04 December 2014 In Cancer

OBJECTIVES: To investigate the role of factors that modulate the association between alcohol and mortality, and to provide estimates of absolute risk of death.

DESIGN: The European Prospective Investigation into Cancer and nutrition (EPIC).

SETTING: 23 centres in 10 countries.

PARTICIPANTS: 380 395 men and women, free of cancer, diabetes, heart attack or stroke at enrolment, followed up for 12.6 years on average.

MAIN OUTCOME MEASURES: 20 453 fatal events, of which 2053 alcohol-related cancers (ARC, including cancers of upper aerodigestive tract, liver, colorectal and female breast), 4187 cardiovascular diseases/coronary heart disease (CVD/CHD), 856 violent deaths and injuries. Lifetime alcohol use was assessed at recruitment.

RESULTS: HRs comparing extreme drinkers (>/=30 g/day in women and >/=60 g/day in men) to moderate drinkers (0.1-4.9 g/day) were 1.27 (95% CI 1.13 to 1.43) in women and 1.53 (1.39 to 1.68) in men. Strong associations were observed for ARC mortality, in men particularly, and for violent deaths and injuries, in men only. No associations were observed for CVD/CHD mortality among drinkers, whereby HRs were higher in never compared to moderate drinkers. Overall mortality seemed to be more strongly related to beer than wine use, particularly in men. The 10-year risks of overall death for women aged 60 years, drinking more than 30 g/day was 5% and 7%, for never and current smokers, respectively. Corresponding figures in men consuming more than 60 g/day were 11% and 18%, in never and current smokers, respectively. In competing risks analyses, mortality due to CVD/CHD was more pronounced than ARC in men, while CVD/CHD and ARC mortality were of similar magnitude in women.

CONCLUSIONS: In this large European cohort, alcohol use was positively associated with overall mortality, ARC and violent death and injuries, but marginally to CVD/CHD. Absolute risks of death observed in EPIC suggest that alcohol is an important determinant of total mortality.

04 December 2014 In Cardiovascular System

Previous meta-analyses have reported either a protective, neutral or detrimental association from chronic heavy drinking in relation to ischaemic heart disease (IHD). We investigated the potential for systematic error because of study design. Using MOOSE guidelines, studies were identified through MEDLINE, EMBASE and Web of Science up to end of March, 2014. Epidemiological studies reporting on chronic heavy drinking and IHD risk in population studies and samples of people with alcohol use disorder (AUD) were included. Random-effects meta-analysis was used to pool eligible studies. The I(2) statistic was used to assess heterogeneity across studies. In total, 34 observational studies with 110 570 chronic heavy drinkers and 3086 IHD events were identified. In population studies among men, the pooled risk for IHD incidence (fatal+non-fatal events) among chronic heavy drinkers (on average >/=60 g pure alcohol/day) in comparison to lifetime abstainers (n=11 studies) was relative risk (RR)=1.04 (95% CI 0.83 to 1.31, I(2)=54%). Few studies were available for women. In patients with AUD, the risk of IHD mortality in comparison to the general population was elevated with a RR=1.62 (95% CI 1.34 to 1.95, I(2)=81%) in men and RR=2.09 (95% CI 1.28 to 3.41, I(2)=67%) in women. There was a general lack of adjustment other than sex and age in studies among patients with AUD. There is no systematic evidence for a protective association from any type of chronic heavy drinking on IHD risk. Patients with AUD were at higher risk for IHD mortality, but better quality evidence is needed with regard to potential confounding.

04 December 2014 In Cardiovascular System

Alcohol consumption at moderate levels has been associated with decreased risk of coronary heart disease (CHD). However, the cardio-protective effect of alcohol may be restricted to subjects with a particular genotype of the cholesteryl ester transfer protein (CETP) polymorphism. There is evidence for this from one study in men, but the finding has not been confirmed since. The present study specifically re-examines the potential modification of the association between alcohol consumption and CHD by the CETP TaqIB (rs708272) polymorphism in a sample including both men and women. The INTERGENE case-control study consists of 618 patients with CHD and 2921 control subjects, of whom 19% were homozygous for the CETP TaqIB B2 allele. Alcohol consumption was categorized into sex-specific tertiles of ethanol intake, with non-drinkers constituting a separate category. Logistic regression was used to determine the association between CHD with genotype, ethanol intake, and their interaction. Participants with intermediate ethanol intake (2nd tertile) had lower risk of CHD than those with low ethanol intake (odds ratio [OR] = 0.65; 95% confidence interval [CI] 0.50-0.85). The strongest protective association was seen in the CETP TaqIB B2 homozygotes for intermediate vs. low ethanol intake (odds ratio OR = 0.21; 95% CI 0.10-0.44). The interaction between ethanol intake and genotype was statistically significant (p = 0.008), and of similar size in men and women though significant only in men (p = 0.01). The effect modification could not be explained by differences in lifestyle, socioeconomics, or alcohol-related biological variables such as HDL-cholesterol. Our study is the first to replicate previous findings of an effect modification in men. It gives only suggestive results for women, possibly due to the small number of female cases (n = 165). The prevented fraction for the favorable combination of genotype and alcohol consumption is about 6%, a value suggesting that the cardio-protective effect of moderate alcohol consumption applies only to a small segment of the general population.

04 December 2014 In Cardiovascular System

Excessive alcohol consumption is associated with increased morbidity and mortality as well as with labour and traffic accidents. However, current evidence suggests beneficial effects of moderate drinking on cardiovascular events including coronary heart disease, ischaemic stroke, peripheral arterial disease and congestive heart failure. The underlying mechanisms to explain these protective effects against coronary heart disease include an increase in high-density lipoprotein cholesterol and an increase in insulin sensitivity, and a decrease in platelet aggregation and circulating concentrations of fibrinogen. However, there are discrepancies regarding the specific effects of different types of beverages on the cardiovascular system, and also whether the possible protective effects of alcoholic beverages are due to their alcohol component (ethanol) or non-alcoholic products containing, mainly polyphenols. Recent randomised clinical trials have shown that wine, a polyphenol-rich alcoholic beverage, provides higher antioxidant and anti-inflammatory effects than some spirits such as gin, a polyphenol-free alcoholic beverage. In addition, dealcoholized red wine decreases blood pressure through a nitric oxide mediated mechanism, suggesting a protective effect of polyphenols on vascular function. Other studies performed in women have observed that daily doses of 15-20 g of alcohol as red wine are sufficient to elicit protective effects similar to those observed in men who consumed higher doses of wine. In conclusion, moderate consumption of wine exerts a protective effect on biomarkers related to the progression and development of atherosclerosis due to its alcoholic (ethanol) and non-alcoholic (polyphenols) content. Women are more sensitive to the beneficial effects of wine.

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