The SU.FOL.OM3 Study: a secondary prevention trial testing the impact of supplementation with folate and B-vitamins and/or Omega-3 PUFA on fatal and non fatal cardiovascular events, design, methods and participants characteristics

<p>Abstract</p> <p>Background</p> <p>During the last decades, many basic and clinical research have pointed to the role of B vitamins (folate, vitamins B6 and B12) and n-3 fatty acids as nutritional factors that might have a protective effect on the development of cardiovascular diseases (CVD).</p> <p>Methods/design</p> <p>The SU.FOL.OM3 (SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids) trial is a randomized double-blind, placebo-controlled, secondary-prevention trial designed to test the efficacy of 5-methyl tetra-hydro-folates (5-MTHF) supplementation, in combination with vitamin B6 and B12 and/or n-3 fatty acids, at nutritional doses, on fatal and non fatal ischemic CVD in a 2 × 2 factorial design. A total of 2501 patients aged between 45 and 80 years who had a past history, in the previous year, of myocardial infarction (n = 1151) or instable angina pectoris (n = 711) or an ischemic stroke (n = 639) were included. Subjects have to be supplemented and followed up for five years. Daily supplementation comprised nutritional doses of 5-MTHF (560 μg), vitamin B6 (3 mg) and B12 (20 μg) and/or n-3 fatty acids (600 mg with an EPA:DHA ratio of 2:1). A factorial design 2 × 2 has been applied to investigate the separate effects of the B-vitamins, and the n-3 fatty acids, as well as their interaction as compared to the placebo.</p> <p>The primary endpoint is a combination of myocardial infarction, ischemic stroke and cardiovascular death. Secondary endpoints are events of the composite endpoint taken separately, total mortality, and other cardiovascular events such as acute coronary syndromes, coronary revascularization, cardiac failure, arrhythmia...</p> <p>Conclusion</p> <p>Baseline socio-demographic and medical characteristics of participants are totally comparable in the four randomized groups.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN41926726</p

Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial

Objective To investigate whether dietary supplementation with B vitamins or omega 3 fatty acids, or both, could prevent major cardiovascular events in patients with a history of ischaemic heart disease or stroke

Association of Healthy Lifestyle Factors and Obesity-Related Diseases in Adults in the UK

Importance: A healthy lifestyle is associated with a reduced risk of cardiovascular disease in adults with obesity. Little is known about the associations between a healthy lifestyle and the risk of other obesity-attributable diseases in this population. Objective: To examine the association between healthy lifestyle factors and the incidence of major obesity-related diseases in adults with obesity compared with those with normal weight. Design, Setting, and Participants: This cohort study evaluated UK Biobank participants aged 40 to 73 years and free of major obesity-attributable disease at baseline. Participants were enrolled from 2006 to 2010 and prospectively followed up for disease diagnosis. Exposures: A healthy lifestyle score was constructed using information on not smoking, exercising regularly, no or moderate alcohol consumption, and eating a healthy diet. For each lifestyle factor, participants scored 1 if they met the criterion for a healthy lifestyle and 0 otherwise. Main Outcomes and Measures: The risk of outcomes according to the healthy lifestyle score in adults with obesity compared with those with normal weight were examined using multivariable Cox proportional hazards models with Bonferroni correction for multiple testing. The data analysis was performed between December 1, 2021, and October 31, 2022. Results: A total of 438 583 adult participants in the UK Biobank were evaluated (female, 55.1%; male, 44.9%; mean [SD] age, 56.5 [8.1] years), of whom 107 041 (24.4%) had obesity. During a mean (SD) follow-up of 12.8 (1.7) years, 150 454 participants (34.3%) developed at least 1 of the studied diseases. Compared with adults with obesity and 0 healthy lifestyle factors, individuals with obesity who met all 4 healthy lifestyle factors were at lower risk of hypertension (HR, 0.84; 95% CI, 0.78-0.90), ischemic heart disease (HR, 0.72; 95% CI, 0.65-0.80), arrhythmias (HR, 0.71; 95% 0.61-0.81), heart failure (HR, 0.65; 95% CI, 0.53-0.80), arteriosclerosis (HR, 0.19; 95% CI, 0.07-0.56), kidney failure (HR, 0.73; 95% CI, 0.63-0.85), gout (HR, 0.51; 95% CI, 0.38-0.69), sleep disorders (HR, 0.68; 95% CI, 0.56-0.83), and mood disorders (HR, 0.66; 95% CI, 0.56-0.78). The lifestyle profiles associated with the lowest risks included a healthy diet and at least 1 of the 2 healthy behaviors of physical activity and never smoking. Compared with adults with normal weight, those with obesity were at higher risk of several outcomes, irrespective of the lifestyle score (adjusted HRs ranged from 1.41 [95% CI, 1.27-1.56] for arrhythmias to 7.16 [95% CI, 6.36-8.05] for diabetes for adults with obesity and 4 healthy lifestyle factors). Conclusion and Relevance: In this large cohort study, adherence to a healthy lifestyle was associated with reduced risk of a wide range of obesity-related diseases, but this association was modest in adults with obesity. The findings suggest that although a healthy lifestyle seems to be beneficial, it does not entirely offset the health risks associated with obesity

Obesity and the microvasculature

Overweight and obesity are thought to significantly influence a person's risk of cardiovascular disease, possibly via its effect on the microvasculature. Retinal vascular caliber is a surrogate marker of microvascular disease and a predictor of cardiovascular events. The aim of this systematic review and meta-analysis was to determine the association between body mass index (BMI) and retinal vascular caliber. Relevant studies were identified by searches of the MEDLINE and EMBASE databases from 1966 to August 2011. Standardized forms were used for data extraction. Among over 44,000 individuals, obese subjects had narrower arteriolar and wider venular calibers when compared with normal weight subjects, independent of conventional cardiovascular risk factors. In adults, a 1 kg/m(2) increase in BMI was associated with a difference of 0.07 μm [95% CI: -0.08; -0.06] in arteriolar caliber and 0.22 μm [95% CI: 0.21; 0.23] in venular caliber. Similar results were found for children. Higher BMI is associated with narrower retinal arteriolar and wider venular calibers. Further prospective studies are needed to examine whether a causative relationship between BMI and retinal microcirculation exists

Obesity and the Microvasculature: A Systematic Review and Meta-Analysis

10.1371/journal.pone.0052708PLoS ONE82

The Nutrinet-Santé Study: a web-based prospective study on the relationship between nutrition and health and determinants of dietary patterns and nutritional status

<p>Abstract</p> <p>Background</p> <p>Nutrition-related chronic diseases such as cardiovascular diseases and cancer are of multiple origin, and may be due to genetic, biologic, behavioural and environmental factors. In order to detangle the specific role of nutritional factors, very large population sample cohort studies comprising precisely measured dietary intake and all necessary information for accurately assessing potential confounding factors are needed. Widespread use of internet is an opportunity to gradually collect huge amounts of data from a large sample of volunteers that can be automatically verified and processed. The objectives of the NutriNet-Santé study are: 1) to investigate the relationship between nutrition (nutrients, foods, dietary patterns, physical activity), mortality and health outcomes; and 2) to examine the determinants of dietary patterns and nutritional status (sociological, economic, cultural, biological, cognitive, perceptions, preferences, etc.), using a web-based approach.</p> <p>Methods/design</p> <p>Our web-based prospective cohort study is being conducted for a scheduled follow-up of 10 years. Using a dedicated web site, recruitment will be carried out for 5 years so as to register 500 000 volunteers aged ≥ 18 years among whom 60% are expected to be included (having complete baseline data) and followed-up for at least 5 years for 240 000 participants. Questionnaires administered via internet at baseline and each year thereafter will assess socio-demographic and lifestyle characteristics, anthropometry, health status, physical activity and diet. Surveillance of health events will be implemented via questionnaires on hospitalisation and use of medication, and linkage with a national database on vital statistics. Biochemical samples and clinical examination will be collected in a subsample of volunteers.</p> <p>Discussion</p> <p>Self-administered data collection using internet as a complement to collection of biological data will enable identifying nutrition-related risks and protective factors, thereby more clearly elucidating determinants of nutritional status and their interactions. These are necessary steps for further refining nutritional recommendations aimed at improving the health status of populations.</p

Genetic Variant in HK1 Is Associated With a Proanemic State and A1C but Not Other Glycemic Control–Related Traits

OBJECTIVE A1C is widely considered the gold standard for monitoring effective blood glucose levels. Recently, a genome-wide association study reported an association between A1C and rs7072268 within HK1 (encoding hexokinase 1), which catalyzes the first step of glycolysis. HK1 deficiency in erythrocytes (red blood cells [RBCs]) causes severe nonspherocytic hemolytic anemia in both humans and mice. RESEARCH DESIGN AND METHODS The contribution of rs7072268 to A1C and the RBC-related traits was assessed in 6,953 nondiabetic European participants. We additionally analyzed the association with hematologic traits in 5,229 nondiabetic European individuals (in whom A1C was not measured) and 1,924 diabetic patients. Glucose control–related markers other than A1C were analyzed in 18,694 nondiabetic European individuals. A type 2 diabetes case-control study included 7,447 French diabetic patients. RESULTS Our study confirms a strong association between the rs7072268–T allele and increased A1C (β = 0.029%; P = 2.22 × 10−7). Surprisingly, despite adequate study power, rs7072268 showed no association with any other markers of glucose control (fasting- and 2-h post-OGTT–related parameters, n = 18,694). In contrast, rs7072268–T allele decreases hemoglobin levels (n = 13,416; β = −0.054 g/dl; P = 3.74 × 10−6) and hematocrit (n = 11,492; β = −0.13%; P = 2.26 × 10−4), suggesting a proanemic effect. The T allele also increases risk for anemia (836 cases; odds ratio 1.13; P = 0.018). CONCLUSIONS HK1 variation, although strongly associated with A1C, does not seem to be involved in blood glucose control. Since HK1 rs7072268 is associated with reduced hemoglobin levels and favors anemia, we propose that HK1 may influence A1C levels through its anemic effect or its effect on glucose metabolism in RBCs. These findings may have implications for type 2 diabetes diagnosis and clinical management because anemia is a frequent complication of the diabetes state

Genome wide association study identifies KCNMA1 contributing to human obesity

<p>Abstract</p> <p>Background</p> <p>Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population. Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity.</p> <p>Methods</p> <p>We performed a GWA analysis in 164 morbidly obese subjects (BMI:body mass index > 40 kg/m²) and 163 Swedish subjects (> 45 years) who had always been lean. The 700 SNPs displaying the strongest association with obesity in the GWA were analyzed in a second cohort comprising 460 morbidly obese subjects and 247 consistently lean Swedish adults. 23 SNPs remained significantly associated with obesity (nominal <it>P</it>< 0.05) and were in a step-wise manner followed up in five additional cohorts from Sweden, France, and Germany together comprising 4214 obese and 5417 lean or population-based control individuals. Three samples, n = 4133, were used to investigate the population-based associations with BMI. Gene expression in abdominal subcutaneous adipose tissue in relation to obesity was investigated for14 adults.</p> <p>Results</p> <p>Potassium channel, calcium activated, large conductance, subfamily M, alpha member <it>(KCNMA1) </it>rs2116830*G and <it>BDNF </it>rs988712*G were associated with obesity in five of six investigated case-control cohorts. In meta-analysis of 4838 obese and 5827 control subjects we obtained genome-wide significant allelic association with obesity for <it>KCNMA1 </it>rs2116830*G with <it>P </it>= 2.82 × 10^-10and an odds ratio (OR) based on cases vs controls of 1.26 [95% C.I. 1.12-1.41] and for <it>BDNF </it>rs988712*G with <it>P </it>= 5.2 × 10^-17and an OR of 1.36 [95% C.I. 1.20-1.55]. <it>KCNMA1 </it>rs2116830*G was not associated with BMI in the population-based samples. Adipose tissue (<it>P </it>= 0.0001) and fat cell (<it>P </it>= 0.04) expression of <it>KCNMA1 </it>was increased in obesity.</p> <p>Conclusions</p> <p>We have identified <it>KCNMA1 </it>as a new susceptibility locus for obesity, and confirmed the association of the <it>BDNF </it>locus at the genome-wide significant level.</p

Post Genome-Wide Association Studies of Novel Genes Associated with Type 2 Diabetes Show Gene-Gene Interaction and High Predictive Value

Recently, several Genome Wide Association (GWA) studies in populations of European descent have identified and validated novel single nucleotide polymorphisms (SNPs), highly associated with type 2 diabetes (T2D). Our aims were to validate these markers in other European and non-European populations, then to assess their combined effect in a large French study comparing T2D and normal glucose tolerant (NGT) individuals. rs7903146 SNP, were combined (8.68-fold for the 14% of French individuals carrying 18 to 30 risk alleles with an allelic OR of 1.24). With an area under the ROC curve of 0.86, only 15 novel loci were necessary to discriminate French individuals susceptible to develop T2D. strongly associate with T2D in French individuals, and mostly in populations of Central European descent but not in Moroccan subjects. Genes expressed in the pancreas interact together and their combined effect dramatically increases the risk for T2D, opening avenues for the development of genetic prediction tests