The relation between different dimensions of alcohol consumption and burden of disease: an overview

Aims As part of a larger study to estimate the global burden of disease and injury attributable to alcohol: to evaluate the evidence for a causal impact of average volume of alcohol consumption and pattern of drinking on diseases and injuries; to quantify relationships identified as causal based on published meta‐analyses; to separate the impact on mortality versus morbidity where possible; and to assess the impact of the quality of alcohol on burden of disease. Methods Systematic literature reviews were used to identify alcohol‐related diseases, birth complications and injuries using standard epidemiological criteria to determine causality. The extent of the risk relations was taken from meta‐analyses. Results Evidence of a causal impact of average volume of alcohol consumption was found for the following major diseases: tuberculosis, mouth, nasopharynx, other pharynx and oropharynx cancer, oesophageal cancer, colon and rectum cancer, liver cancer, female breast cancer, diabetes mellitus, alcohol use disorders, unipolar depressive disorders, epilepsy, hypertensive heart disease, ischaemic heart disease (IHD), ischaemic and haemorrhagic stroke, conduction disorders and other dysrhythmias, lower respiratory infections (pneumonia), cirrhosis of the liver, preterm birth complications and fetal alcohol syndrome. Dose–response relationships could be quantified for all disease categories except for depressive disorders, with the relative risk increasing with increased level of alcohol consumption for most diseases. Both average volume and drinking pattern were linked causally to IHD, fetal alcohol syndrome and unintentional and intentional injuries. For IHD, ischaemic stroke and diabetes mellitus beneficial effects were observed for patterns of light to moderate drinking without heavy drinking occasions (as defined by 60+ g pure alcohol per day). For several disease and injury categories, the effects were stronger on mortality compared to morbidity. There was insufficient evidence to establish whether quality of alcohol had a major impact on disease burden. Conclusions Overall, these findings indicate that alcohol impacts many disease outcomes causally, both chronic and acute, and injuries. In addition, a pattern of heavy episodic drinking increases risk for some disease and all injury outcomes. Future studies need to address a number of methodological issues, especially the differential role of average volume versus drinking pattern, in order to obtain more accurate risk estimates and to understand more clearly the nature of alcohol–disease relationships.     

Analgesics and Risk of Coronary and other Death in Middle-aged Men in Eastern Finland

Abstract The association between oral analgesics and the risk of death from ischaemic heart disease (IHD), cardiovascular disease, disease other than IHD, and any disease was studied in a cohort of 3 551 men aged 30–59 years, based on a random sample from the population of eastern Finland. A number of potential coronary risk factors were allowed for in multiple logistic models. On the basis of these data, a regular use of oral analgesics is associated with a decreased risk of death from IHD. The relative risk was 0.6 with 95 % confidence interval (CI) of 0.2–0.9 for IHD death and 0.6 (95 % CI = 0.4–0.9) for cardiovascular death. No significant association was found between oral analgesics and the risk of death from diseases other than IHD.     

Per capita alcohol consumption and ischaemic heart disease mortality

Aim. To test the hypothesis that alcohol consumption is inversely related to ischaemic heart disease (IHD) mortality at the population level. Most individual-level studies find a reduced risk of IHD with a moderate level of alcohol consumption, but it is as yet unknown whether this association also exists at the aggregate level. Measurements. The study period was approximately 1950 to 1995; 14 EU countries and Norway were included. Time series analyses on differenced data were utilized, and age-standardized IHD mortality for men and women in the age groups 30-44, 45-59, 60-74 and 30-74 years was measured. The effects of alcohol (sales per capita) were controlled for a weighted lag of per capita sales of cigarettes. Findings. There was a random distribution of insignificant negative and positive alcohol effect estimates. A slight indication of a cardioprotective effect of alcohol among 30- to 44-year-old women in high consumption countries could be observed (significant for Italy). Mean alcohol effect estimates were nearly exactly zero (absent alcohol effect) among men and weakly positive among women. Because changes in cigarette consumption were often significantly and positively related to subsequent changes in IHD mortality, poor validity in the IHD time series cannot explain the unsystematic findings. Including a 6-year weighted lag of alcohol consumption changed the weak positive effect among women to an absent alcohol effect. A brief analysis of abstinence rates indicated no particular relationship to IHD mortality. Conclusion. The alleged cardioprotective alcohol effect is absent at the population level, and great caution should be taken concerning alcohol policies for cardioprotective purposes.     

The combined influence of leisure-time physical activity and weekly alcohol intake on fatal ischaemic heart disease and all-cause mortality.

AIMS: To determine the combined influence of leisure-time physical activity and weekly alcohol intake on the risk of subsequent fatal ischaemic heart disease (IHD) and all-cause mortality. METHODS AND RESULTS: Prospective cohort study of 11 914 Danes aged 20 years or older and without pre-existing IHD. During approximately 20 years of follow-up, 1242 cases of fatal IHD occurred and 5901 died from all causes. Within both genders, being physically active was associated with lower hazard ratios (HR) of both fatal IHD and all-cause mortality than being physically inactive. Further, weekly alcohol intake was inversely associated with fatal IHD and had a U-shaped association with all-cause mortality. Within level of physical activity, non-drinkers had the highest HR of fatal IHD, whereas both non-drinkers and heavy drinkers had the highest HR of all-cause mortality. Further, the physically inactive had the highest HR of both fatal IHD and all-cause mortality within each category of weekly alcohol intake. Thus, the HR of both fatal IHD and all-cause mortality were low among the physically active who had a moderate alcohol intake. Conclusion Leisure-time physical activity and a moderate weekly alcohol intake are both important to lower the risk of fatal IHD and all-cause mortality.     

Coffee consumption and risk of ischaemic heart disease — a settled issue?

Abstract. Objective . Based on a meta-analysis, it was recently stated that there is no association between coffee consumption and the risk of coronary heart disease. Why then, have studies on the issue shown quite variable results? Design, setting and subjects . A prospective study was performed in the Copenhagen Male Study on 2975 men (53–74 years) without cardiovascular disease at the baseline in 1985/1986. They were classified according to self-reported consumption of filter coffee. Some 147 men (5%) were coffee abstainers. Potential confounders were alcohol use, physical activity, smoking, serum cotinine, serum lipids, serum selenium, body mass index, blood pressure, Lewis blood group, hypertension, non-insulin-dependent diabetes mellitus and social class. Main outcome measures . The incidence of ischaemic heart disease (IHD) 1985/86–1991. Results . Some 184 men had a first IHD event. There was no significant difference between those consuming 1–4, 5–8 or ≥ 9 cups per day after controlling for confounders (P-value of trend test: 0.14). The crude incidence rates were 6.8, 6.7 and 4.6%, respectively; the adjusted rates were 6.8, 6.7 and 4.0%, respectively. Coffee consumption was significantly (P < 0.05) inversely correlated with serum selenium concentration (never previously described) and, positively or negatively, with a number of other potential risk factors: smoking, alcohol use, serum triglycerides, serum cholesterol, blood pressure, social class, body mass index, and serum selenium. In nonsmokers and smokers of only a small amount of tobacco, coffee consumption was associated with a lower risk of IHD (P < 0.05). Conclusion . We conclude that the association between coffee consumption and risk of IHD is conditioned by known risk factors correlated with use of coffee, which may partly explain the inconsistencies in the results of previous studies.     

Declining cardiovascular disease incidence and environmental components

After rising for many years in the mid-to-late 1960s the mortality from ischaemic heart disease (IHD) began to decline in many countries. This represents a decline in both out-of-hospital (community) and hospital deaths. Non-fatal myocardial infarction (MI) has also declined. A literature review was conducted to examine lifestyle and environmental factors contributing to the decline. Half of the decline is attributable to changes in lifestyle and in the known major risk factors. Changes in nutrition appear relevant to the decline, in particular an increased ratio of polyunsaturated to saturated fat intake and a reduced saturated fat intake overall. There is little evidence to support a role of changing alcohol consumption, changing coffee consumption, changing exercise levels or reduction in excess weight in the declining incidence of IHD. While the benefit of smoking cessation is a clear one, its impact on the differing trends in various countries is not clear. Socio-economic factors appear to influence the rate and extent of decline in IHD in different groups and may help explain some of the regional differences in IHD incidence. Reductions in blood pressure within the ‘normal range’ which may occur with lifestyle changes may also be an important contributor.     

How does variability in alcohol consumption over time affect the relationship with mortality and coronary heart disease?

Objective To examine the relationship between alcohol consumption and risk of mortality and incident coronary heart disease (CHD), taking account of variation in intake during follow‐up. Method Prospective cohort study of 5411 male civil servants aged 35–55 years at entry to the Whitehall II study in 1985–88. Alcohol consumption was reported five times over a 15‐year period. Mortality, fatal CHD, clinically verified incident non‐fatal myocardial infarction and definite angina were ascertained during follow‐up. Results We found evidence that drinkers who vary their intake during follow‐up, regardless of average level, have increased risk of total mortality (hazard ratio of high versus low variability 1.52: 95% CI: 1.07–2.17), but not of incident CHD. Using average consumption level, as opposed to only a baseline measure, gave slightly higher risk estimates for CHD compared to moderate drinkers at the extremes of the drinking range. Conclusions Multiple repeated measures are required to explore the effects of variation in exposure over time. Caution is needed when interpreting risks of exposures measured only once at baseline, without consideration of changes over time.     

Alcohol and its relation to all-cause and cardiovascular mortality

There exists a considerable body of evidence indicating that light-to-moderate alcohol consumption is associated with a reduced mortality from ischaemic heart disease (IHD). However, an L-shaped saturation curve has been observed in many prospective studies on alcohol consumption and IHD mortality. No further risk reduction is expected if more than 30 grams of ethanol per day is consumed. In ecological studies, particularly wine showed a strongly negative correlation with IHD mortality. This possible specific effect of wine has not yet been confirmed in observational prospective studies. The evidence found in the ecological studies may partly be explained by several healthy dietary habits associated with wine drinking. Although the results of the prospective studies are less consistent for stroke mortality, the largest risk reduction was observed among the drinkers with 10-20 grams of ethanol per day, and then the risk increased. However as an opposite effect of alcohol is expected to ischaemic and haemorrhagic stroke, further studies with consideration to the type of stroke are needed. Several prospective studies demonstrated a J-shaped curve between alcohol consumption and all-cause mortality both in men and women. It is usually explained by a risk reduction of mortality from IHD and stroke among light drinkers. Considering that the risk reduction for all-cause mortality is limited in light-to-moderate drinkers and the reduction is small and that heavy alcohol consumption has an apparently harmful effect, a general increase in alcohol consumption at the population level is not recommended.     

ALCOHOL AND ISCHEMIC HEART DISEASE: A REVIEW

Evidence from epidemiological studies suggests that consumption of alcohol at moderate levels might be protective against IHD. The alcohol-IHD relationship appears to be U-shaped, so that the risk of IHD associated with moderate levels of alcohol consumption is lower than that for abstainers and heavy drinkers. However, the effects of alcohol upon the risk of IHD must be examined in the context of its overall effects upon health. When this is done, the potential benefits are not clear-cut. This paper reviews the epidemiological evidence relating to the alcohol-IHD association, considers the mechanisms by which alcohol might exert its effects upon IHD risk, and suggests some avenues for future research in this area. (Aust NZ J Med 1984; 14: 75–80).     

Per capita alcohol consumption and ischemic heart disease mortality in a panel of US states from 1950 to 2002

Aims To estimate the overall impact of alcohol on ischemic heart disease (IHD) mortality in the United States using aggregate‐level models and to consider beverage‐specific effects that may represent more effectively the changes in drinking patterns over time that are related to both harmful and protective impacts of alcohol consumption on IHD. Design Several model specifications are estimated, including state‐specific autoregressive integrated moving average (ARIMA) models and generalized least squares (GLS) panel models on first‐differenced data. Setting US states from 1950 to 2002. Participants US general population. Measurements Per capita alcohol sales and cigarette sales, age‐standardized IHD and cirrhosis mortality rates. Findings Apparent consumption of total alcohol was associated with a significant overall increase of IHD of about 1% mortality per litre of ethanol. Beverage‐specific models found that spirits consumption was significantly positively related to IHD mortality overall, for both genders and in three regions defined by drinking culture (or ‘wetness’), while beer was found to have a significant protective relationship overall and in the wet region. The results for wine also suggest a protective relationship, but only marginally significant effects were found. Cirrhosis mortality rates were consistently positively related to IHD mortality. Combined results from state‐specific ARIMA models including both cigarette sales and cirrhosis rates were generally consistent with the GLS results. Conclusions Population‐level models confirm individual‐level findings of both harmful and protective relationships between alcohol use patterns and ischemic heart disease mortality. However, an overall harmful impact of per capita alcohol consumption on IHD mortality was found.     

Different measures of alcohol consumption and risk of coronary heart disease and all-cause mortality: 11-year follow-up of the Whitehall II Cohort Study

Aims To investigate the relationship between three measures of alcohol consumption obtained simultaneously in a large cohort and the validated risk of coronary heart disease and all‐cause mortality during follow‐up. Design Prospective cohort study with median follow‐up of 11 years. Setting The Whitehall II Cohort Study: London‐based civil service. Participants A total of 10 308 (33% female) civil servants aged 35–55 years at baseline (1985–88). Measurements Self‐reported volume of alcohol consumed during past week, frequency of drinking over past year, usual amount consumed per drinking session. Main outcome measures Coronary heart disease and all‐cause mortality until 1999. Findings A U‐shaped relationship was found between volume of alcohol consumed per week and outcome. Compared to those who drank moderately (10–80 g alcohol per week), non‐drinkers and those drinking more than 248 g per week had approximately a twofold increased risk of mortality. The optimal frequency of drinking was between once or twice a week and daily, after adjustment for average volume consumed per week. Those drinking twice a day or more had an increased risk of mortality (male hazard ratio 2.44 95% CI 1.31–4.52) compared to those drinking once or twice a week. Drinking only once a month or only on special occasions had a 50% increased risk of mortality. The usual amount consumed per drinking session was not indicative of increased health risk in this cohort. Conclusions Epidemiological studies should collect information on frequency of drinking in addition to average volume consumed in order to inform sensible drinking advice.     

The relationship of average volume of alcohol consumption and patterns of drinking to burden of disease: an overview

Aims As part of a larger study to estimate the global burden of disease attributable to alcohol:

• ? to quantify the relationships between average volume of alcohol consumption, patterns of drinking and disease and injury outcomes, and
• ? to combine exposure and risk estimates to determine regional and global alcohol‐attributable fractions (AAFs) for major disease and injury categories.

Design, methods, setting Systematic literature reviews were used to select diseases related to alcohol consumption. Meta‐analyses of the relationship between alcohol consumption and disease and multi‐level analyses of aggregate data to fill alcohol–disease relationships not currently covered by individual‐level data were used to determine the risk relationships between alcohol and disease. AAFs were estimated as a function of prevalence of exposure and relative risk, or from combining the aggregate multi‐level analyses with prevalence data. Findings Average volume of alcohol consumption was found to increase risk for the following major chronic diseases: mouth and oropharyngeal cancer; oesophageal cancer; liver cancer; breast cancer; unipolar major depression; epilepsy; alcohol use disorders; hypertensive disease; hemorrhagic stroke; and cirrhosis of the liver. Coronary heart disease (CHD), unintentional and intentional injuries were found to depend on patterns of drinking in addition to average volume of alcohol consumption. Most effects of alcohol on disease were detrimental, but for certain patterns of drinking, a beneficial influence on CHD, stroke and diabetes mellitus was observed. Conclusions Alcohol is related to many major disease outcomes, mainly in a detrimental fashion. While average volume of consumption was related to all disease and injury categories under consideration, pattern of drinking was found to be an additional influencing factor for CHD and injury. The influence of patterns of drinking may be underestimated because pattern measures have not been included in many epidemiologic studies. Generalizability of the results is limited by methodological problems of the underlying studies used in the present analyses. Future studies need to address these methodological issues in order to obtain more accurate risk estimates.     

Alcohol and cardiovascular diseases: where do we stand today?

For centuries, multiple medical risks of heavy alcohol drinking have been evident with simultaneous awareness of a less harmful or sensible drinking limit. The increased risks of heavy drinking, defined as three or more standard‐sized drinks per day, are both cardiovascular (CV) and non‐CV. The CV risks include the following: (i) alcoholic cardiomyopathy (ACM), (ii) systemic hypertension, (iii) atrial arrhythmias, (iv) haemorrhagic stroke and, probably, ischaemic stroke. By contrast, modern epidemiological studies have shown lower morbidity and mortality amongst light–moderate drinkers, due mostly to a reduced risk of coronary artery disease (CAD), with contributions from ischaemic stroke and heart failure (HF). A low level of alcohol drinking has no clear relation to increased risk of any CV condition, except for haemorrhagic stroke. There is good evidence that supports the existence of mechanisms by which alcohol might protect against CAD, but the mechanisms for other alcohol–CV associations remain unclear. Interrelationships amongst the CV conditions affect the individual alcohol–disease relationships; for example, lower CAD risk in light–moderate drinkers is to a large extent responsible for the reduced HF risk. International comparison data plus the presence of proposed beneficial nonalcohol components in wine (particularly in red wine) suggest that this beverage type might afford extra CAD protection. However, the effect of beverage choice is confounded by a healthier drinking pattern and more favourable risk traits in wine drinkers. Debate persists about methodological and public health issues related to the epidemiology of alcohol‐related CV disease.     

Mutation in APOA1 predicts increased risk of ischaemic heart disease and total mortality without low HDL cholesterol levels

Abstract. Haase CL, Frikke‐Schmidt R, Nordestgaard BG, Kateifides AK, Kardassis D, Nielsen LB, Andersen CB, Køber L, Johnsen AH, Grande P, Zannis VI, Tybjærg‐Hansen A (Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Denmark; University of Crete Medical School, Heraklion, Greece; Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA). Mutation in APOA1 predicts increased risk of ischaemic heart disease and total mortality without low HDL cholesterol levels. J Intern Med 2011; 270 : 136–146. Objectives. To determine whether mutations in APOA1 affect levels of high‐density lipoprotein (HDL) cholesterol and to predict risk of ischaemic heart disease (IHD) and total mortality in the general population. Background. Epidemiologically, risk of IHD is inversely related to HDL cholesterol levels. Mutations in apolipoprotein (apo) A‐I, the major protein constituent of HDL, might be associated with low HDL cholesterol and predispose to IHD and early death. Design. We resequenced APOA1 in 190 individuals and examined the effect of mutations on HDL cholesterol, risk of IHD, myocardial infarction (MI) and mortality in 10 440 individuals in the prospective Copenhagen City Heart Study followed for 31 years. Results were validated in an independent case–control study (n = 16 035). Additionally, we determined plasma ratios of mutant to wildtype (WT) apoA‐I in human heterozygotes and functional effects of mutations in adenovirus‐transfected mice. Results. We identified a new mutation, A164S (1 : 500 in the general population), which predicted hazard ratios for IHD, MI and total mortality of 3.2 [95% confidence interval (CI): 1.6–6.5], 5.5 (95% CI: 2.6–11.7) and 2.5 (95% CI: 1.3–4.8), respectively, in heterozygotes compared with noncarriers. Mean reduction in survival time in heterozygotes was 10 years (P < 0.0001). Results for IHD and MI were confirmed in the case–control study. Furthermore, the ratio of mutant S164 to WT A164 apoA‐I in plasma of heterozygotes was reduced. In addition, A164S heterozygotes had normal plasma lipid and lipoprotein levels, including HDL cholesterol and apoA‐I, and this finding was confirmed in adenovirus‐transfected mice. Conclusions. A164S is the first mutation in APOA1 to be described that predicts an increased risk of IHD, MI and total mortality without low HDL cholesterol levels.     

Alcohol use disorders and the heart

Alcohol use is an important preventable and modifiable cause of non‐communicable disease, and has complex effects on the cardiovascular system that vary with dose. Observational and prospective studies have consistently shown a lower risk of cardiovascular and all‐cause mortality in people with low levels of alcohol consumption when compared to abstainers (the ‘J’‐shaped curve). Maximum potential benefit occurs at 0.5 to one standard drinks (7–14 g pure ethanol) per day for women (18% lower all‐cause mortality, 95% confidence interval (CI) = 13–22%) and one to two standard drinks (14–28 g ethanol) per day for men (17% lower all‐cause mortality, 95% CI = 15–19%). However, this evidence is contested, and overall the detrimental effects of alcohol far outweigh the beneficial effects, with the risk of premature mortality increasing steadily after an average consumption of 10 g ethanol/day. Blood pressure (BP) is increased by regular alcohol consumption in a dose‐dependent manner, with a relative risk for hypertension (systolic BP > 140 mm Hg or diastolic > 90 mm Hg) of 1.7 for 50 g ethanol/day and 2.5 at 100 g/day. Important reductions in BP readings can be expected after as little as 1 month of abstinence from alcohol. Heavy alcohol consumption in a binge pattern is associated with the development of acute cardiac arrhythmia, even in people with normal heart function. Atrial fibrillation is the most common arrhythmia associated with chronic high‐volume alcohol intake, and above 14 g alcohol/day the relative risk increases 10% for every extra standard drink (14 g ethanol). Ethanol and its metabolites have toxic effects on cardiac myocytes, and alcoholic cardiomyopathy (ACM) accounts for a third of all cases of non‐ischaemic dilated cardiomyopathy. Screening people drinking alcohol above low‐volume levels and delivering a brief intervention may prevent the development of cardiovascular complications. Although people with established cardiovascular disease show improved outcomes with a reduction to low‐volume alcohol consumption, there is no safe amount of alcohol to drink and patients with ACM should aim for abstinence in order to optimize medical treatment.     

Drinking pattern and risk of non-fatal myocardial infarction: a population-based case-control study

Aims Alcohol consumption has been associated with a reduced risk of heart disease incidence and mortality. However, most studies have focused on an average volume per specific time period and have paid little attention to the pattern of drinking. The aim of this study was to examine the association between various drinking patterns and myocardial infarction (MI). Design A population‐based case–control study. Methods Participants were 427 white males with incident MI and 905 healthy white male controls (age 35–69 years) selected randomly from two Western New York counties. During computer‐assisted interviews detailed information was collected regarding patterns of alcohol consumption during the 12–24 months prior to interview (controls) or MI (cases). Findings Compared to life‐time abstainers, adjusted odds ratios (ORs) and 95% confidence interval (CI) for non‐current and current drinkers were 0.66 (0.31–1.39) and 0.50 (0.24–1.02), respectively. Daily drinkers exhibited a significantly lower OR (0.41) compared to life‐time abstainers. Participants who drank mainly without food had an OR of 1.49 (0.96–2.31) compared to those who drank mainly with food and 0.62 (0.28–1.37) compared to life‐time abstainers. Men who reported drinking only at weekends had a significantly greater MI risk [1.91; (1.21–3.01)] compared to men who drank less than once/week, but not compared to life‐time abstainers [0.91 (0.40–2.07)]. Conclusions Our results indicate that patterns of alcohol use have important cardiovascular health implications.     

Adherence to recommendations for fruit and vegetable intake,ethnicity and ischemic heart disease mortality

Background and aimsIschemic heart disease (IHD) accounts for one-third of annual deaths in the U.S. and mortality rates vary by ethnicity. The association between adherence to dietary guidelines for fruit and vegetable intake with IHD mortality among different ethnic groups has not previously been examined.Methods and resultsA prospective cohort design was used to examine the incidence of fatal IHD among participants in the Multiethnic Cohort Study. Participants included 164,617 men and women from five ethnic groups: African American, Native Hawaiian, Japanese American, Latino, and Caucasian. Cox proportional hazards models, stratified by ethnicity and sex, were used to examine associations between adherence with recommended dietary guidelines for fruit and vegetable intake and risk for fatal IHD. The results did not provide evidence that the association between adherence with dietary recommendations for fruit or vegetable intake and IHD mortality varies by ethnicity. Pooled data did provide evidence that adhering to the recommendations for vegetables lowered risk among men (RR = 0.84, 95% CI: 0.74–0.96) and women (RR = 0.80, 95% CI: 0.69–0.94). No significant effects were observed for fruit intake.ConclusionsThe effect of dietary intake of fruit and vegetables did not vary by ethnicity, providing evidence that recommendations do not need to be individualized for these special populations. The protective effect observed for vegetable intake among both sexes confirms previous findings and supports the evidence base for promoting diet modification in this direction.     

Association between coffee intake and gastroesophageal reflux disease: a meta‐analysis

Gastroesophageal reflux disease (GERD) is one of the most common diseases affecting patients worldwide, but its risk factors and causes are not clearly known. The aim of this study was to investigate the effect of coffee intake on GERD by a meta‐analysis. We searched online published research databases such as PubMed, EMBASE, and Cochrane Library for studies that were published up to December 2012. These publications were reviewed by two independent authors, and studies that fulfilled the criteria were selected. Whenever there was a disagreement between the authors, a consensus was reached by discussion. Fifteen case–control studies were included in the final analysis. A meta‐analysis showed that there was no significant association between coffee intake and GERD. The odds ratio was 1.06 (95% confidence interval, 0.94–1.19). In subgroup analyses in which the groups were subdivided based on the definition of GERD (diagnosed by endoscopy or by symptoms alone), only the endoscopy group showed a significantly higher odds ratio. In subgroup analyses in which the groups were subdivided based on the amount of coffee intake, quality of study, and assessment of exposure, there was no significant association between coffee intake and GERD.     

Serum selenium concentration and risk of ischaemic heart disease in a prospective cohort study of 3000 males.

Whether an association, causative or not, exists between the level of serum selenium and the risk of ischaemic heart disease (IHD) remains unsettled. We investigated the issue in a cohort of 3387 males aged 53-74 years (mean 63). Based on information about health status, life-style and socioeconomic factors given in a prefilled comprehensive questionnaire, the men were interviewed and the information validated. Following the interview, they underwent a clinical examination and had a venous blood sample drawn for the determination of a number of biochemical characteristics. Three hundred and forty-six men were excluded due to prevalent cardiovascular disease, including stroke. During the next three years (1986-1989) 107 men (approximately 3%) suffered an IHD event; 25 events were fatal. Compared to others, men with serum selenium levels less than or equal to 1 mumol/l, approximately the lowest tertile, had a 70% increased risk of IHD, relative risk (RR) with 95% confidence limits was 1.70 (1.14-2.53). After multivariate adjustment for cholesterol, social class, smoking and age, RR was 1.55 (1.00-2.39). Serum selenium level was significantly (P less than 0.05), but not strongly, correlated with a number of IHD risk factors: serum cotinine, tobacco smoking, social class, alcohol consumption, total cholesterol, hypertension, age and physical inactivity. Body mass index, HDL-cholesterol and triglycerides were not significantly associated with serum selenium. We conclude that middle-aged and elderly Danish men with serum selenium less than or equal to 1 mumol/l had a significantly increased risk of ischaemic heart disease. This association was not explained by the interrelationship of serum selenium and major cardiovascular risk factors.     

Alcohol,ischemic heart disease,and the french paradox

Many studies have shown either an inverse relation between alcohol intake and ischemic heart disease or a U-shaped curve in which the equivalent of two drinks per day of any kind of alcohol is associated with a decreased incidence of coronary disease compared with no drinks, while higher doses result in an increased risk of infarction and stroke. Although the cardioprotective effects of most alcoholic beverages are probably due to an elevation of high-density lipoprotein as well as the ability of alcohol to prevent platelet aggregation and increased fibrinolysis, there is an increased favorable effect of red wine. The unique cardioprotective properties of red wine reside in the action of flavonoids which are absent in white wine (with the exception of champagne) and sparse in beer (with the exception of dark beers). The best researched flavonoids are resveritrol and quercetin, which confer antioxidant properties more potent than alpha-tocopherol. Grape juice has about half the amount of flavonoids by volume as does red wine.