05 December 2018 In Liver Disease

BACKGROUND: Alcohol is a known cause of cirrhosis, but it is unclear if the associated risk varies by whether alcohol is drunk with meals, or by the frequency or type of alcohol consumed. Here we aim to investigate the associations between alcohol consumption with meals, daily frequency of consumption, and liver cirrhosis.

METHODS: The Million Women Study is a prospective study that includes one in every four UK women born between 1935 and 1950, recruited between 1996 and 2001. In 2001 (IQR 2000-03), the participants reported their alcohol intake, whether consumption was usually with meals, and number of days per week it was consumed. Cox regression analysis yielded adjusted relative risks (RRs) for incident cirrhosis, identified by follow-up through electronic linkage to routinely collected national hospital admission, and death databases.

FINDINGS: During a mean of 15 years (SD 3) of follow-up of 401 806 women with a mean age of 60 years (SD 5), without previous cirrhosis or hepatitis, and who reported drinking at least one alcoholic drink per week, 1560 had a hospital admission with cirrhosis (n=1518) or died from the disease (n=42). Cirrhosis incidence increased with amount of alcohol consumed (>/=15 drinks [mean 220 g of alcohol] vs one to two drinks [mean 30 g of alcohol] per week; RR 3.43, 95% CI 2.87-4.10; p<0.0001). About half of the participants (203 564 of 401 806) reported usually drinking with meals and, after adjusting for amount consumed, cirrhosis incidence was lower for usually drinking with meals than not (RR 0.69, 0.62-0.77; p<0.0001; wine-only drinkers RR 0.69, 0.56-0.85; all other drinkers RR 0.72, 0.63-0.82). Among 175 618 women who consumed seven or more drinks per week, cirrhosis incidence was greater for daily consumption than non-daily consumption (adjusted RR 1.61, 1.40-1.85; p<0.0001). Daily consumption, together with not drinking with meals, was associated with more than a doubling of cirrhosis incidence (adjusted RR 2.47, 1.96-3.11; p<0.0001).

INTERPRETATION: In middle-aged women, cirrhosis incidence increases with total alcohol intake, even at moderate levels of consumption. For a given weekly intake of alcohol, this excess incidence of cirrhosis is higher if consumption is usually without meals, or with daily drinking. FUNDING: UK Medical Research Council and Cancer Research UK.

27 September 2018 In General Health

The Mediterranean diet (MD) has been associated with prolonged survival in the general population, but no meta-analysis has apparently investigated the potential health benefits in relation to mortality in the elderly. We performed a longitudinal analysis on 5200 individuals aged >/=65 years identified within the general population recruited in the Moli-sani study cohort (2005-2010). Adherence to the MD was appraised by the a priori Mediterranean diet score (MDS; range 0-9). Survival estimates were derived using Cox regression and competing risk models. For the meta-analysis, PubMed and Scopus databases were searched from inception until April 2018 to identify prospective studies on the MD and death risk in the elderly. Over a median follow-up of 8.1 years, a total of 900 deaths were ascertained in the elderly sub-sample of the Moli-sani cohort. A one-point increase in the MDS was associated with lower risk of all-cause, coronary artery disease/cerebrovascular and non-cardiovascular/non-cancer mortality (multi-variable hazard ratio (HR)=0.94; 95 % CI 0.90, 0.98; HR=0.91; 95 % CI 0.83, 0.99 and HR=0.89; 95 % CI 0.81, 0.96, respectively). In a meta-analysis of seven prospective studies, including our results, for a total of 11 738 participants and 3874 deaths, one-point increment in MDS was associated with 5 % (4-7 %) lower risk of all-cause death. An inverse linear dose-response relationship was found from a meta-analysis including three studies. In conclusion, a prospective cohort study and a meta-analysis showed that closer adherence to the MD was associated with prolonged survival in elderly individuals, suggesting the appropriateness for older persons to adopt/preserve the MD to maximise their prospects for survival.

18 May 2018 In General Health

BACKGROUND: We examined the associations of alcohol consumption and liver holidays with all-cause mortality and with mortality due to cancer, heart disease, cerebrovascular disease, respiratory disease, and injury using a large-scale prospective study in Japan.

METHODS: We followed 102,849 Japanese who were aged between 40 and 69 years at baseline for 18.2 years on average, during which 15,203 deaths were reported. Associations between alcohol intake and mortality risk were assessed using a Cox proportional hazards model, with analysis by the number of liver holidays (in which a person abstains from drinking for several days a week).

RESULTS: A J-shaped association was observed between alcohol intake and total mortality in men (nondrinkers: reference; occasional drinkers: hazard ratio [HR] 0.74; 95% confidence interval [CI], 0.68-0.80; 1-149 g/week: HR 0.76; 95% CI, 0.71-0.81; 150-299 g/week: HR 0.75; 95% CI, 0.70-0.80; 300-449 g/week: HR 0.84; 95% CI, 0.78-0.91; 450-599 g/week: HR 0.92; 95% CI, 0.83-1.01; and >/=600 g/week: HR 1.19; 95% CI, 1.07-1.32) and in women (nondrinkers: reference; occasional: HR 0.75; 95% CI, 0.70-0.82; 1-149 g/week: HR 0.80; 95% CI, 0.73-0.88; 150-299 g/week: HR 0.91; 95% CI, 0.74-1.13; 300-449 g/week: HR 1.04; 95% CI, 0.73-1.48; and >/=450 g/week: HR 1.59; 95% CI, 1.07-2.38). In current drinkers, alcohol consumption was associated with a linear, positive increase in mortality risk from all causes, cancer, and cerebrovascular disease in both men and women, but not heart disease in men. Taking of liver holidays was associated with a lower risk of cancer and cerebrovascular disease mortality in men.

CONCLUSIONS: Alcohol intake showed J-shaped associations with the risk of total mortality and three leading causes of death. However, heavy drinking increases the risk of mortality, which highlights the necessity of drinking in moderation coupled with liver holidays.

18 May 2018 In General Health

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 >0-100-200-350 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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