Risk thresholds for alcohol consumption : combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

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 loglinearly 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. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

APOE genotype and MRI markers of cerebrovascular disease: systematic review and meta-analysis.

International audienceWe aimed to examine the association of APOE ε genotype with MRI markers of cerebrovascular disease (CVD): white matter hyperintensities, brain infarcts, and cerebral microbleeds. We performed a systematic review and meta-analysis of 42 cross-sectional or longitudinal studies identified in PubMed from 1966 to June 2012 (n = 29,965). This included unpublished data from 3 population-based studies: 3C-Dijon, Framingham Heart Study, and Sydney Memory and Ageing Study. When necessary, authors were contacted to provide effect estimates for the meta-analysis. APOE ε4 carrier status and APOE ε44 genotype were associated with increasing white matter hyperintensity burden (sample size-weighted z score meta-analysis [meta]-p = 0.0034 and 0.0030) and presence of cerebral microbleeds (meta odds ratio [OR] = 1.24, 95% confidence interval [CI] [1.07, 1.43], p = 0.004, and 1.87 [1.26, 2.78], p = 0.002), especially lobar. APOE ε2 carrier status was associated with increasing white matter hyperintensity load (z score meta-p = 0.00053) and risk of brain infarct (meta OR = 1.41[1.09, 1.81], p = 0.008). APOE ε4 and APOE ε2 were associated with increasing burden in MRI markers for both hemorrhagic and ischemic CVD. While the association of APOE ε4 with an increased burden of CVD could be partly contributing to the relationship between APOE ε4 and AD, APOE ε2 was associated with MRI markers of CVD in the opposite direction compared to AD

Mortalidade de adultos de 15 a 74 anos de idade em São Paulo, Botucatu e São Manuel (Brasil), 1974/1975

Submitted by Guilherme Lemeszenski ([email protected]) on 2013-08-22T19:01:02Z No. of bitstreams: 1 S0034-89101979000600001.pdf: 4629798 bytes, checksum: 87616593c4c8d0d9533dfb4004b468c4 (MD5)Made available in DSpace on 2013-08-22T19:01:02Z (GMT). No. of bitstreams: 1 S0034-89101979000600001.pdf: 4629798 bytes, checksum: 87616593c4c8d0d9533dfb4004b468c4 (MD5) Previous issue date: 1979-12-01Made available in DSpace on 2013-09-30T20:00:33Z (GMT). No. of bitstreams: 2 S0034-89101979000600001.pdf: 4629798 bytes, checksum: 87616593c4c8d0d9533dfb4004b468c4 (MD5) S0034-89101979000600001.pdf.txt: 100375 bytes, checksum: fb22745427d122988ffc9bb1b13809eb (MD5) Previous issue date: 1979-12-01Submitted by Vitor Silverio Rodrigues ([email protected]) on 2014-05-20T15:15:31Z No. of bitstreams: 2 S0034-89101979000600001.pdf: 4629798 bytes, checksum: 87616593c4c8d0d9533dfb4004b468c4 (MD5) S0034-89101979000600001.pdf.txt: 100375 bytes, checksum: fb22745427d122988ffc9bb1b13809eb (MD5)Made available in DSpace on 2014-05-20T15:15:31Z (GMT). No. of bitstreams: 2 S0034-89101979000600001.pdf: 4629798 bytes, checksum: 87616593c4c8d0d9533dfb4004b468c4 (MD5) S0034-89101979000600001.pdf.txt: 100375 bytes, checksum: fb22745427d122988ffc9bb1b13809eb (MD5) Previous issue date: 1979-12-01Universidade de São Paulo Faculdade de Saúde Pública Departamento de Prática de Saúde PúblicaUniversidade de São Paulo Faculdade de Saúde Pública Departamento de EpidemiologiaUniversidade de São Paulo Faculdade de Saúde Pública Centro Brasileiro de Classificação de DoençasUniversidade Estadual Paulista Faculdade de Medicina Departamento de Medicina Legal e Medicina em Saúde PúblicaUniversidade Estadual Paulista Faculdade de Medicina Departamento de Medicina Legal e Medicina em Saúde Públic

Vitamin K supplementation and progression of coronary artery calcium in older men and women1234

Background: Coronary artery calcification (CAC) is an independent predictor of cardiovascular disease. A preventive role for vitamin K in CAC progression has been proposed on the basis of the properties of matrix Gla protein (MGP) as a vitamin K–dependent calcification inhibitor