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Objective: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease., Design: Mendelian randomisation meta-analysis of 56 epidemiological studies., Participants: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers., Main Outcome Measures: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption., Results: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95))., Conclusions: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health., (© Holmes et al 2014.)

Background: It has been suggested that the effects of alcohol on body weight and fat distribution may be influenced by the quantity and type of drink and may differ according to whether the alcohol is consumed with meals or not., Objective: We have examined the cross-sectional association between alcohol intake, patterns of drinking and adiposity (body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC) and percentage body fat (%BF))., Methods: We studied 3327 men aged 60-79 y with no history of myocardial infarction, stroke or diabetes drawn from general practices in 24 British towns., Results: BMI, WHR, WC and %BF increased significantly with increasing alcohol intake even after adjustment for potential confounders (all P < 0.0001), although the effects were stronger for WC and WHR (measures of central adiposity). Men who consumed > or = 21 units/week showed higher levels of central adiposity (WHR, WC) and general adiposity (BMI, %BF) than nondrinkers and lighter drinkers, irrespective of the predominant type of drink consumed (wine, beer, spirits or mixed). The positive association was most clearly seen in beer and spirit drinkers; positive but weaker associations were seen for wine. Among drinkers, a positive association was seen between alcohol intake and the adiposity variables irrespective of whether the alcohol was drunk with or separately from meals., Conclusion: Higher alcohol consumption (> or = 21 units/week) is positively associated with general and to a greater extent with central adiposity, irrespective of the type of drink and whether the alcohol is drunk with meals or not.

Moderate alcohol consumption is associated with a decreased risk of cardiovascular disease. However, the impact of variation in alcohol intake over time on estimated risk relations has not been adequately addressed. In this study, 6,544 middle-aged British men without previous cardiovascular disease were followed for cardiovascular events and all-cause mortality over 20 years from 1978/1980 to 1998/2000. Alcohol intake was ascertained at regular points throughout the study. A total of 922 men had a major coronary event within 20 years, 352 men had a stroke, and 1,552 men died of all causes. Baseline alcohol intake displayed U-shaped relations with cardiovascular disease and all-cause mortality, with light drinkers having the lowest risks and nondrinkers and heavy drinkers having similarly high risks. However, the nature of these relations changed after adjustment for intake variation; risks associated with nondrinking were lowered, and risks associated with moderate and heavy drinking increased. Regular heavy drinkers had a 74% higher risk of a major coronary event, a 133% higher risk of stroke, and a 127% higher risk of all-cause mortality than did occasional drinkers (these estimates were 8%, 54%, and 44% before adjustment for intake variation). The findings suggest that considerable caution may be needed before any recommendations regarding acceptable limits of alcohol consumption are made.

Objective: To examine prospectively the relationship between alcohol and 8-year weight gain in women., Research Methods and Procedures: A prospective study of 49,324 women 27 to 44 years old who did not have a history of cardiovascular disease, cancer, or diabetes, who were not pregnant during the study period, and who reported weights in 1991 and 1999., Results: In cross-sectional analyses, there was a significant inverse relationship between alcohol and BMI even after adjustment for dietary factors and a wide range of confounders. In multivariate prospective analyses, a nonlinear relationship was seen between alcohol and weight gain (>or=5 kg) in all women. Compared with nondrinkers, the adjusted relative odds [95% confidence interval (CI)] of weight gain according to grams per day were 0.94 (0.89, 0.99) for those consuming 0.1 to 4.9 g/d, 0.92 (0.85,0.99) for 5 to 14.9 g/d, 0.86 (0.76, 0.78) for 15 to 29.9 g/d, and 1.07 (0.89,1.28) for those consuming 30+ g/d (p < 0.0001 for quadratic trend). Women who continued to drink heavily and those who became heavy drinkers showed similar increased odds of weight gain. The increased odds of weight gain associated with heavy drinking (30+ g/d) were most marked in the younger women (<35 years) (odds ratio 1.64; 5% CI 1.03 to 2.61). In African-American women, light drinking was associated with increased odds of weight gain compared with nondrinkers (odds ratio = 2.43; 95% CI 1.22 to 4.82)., Discussion: Our data suggest that light to moderate drinking (up to 30 g/d) is not associated with weight gain in women except possibly in African-American women. Heavier drinking may promote weight gain in women.

Light to moderate drinking is associated with lower risk of coronary heart (CHD) than non-drinkers. We have examined the relationships between total alcohol intake and type of alcoholic beverage and several potential biological mechanisms. We carried out the study in 3158 men aged 60-79 years drawn from general practices in 24 British towns with no history of myocardial infarction, stroke or diabetes and who were not on warfarin. Total alcohol consumption showed a significant positive dose-response relationship with high density lipoprotein cholesterol (HDL-C), coagulation factor IX, haematocrit, blood viscosity, and tissue plasminogen (t-PA) antigen, and an inverse dose-response relationship with insulin, fibrinogen, von Willebrand factor (vWF) and triglycerides after adjustment for possible confounders. Total alcohol consumption showed weak associations with plasma viscosity and fibrin D-dimer, and no association with factors VII, VIII, or C-reactive protein (CRP). Wine was specifically associated with lower CRP, plasma viscosity, factor VIII and triglycerides. The findings are consistent with the suggestion that HDL-C in particular but also insulin and haemostatic factors may contribute to the beneficial effect of light to moderate drinking on risk of CHD. Wine has effects that may confer greater protection than other alcoholic beverages.

Objective: To examine the relationship between alcohol consumption and the incidence of type 2 diabetes mellitus among relatively young and middle-aged women., Methods: In a prospective study, 109 690 women, aged 25 to 42 years, without a history of coronary heart disease, stroke, cancer, or diabetes mellitus completed a detailed lifestyle and medical history questionnaire in 1989. During 10 years of follow-up, we documented 935 incident cases of type 2 diabetes mellitus., Results: We found a nonlinear relationship between alcohol consumption and risk of type 2 diabetes mellitus after adjustment for multiple confounders, including body mass index, smoking, physical activity, and family history of diabetes mellitus (quadratic trend P =.003). Compared with lifelong abstainers, the adjusted relative risks (95% confidence intervals) were 0.80 (0.66-0.96) for those consuming 0.1 to 4.9 g/d, 0.67 (0.50-0.89) for those consuming 5.0 to 14.9 g/d, 0.42 (0.20-0.90) for those consuming 15.0 to 29.9 g/d, and 0.78 (0.34-1.78) for those consuming 30.0 g/d or more. Further adjustment for dietary factors, including glycemic load, trans-fatty acid, polyunsaturated fat, and total fiber intake, did not appreciably alter these findings. The inverse association with light to moderate drinking was most apparent in women who reported wine or beer drinking. Women who reported 30.0 g/d or more of liquor intake showed a significantly increased risk of diabetes mellitus compared with those who did not report liquor intake (adjusted relative risk, 2.50; 95% confidence interval, 1.00-6.23)., Conclusion: Light to moderate alcoholic beverage consumption may be associated with a lower risk of type 2 diabetes mellitus among women aged 25 to 42 years, although this benefit may not persist at higher levels.

Background: There is uncertainty as to whether regular alcohol consumption contributes directly to weight gain and the risk of obesity., Objective: We examined the relation between alcohol intake and body weight and the association between changes in alcohol intake and in body weight over 5 y of follow-up., Design: This was a prospective study of 7608 men aged 40-59 y drawn from general practices in 24 British towns, excluding persons with known diabetes. Five years after screening, 6832 men then aged 45-64 y and without diabetes completed a postal questionnaire on changes in alcohol intake and body weight., Results: Mean body mass index (BMI; in kg/m(2)) and the prevalence of men with a high BMI (>or= 28; top quintile of the BMI distribution) increased significantly from the light-moderate to the very heavy alcohol intake group even after adjustment for potential confounders. Similar patterns were seen for all types and combinations of alcohol. After 5 y of follow-up, stable and new heavy drinkers (including very heavy drinkers of >or= 30 g/d) showed the greatest weight gain and had the highest prevalence rates of high BMI. Weight change patterns in heavy drinkers at baseline who reduced their intake were not significantly different from those in the stable none-occasional group but showed more weight loss and less weight gain than in the stable or new heavy drinkers., Conclusion: Heavy alcohol intake (>or= 30 g/d) contributes directly to weight gain and obesity, irrespective of the type of alcohol consumed.

Background: This study examines the relation between alcohol and type II diabetes and the possible mediating effects of HDL-cholesterol and serum insulin., Methods: Prospective study of 5221 men aged 40-59 years with no history of coronary heart disease, diabetes, or stroke drawn from general practices in 18 British towns., Results: During the mean follow up of 16.8 years there were 198 incident cases of type II diabetes. Occasional drinkers were the reference group. A non-linear relation was seen between alcohol intake and age adjusted risk of diabetes, with risk lowest in light and moderate drinkers and highest in heavy drinkers (quadratic trend p=0.03). Further adjustment for body mass index decreased risk in heavy drinkers. After additional adjustment for physical activity, smoking, and (undiagnosed) pre-existing coronary heart disease, only moderate drinkers showed significantly lower risk than occasional drinkers (RR=0.66 95% CI 0.44 to 0.99). Alcohol intake was inversely associated with serum insulin and positively associated with HDL-cholesterol. Adjustment for these factors reduced the "protective" effect in moderate drinkers (adjusted RR=0.73 95% CI 0.48 to 1.10) but the quadratic trend remained significant (p=0.02)., Conclusion: There is a non-linear relation between alcohol intake and the risk of type II diabetes. Serum insulin and HDL-cholesterol explained a small amount (20%) of the reduction in risk of type II diabetes associated with moderate drinking. The adverse effect of heavy drinking seemed to be partially mediated through its effect on body weight.

Aim: To examine effects of taking up regular drinking by middle aged non-drinkers and occasional drinkers on major coronary heart disease events and total mortality., Methods: A prospective study of 7735 men from general practices in 24 British towns screened in 1978-80 at age 40-59 years (Q1). Five years after screening, 7157 men then aged 45-64 completed postal questionnaires (Q5) on changes in alcohol intake., Results: In 6503 men without diagnosed coronary heart disease, there were 874 major coronary heart disease events and 1613 total deaths during 16.8 years of follow up after Q5. With stable occasional drinkers as baseline, men who continued to drink regularly had a significantly lower risk of major coronary heart disease events, coronary heart disease mortality, and overall cardiovascular mortality, but a slightly increased risk of non-cardiovascular mortality. New regular drinkers (89% light), even after adjustment for their many advantageous characteristics, showed a lower risk of major coronary heart disease events than stable occasional drinkers (relative risk (RR) = 0.70; 95% confidence interval (CI) 0.48 to 1.03; p = 0.07). New drinkers showed no reduction in coronary heart disease or cardiovascular mortality and experienced an increase in risk of non-cardiovascular mortality (RR = 1.40; 95% CI 0.99 to 1.97; p = 0.06). In 654 men with diagnosed coronary heart disease, new drinkers experienced no mortality benefit compared with stable occasional drinkers., Conclusions: Middle aged new regular drinkers experienced lower risk of major coronary heart disease events than stable occasional drinkers or non-drinkers, but had increased risk of non-cardiovascular mortality and total mortality. These findings provide little support for encouraging older men who do not drink or who only drink occasionally to take up regular drinking, whether or not they have coronary heart disease.

Objective: To examine the effects of alcohol on risk of mortality from coronary heart disease (CHD), cardiovascular disease, and all causes in men with established CHD., Methods and Results: In a population based prospective study of 7169 men aged 45-64 years followed for a mean of 12.8 years, 655 men (9.1%) had a physician diagnosis of CHD (myocardial infarction 455, angina only 200). In these 655 men, there were 294 deaths from all causes including 175 CHD deaths. Ex-drinkers had the highest risk of CHD, cardiovascular mortality, and all cause mortality even after adjustment for lifestyle characteristics and pre-existing disease. Using occasional drinkers as the reference group, lifelong teetotallers, occasional drinkers, and light drinkers all showed similar risks of mortality from CHD, cardiovascular disease, and all causes. Moderate/heavy drinkers showed increased risk of mortality from CHD, cardiovascular disease, and all causes compared to occasional drinkers. The adverse effect of moderate/heavy drinking was confined to the 455 men with previous myocardial infarction (adjusted relative risk for all cause mortality 1.50, 95% confidence interval 1.01 to 2.23). In contrast to lighter drinking, giving up smoking within five years of the start of follow up was associated with a considerable reduction in risk of all cause and cardiovascular mortality compared to those who continued to smoke., Conclusion: Compared to occasional drinking, regular light alcohol consumption (1-14 units per week) in men with established coronary heart disease is not associated with any significant benefit or deleterious effect for CHD, cardiovascular disease or all cause mortality. Higher levels of intake (>/= 3 drinks per day) are associated with increased mortality in men with previous myocardial infarction. In contrast, smoking cessation in men with established CHD substantially reduces the risk of mortality.

Objectives: This study examined the effects of beer, spirits, and wine drinking on coronary heart disease (CHD) events (fatal and nonfatal) and all-cause mortality., Methods: Men aged 40 to 59 years (n = 7735) were drawn at random from one general practice in each of 24 British towns and followed up for an average of 16.8 years., Results: Regular drinkers showed a significantly lower relative risk of CHD, but no all-cause mortality, than occasional drinkers, even after adjustment for potential confounders. The benefit for CHD of regular drinking was seen within both beer drinkers and spirit drinkers but not among men who reported wine drinking. However, all men who reported wine drinking (both occasional and regular) showed significantly lower age-adjusted risks of CHD and all-cause mortality than men drinking beer or spirits; beer and spirit drinkers showed similar risks., Conclusions: The findings suggest that regular intake of all alcoholic drinks is associated with a lower risk of CHD, but not all-cause mortality, than occasional drinking. A large part, but not all, of the greater benefit seen in wine drinkers relative to other drinkers can be attributed to advantageous lifestyle characteristics (e.g., low rates of smoking and obesity).

The accepted interpretation of the J-shaped curve relating alcohol intake to mortality or coronary heart disease is that the lowest point on the curve (light/moderate drinking) represents optimum exposure to alcohol and that the increased risk in non-drinkers reflects the consequence of sub-optimum exposure. However, non-drinkers, both ex-drinkers and lifelong teetotallers, consistently show an increased prevalence of conditions likely to increase morbidity and mortality compared with occasional or light drinkers. In addition, regular light drinkers tend to have characteristics extremely advantageous to health. Changes take place in alcohol intake in individuals over time, with a strong downward drift from heavy or moderate drinking towards non-drinking, affected to a considerable extent by the accumulation of ill health. Reduction in alcohol intake or giving up drinking is associated with higher rates of new diagnoses than remaining stable in alcohol intake and also with higher rates of both cardiovascular and non-cardiovascular mortality. The use of non-drinkers as a baseline, and failure or inability to adequately take into account the characteristics of subjects in the different alcohol intake categories, exaggerates the risk of coronary heart disease events and all cause mortality in non-drinkers and the benefits of light/moderate alcohol intake.

The consistent findings of higher risk of coronary heart disease (CHD) and total mortality in non-drinkers compared to light to moderate drinking has been interpretated as showing that light or moderate drinking is beneficial to health. Non-drinkers, both ex-drinkers and lifelong teetotallers, have an increased prevalence of conditions likely to increase morbidity and mortality compared with occasional or light drinkers. In addition, regular light drinkers tend to have characteristics extremely advantageous to health. Whilst there is considerable evidence that alcohol intake at some level has a beneficial effect on CHD, the degree of protection claimed is almost certainly exaggerated by comparison with an inappropriate control group and by the limited adjustment procedures used to take into account the differing characteristics of the various alcohol intake groups. The benefit of light to moderate drinking for stroke and all-cause mortality is less convincing than the benefit for CHD. If occasional drinkers are used as a baseline, no benefit is seen for stroke or all-cause mortality in regular or light drinkers and all-cause mortality increases progressively from levels of 2 drinks a day. Non-drinkers or lifelong abstainers are unsuitable as a baseline group in studies of the effects of alcohol on morbidity and mortality. The public health message should emphasise the potential harm of heavier drinking rather than concentrating on the possible benefits of light drinking.

Background: To determine the risk of all cause mortality and the incidence of major coronary heart disease (CHD) events in lifelong teetotallers and in ex-drinkers compared with occasional and regular drinkers., Methods: A prospective study of middle-aged men drawn at random from one general practice in each of 24 British towns. Five years after the screening of 7735 men aged 40-59 years, 7167 provided further information on postal questionnaire enabling separation of non-drinkers into lifelong teetotallers and ex-drinkers., Results: During the follow-up period of 9.8 years after the postal questionnaire there were 929 deaths from all causes and 490 major CHD events. Ex-drinkers exhibited increased cardiovascular and non-cardiovascular mortality; lifelong teetotallers showed the lowest cardiovascular mortality but a significantly increased non-cardiovascular mortality. After adjustment for confounding factors and pre-existing disease, the two non-drinking groups did not differ significantly in all cause mortality from occasional and regular drinkers (light, moderate or heavy) but lifelong teetotallers still showed a significant increase in non-cardiovascular mortality. Adjustment considerably attenuated the risk of both cardiovascular and non-cardiovascular mortality in the ex-drinkers. In men without a diagnosis of CHD, lifelong teetotallers and ex-drinkers showed similar increased relative risk (RR) of heart attacks, with regular drinkers (combined) having a significantly decreased risk compared to occasional drinkers (RR = 0.78, 95% confidence interval [CI] : 0.64-0.96) and non-drinkers (RR = 0.69, 95% CI : 0.52-0.91). This decreased risk was small in absolute terms at around 2-3 major CHD events/1000 person-years., Conclusions: Lifelong teetotallers and ex-drinkers showed a significantly increased RR of major CHD events compared with regular drinkers, although this risk is small in absolute terms. Lifelong teetotallers have a low risk of overall cardiovascular mortality and an increased risk of non-cardiovascular mortality. Non-drinkers constitute an unsuitable reference group in alcohol-related studies; occasional or even light drinkers may be more appropriate. Overall, there is no convincing evidence that light or moderate drinking has a protective effect on total or cardiovascular mortality in these middle-aged British men.

Background and Purpose: The relationship between the pattern of alcohol intake and the risk of stroke is unclear, in particular the increased risk observed in abstainers and the possible protective effect of light to moderate drinking. For that reason, we examined in a large prospective study the role of alcohol consumption in the risk of a first major cerebrovascular event (stroke)., Methods: We prospectively studied 7735 middle-aged men drawn from general practices in 24 British towns. With exclusion of those who had recall of physician diagnosis of ischemic heart disease or stroke, data were available for 7273 men all followed for 13.5 years, with 216 major stroke events (fatal and nonfatal)., Results: Compared with occasional drinkers, nondrinkers (lifelong abstainers plus ex-drinkers) had an increased risk of stroke even after adjustment for age, lifestyle factors, and preexisting cardiovascular disease (relative risk [RR] = 1.6; 95% CI, 1.0 to 2.7). All regular weekend drinkers (1 to 2, 3 to 6, and > 6 drinks/d) and daily 1 to 2 and 3 to 6 drinkers showed no significant difference in adjusted risk of stroke compared with occasional drinkers. Heavy drinkers (daily > 6 drinks) showed significantly increased risk evident within the first 8 years of follow-up only (RR = 1.9; 95% CI, 1.0 to 3.5); however, this finding was attenuated after additional adjustment for systolic blood pressure (RR = 1.5; 95% CI, 0.8 to 2.7). Information obtained 5 years after screening was used to separate lifelong abstainers and ex-drinkers. On subsequent 8.5 years of follow-up, both groups showed similar increased risk (RR = 1.5) compared with occasional drinkers, but the risk in ex-drinkers was reduced after adjustment for lifestyle factors and cardiovascular disease status (RR = 1.2). Lifelong abstainers, however, showed an increase in risk after adjustment of 1.8 (95% CI, 0.7 to 4.6)., Conclusions: Heavy drinking is associated with an increased risk of total stroke that is largely mediated through blood pressure. The apparent increased risk seen in lifelong abstainers but not in ex-drinkers or occasional drinkers is unexplained but is unlikely to be attributed to abstinence from alcohol. There is no convincing evidence that light or moderate drinking is beneficial for stroke risk compared with occasional drinking.