: Light-to-moderate alcohol consumption has been reported to be cardio-protective among apparently healthy individuals; however, it is unclear whether this association is also present in those with disease. To examine the association between alcohol consumption and prognosis in individuals with pre-existing cardiovascular disease (CVD), we conducted a series of meta-analyses of new findings from three large-scale cohorts and existing published studies. METHODS: We assessed alcohol consumption in relation to all-cause mortality, cardiovascular mortality, and subsequent cardiovascular events via de novo analyses of 14,386 patients with a previous myocardial infarction, angina, or stroke in the UK Biobank Study (median follow-up 8.7 years, interquartile range [IQR] 8.0-9.5), involving 1640 deaths and 2950 subsequent events, and 2802 patients and 1257 deaths in 15 waves of the Health Survey for England 1994-2008 and three waves of the Scottish Health Survey 1995, 1998, and 2003 (median follow-up 9.5 years, IQR 5.7-13.0). This was augmented with findings from 12 published studies identified through a systematic review, providing data on 31,235 patients, 5095 deaths, and 1414 subsequent events. To determine the best-fitting dose-response association between alcohol and each outcome in the combined sample of 48,423 patients, models were constructed using fractional polynomial regression, adjusting at least for age, sex, and smoking status. RESULTS: Alcohol consumption was associated with all assessed outcomes in a J-shaped manner relative to current non-drinkers, with a risk reduction that peaked at 7 g/day (relative risk 0.79, 95% confidence interval 0.73-0.85) for all-cause mortality, 8 g/day (0.73, 0.64-0.83) for cardiovascular mortality and 6 g/day (0.50, 0.26-0.96) for cardiovascular events, and remained significant up to 62, 50, and 15 g/day, respectively. No statistically significant elevated risks were found at higher levels of drinking. In the few studies that excluded former drinkers from the non-drinking reference group, reductions in risk among light-to-moderate drinkers were attenuated. CONCLUSIONS: For secondary prevention of CVD, current drinkers may not need to stop drinking. However, they should be informed that the lowest risk of mortality and having another cardiovascular event is likely to be associated with lower levels of drinking, that is up to approximately 105g (or equivalent to 13 UK units, with one unit equal to half a pint of beer/lager/cider, half a glass of wine, or one measure of spirits) a week.

Use of AUDIT-C alcohol screening tool in NHS general dental practices in North London.

Background The numerous health risks of excessive alcohol consumption are well documented. Individuals at risk of harm from alcohol consumption can be identified through alcohol screening tools; however, there is limited research regarding their use in general dental practices.Methods Data were collected as part of a feasibility trial evaluating delivery of brief alcohol advice in general dental practices in North London. Patient demographics and health-related behaviours were collected, and the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) tool was used to assess alcohol consumption patterns.Results The analytical sample comprised 552 dental patients, of whom approximately half (46%) were drinking alcohol at hazardous levels. Males, younger adults, those who consumed red meat weekly and smokers all had significantly increased risks of excessive alcohol consumption. Smokers were more likely to consume excessive levels of alcohol irrespective of smoking frequency. Notable sex differences in alcohol consumption were identified, with males being more likely to consume alcohol frequently and in larger quantities than females.Conclusion The AUDIT-C tool can be used in general dental practice to screen for harmful levels of alcohol consumption. Clear associations exist between patient demographics, health behaviours and excessive alcohol consumption.

Sex differences and the role of education in cognitive ageing: analysis of two UK-based prospective cohort studies.

BACKGROUND: Previous studies have shown an excess risk of Alzheimer's disease and related dementias among women. Education is thought to have a causal association with dementia onset. We aimed to investigate the role of education in influencing sex differences in cognitive ageing. METHODS: We analysed data from two prospective cohort studies in the UK; the English Longitudinal Study of Ageing (ELSA) and the Whitehall II study, to assess sex differences in cognitive performance and cognitive decline by birth cohort (birth year 1930-38, 1939-45, or 1946-55), before and after adjustment for education, and by high and low education level. Memory was assessed using immediate recall, for which data were available from all waves of the ELSA (2002-14) and Whitehall II (1997-2015) studies. Fluency was assessed using a semantic fluency test based on an animal naming task, with data available from all waves of the Whitehall II study and waves one to five (2002-10) and wave seven (2014) of the ELSA study. Cognitive scores were standardised separately in each study based on the mean and SD of the corresponding test among participants aged 50-59 years with secondary education. FINDINGS: 15 924 participants were included from the two studies. In pooled analyses, women had better memory scores than men in all birth cohorts, irrespective of adjustment for education (eg, at age 60 years, birth cohort 1930-38, mean difference between sexes [male scores minus female scores] -0·25 SDs [95% CI -0·32 to -0·19] after adjustment for education), and in both education level groups. Memory decline was faster in men than in women (at age 60 years, birth cohort 1946-55, mean difference in 13-year change -0·15 SDs [-0·20 to -0·09]; after adjustment for education -0·14 SDs [-0·20 to -0·08]). Men had better fluency scores than women in earlier birth cohorts and in the low education group (at age 60 years, birth cohort 1930-38, mean difference 0·20 SDs [95% CI 0·05 to 0·36]); but women had better fluency scores than men in later birth cohorts and in the high education group (at age 60 years, birth cohort 1946-55, mean difference -0·17 SDs [-0·24 to -0·10]). No sex differences were observed for fluency decline. INTERPRETATION: Our findings suggest that decreasing disparities between sexes in education, due to secular increases in educational opportunities, could attenuate sex differences in dementia risk and cognitive decline in the future. FUNDING: National Institute on Aging, National Institutes of Health; UK Medical Research Council; British Heart Foundation; and National Institute for Health Research.

Sustained heavy drinking over 25 years is associated with increased N-terminal-pro-B-type natriuretic peptides in early old age: Population-based cohort study.

Heavy alcohol consumption is associated with an increased risk of heart failure. We sought to investigate whether levels of NT-proBNP differ by alcohol consumption profiles, both current drinking as well as cumulative exposure to drinking over several decades in a general population sample. METHODS: Data on 2054 participants (49% male) were taken from the UK Medical Research Council National Survey for Health and Development, a longitudinal cohort study based on a nationally representative sample of births in 1946. Categories of long-term alcohol consumption were created based on consumption over 25 years of observations and compared with levels of NT-proBNP measured at mean age 63. RESULTS: We found that those who drank heavily (both currently and long-term) had higher levels of NT-proBNP than moderate drinkers, after adjusting for major confounders (age, sex, socio-economic position and smoking). As NT-proBNP has attracted attention as a biomarker for heart failure, this suggests a critical pathway through which heavy drinking may increase risk of this cardiovascular disease. When we looked at heavy drinkers who varied their intake over the decades, it was only the recently heavy group that had higher levels of NT-proBNP. Further work is needed to demonstrate whether effects are reversible upon cessation of heavy drinking, but this finding highlights the need to have repeated data to unpack dynamics over time. CONCLUSION: Our findings suggest heavy drinkers could be screened for NT-proBNP levels in order to identify those at high risk earlier in the clinical stages of heart failure and targeted for risk reduction strategies.

A life-time of hazardous drinking and harm to health among older adults: findings from the Whitehall II prospective cohort study.

AIMS: To investigate associations of life-time hazardous and binge drinking with biomarkers of cardiometabolic health, liver function, cardiovascular disease (CVD) and mortality. DESIGN: Prospective cohort study with median follow-up time to CVD incidence of 4.5 years. SETTING: London, UK: civil servants within the Whitehall II Study. PARTICIPANTS: A total of 4820 drinkers aged 59-83 years with biological measurements during the 2011-12 survey. MEASUREMENTS: Hazardous drinking was defined as having an AUDIT-C score ≥ 5 calculated at each decade of life, forming the following groups: never hazardous drinker, former early (stopping before age 50), former later (stopping after age 50), current hazardous drinker and consistent hazardous drinker (hazardous drinker at each decade of life). FINDINGS: More than half the sample had been hazardous drinkers at some point during their life-time, comprising former early (< age 50) (19%), former later (≥ age 50) (11%), current (21%) and consistent hazardous drinker (AUDIT-C ≥ 5 across life (5%). After adjusting for covariates, waist circumference was larger with more persistent hazardous drinking (e.g. compared with never hazardous drinkers, former early had increased waist circumference by 1.17 cm [95% confidence interval (CI) = 0.25-2.08]; former later by 1.88 cm (CI = 0.77-2.98); current by 2.44 cm (CI = 1.50-3.34) and consistent hazardous drinker by 3.85 cm (CI = 2.23-5.47). Current hazardous drinkers had higher systolic blood pressure (2.44 mmHg, CI = 1.19-3.68) and fatty liver index scores (4.05 mmHg, CI = 2.92-5.18) than never hazardous drinkers. Current hazardous drinkers [hazard ratio (HR) = 2.75, CI = 1.44-5.22) had an elevated risk of stroke, and former later hazardous drinkers had an elevated risk of non-CVD mortality (HR = 1.93, CI = 1.19-3.14) than never hazardous drinkers. Life-time binge drinking was associated with larger waist circumferences and poorer liver function compared with never binge drinkers. CONCLUSION: Hazardous drinking may increase cardiometabolic risk factors; this is made worse by persistent hazardous drinking throughout life, particularly in relation to weight gain, suggesting benefits of early intervention.

The association between alcohol consumption and sleep disorders among older people in the general population.

The relationship between alcohol consumption and sleep disturbance is complex. The association of alcohol dependence with insomnia is likely to be bidirectional in nature. Alcohol use is common among older people in many societies and the prevalence of insomnia tends to increase with age, therefore this group warrants particular consideration. We explored the cross sectional and long term (30 years) associations between alcohol drinking (volume and hazardous drinking) and sleep duration and insomnia in a general population study of older adults (6,117 male and female civil servants followed for 30 years). For men, drinking more than 21 units (approximately 168 grams) of alcohol per week, compared with not drinking, was associated with waking several times a night (odds ratio 1.30, confidence intervals 1.02-1.66). Men who maintained a heavy volume of drinking over the three decades of observation, or who had an unstable consumption pattern, tended to have worse sleep profiles in terms of waking tired and waking several times. Sustained male hazardous drinking (as measured by the AUDIT-C scale) was also associated with worse sleep profiles. Findings for women were not so clear. In this population based setting, drinking high volumes of alcohol may contribute to the prevalence of sleep problems in older age, particularly for men. People in this age group should be discouraged from using alcohol as a sleep aid.

Healthy Lifestyle and Cardiac Vagal Modulation Over 10 Years: Whitehall II Cohort Study.

Background Increased vagal modulation is a mechanism that may partially explain the protective effect of healthy lifestyles. However, it is unclear how healthy lifestyles relate to vagal regulation longitudinally. We prospectively examined associations between a comprehensive measure of 4 important lifestyle factors and vagal modulation, indexed by heart rate variability (HRV) over 10 years. Methods and Results The fifth (1997-1999), seventh (2002-2004), and ninth (2007-2009) phases of the UK Whitehall II cohort were analyzed. Analytical samples ranged from 2059 to 3333 (mean age: 55.7 years). A healthy lifestyle score was derived by giving participants 1 point for each healthy factor: physically active, not smoking, moderate alcohol consumption, and healthy body mass index. Two vagally mediated HRV measures were used: high-frequency HRV and root mean square of successive differences of normal-to-normal R-R intervals. Cross-sectionally, a positively graded association was observed between the healthy lifestyle score and HRV at baseline (Poverall≤0.001). Differences in HRV according to the healthy lifestyle score remained relatively stable over time. Compared with participants who hardly ever adhered to healthy lifestyles, those with consistent healthy lifestyles displayed higher high-frequency HRV (ß=0.23; 95% CI, 0.10-0.35; P=0.001) and higher root mean square of successive differences of normal-to-normal R-R intervals (ß=0.15; 95% CI, 0.07-0.22; P≤0.001) at follow-up after covariate adjustment. These differences in high-frequency HRV and root mean square of successive differences of normal-to-normal R-R intervals are equivalent to ≈6 to 20 years differences in chronological age. Compared with participants who reduced their healthy lifestyle scores, those with stable scores displayed higher subsequent high-frequency HRV (ß=0.24; 95% CI, 0.01-0.48; P=0.046) and higher root mean square of successive differences of normal-to-normal R-R intervals (ß=0.15; 95% CI, 0.01-0.29; P=0.042). Conclusions Maintaining healthy lifestyles is positively associated with cardiac vagal functioning, and these beneficial adaptations may be lost if not sustained.