Reducing socio-economic inequalities in all-cause mortality: a counterfactual mediation approach.

Socio-economic inequalities in mortality are well established, yet the contribution of intermediate risk factors that may underlie these relationships remains unclear. We evaluated the role of multiple modifiable intermediate risk factors underlying socio-economic-associated mortality and quantified the potential impact of reducing early all-cause mortality by hypothetically altering socio-economic risk factors. Data were from seven cohort studies participating in the LIFEPATH Consortium (total n = 179 090). Using both socio-economic position (SEP) (based on occupation) and education, we estimated the natural direct effect on all-cause mortality and the natural indirect effect via the joint mediating role of smoking, alcohol intake, dietary patterns, physical activity, body mass index, hypertension, diabetes and coronary artery disease. Hazard ratios (HRs) were estimated, using counterfactual natural effect models under different hypothetical actions of either lower or higher SEP or education. Lower SEP and education were associated with an increase in all-cause mortality within an average follow-up time of 17.5 years. Mortality was reduced via modelled hypothetical actions of increasing SEP or education. Through higher education, the HR was 0.85 [95% confidence interval (CI) 0.84, 0.86] for women and 0.71 (95% CI 0.70, 0.74) for men, compared with lower education. In addition, 34% and 38% of the effect was jointly mediated for women and men, respectively. The benefits from altering SEP were slightly more modest. These observational findings support policies to reduce mortality both through improving socio-economic circumstances and increasing education, and by altering intermediaries, such as lifestyle behaviours and morbidities

Hiper-homocisteinemia como fator de risco para doença aterosclerótica coronariana em idosos Hyperhomocysteinemia as a risk factor for coronary atherosclerotic diseases in the elderly

OBJETIVO: Investigar se a hiper-homocisteinemia é fator de risco independente para doença aterosclerótica coronariana em idosos. MÉTODOS: Estudo caso-controle com 172 idosos, 88 pertencentes ao grupo controle e 84 ao grupo caso, que apresentavam cineangiocoronariografia solicitada por indicações clínicas. Angiografia coronariana quantitativa foi realizada em 91% dos pacientes. Homocisteinemia foi avaliada sob forma contínua e categorizada, por análise univariada e multivariada. RESULTADOS: Quando analisada sob forma contínua, verificou-se que, na análise univariada, os idosos do grupo caso apresentaram média de níveis de homocisteinemia significativamente mais elevada que a dos idosos do grupo controle (14,33&plusmn;4,59 µmol/l versus 11,99&plusmn; 4,59 µmol/l , p=0,015). Na análise multivariada, a homocisteinemia sob forma contínua associou-se a razão de risco para doença arterial coronariana de 1,07 a cada aumento de 1 µmol/l de nível de homocisteína. Aumento de 5 µmol/l correspondeu a razão de risco de 1,40. Quando analisada sob forma categorizada, definiu-se como hiper-homocisteinemia os valores encontrados acima do percentil 75 do grupo controle (14 µmol/l ). Hiper-homocisteinemia foi encontrada em 34% dos idosos, sendo 37,3% no grupo controle e 62,7% no grupo caso (p=0,009). Na análise multivariada, a hiperhomocisteinemia constituiu fator de risco independente para doença aterosclerótica coronariana em idosos, com razão de risco para doença arterial coronariana de 2,03, intervalo de confiança 95%, 1,02-4,03. CONCLUSÃO: Hiper-homocisteinemia foi fator de risco independente para doença arterial coronariana em idosos.<br>OBJECTIVE: To investigate whether hyperhomocysteinemia is an independent risk factor for atherosclerotic disease in elderly individuals METHODS: A case-control study with 172 elderly individuals, 88 belonging to control group and 84 to case group, who showed coronary angiography requested for clinical indications. Quantitative coronary angiography was performed in 91% of the patients. Homocysteinemia was assessed in a continuous and categorized way, through univariate and multivariate analysis. RESULTS: When analyzed continuously, in univariate analysis, it was verified that case group elderly individuals showed an average homocysteinemia levels significantly higher than the control group individuals' (14.33&plusmn;4.59 µmol/l against 11.99&plusmn;4.59 µmol/l, p=0.015). In multivariate analysis, continuous homocysteinemia was associated to the risk rate for coronary artery disease of 1.07 for each 1 µmol/l increase of homocysteine level. Na increase of 5 µmol/l corresponded to the risk rate of 1.40. When analyzed in categorized way, the values found over percentile 75 of control group (14 µmol/l) were defined as hyperhomocysteinemia. Hyperhomocysteinemia was found in 34% of elderly individuals, being 37.3% in control group and 62.7% in case group (p= 0.009). In multivariate analysis, hyperhomocysteinemia constituted an independent risk factor for coronary atherosclerotic disease for elderly individuals, with a risk rate for coronary artery disease of 2.03, confidence interval 95%, 1.02-4.03. CONCLUSION: Hyperhomocysteinemia was an independent risk factor for coronary artery disease in elderly individuals

A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk

The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms