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.

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.

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.

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.

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.

The stability of health-related behaviour clustering during mid-adulthood and the influence of social circumstances on health-related behaviour change.

Evidence suggests that health-related behaviours (HRBs) cluster in mid-adulthood and are associated with social circumstances (i.e. economic circumstances, cultural norms, employment relations) at the same age. However, little is known about the level of stability in HRB cluster membership during mid-adulthood and how social circumstances in early mid-adulthood may influence movement between HRB clusters during mid-life. Data were taken from a British cohort born in 1958 (N = 12,784), to examine the stability of membership of three HRB clusters: 'Risky', 'Moderate Smokers' and 'Mainstream' (the latter pattern consisting of more beneficial HRBs such as not smoking, moderate alcohol consumption, being physically active), between ages 33 and 42. The relationship between social circumstances at age 33 and movement between HRB clusters during mid-adulthood was also examined. HRB cluster membership was relatively stable during mid-adulthood, over 60% of the participants remained in the same cluster at both ages. However, there was considerable probability of movement from the 'Risky' and 'Moderate Smokers' clusters at age 33 to the 'Mainstream' cluster at age 42. Members of the 'Risky' cluster had a lower probability of transitioning to the 'Mainstream' cluster (men = 17%, women = 9%, p < 0.001) in comparison to the 'Moderate Smokers' cluster (men = 26%, women = 27%, p < 0.001). Social circumstances at age 33 did not influence change in HRB cluster membership between ages 33 and 42 (p > 0.05). Movement from the 'Risky' and 'Moderate Smokers' cluster to the 'Mainstream' cluster during mid-adulthood highlights improvements for most HRBs. Person-centred interventions are required to prevent persistent negative HRBs amongst 'Risky' cluster members.

Alcohol Screening and Brief Advice in NHS General Dental Practices: A Cluster Randomized Controlled Feasibility Trial.

AIM: To assess the feasibility and acceptability of screening for alcohol misuse and delivering brief advice to eligible patients attending NHS dental practices in London. METHODS: A two-arm cluster randomized controlled feasibility trial was conducted. Twelve dental practices were recruited and randomized to intervention and control arms. Participants attending for a dental check were recruited into the study and were eligible if they consumed alcohol above recommended levels assessed by the AUDIT-C screening tool. All eligible participants were asked to complete a baseline socio-demographic questionnaire. Six months after the completion of baseline measures, participants were contacted via telephone by a researcher masked to their allocation status. The full AUDIT tool was then administered. Alcohol consumption in the last 90 days was also assessed using the Form 90. A process evaluation assessed the acceptability of the intervention. RESULTS: Over a 7-month period, 229 participants were recruited (95.4% recruitment rate) and at the 6 months follow-up, 176 participants were assessed (76.9% retention rate). At the follow-up, participants in the intervention arm were significantly more likely to report a longer abstinence period (3.2 vs. 2.3 weeks respectively, P = 0.04) and non-significant differences in AUDIT (44.9% vs. 59.8% AUDIT positive respectively, P = 0.053) and AUDIT C difference between baseline and follow-up (-0.67 units vs. -0.29 units respectively, P = 0.058). Results from the process evaluation indicated that the intervention and study procedures were acceptable to dentists and patients. CONCLUSIONS: This study has demonstrated the feasibility and acceptability of dentists screening for alcohol misuse and providing brief advice.

Association of longitudinal alcohol consumption trajectories with coronary heart disease: a meta-analysis of six cohort studies using individual participant data.

BACKGROUND: Studies have shown that alcohol intake trajectories differ in their associations with biomarkers of cardiovascular functioning, but it remains unclear if they also differ in their relationship to actual coronary heart disease (CHD) incidence. Using multiple longitudinal cohort studies, we evaluated the association between long-term alcohol consumption trajectories and CHD. METHODS: Data were drawn from six cohorts (five British and one French). The combined analytic sample comprised 35,132 individuals (62.1% male; individual cohorts ranging from 869 to 14,247 participants) of whom 4.9% experienced an incident (fatal or non-fatal) CHD event. Alcohol intake across three assessment periods of each cohort was used to determine participants' intake trajectories over approximately 10 years. Time to onset for (i) incident CHD and (ii) fatal CHD was established using surveys and linked medical record data. A meta-analysis of individual participant data was employed to estimate the intake trajectories' association with CHD onset, adjusting for demographic and clinical characteristics. RESULTS: Compared to consistently moderate drinkers (males: 1-168 g ethanol/week; females: 1-112 g ethanol/week), inconsistently moderate drinkers had a significantly greater risk of incident CHD [hazard ratio (HR) = 1.18, 95% confidence interval (CI) = 1.02-1.37]. An elevated risk of incident CHD was also found for former drinkers (HR = 1.31, 95% CI = 1.13-1.52) and consistent non-drinkers (HR = 1.47, 95% CI = 1.21-1.78), although, after sex stratification, the latter effect was only evident for females. When examining fatal CHD outcomes alone, only former drinkers had a significantly elevated risk, though hazard ratios for consistent non-drinkers were near identical. No evidence of elevated CHD risk was found for consistently heavy drinkers, and a weak association with fatal CHD for inconsistently heavy drinkers was attenuated following adjustment for confounding factors. CONCLUSIONS: Using prospectively recorded alcohol data, this study has shown how instability in drinking behaviours over time is associated with risk of CHD. As well as individuals who abstain from drinking (long term or more recently), those who are inconsistently moderate in their alcohol intake have a higher risk of experiencing CHD. This finding suggests that policies and interventions specifically encouraging consistency in adherence to lower-risk drinking guidelines could have public health benefits in reducing the population burden of CHD. The absence of an effect amongst heavy drinkers should be interpreted with caution given the known wider health risks associated with such intake. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03133689 .

Social influences on health-related behaviour clustering during adulthood in two British birth cohort studies.

Building upon evidence linking socio-economic position (SEP) in childhood and adulthood with health-related behaviours (HRB) in adulthood, we examined how pre-adolescent SEP predicted membership of three HRB clusters: "Risky", "Moderate Smokers" and "Mainstream" (the latter pattern consisting of more beneficial HRBs), that were detected in our previous work. Data were taken from two British cohorts (born in 1958 and 1970) in pre-adolescence (age 11 and 10, respectively) and adulthood (age 33 and 34). SEP constructs in pre-adolescence and adulthood were derived through Confirmatory Factor Analysis. Conceptualised paths from pre-adolescent SEP to HRB cluster membership via adult SEP in our path models were tested for statistical significance separately by gender and cohort. Adult SEP mediated the path between pre-adolescent SEP and adult HRB clusters. More disadvantaged SEP in pre-adolescence predicted more disadvantaged SEP in adulthood which was associated with membership of the "Risky" and "Moderate Smokers" clusters compared to the "Mainstream" cluster. For example, large positive indirect effects between pre-adolescent SEP and adult HRB via adult SEP were present (coefficient 1958 Women = 0.39; 1970 Women = 0.36, 1958 Men = 0.51; 1970 Men = 0.39; p < 0.01) when comparing "Risky" and "Mainstream" cluster membership. Amongst men we found a small significant direct association (p < 0.001) between pre-adolescent SEP and HRB cluster membership. Our findings suggest that associations between adult SEP and HRBs are not likely to be pre-determined by earlier social circumstances, providing optimism for interventions relevant to reducing social gradients in HRBs. Observing consistent findings across the cohorts implies the social patterning of adult lifestyles may persist across time.

Validity of Cardiovascular Disease Event Ascertainment Using Linkage to UK Hospital Records.

BACKGROUND: Use of electronic health records for ascertainment of disease outcomes in large population-based studies holds much promise due to low costs, diminished study participant burden, and reduced selection bias. However, the validity of cardiovascular disease endpoints derived from electronic records is unclear. METHODS: Participants were 7860 study members of the UK Whitehall II cohort study. We compared cardiovascular disease ascertainment using linkage to the National Health Service's Hospital Episode Statistics database records (hereafter, "HES-ascertainment") against repeated biomedical examinations-our gold standard ascertainment method (Whitehall-ascertainment). Follow-up for both methods was from 1997 to 2013 for coronary heart disease and from 1997 to 2009 for stroke. RESULTS: We identified 950 prevalent or incident nonfatal coronary heart disease cases and 118 prevalent or incident nonfatal stroke cases using Whitehall-ascertainment. The corresponding figures for HES-ascertainment were 926 and 107. For coronary heart disease, the sensitivity of HES-ascertainment was 70%, positive predictive value 72%, specificity 96%, and the negative predictive value 96%. The pattern of results for stroke was similar. These statistics did not differ in analyses stratified by age, sex, baseline risk factor status, or after exclusion of prevalent cases. Estimates of risk factor-disease associations were similar between the two ascertainment methods. Including fatal cardiovascular disease in the outcomes improved the agreement between the methods. CONCLUSION: Our analyses support the validity of cardiovascular disease ascertainment using linkage to the UK Hospital Episode Statistics database records by showing agreement with high resolution disease data collected in the Whitehall II cohort.

Alcohol Consumption and Common Carotid Intima-Media Thickness: The USE-IMT Study.

AIMS: Epidemiological evidence indicates a protective effect of light to moderate alcohol consumption compared to non-drinking and heavy drinking. Although several mechanisms have been suggested, the effect of alcohol on atherosclerotic changes in vessel walls is unclear. Therefore, we explored the relationship between alcohol consumption and common carotid intima media thickness, a marker of early atherosclerosis in the general population. METHODS: Individual participant data from eight cohorts, involving 37,494 individuals from the USE-IMT collaboration were used. Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) with alcohol consumption. RESULTS: The mean age was 57.9 years (SD 8.6) and the mean CIMT was 0.75 mm (SD 0.177). About, 40.5% reported no alcohol consumed, and among those who drank, mean consumption was 13.3 g per day (SD 16.4). Those consuming no alcohol or a very small amount (<5 g per day) had significantly lower common CIMT values than those consuming >10 g per day, after adjusting for a range of confounding factors. CONCLUSION: In this large CIMT consortium, we did not find evidence to support a protective effect of alcohol on CIMT.

Sitting behaviour is not associated with incident diabetes over 13 years: the Whitehall II cohort study.

BACKGROUND: Although certain types of sedentary behaviour have been linked to metabolic risk, prospective studies describing the links between sitting with incident diabetes are scarce and often do not account for baseline adiposity. We investigate the associations between context-specific sitting and incident diabetes in a cohort of mid-aged to older British civil servants. METHODS: Using data from the Whitehall II study (n=4811), Cox proportional hazards models (adjusted for age, sex, ethnicity, employment grade, smoking, alcohol intake, fruit and vegetable consumption, self-rated health, physical functioning, walking and moderate-to-vigorous physical activity, and body mass index (BMI)) were fitted to examine associations between total sitting and context-specific sitting time (work, television (TV), non-TV leisure time sitting at home) at phase 5 (1997-1999) and fasting glucose-defined incident diabetes up to 2011. RESULTS: Total sitting (HR of the top compared with the bottom group: 1.26; 95% CI 1.00 to 1.62; p=0.01) and TV sitting (1.33; 95% CI 1.03 to 1.88; p=0.05) showed associations with incident diabetes; once BMI was included in the model these associations were attenuated for both total sitting (1.19; 95% CI 0.92 to 1.55; p=0.22) and TV sitting (1.31; 95% CI 0.96 to 1.76; p=0.14). CONCLUSION: We found limited evidence linking sitting and incident diabetes over 13 years in this occupational cohort of civil servants.

Twenty-year trajectories of alcohol consumption during midlife and atherosclerotic thickening in early old age: findings from two British population cohort studies.

BACKGROUND: Epidemiological evidence indicates a protective effect of light-moderate drinking on cardiovascular disease and an increased risk for heavier drinking. Nevertheless, the effect of alcohol on atherosclerotic changes in vessel walls is disputed. Most previous studies have only looked at the cross-sectional relationship between alcohol and carotid intima media thickness (cIMT) - a surrogate marker of atherosclerosis. Single measurements of alcohol assume that alcohol exposure is stable and ignore the possible cumulative effects of harm, leading to possibly incorrect inferences. METHODS: Data were retrieved from two UK population based cohort studies: the Whitehall II cohort of civil servants and the MRC National Survey of Health and Development (combined sample size of 5403 men and women). Twenty year-drinking trajectories during midlife were linked to measures of cIMT when participants were in early old age, and adjusted for age, sex, socioeconomic position, ethnicity and smoking. RESULTS: Those who consistently drank heavily had an increased cIMT compared to stable moderate drinkers (pooled difference in cIMT 0.021 mm; 95 % CI 0.002 to 0.039), after adjustment for covariates. This was not detected in cross-sectional analyses. Former drinkers also had an increased cIMT compared to moderate drinkers (pooled difference in cIMT 0.021; 95 % CI 0.005 to 0.037). There were no appreciable differences in cIMT between non-drinkers and consistent moderate drinkers. CONCLUSION: The drinking habits among adults during midlife affect the atherosclerotic process and sustained heavy drinking is associated with an increased cIMT compared to stable moderate drinkers. This finding was not seen when only using cross-sectional analyses, thus highlighting the importance of taking a life course approach. There was no evidence of a favourable atherosclerotic profile from stable moderate drinking compared to stable non-drinking.

The clustering of health-related behaviours in a British population sample: Testing for cohort differences.

Research findings indicate that health-related behaviours (HRBs) do not co-occur within individuals by chance and therefore cluster. This study uses Latent Profile Analysis (LPA), to identify the clustered patterns and prevalence of four HRBs: smoking, alcohol, diet, physical activity. We used data, collected from participants in their early 30s, from two British cohorts born in 1958 and 1970 (N=21,019). Multi-group LPA models were run separately by gender testing for cohort differences in HRB cluster patterns. For both genders three clusters emerged: 'Risky' (1-9%), 'Moderate Smokers' (20-30%) and 'Mainstream' (68-77%). HRBs amongst members of the 'Mainstream' cluster were more beneficial than HRBs amongst members of the other two clusters, characterised as not smoking, frequent fruit and vegetable consumption, less frequent consumption of chips and fried food and being more physically active. Nevertheless, frequent consumption of sweet foods was common in the 'Mainstream' cluster. There was a large shift in membership to the 'Mainstream' cluster for men and women born in 1970. Amongst women members of the 'Mainstream' cluster, a higher proportion of those born in 1970 appeared to have drunk alcohol above the contemporaneous UK recommended limits but consumed sweet foods less frequently, than those born in 1958. In summary our findings provide additional evidence of HRB clustering, identifying largely consistent HRBs cluster patterns across cohort and gender groups, with some differences in prevalence. This evidence of HRB clustering across time and by gender provides a person-centred understanding that can inform interventions to improve HRBs.

Drunkenness and heavy drinking among 11year olds - Findings from the UK Millennium Cohort Study.

Heavy drinking among young people is linked to negative consequences including other risky behaviours, educational failure and premature mortality. There is a lack of research examining factors that influence heavy and binge drinking in early adolescence as prior work has focused on older teenagers. The objective of this paper was to identify individual and family factors associated with drunkenness and episodes of heavy drinking in early adolescence. We analysed data on 11,046 11year olds from the UK Millennium Cohort Study. Multivariate logistic regression was used to estimate odds ratios for associations. 1.2% of participants reported having been drunk, and 0.6% reported having had 5 or more drinks in a single episode. Participants who reported drunkenness were more likely to be boys (1.6% vs 0.7%, p<0.01), to have socioemotional difficulties (2.6% vs 1.0%, p<0.001), to report antisocial behaviours (none=0.6%, 1=2.0%, 2 or more=7.0%, p<0.001), report truancy (6.0% vs 1.0%, p<0.001), smoke cigarettes (12.0% vs 0.8%, p<0.001). Parental drinking did not appear to be associated with the odds of drunkenness. Associated with higher odds of drunkenness were: having friends who drank (OR=5.17); having positive expectancies towards alcohol (OR 2+=2.02); ever having smoked cigarettes (OR=5.32); the mother-child relationship not being close (OR=2.17). Associated with a reduced odds of drunkenness was having a heightened perception of harm from drinking 1-2 drinks daily (OR - some risk=0.48, great risk=0.40). Our findings support policies aimed at multiple levels, starting in the preadolescent years, which incorporate individual, family, and peer factors.

Adverse Childhood Experiences and Alcohol Consumption in Midlife and Early Old-Age.

AIMS: To examine the individual and cumulative effects of adverse childhood experiences (ACEs) on alcohol consumption in midlife and early old-age, and the role of ACEs in 10-year drinking trajectories across midlife. METHODS: Data were from the Whitehall II study, a longitudinal British civil service-based cohort study (N = 7870, 69.5% male). Multinomial logistic regression was used to examine the individual and cumulative effects of ACEs on weekly alcohol consumption. Mixed-effect multilevel modelling was used to explore the relationship between ACEs and change in alcohol consumption longitudinally. RESULTS: Participants who were exposed to parental arguments/fights in childhood were 1.24 (95% CI 1.06, 1.45) times more likely to drink at hazardous levels in midlife (mean age 56 years) after controlling for covariates and other ACEs. For each additional exposure to an ACE, the risk of hazardous drinking versus moderate drinking was increased by 1.12 (95% CI 1.03, 1.21) after adjusting for sex, age, adult socio-economic status, ethnicity and marital status. No associations between ACEs and increased risk of hazardous drinking in early old-age (mean age 66 years) were found. In longitudinal analyses, ACEs did not significantly influence 10-year drinking trajectories across midlife. CONCLUSION: The effect of exposure to parental arguments on hazardous drinking persists into midlife.

Underestimating the Alcohol Content of a Glass of Wine: The Implications for Estimates of Mortality Risk.

AIMS: Increases in glass sizes and wine strength over the last 25 years in the UK are likely to have led to an underestimation of alcohol intake in population studies. We explore whether this probable misclassification affects the association between average alcohol intake and risk of mortality from all causes, cardiovascular disease and cancer. METHODS: Self-reported alcohol consumption in 1997-1999 among 7010 men and women in the Whitehall II cohort of British civil servants was linked to the risk of mortality until mid-2015. A conversion factor of 8 g of alcohol per wine glass (1 unit) was compared with a conversion of 16 g per wine glass (2 units). RESULTS: When applying a higher alcohol content conversion for wine consumption, the proportion of heavy/very heavy drinkers increased from 28% to 41% for men and 15% to 28% for women. There was a significantly increased risk of very heavy drinking compared with moderate drinking for deaths from all causes and cancer before and after change in wine conversion; however, the hazard ratios were reduced when a higher wine conversion was used. CONCLUSIONS: In this population-based study, assuming higher alcohol content in wine glasses changed the estimates of mortality risk. We propose that investigator-led cohorts need to revisit conversion factors based on more accurate estimates of alcohol content in wine glasses. Prospectively, researchers need to collect more detailed information on alcohol including serving sizes and strength. SHORT SUMMARY: The alcohol content in a wine glass is likely to be underestimated in population surveys as wine strength and serving size have increased in recent years. We demonstrate that in a large cohort study, this underestimation affects estimates of mortality risk. Investigator-led cohorts need to revisit conversion factors based on more accurate estimates of alcohol content in wine glasses.

What influences 11-year-olds to drink? Findings from the Millennium Cohort Study.

BACKGROUND: Drinking in youth is linked to other risky behaviours, educational failure and premature death. Prior research has examined drinking in mid and late teenagers, but little is known about the factors that influence drinking at the beginning of adolescence. Objectives were: 1. to assess associations of parental and friends' drinking with reported drinking among 11 year olds; 2. to investigate the roles of perceptions of harm, expectancies towards alcohol, parental supervision and family relationships on reported drinking among 11 year olds. METHODS: Analysis of data from the UK Millennium Cohort Study on 10498 11-year-olds. The outcome measure was having drank an alcoholic drink, self-reported by cohort members. RESULTS: 13.6 % of 11 year olds reported having drank. Estimates reported are odds ratios and 95 % confidence intervals. Cohort members whose mothers drank were more likely to drink (light/moderate = 1.6, 1.3 to 2.0, heavy/binge = 1.8, 1.4 to 2.3). Cohort members whose fathers drank were also more likely to drink but these estimates lost statistical significance when covariates were adjusted for (light/moderate = 1.3, 0.9 to 1.9, heavy/binge = 1.3, 0.9 to 1.9). Having friends who drank was strongly associated with cohort member drinking (4.8, 3.9 to 5.9). Associated with reduced odds of cohort member drinking were: heightened perception of harm from 1-2 drinks daily (some = 0.9, 0.7 to 1.1, great = 0.6, 0.5 to 0.7); and negative expectancies towards alcohol (0.5, 0.4 to 0.7). Associated with increased odds of cohort member drinking were: positive expectancies towards alcohol (1.9, 1.4 to 2.5); not being supervised on weekends and weekdays (often = 1.2, 1.0 to 1.4); frequent battles of will (1.3, 1.1 to 1.5); and not being happy with family (1.2, 1.0 to 1.5). CONCLUSIONS: Examining drinking at this point in the lifecourse has potentially important public health implications as around one in seven 11 year olds have drank, although the vast majority are yet to explore alcohol. Findings support interventions working at multiple levels that incorporate family and peer factors to help shape choices around risky behaviours including drinking.

Job strain and the risk of stroke: an individual-participant data meta-analysis.

BACKGROUND AND PURPOSE: Psychosocial stress at work has been proposed to be a risk factor for cardiovascular disease. However, its role as a risk factor for stroke is uncertain. METHODS: We conducted an individual-participant-data meta-analysis of 196 380 males and females from 14 European cohort studies to investigate the association between job strain, a measure of work-related stress, and incident stroke. RESULTS: In 1.8 million person-years at risk (mean follow-up 9.2 years), 2023 first-time stroke events were recorded. The age- and sex-adjusted hazard ratio for job strain relative to no job strain was 1.24 (95% confidence interval, 1.05;1.47) for ischemic stroke, 1.01 (95% confidence interval, 0.75;1.36) for hemorrhagic stroke, and 1.09 (95% confidence interval, 0.94;1.26) for overall stroke. The association with ischemic stroke was robust to further adjustment for socioeconomic status. CONCLUSION: Job strain may be associated with an increased risk of ischemic stroke, but further research is needed to determine whether interventions targeting job strain would reduce stroke risk beyond existing preventive strategies.

Life course trajectories of alcohol consumption in the United Kingdom using longitudinal data from nine cohort studies.

BACKGROUND: Alcohol consumption patterns change across life and this is not fully captured in cross-sectional series data. Analysis of longitudinal data, with repeat alcohol measures, is necessary to reveal changes within the same individuals as they age. Such data are scarce and few studies are able to capture multiple decades of the life course. Therefore, we examined alcohol consumption trajectories, reporting both average weekly volume and frequency, using data from cohorts with repeated measures that cover different and overlapping periods of life. METHODS: Data were from nine UK-based prospective cohorts with at least three repeated alcohol consumption measures on individuals (combined sample size of 59,397 with 174,666 alcohol observations), with data spanning from adolescence to very old age (90 years plus). Information on volume and frequency of drinking were harmonised across the cohorts. Predicted volume of alcohol by age was estimated using random effect multilevel models fitted to each cohort. Quadratic and cubic polynomial terms were used to describe non-linear age trajectories. Changes in drinking frequency by age were calculated from observed data within each cohort and then smoothed using locally weighted scatterplot smoothing. Models were fitted for men and women separately. RESULTS: We found that, for men, mean consumption rose sharply during adolescence, peaked at around 25 years at 20 units per week, and then declined and plateaued during mid-life, before declining from around 60 years. A similar trajectory was seen for women, but with lower overall consumption (peak of around 7 to 8 units per week). Frequent drinking (daily or most days of the week) became more common during mid to older age, most notably among men, reaching above 50% of men. CONCLUSIONS: This is the first attempt to synthesise longitudinal data on alcohol consumption from several overlapping cohorts to represent the entire life course and illustrates the importance of recognising that this behaviour is dynamic. The aetiological findings from epidemiological studies using just one exposure measure of alcohol, as is typically done, should be treated with caution. Having a better understanding of how drinking changes with age may help design intervention strategies.