Objective To conduct a comprehensive systematic review and meta-analysis of studies assessing the effect of alcohol consumption on multiple cardiovascular outcomes. Design Systematic review and meta-analysis. Inclusion criteria Prospective cohort studies on the association between alcohol consumption and overall mortality from cardiovascular disease, incidence of and mortality from coronary heart disease, and incidence of and mortality from stroke. Studies reviewed Of 4235 studies reviewed for eligibility, quality, and data extraction, 84 were included in the final analysis. Results The pooled adjusted relative risks for alcohol drinkers relative to non-drinkers in random effects models for the outcomes of interest were 0.75 (95% confidence interval 0.70 to 0.80) for cardiovascular disease mortality (21 studies), 0.71 (0.66 to 0.77) for incident coronary heart disease (29 studies), 0.75 (0.68 to 0.81) for coronary heart disease mortality (31 studies), 0.98 (0.91 to 1.06) for incident stroke (17 studies), and 1.06 (0.91 to 1.23) for stroke mortality (10 studies). Dose-response analysis revealed that the lowest risk of coronary heart disease mortality occurred with 1-2 drinks a day, but for stroke mortality it occurred with ≤1 drink per day. Secondary analysis of mortality from all causes showed lower risk for drinkers compared with non-drinkers (relative risk 0.87 (0.83 to 0.92)). Conclusions Light to moderate alcohol consumption is associated with a reduced risk of multiple cardiovascular outcomes.

BACKGROUND The extent to which diabetes mellitus or hyperglycemia is related to risk of death from cancer or other nonvascular conditions is uncertain. METHODS We calculated hazard ratios for cause-specific death, according to baseline diabetes status or fasting glucose level, from individual-participant data on 123,205 deaths among 820,900 people in 97 prospective studies. RESULTS After adjustment for age, sex, smoking status, and body-mass index, hazard ratios among persons with diabetes as compared with persons without diabetes were as follows: 1.80 (95% confidence interval [CI], 1.71 to 1.90) for death from any cause, 1.25 (95% CI, 1.19 to 1.31) for death from cancer, 2.32 (95% CI, 2.11 to 2.56) for death from vascular causes, and 1.73 (95% CI, 1.62 to 1.85) for death from other causes. Diabetes (vs. no diabetes) was moderately associated with death from cancers of the liver, pancreas, ovary, colorectum, lung, bladder, and breast. Aside from cancer and vascular disease, diabetes (vs. no diabetes) was also associated with death from renal disease, liver disease, pneumonia and other infectious diseases, mental disorders, nonhepatic digestive diseases, external causes, intentional self-harm, nervous-system disorders, and chronic obstructive pulmonary disease. Hazard ratios were appreciably reduced after further adjustment for glycemia measures, but not after adjustment for systolic blood pressure, lipid levels, inflammation or renal markers. Fasting glucose levels exceeding 100 mg per deciliter (5.6 mmol per liter), but not levels of 70 to 100 mg per deciliter (3.9 to 5.6 mmol per liter), were associated with death. A 50-year-old with diabetes died, on average, 6 years earlier than a counterpart without diabetes, with about 40% of the difference in survival attributable to excess nonvascular deaths. CONCLUSIONS In addition to vascular disease, diabetes is associated with substantial premature death from several cancers, infectious diseases, external causes, intentional self-harm, and degenerative disorders, independent of several major risk factors. (Funded by the British Heart Foundation and others.)

Objective To systematically review interventional studies of the effects of alcohol consumption on 21 biological markers associated with risk of coronary heart disease in adults without known cardiovascular disease. Design Systematic review and meta-analysis. Study selection Two reviewers independently selected studies that examined adults without known cardiovascular disease and that compared fasting levels of specific biological markers associated with coronary heart disease after alcohol use with those after a period of no alcohol use (controls). 4690 articles were screened for eligibility, the full texts of 124 studies reviewed, and 63 relevant articles selected. Results Of 63 eligible studies, 44 on 13 biomarkers were meta-analysed in fixed or random effects models. Quality was assessed by sensitivity analysis of studies grouped by design. Analyses were stratified by type of beverage (wine, beer, spirits). Alcohol significantly increased levels of high density lipoprotein cholesterol (pooled mean difference 0.094 mmol/L, 95% confidence interval 0.064 to 0.123), apolipoprotein A1 (0.101 g/L, 0.073 to 0.129), and adiponectin (0.56 mg/L, 0.39 to 0.72). Alcohol showed a dose-response relation with high density lipoprotein cholesterol (test for trend P=0.013). Alcohol decreased fibrinogen levels (−0.20 g/L, −0.29 to −0.11) but did not affect triglyceride levels. Results were similar for crossover and before and after studies, and across beverage types. Conclusions Favourable changes in several cardiovascular biomarkers (higher levels of high density lipoprotein cholesterol and adiponectin and lower levels of fibrinogen) provide indirect pathophysiological support for a protective effect of moderate alcohol use on coronary heart disease. INTRODUCTIONModerate alcohol consumption (up to one drink a day for women and up to two for men) has been associated with a decreased risk for certain cardiovascular

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 measuresOdds 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.

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Among men, consumption of alcohol at least three to four days per week was inversely associated with the risk of myocardial infarction. Neither the type of beverage nor the proportion consumed with meals substantially altered this association. Men who increased their alcohol consumption by a moderate amount during follow-up had a decreased risk of myocardial infarction.

EMENTIA IMPOSES A TREMENdous burden on patients, caregivers, and society. Alzheimer disease alone causes more than 360 000 new cases in the United States annually, 1 with a national annual cost of caring for such patients of more than $50 billion. 2 This burden has spurred a search for modifiable factors that cause or prevent dementia.Atherosclerotic vascular disease may be 1 such risk factor for vascular and nonvascular dementia. 3 Because moderate alcohol consumption is associated with a lower risk of cardiovascular disease in the elderly, 4 such consumption might be expected to lower risk of dementia. However, even moderate alcohol consumption may have effects that increase dementia risk. Blood alcohol levels as low as 0.02% impair driving ability, 5 and moderate alcohol use is associated with a greater risk of cerebral hemorrhage. 6 In an analysis of subclinical abnormalities of the brain seen on magnetic resonance imaging (MRI) studies among Cardiovascular Health Study (CHS) participants, moderate alcohol consumption was associated with greater brain atrophy but fewer silent infarcts and less white matter disease, associations that might influence risk of dementia in opposite directions. 7 Previous studies of alcohol consumption and cognitive decline [8][9][10][11][12][13][14][15][16][17][18][19][20] or dementia [21][22][23][24][25] have reported conflicting re-sults. However, to our knowledge, no previous study has addressed the risk of confirmed dementia in a large cohort of adults with repeated measures of alcohol use.To address the relationship of alcohol consumption and risk of dementia further, we performed a nested casecontrol study of alcohol consumption and risk of incident dementia in the CHS, a prospective, population-based study of adults aged 65 years and older in the United States. 26,27 METHODS Study Population and DesignCardiovascular Health Study participants include 5888 men and women aged 65 years or older who were randomly selected from Medicare-

Objective To determine the associations of FGF23 with death, HF, and CVD and investigate the influence of CKD in a general community-living population. Background FGF23 increases renal phosphorus excretion and inhibits vitamin D activation. In ESRD, high FGF23 levels are associated with mortality. The associations of FGF23 with death, heart failure (HF), and cardiovascular disease (CVD) in teh general population are unknown. Methods Plasma FGF23 was measured in 3,107 community-living persons ≥ 65 years in 1996–97, and participants were followed through 2008. HF and CVD events were adjudicated by a panel of experts. Associations of FGF23 with each outcome were evaluated using Cox proportional hazards models, and we tested whether associations differed by CKD status. Results Both lower eGFR and higher urine ACR were associated with high FGF23 at baseline. During 10.5 years (median) follow-up, there were 1,730 deaths, 697 incident HF events, and 797 incident CVD events. Although high FGF23 concentrations were associated with each outcome in combined analyses, the associations were consistently stronger for those with CKD (P interactions all < 0.006). In the CKD group (n=1,128), the highest FGF23 quartile had adjusted hazards ratios (HR) of 1.87 (1.47, 2.38) for all-cause death, 1.94 (1.32, 2.83) for incident HF, and 1.49 (1.02, 2.18) for incident CVD events compared to the lowest quartile. Corresponding HRs in those without CKD (n=1,979) were 1.29 (1.05, 1.59), 1.37 (0.99, 1.89), and 1.07 (0.79, 1.45). Conclusions FGF23, a hormone involved in phosphorous and vitamin D homeostasis, is independently associated with all-cause death and incident HF in community-living older persons. These associations appear stronger in persons with CKD.