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Background: Few studies have examined simultaneously the prognostic value of traditional and emerging biomarkers including atrial natriuretic peptide (ANP) and brain-type natriuretic peptide (BNP), for major cardiovascular disease (CVD) outcomes in patients with stable CVD, and results are equivocal., Design: and, Methods: Mid-regional pro-ANP (MR-proANP) and N-Terminal pro-BNP (NT-proBNP), CRP and homocysteine were measured in stable CVD patients (n = 1456; age: 61.8 y) at inclusion in the SU.FOL.OM3 cohort. Prospective association of biomarkers with risk of heart failure, major cardiovascular (non-fatal myocardial infarction, ischemic stroke or death from CVD) or overall cardiovascular event were examined with Cox proportional-hazards analyses. Increase in prediction risk upon addition of biomarker(s) to the traditional risk model was examined by change in C-statistic, NRI and IDI., Results: During follow-up (median: 4.7 y), 40 heart failure, 145 major cardiovascular and 493 overall cardiovascular events were diagnosed. In models adjusted for age, sex, smoking, diabetes, serum creatinine and CVD inclusion criteria, NT-proBNP and CRP associated significantly with heart failure. Both natriuretic peptides predicted the risk of major cardiovascular events in adjusted models; Hazard ratio (HR) and 95% CI for each SD increase in MR-proANP and NT-proBNP were 1.24 (1.04-1.47), and 1.31 (1.09-1.57), respectively. The addition of NT-proBNP to a traditional risk model increased significantly the area-under-curve for heart failure and overall cardiovascular events (by 6 and 12%, respectively); addition of MR-proANP or homocysteine yielded modest (2%) but statistically significant increase for major cardiovascular events., Conclusion: NT-proBNP consistently predicted CVD outcomes and may be useful singly or in combination with MR-proANP for risk-stratification in high-risk patients., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Aim: Dynamics of improvement in health-related quality of life (QoL) after bariatric surgery have never been fully assessed, and neither has the potential influence of body mass index (BMI) and comorbidity modification. The objective of this study was to investigate early and medium-term changes in QoL following Roux-en-Y gastric bypass (RYGB), and their relationship to BMI and comorbidity variations., Methods: A total of 71 obese subjects (80% women, mean age 42.1±11.2 years, mean baseline BMI 47.6±6.2kg/m(2)) undergoing RYGB filled in QoL questionnaires (SF-36) before and 3, 6 and 12 months after surgery. QoL was assessed using repeated-measures Anova, with associations between its changes and changes in BMI and comorbidities (diabetes, hypertension, dyslipidaemia, sleep apnoea, knee pain) assessed by mixed-effects models., Results: Physical QoL scales (physical component summary, PCS) significantly increased over time (from 38.9±9.3 to 52.6±7.9; P<0.001) as did other physical SF-36 scales (all P<0.001), whereas mental QoL summary scale did not vary significantly (from 45.7±9.5 to 48.6±11.5; P=0.072). Major changes in QoL occurred at 3 months after surgical intervention to reach values comparable to those in the general population. PCS was mostly associated with changes in either BMI or comorbidity status except for diabetes, dyslipidaemia and sleep apnoea., Conclusion: Results show that improvements in physical QoL after RYGB are observed as early as 3 months after intervention, and are independently associated with weight loss and improvements in comorbidities., (Copyright © 2013. Published by Elsevier Masson SAS.)

Experimental and prevalent case-control studies suggest an association between biomarkers of inflammation, endothelial function, and adiposity and cancer risk, but results from prospective studies have been limited. The authors' objective was to prospectively examine the relations between these biomarkers and cancer risk. A nested case-control study was designed within the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) Study, a nationwide French cohort study, to include all first primary incident cancers diagnosed between 1994 and 2007 (n = 512). Cases were matched with randomly selected controls (n = 1,024) on sex, age (in 2-year strata), body mass index (weight (kg)/height (m)(2); <25 vs. ≥25), and SU.VI.MAX intervention group. Conditional logistic regression was used to study the associations between prediagnostic levels of high-sensitivity C-reactive protein (hs-CRP), adiponectin, leptin, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1, soluble E-selectin, and monocyte chemoattractant protein 1 and cancer risk. All statistical tests were 2-sided. Plasma sICAM-1 level was positively associated with breast cancer risk (for quartile 4 vs. quartile 1, multivariate odds ratio (OR) = 1.86, 95% confidence interval (CI): 1.06, 3.26; P(trend) = 0.048). Plasma hs-CRP level was positively associated with prostate cancer risk (for quartile 4 vs. quartile 1, multivariate OR = 3.04, 95% CI: 1.28, 7.23; P(trend) = 0.03). These results suggest that prediagnostic hs-CRP and sICAM-1 levels are associated with increased prostate and breast cancer risk, respectively.

Background: Dietary factors might affect depressive symptoms., Objective: In secondary data analyses, we examined effects of supplementation with B vitamins or n-3 (omega-3) fatty acids on depressive symptoms in cardiovascular disease survivors., Design: The SUpplementation with FOLate, vitamins B-6 and B-12 and/or OMega-3 fatty acids (SU.FOL.OM3) trial was a secondary prevention trial (2003-2009; n = 2501) in which individuals aged 45-80 y were randomly assigned, by using a 2 × 2 factorial design, to receive 0.56 mg 5-methyl-tetrahydrofolate and vitamins B-6 (3 mg) and B-12 (0.02 mg); EPA and DHA (600 mg) in a 2:1 ratio; B vitamins and n-3 fatty acids; or a placebo. Depressive symptoms were evaluated at years 3 and 5 with the 30-item Geriatric Depression Scale (GDS). Overall and sex-specific ORs and 95% CIs were estimated in 2000 participants by using factorial logistic regression., Results: After a median of 4.7 y of supplementation, there was no association between allocation to receive B vitamins and depressive symptoms. However, the allocation to receive n-3 fatty acids was positively associated with depressive symptoms (GDS >10) in men (adjusted OR: 1.28; 95% CI: 1.03, 1.61) but not in women., Conclusions: We showed no beneficial effects of a long-term, low-dose supplementation with B vitamins or n-3 fatty acids on depressive symptoms in cardiovascular disease survivors. The adverse effects of n-3 fatty acids in men merit confirmation.

Aim: To examine the relationships between pre-diagnostic biomarkers and colorectal cancer risk and assess their relevance in predictive models., Methods: A nested case-control study was designed to include all first primary incident colorectal cancer cases diagnosed between inclusion in the SUpplémentation en VItamines et Minéraux AntioXydants cohort in 1994 and the end of follow-up in 2007. Cases (n = 50) were matched with two randomly selected controls (n = 100). Conditional logistic regression models were used to investigate the associations between pre-diagnostic levels of hs-CRP, adiponectin, leptin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1, E-selectin, monocyte chemoattractant protein-1 and colorectal cancer risk. Area under the receiver operating curves (AUC) and relative integrated discrimination improvement (RIDI) statistics were used to assess the discriminatory potential of the models., Results: Plasma adiponectin level was associated with decreased colorectal cancer risk (P for linear trend = 0.03). Quartiles of sVCAM-1 were associated with increased colorectal cancer risk (P for linear trend = 0.02). No association was observed with any of the other biomarkers. Compared to standard models with known risk factors, those including both adiponectin and sVCAM-1 had substantially improved performance for colorectal cancer risk prediction (P for AUC improvement = 0.01, RIDI = 26.5%)., Conclusion: These results suggest that pre-diagnostic plasma adiponectin and sVCAM-1 levels are associated with decreased and increased colorectal cancer risk, respectively. These relationships must be confirmed in large validation studies.

Background: To advance knowledge about the cancer-chemopreventive potential of individual nutrients, we investigated the effects of B vitamin and/or ω-3 fatty acid supplements on cancer outcomes among survivors of cardiovascular disease., Methods: This was an ancillary study of the Supplementation With Folate, Vitamins B(6) and B(12) and/or Omega-3 Fatty Acids (SU.FOL.OM3) secondary prevention trial (2003-2009). In all, 2501 individuals aged 45 to 80 years were randomized in a 2 × 2 factorial design to one of the following 4 daily supplementation groups: (1) 5-methyltetrahydrofolate (0.56 mg), pyridoxine hydrochloride (vitamin B(6); 3 mg) and cyanocobalamin (vitamin B(12); 0.02 mg); (2) eicosapentaenoic and docosahexaenoic acid (600 mg) in a 2:1 ratio; (3) B vitamins and ω-3 fatty acids; or (4) placebo. Overall and sex-specific hazard ratios (HRs) and 95% CIs regarding the cancer outcomes were estimated with Cox proportional hazards models., Results: After 5 years of supplementation, incident cancer was validated in 7.0% of the sample (145 events in men and 29 in women), and death from cancer occurred in 2.3% of the sample. There was no association between cancer outcomes and supplementation with B vitamins (HR, 1.15 [95% CI, 0.85-1.55]) and/or ω-3 fatty acids (HR, 1.17 [95% CI, 0.87-1.58]). There was a statistically significant interaction of treatment by sex, with no effect of treatment on cancer risk among men and increased cancer risk among women for ω-3 fatty acid supplementation (HR, 3.02 [95% CI, 1.33-6.89])., Conclusion: We found no beneficial effects of supplementation with relatively low doses of B vitamins and/or ω-3 fatty acids on cancer outcomes in individuals with prior cardiovascular disease. Trial Registration  isrctn.org Identifier: ISRCTN41926726.

Certain epidemiological and experimental studies suggest that n-3 fatty acids and folate can reduce blood pressure (BP). We investigated the effect of a daily supplementation with dietary doses of B-vitamins or n-3 fatty acids for 5 years on BP in patients with a history of CVD who participated in the Supplémentation en Folates et Omega-3 trial. The patients (n 2501; 1987 men and 514 women) were randomly assigned in a 2 × 2 factorial design to one of four groups: B-vitamins (5-methyl-THF (560 μg); vitamin B₆ (3 mg) and vitamin B₁₂ (20 μg)) and a placebo capsule for n-3 fatty acids; n-3 fatty acids (600 mg of EPA and DHA at a ratio of 2:1) and a placebo capsule for B-vitamins; both B-vitamins and n-3 fatty acids; or placebo capsules for both treatments. The patients took two capsules daily in a double-blind manner for a median duration of 4·7 years. At baseline and annual examination for 5 years, the patients underwent a clinical examination where BP and clinical and biological parameters were assessed. No effect of supplementation with either n-3 PUFA or B-vitamins on BP was observed in crude and adjusted multivariate models. Change in BP was not associated with change in homocysteine. In conclusion, the present results do not support the routine use of dietary supplements containing B-vitamins, or of n-3 fatty acids, to reduce BP in people with prior CVD.

Background: During the early 19th century, contagionists' and anti-contagionists' explanations of disease causes opposed one another, and the Hippocratic miasma theory still predominated. According to that theory, geographic health disparities could be explained by topographical factors: differences in altitude, population density or proximity to a river. This article summarizes the life of Louis-René Villermé (1782-1863) and his major contributions to social epidemiology that proved the association between poverty and mortality., Methods: In this study, data reported by Villermé to study the mortality-rate variations across the 12 districts (arrondissements) of Paris-that is, 1817-1826 Parisian death rates by district, population density and income indicators-are presented and reanalyzed., Results: Results obtained with today's statistical techniques (correlation analysis) support Villermé's claims of a direct poverty-high death rate link: the three income indicators that he chose were significantly correlated with at-home mortality: taxation index (r=-0.83, p<0.002), average rent (r=-0.83, p<0.002), trade taxation index (r=-0.67, p<0.05), while population density variables were not associated with mortality., Conclusion: Villermé was not only a forerunner of social epidemiology, he was also a scientific pioneer by relying on data, not opinions, to challenge or support medical hypotheses.

The aim of this study was to assess the association between obesity and the risk of intensive care unit (ICU) admission and death among patients hospitalized for influenza A (H1N1) viral infection. A systematic review of the Medline and Cochrane databases using 'obesity', 'hospitalization', 'influenza A viral infection', various synonyms, and reference lists of retrieved articles from January 2009 to January 2010. Studies comparing the prevalence of obesity among patients with confirmed infection for influenza A virus and who were either hospitalized or admitted to ICU/died were included. A total of 3059 subjects from six cross-sectional studies, who were hospitalized for influenza A (H1N1) viral infection, were included in this meta-analysis. Severely obese H1N1 patients (body mass index ≥ 40 kg m(-2), n = 804) were as twice as likely to be admitted to ICU or die (odds ration: 2.01, 95% confidence interval: 1.29-3.14, P < 0.002) compared with H1N1 patients who were not severely obese. Having a body mass index ≥ 30 kg m(-2) was similarly associated with a more than twofold increased risk of ICU admission or death although this did not reach statistical significance (2.14, 0.92-4.99, P < 0.07). This meta-analysis supports the view that obesity is associated with higher risks of ICU admission or death in patients with influenza A (H1N1) infection. Therefore, morbid obese patients should be monitored more intensively when hospitalized., (© 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.)

Objective: The objective of this study was to investigate the relationship between adherence to French diet and physical activity recommendations and metabolic syndrome (MetS) risk., Methods: 18-74-year-old subjects who underwent dietary assessment and health examination in the 2006-2007 French Nutrition and Health Survey (Etude Nationale Nutrition Santé, ENNS 2006-2007) were included in the analyses (n=1608). Quintiles of PNNS-GS, the score measuring adherence to French recommendations, were generated. The prevalence of overall MetS risk and separate components across quintiles of PNNS-GS was estimated by adjusted logistic regressions. Interactions were searched for between PNNS-GS and sex, age and currently used medication., Results: The PNNS-GS was inversely associated with overall MetS risk in subjects not taking antidiabetic, antihypertensive or lipid-lowering medication (12.8% in the lowest quintile vs. 4.6% in the highest PNNS-GS quintile; P<0.01). This was true in 18-49-year-old subjects (10.0% vs. 1.7%, P<0.01), but not in 50-74-year-olds (23.8% vs. 11.2%; P=0.15). In 18-49-year-old adults, including those taking such medication, the HDL component was associated with PNNS-GS (22.1% vs. 7.9%; P<0.01)., Conclusion: Improvement in diet and physical activity in line with recommendations could be effective in young adults for MetS prevention so as to decrease the risk of cardiovascular disease in France., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Supplementation with high doses of antioxidant vitamins prevents the insulin-sensitizing effects of physical exercise. However, little is known whether antioxidant supplementation affects the incidence of impaired fasting glucose (IFG). Data from 8938 subjects included in a randomized controlled trial on supplementation with antioxidants vitamins and trace elements at nutritional doses (SU.VI.MAX) were used to examine the effects of antioxidants on incident IFG after 7.5 years of follow-up, with and without stratification for daily physical exercise. The odds-ratio (95% CI) for developing an IFG among study participants receiving antioxidant supplementation was 1.34 (0.90-1.97) (p=0.33), in comparison to placebo. This risk did not vary significantly according to physical activity level (p for homogeneity=0.10). Supplementation with trace elements and antioxidants at nutritional doses apparently does not affect the incidence of IFG irrespective of self-reported physical exercise habits., (© Georg Thieme Verlag KG Stuttgart · New York.)

Specular microscopic studies indicate that the size (polymegathism) and shape (pleomorphism) of the hexagonal corneal endothelial cells change in diabetics. Similar morphometric changes of the corneal endothelium have also been experimentally observed in diabetic rats as well as in diabetic and galactose-fed dogs and concomitant administration of aldose reductase inhibitors reduced these morphological changes. The purpose of this study was to examine whether corneal endothelial changes in galactose-fed dogs are reversible by the marked reduction of galactitol production after stopping prolonged galactose feeding. Ten control dogs were fed a normal diet, while 48 dogs were fed a diet containing 30% galactose. The galactose diet was removed from 15 dogs after 24 months at which time pericyte ghosts in the retina had developed and another 15 dogs were removed from the galactose diet after 31 months when retinal microaneurysms had developed. Eighteen dogs remained on galactose diet throughout the study (38 months). Specular microscopy was conducted on members of all groups after 38 months of study and the photographs were analyzed in masked fashion on the Bambi image analysis system. The evaluation of the corneal endothelial cells revealed significant differences in the cell size and density between galactose-fed dogs in the three groups and normal, age-matched control dogs. Corneal endothelial changes were not significantly reduced in dogs fed galactose for either 24 months or 31 months and then fed a normal diet for 14 and 7 months, respectively, indicating that amelioration of endothelial cell changes requires therapy prior to the advent of endothelial morphologic changes.