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      Quantifying Alcohol Consumption in the General Population by Analysing Phosphatidylethanol Concentrations in Whole Blood: Results from 24,574 Subjects Included in the HUNT4 Study

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          Abstract

          Aims

          To evaluate the association between self-reported alcohol consumption and phosphatidylethanol (PEth) concentrations in blood in a large general population study, and discuss optimal cut-off PEth concentrations for defined levels of alcohol consumption.

          Methods

          Population based, longitudinal cohort study including 24,574 adults from The Trøndelag Health Study 4 (HUNT4) conducted in Trøndelag County, Norway. Data included PEth concentration, self-reported alcohol consumption and CAGE score.

          Results

          PEth levels in whole blood increased with the number of alcohol units consumed, the frequency of alcohol consumption, the frequency of binge drinking and the CAGE score (lifetime, i.e. ‘have you ever’). The cut-off concentrations with highest combined sensitivity and specificity were 0.057 μmol/l (40 ng/ml) for identification of those consuming >1 alcohol unit per day (sensitivity 86%, specificity 76%), 0.087 μmol/l (61 ng/ml) for consuming >2 units per day (sensitivity 87%, specificity 81%) and 0.122 μmol/l (86 ng/ml) for consuming >3 alcohol units per day (sensitivity 80%, specificity 86%). By defining a CAGE score ≥ 2 as potentially harmful consumption, a cut-off of 0.100 μmol/l (70 ng/ml) identified 52% of all those subjects.

          Conclusions

          Cut-off limits of PEth concentrations should take into account the indication for sampling. Using cut-offs for the PEth concentrations of about 0.05 μmol/l (35 ng/ml) and 0.08 μmol/l (56 ng/ml) would identify about 90% of the subjects consuming more than 1 and 2 alcohol units per day, respectively. Concentrations above these cut-offs should lead to a more detailed interview related to alcohol use.

          Abstract

          Short Summary: A study of the association between PEth in blood and alcohol consumption in 24,574 subjects in the HUNT4 study. A cut-off of 0.03–0.06 μmol/l (or 20–40 ng/ml) detects alcohol consumption above 1–2 units/day, with a threshold of three units per day a cut-off of 0.1 μmol/l (70 ng/ml) is appropriate.

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          Most cited references31

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          Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

          Summary Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2·2% (95% uncertainty interval [UI] 1·5–3·0) of age-standardised female deaths and 6·8% (5·8–8·0) of age-standardised male deaths. Among the population aged 15–49 years, alcohol use was the leading risk factor globally in 2016, with 3·8% (95% UI 3·2–4·3) of female deaths and 12·2% (10·8–13·6) of male deaths attributable to alcohol use. For the population aged 15–49 years, female attributable DALYs were 2·3% (95% UI 2·0–2·6) and male attributable DALYs were 8·9% (7·8–9·9). The three leading causes of attributable deaths in this age group were tuberculosis (1·4% [95% UI 1·0–1·7] of total deaths), road injuries (1·2% [0·7–1·9]), and self-harm (1·1% [0·6–1·5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2–33·3) of total alcohol-attributable female deaths and 18·9% (15·3–22·6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0–0·8) standard drinks per week. Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption. Funding Bill & Melinda Gates Foundation.
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            Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

            Summary Background Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. Methods We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies. Findings In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10–1·17), coronary disease excluding myocardial infarction (1·06, 1·00–1·11), heart failure (1·09, 1·03–1·15), fatal hypertensive disease (1·24, 1·15–1·33); and fatal aortic aneurysm (1·15, 1·03–1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91–0·97). In comparison to those who reported drinking >0–≤100 g per week, those who reported drinking >100–≤200 g per week, >200–≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1–2 years, or 4–5 years, respectively. Interpretation In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. Funding UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.
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              Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies.

              Moderate consumption of alcohol is inversely related with coronary disease, but its association with mortality is controversial. We performed a meta-analysis of prospective studies on alcohol dosing and total mortality. We searched PubMed for articles available until December 2005, supplemented by references from the selected articles. Thirty-four studies on men and women, for a total of 1 015 835 subjects and 94 533 deaths, were selected. Data were pooled with a weighed regression analysis of fractional polynomials. A J-shaped relationship between alcohol and total mortality was confirmed in adjusted studies, in both men and women. Consumption of alcohol, up to 4 drinks per day in men and 2 drinks per day in women, was inversely associated with total mortality, maximum protection being 18% in women (99% confidence interval, 13%-22%) and 17% in men (99% confidence interval, 15%-19%). Higher doses of alcohol were associated with increased mortality. The inverse association in women disappeared at doses lower than in men. When adjusted and unadjusted data were compared, the maximum protection was only reduced from 19% to 16%. The degree of association in men was lower in the United States than in Europe. Low levels of alcohol intake (1-2 drinks per day for women and 2-4 drinks per day for men) are inversely associated with total mortality in both men and women. Our findings, while confirming the hazards of excess drinking, indicate potential windows of alcohol intake that may confer a net beneficial effect of moderate drinking, at least in terms of survival.
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                Author and article information

                Contributors
                Journal
                Alcohol Alcohol
                Alcohol Alcohol
                alcalc
                Alcohol and Alcoholism (Oxford, Oxfordshire)
                Oxford University Press
                0735-0414
                1464-3502
                May 2023
                16 March 2023
                16 March 2023
                : 58
                : 3
                : 258-265
                Affiliations
                Department of Clinical Pharmacology, St. Olav University Hospital , 7006 Trondheim, Norway
                Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Science, Norwegian University of Science and Technology , 7030 Trondheim, Norway
                Department of Clinical Pharmacology, St. Olav University Hospital , 7006 Trondheim, Norway
                Department of Clinical Pharmacology, St. Olav University Hospital , 7006 Trondheim, Norway
                Department of Clinical Pharmacology, St. Olav University Hospital , 7006 Trondheim, Norway
                K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Science, Norwegian University of Science and Technology , 7030 Trondheim, Norway
                HUNT Research Centre, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology , 7600 Levanger, Norway
                HUNT Research Centre, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology , 7600 Levanger, Norway
                Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology , 7030 Trondheim, Norway
                Department of Clinical Pharmacology, St. Olav University Hospital , 7006 Trondheim, Norway
                Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Science, Norwegian University of Science and Technology , 7030 Trondheim, Norway
                Author notes
                Corresponding author: Ragnhild Bergene Skråstad, St. Olavs Hospital HF, Avdeling for klinisk farmakologi, Postboks 3250 Torgarden, 7006 Trondheim, Norway. E-mail: ragnhild.skrastad@ 123456stolav.no
                Article
                agad015
                10.1093/alcalc/agad015
                10168712
                36928303
                2a9c7768-24cc-4074-aed2-6991da69f247
                © The Author(s) 2023. Medical Council on Alcohol and Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 11 October 2022
                : 13 January 2023
                : 8 February 2023
                Page count
                Pages: 8
                Funding
                Funded by: Clinic of Laboratory Medicine and the Department of Clinical Pharmacology at St. Olav University Hospital, Trondheim, Norway;
                Categories
                AcademicSubjects/MED00860
                Article

                Health & Social care
                Health & Social care

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