Combinatorial, additive and dose-dependent drug-microbiome associations.

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease.

Consistency of the Initial and Updated Version of the Nutri-Score with Food-Based Dietary Guidelines: A French Perspective.

BACKGROUND: To help consumers to make healthier food choices, 7 European countries have implemented the front-of-pack nutrition label Nutri-Score. The algorithm was updated in 2022-2023 by the Nutri-Score European scientific committee, based on the current scientific knowledge. OBJECTIVES: The aim of this study was to investigate the consistency of the newly internationally developed algorithm with the French food-based dietary guidelines (FBDG) and compare the respective performances of the initial and updated algorithm. METHODS: Three complementary French food composition databases were used to access extensive coverage of the food supply in France (n = 46,752): the Oqali, OpenFoodFacts, and CIQUAL databases. Based on the French FBDG, a list of 41 criteria was defined by which the consistency between French FBDG and the Nutri-Score was assessed (eg, consumption of fresh vegetables is promoted in FBDG, thus the Nutri-Score should rate favorably such products). RESULTS: Of all criteria, the initial algorithm met 63% (26/41) of them, whereas the revised algorithm met 85% (35/41) of them. Improvements achieved by the updated version of the Nutri-Score in alignment with the FBDG were particularly observed for high-fat products (ie, fatty fish, nuts, and seeds), sweet products (ie, ice creams and sweet spreads), salty products (ie, savory snacks and salted nuts), dairy beverages, and beverages with artificial sweeteners. CONCLUSIONS: The Nutri-Score's updated nutrient profiling system appears to rate foods more consistently regarding the French dietary guidelines and improved the currently existing system. This work supports the implementation of the updated nutrient profiling system underlying Nutri-Score.

Complementarity between the updated version of the front-of-pack nutrition label Nutri-Score and the food-processing NOVA classification.

OBJECTIVE: To compare the initial and the updated versions of the front-of-pack label Nutri-Score (related to the nutritional content) with the NOVA classification (related to the degree of food processing) at the food level. DESIGN: Using the OpenFoodFacts database - 129,950 food products - we assessed the complementarity between the Nutri-Score (initial and updated) with the NOVA classification through a correspondence analysis. Contingency tables between the two classification systems were used. SETTINGS: The food offer in France. PARTICIPANTS: Not applicable. RESULTS: With both versions (i.e. initial and updated) of the Nutri-Score, the majority of ultra-processed products received medium to poor Nutri-Score ratings (between 77·9 % and 87·5 % of ultra-processed products depending on the version of the algorithm). Overall, the update of the Nutri-Score algorithm led to a reduction in the number of products rated A and B and an increase in the number of products rated D or E for all NOVA categories, with unprocessed foods being the least impacted (-3·8 percentage points (-5·2 %) rated A or B and +1·3 percentage points (+12·9 %) rated D or E) and ultra-processed foods the most impacted (-9·8 percentage points (-43·4 %) rated A or B and +7·8 percentage points (+14·1 %) rated D or E). Among ultra-processed foods rated favourably with the initial Nutri-Score, artificially sweetened beverages, sweetened plant-based drinks and bread products were the most penalised categories by the revision of Nutri-Score while low-sugar flavoured waters, fruit and legume preparations were the least affected. CONCLUSION: These results indicate that the update of the Nutri-Score reinforces its coherence with the NOVA classification, even though both systems measure two distinct health dimensions at the food level.

Body composition and anthropometric indicators as predictors of blood pressure: a cross-sectional study conducted in young Algerian adults.

Various body indicators are used to predict health risks. However, controversies still exist regarding the best indicators to predict CVD. Using a large number of measurements, our aim was to assess their associations with blood pressure (BP) and to identify the most relevant parameters to be used in health surveillance studies. The population included 589 students (67·2 % women) aged 20-25 years from Constantine (Algeria). Sixteen parameters were considered, including crude body measurements, ratios and body fat indicators based on bioelectrical impedance analysis (BIA). We used multi-adjusted linear regression models to assess the associations between body measurements and BP. According to WHO definitions, underweight, overweight-without obesity, obesity and hypertension (HT) were identified in 6·1, 18·0, 2·4 and 5·1 % of the subjects, respectively. Prevalence of HT was higher in men than in women (11·9 % v. 1·8 %; P < 0·001). In the whole sample, almost all indicators were positively associated with systolic and diastolic BP. The suprailiac skinfold had the strongest associations with systolic (ß = 3·498; P < 0·001) and diastolic (ß = 2·436; P < 0·001) BP, and as a whole, arm circumferences and weight were also good candidates. The currently used BMI, waist-to-hip, waist-to-height ratio and BIA indictors also predicted BP, but they did not seem to be better determinants of BP than crude anthropometric measurements. This study showed that overweight and HT were already found in the present population of young Algerian adults. Most body indicators were highly associated with BP, but simple anthropometric measurements appeared to be particularly useful to predict BP.

Exposome Profiles and Asthma among French Adults.

Rationale: Although previous studies in environmental epidemiology focused on single or a few exposures, a holistic approach combining multiple preventable risk factors is needed to tackle the etiology of multifactorial diseases such as asthma. Objectives: To investigate the association between combined socioeconomic, external environment, early-life environment, and lifestyle-anthropometric factors and asthma phenotypes. Methods: A total of 20,833 adults from the French NutriNet-Santé cohort were included (mean age, 56.2 yr; SD, 13.2; 72% women). The validated asthma symptom score (continuous) and asthma control (never asthma, controlled asthma, and uncontrolled asthma) were considered. The exposome (n = 87 factors) covered four domains: socioeconomic, external environment, early-life environment, and lifestyle-anthropometric. Cluster-based analyses were performed within each exposome domain, and the identified profiles were studied in association to asthma outcomes in negative binomial (asthma symptom score) or multinomial logistic (asthma control) regression models. Measurements and Main Results: In total, 5,546 (27%) individuals had an asthma symptom score ⩾1, and 1,206 (6%) and 194 (1%) had controlled and uncontrolled asthma, respectively. Three early-life exposure profiles ("high passive smoking-own dogs," "poor birth parameters-daycare attendance-city center," or "⩾2 siblings-breastfed" compared with "farm-pet owner-molds-low passive smoking") and one lifestyle-anthropometric profile ("unhealthy diet-high smoking-overweight" compared with "healthy diet-nonsmoker-thin") were associated with more asthma symptoms and uncontrolled asthma. Conclusions: This large-scale exposome-based study revealed early-life and lifestyle exposure profiles that were at risk for asthma in adults. Our findings support the importance of multiinterventional programs for the primary and secondary prevention of asthma, including control of specific early-life risk factors and promotion of a healthy lifestyle in adulthood.

Prospective association between adherence to the 2017 French dietary guidelines and risk of death, CVD and cancer in the NutriNet-Santé cohort.

Non-communicable diseases, such as cancers and CVD, represent a major public health concern, and diet is an important factor in their development. French dietary recommendations were updated in 2017, and an adherence score, the Programme National Nutrition Santé Guidelines Score (PNNS-GS2), has been developed and validated using a standardised procedure. The present study aimed to analyse the prospective association between PNNS-GS2 and the risk of death, cancer and CVD. Our sample consisted of French adults included in the prospective NutriNet-Santé cohort (n 67 748, 75 634 and 80 269 for the risk of death, cancer and CVD, respectively). PNNS-GS2 (range: -∞ to 14·25) was calculated from the 24-h dietary records of the first 2 years of monitoring. Association between PNNS-GS2 (in quintiles, Q) and the risk of death, cancer and CVD was studied using Cox models adjusted for the main confounding factors. The sample included 78 % of women, aged on average 44·4 years (sd 14·6) with on average 6·6 (sd 2·3) dietary records. Average PNNS-GS2 was 1·5 (sd 3·4) and median follow-up was 6·6 years for cancers and 6·2 years for CVD and deaths. PNNS-GS2 was significantly associated with the risk of death (hazard ratio (HR)Q5vsQ1: 0·77 (95 % CI 0·60, 1·00), 828 cases), cancer (HRQ5vsQ1 = 0·80 (95 % CI 0·69, 0·92), 2577 cases) and CVD (HRQ5vsQ1 0·64 (95 % CI 0·51, 0·81), 964 cases). More specifically, PNNS-GS2 was significantly associated with colorectal and breast cancer risks but not prostate cancer risk. Our results suggest that strong adherence to the 2017 French dietary recommendations is associated with a lower risk of death, cancer or CVD. This reinforces the validity of these new recommendations and will help to promote their dissemination.

Consumption of dairy products and CVD risk: results from the French prospective cohort NutriNet-Santé.

In France, dairy products contribute to dietary saturated fat intake, of which reduced consumption is often recommended for CVD prevention. Epidemiological evidence on the association between dairy consumption and CVD risk remains unclear, suggesting either null or inverse associations. This study aimed to investigate the associations between dairy consumption (overall and specific foods) and CVD risk in a large cohort of French adults. This prospective analysis included participants aged ≥18 years from the NutriNet-Santé cohort (2009-2019). Daily dietary intakes were collected using 24-h dietary records. Total dairy, milk, cheese, yogurts, fermented and reduced-fat dairy intakes were investigated. CVD cases (n 1952) included cerebrovascular disease (n 878 cases) and CHD (n 1219 cases). Multivariable Cox models were performed to investigate associations. This analysis included 104 805 French adults (mean age at baseline 42·8 (sd 14·6) years, mean follow-up 5·5 (sd 3·0) years, i.e. 579 155 person-years). There were no significant associations between dairy intakes and total CVD or CHD risks. However, the consumption of at least 160 g/d of fermented dairy (e.g. cheese and yogurts) was associated with a reduced risk of cerebrovascular diseases compared with intakes below 57 g/d (hazard ratio = 0·81 (95 % CI 0·66, 0·98), Ptrend = 0·01). Despite being a major dietary source of saturated fats, dairy consumption was not associated with CVD or CHD risks in this study. However, fermented dairy was associated with a lower cerebrovascular disease risk. Robust randomised controlled trials are needed to further assess the impact of consuming different dairy foods on CVD risk and potential underlying mechanisms.

Prospective association between dietary pesticide exposure profiles and type 2 diabetes risk in the NutriNet-Santé cohort.

BACKGROUND: Studies focusing on dietary pesticides in population-based samples are scarce and little is known about potential mixture effects. We aimed to assess associations between dietary pesticide exposure profiles and Type 2 Diabetes (T2D) among NutriNet-Santé cohort participants. METHODS: Participants completed a Food Frequency Questionnaire at baseline, assessing conventional and organic food consumption. Exposures to 25 active substances used in European Union pesticides were estimated using the Chemisches und Veterinäruntersuchungsamt Stuttgart residue database accounting for farming practices. T2D were identified through several sources. Exposure profiles were established using Non-Negative Matrix Factorization (NMF), adapted for sparse data. Cox models adjusted for known confounders were used to estimate hazard ratios (HR) and 95% confidence interval (95% CI), for the associations between four NMF components, divided into quintiles (Q) and T2D risk. RESULTS: The sample comprised 33,013 participants aged 53 years old on average, including 76% of women. During follow-up (median: 5.95 years), 340 incident T2D cases were diagnosed. Positive associations were detected between NMF component 1 (reflecting highest exposure to several synthetic pesticides) and T2D risk on the whole sample: HRQ5vsQ1 = 1.47, 95% CI (1.00, 2.18). NMF Component 3 (reflecting low exposure to several synthetic pesticides) was associated with a decrease in T2D risk, among those with high dietary quality only (high adherence to French dietary guidelines, including high plant foods consumption): HRQ5vsQ1 = 0.31, 95% CI (0.10, 0.94). CONCLUSIONS: These findings suggest a role of dietary pesticide exposure in T2D risk, with different effects depending on which types of pesticide mixture participants are exposed to. These associations need to be confirmed in other types of studies and settings, and could have important implications for developing prevention strategies (regulation, dietary guidelines). TRIAL REGISTRATION: This study is registered in ClinicalTrials.gov ( NCT03335644 ).

Teenage childbearing and school dropout in a sample of 18,791 single mothers in Cameroon.

BACKGROUND: Adolescent childbearing increases the risk of adverse health and social consequences including school dropout (SDO). However, it remains unclear why some teenage mothers drop out of school and others do not, especially in sub-Saharan Africa settings. We aimed to investigate the background and behavioral characteristics of single mothers, associated with school dropout in a sample of 18,791 Cameroonian girls, who had their first child during adolescence. METHODS: We used data from a national registry of single mothers, collected during the years 2005-2008 and 2010-2011. Both bivariate analysis and logistic binary regression models were used to explore the relationship between adolescence motherhood and SDO controlling for a range of socio-economic, family, sexual and health seeking behavior characteristics. RESULTS: Among the 18,791 single mothers, 41.6% had dropped out of school because of pregnancy. The multivariable regression model showed that SDO was more common in those who were evicted from their parental home (aOR: 1.85; 95% CI: 1.69-2.04), those who declared having other single mothers in their family (aOR: 1.16; 95% CI 1.08-1.25) and in mothers who had their first child before 15. Using modern contraceptive methods, having declared no sexual partner during the last year and having less than 2 children were associated with a reduced likelihood of school dropout. CONCLUSIONS: Strong social support is essential to ensure school continuity in this vulnerable population. Dropping out of school may put the teenage mother more at risk of unsafe health behaviour and new pregnancies.

There is compelling, worldwide evidence that pregnancy and birth during teenage years are significant contributors to high school dropout rates, especially in developing countries. Research has also shown that education continuity of teenage mothers can lessen the long term negative social consequences of teenage pregnancies and childbearing. In this study, we investigated the factors associated with school dropout in a sample of Cameroonian teenage mothers.The information collected included socio-economic, family, sexual characteristics, and health-seeking behavior.Among the 18,791 single mothers, 41.6% had dropped out of school because of pregnancy. School dropout was more common in those who were evicted from their parental home, those who declared having other single mothers in their family and in mothers who had their 1st child before 15. Using modern contraceptive methods, having declared no sexual partner during the last year and having less than 2 children were associated with a reduced likelihood of school dropout.In conclusion, strong social support is essential to ensure school continuity in this vulnerable population. Dropping out of school may put the teenage mother more at risk of unsafe health behaviour and new pregnancies.

The Plasma Oxylipin Signature Provides a Deep Phenotyping of Metabolic Syndrome Complementary to the Clinical Criteria.

Metabolic syndrome (MetS) is a complex condition encompassing a constellation of cardiometabolic abnormalities. Oxylipins are a superfamily of lipid mediators regulating many cardiometabolic functions. Plasma oxylipin signature could provide a new clinical tool to enhance the phenotyping of MetS pathophysiology. A high-throughput validated mass spectrometry method, allowing for the quantitative profiling of over 130 oxylipins, was applied to identify and validate the oxylipin signature of MetS in two independent nested case/control studies involving 476 participants. We identified an oxylipin signature of MetS (coined OxyScore), including 23 oxylipins and having high performances in classification and replicability (cross-validated AUCROC of 89%, 95% CI: 85-93% and 78%, 95% CI: 72-85% in the Discovery and Replication studies, respectively). Correlation analysis and comparison with a classification model incorporating the MetS criteria showed that the oxylipin signature brings consistent and complementary information to the clinical criteria. Being linked with the regulation of various biological processes, the candidate oxylipins provide an integrative phenotyping of MetS regarding the activation and/or negative feedback regulation of crucial molecular pathways. This may help identify patients at higher risk of cardiometabolic diseases. The oxylipin signature of patients with metabolic syndrome enhances MetS phenotyping and may ultimately help to better stratify the risk of cardiometabolic diseases.

Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort.

BACKGROUND: Nutritional factors are essential for the functioning of the immune system and could therefore play a role in COVID-19 but evidence is needed. Our objective was to study the associations between diet and the risk of SARS-CoV-2 infection in a large population-based sample. METHODS: Our analyses were conducted in the French prospective NutriNet-Santé cohort study (2009-2020). Seroprevalence of anti-SARS-CoV-2 antibodies was assessed by ELISA on dried blood spots. Dietary intakes were derived from repeated 24 h dietary records (at least 6) in the two years preceding the start of the COVID-19 pandemic in France (February 2020). Multi-adjusted logistic regression models were computed. RESULTS: A total of 7766 adults (70.3% women, mean age: 60.3 years) were included, among which 311 were positive for anti-SARS-CoV-2 antibodies. Dietary intakes of vitamin C (OR for 1 SD=0.86 (0.75-0.98), P=0.02), vitamin B9 (OR=0.84 (0.72-0.98), P=0.02), vitamin K (OR=0.86 (0.74-0.99), P=0.04), fibers (OR=0.84 (0.72-0.98), P=0.02), and fruit and vegetables (OR=0.85 (0.74-0.97), P=0.02) were associated to a decreased probability of SARS-CoV-2 infection while dietary intakes of calcium (OR=1.16 (1.01-1.35), P=0.04) and dairy products (OR=1.19 (1.06-1.33), P=0.002) associated to increased odds. No association was detected with other food groups or nutrients or with the overall diet quality. CONCLUSIONS: Higher dietary intakes of fruit and vegetables and, consistently, of vitamin C, folate, vitamin K and fibers were associated with a lower susceptibility to SARS-CoV-2 infection. Beyond its established role in the prevention of non-communicable diseases, diet could therefore also contribute to prevent some infectious diseases such as COVID-19.

Dietary macronutrient intake according to sex and trait anxiety level among non-diabetic adults: a cross-sectional study.

BACKGROUND: Studies suggest that anxiety is correlated with eating behavior, however, little is known about the association between anxiety status as predictor of dietary macronutrient intake. The aim of the present study was to investigate the sex-stratified cross-sectional associations of trait anxiety with intake of various macronutrients in a large population-based sample of non-diabetic adults. METHODS: N = 20,231 participants (mean age = 53.7 ± 13.6 years) of the NutriNet-Santé web-cohort, who had completed the trait anxiety subscale of the Spielberger State-Trait Anxiety Inventory (T-STAI; 2013-2016) were included in the analyses. Dietary intake was calculated from at least 3 self-administered 24-h dietary records. The associations of interest were assessed by multiple linear regression stratified by sex, owing to significant interaction tests. RESULTS: In total, 74.3% (n = 15,033) of the sample were females who had a significantly higher mean T-STAI score than did males (39.0 versus 34.8; p < 0.01). Among females, the fully-adjusted analyses showed significant positive associations of T-STAI with total carbohydrate intake (ß = 0.04; p < 0.04), complex carbohydrate intake (ß = 0.05; p < 0.02), and percentage energy from carbohydrates (ß = 0.01; p < 0.03), as well as a significant inverse association of T-STAI with percentage energy from fat (ß = -0.01; p < 0.05). As regards males, the only significant finding was an inverse association between T-STAI and percent of the mean daily energy from protein (fully-adjusted model: ß = -0.01; p = 0.05). CONCLUSION: This cross-sectional study found modest sex-specific associations between anxiety status and macronutrient intake among French non-diabetic adults. Prospective studies are needed to further elucidate the observed associations.

Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Santé study.

BACKGROUND: High consumption of red and processed meat is commonly associated with increased cancer risk, particularly colorectal cancer. Antibodies against the red meat-derived carbohydrate N-glycolylneuraminic acid (Neu5Gc) exacerbate cancer in "human-like" mice. Human anti-Neu5Gc IgG and red meat are both independently proposed to increase cancer risk, yet how diet affects these antibodies is largely unknown. METHODS: We used world global data to demonstrate that colorectal cancer incidence and mortality are associated with increased national meat consumption. In a well-defined large cohort, we used glycomics to measure daily Neu5Gc intake from red meat and dairy, and investigated serum as well as affinity-purified anti-Neu5Gc antibodies. Based on 24-h dietary records, daily Neu5Gc intake was calculated for 19,621 subjects aged ≥ 18 years of the NutriNet-Santé study. Serum and affinity-purified anti-Neu5Gc antibodies were evaluated by ELISA and glycan microarrays in representative 120 individuals, each with at least eighteen 24-h dietary records (aged 45-60, Q1-Q4; aged > 60, Q1 and Q4; 10 men/women per quartile). RESULTS: We found that high-Neu5Gc diet, gender, and age affect the specificity, levels, and repertoires of anti-Neu5Gc IgG immune responses, but not their affinity. Men consumed more Neu5Gc than women, mostly from red meat (p = 0.0015), and exhibited higher overall serum anti-Neu5Gc IgG levels by ELISA (3.94 ng/µl versus 2.22 ng/µl, respectively; p = 0.039). Detailed glycan microarray analysis against 56 different glycans revealed high Neu5Gc-specificity with increased anti-Neu5Gc IgG and altered repertoires, associated with higher consumption of Neu5Gc from red meat and cow dairy. Affinity purification of serum anti-Neu5Gc antibodies revealed increased levels and biased array repertoire patterns, without an increase in antibody affinity, in individuals consuming higher Neu5Gc levels. Furthermore, in a high-meat diet, antibody diversity patterns on glycan microarrays shifted towards Neu5Gcα3-linked glycans, increasing the α3/α6-glycans ratio score. CONCLUSIONS: We found a clear link between the levels and repertoire of serum anti-Neu5Gc IgG and Neu5Gc intake from red meat and dairy. These precise rational methodologies allowed to develop a Gcemic index to simplify the assessment of Neu5Gc in foods that could potentially be adapted for dietary recommendations to reduce cancer risk.

Prospective association between organic food consumption and the risk of type 2 diabetes: findings from the NutriNet-Santé cohort study.

BACKGROUND: Organic food (OF) consumption has substantially increased in high income countries, mostly driven by environmental concerns and health beliefs. Lower exposure to synthetic pesticides has been systematically documented among consumers of organic products compared to non-consumers. While experimental studies suggest that pesticides currently used in food production may be associated with type 2 diabetes (T2D), no well-conducted prospective studies have investigated the potential association between consumption of organic products and the risk of T2D, controlling for potential confounding factors. The objective of this prospective study was to estimate the association between OF consumption and the risk of T2D. METHODS: A total of 33,256 participants (76% women, mean (SD) age: 53 years (14)) of the French NutriNet-Santé prospective cohort study who completed the organic food frequency questionnaire were included (2014-2019). The proportion of OF in the diet (as weight without drinking water) was computed. The associations between the proportion of OF in the diet (as 5% increment and as quintiles) and the risk of T2D were estimated using multivariable Hazard Ratio (HR) and 95% confidence interval (95% CI) derived from proportional hazards models adjusted for confounders (sociodemographic, anthropometric, lifestyle, medical and nutritional factors). RESULTS: During follow-up (mean = 4.05 y, SD = 1.03 y, 134,990 person-years), 293 incident cases of T2D were identified. After adjustment for confounders including lifestyle (physical activity, smoking status, alcohol consumption) and nutritional quality of the diet assessed by the adherence to the French food-based dietary guidelines, OF consumption was associated with a lower risk of T2D. Participants with the highest quintile of OF consumption, compared with those with the lowest quintile, had 35% lower risk of T2D (95% CI = 0.43-0.97). Each increment of 5% in the proportion of OF in the diet was associated with 3% lower risk of T2D (HR 0.97, 95% CI = 0.95-0.99). CONCLUSIONS: In this large prospective cohort study, OF consumption was inversely associated with the risk of T2D. Further experimental and prospective studies should be conducted to confirm these observations. CLINICAL TRIAL REGISTRY: The study was registered at ClinicalTrials.gov ( NCT03335644 ).

Relationship between sensory liking for fat, sweet or salt and cardiometabolic diseases: mediating effects of diet and weight status.

PURPOSE: Previous works have been suggested that individual sensory liking is a predictor of dietary intake and weight status, and may consequently influence development of cardiometabolic diseases (CMDs). We investigated the association between sensory liking for fat-and-salt, fat-and-sweet, sweet or salt and the onset of hypertension, diabetes and cardiovascular diseases (CVDs) over 6 years in adults, and the mediating effects of dietary intake and body mass index (BMI). METHODS: We examined the CMDs risk among 41,332 (for CVD and diabetes) and 37,936 (for hypertension) French adults (NutriNet-Santé cohort). Liking scores, individual characteristics, diet and anthropometry were assessed at baseline using questionnaires. Health events were collected during 6 years. Associations between sensory liking and CMDs risk, and the mediating effect of diet and BMI, were assessed using Cox proportional hazards models. RESULTS: Sensory liking for fat-and-salt was associated with an increased risk of diabetes, hypertension and CVD [hazard ratios (HR) for 1-point increment of the sensory score: HR 1.30 (95% CI 1.18, 1.43), HR 1.08 (1.04, 1.13) and HR 1.10 (1.02, 1.19), respectively]. BMI and dietary intake both explained 93%, 98% and 70%, of the overall variation of liking for fat-and-salt liking in diabetes, hypertension and CVD, respectively. Liking for fat-and-sweet and liking for salt were also associated with an increased risk of diabetes [HR 1.09 (1.01, 1.17) and HR 1.09 (1.01, 1.18), respectively], whereas liking for sweet was associated with a decreased risk [HR 0.76 (0.69, 0.84)]. CONCLUSIONS: Higher liking for fat-and-salt is significantly associated with CMDs risk, largely explained by dietary intake and BMI. Our findings may help to guide effective targeted measures in prevention.

Prospective association between several dietary scores and risk of cardiovascular diseases: Is the Mediterranean diet equally associated to cardiovascular diseases compared to National Nutritional Scores?

BACKGROUND: Mediterranean diet has been consistently negatively associated with cardiovascular diseases (CVD) but the superiority compared to official nutritional guidelines has not been tested yet. Our objective was to prospectively investigate the association between several nutritional scores and incidence of cardiovascular diseases. METHODS AND FINDINGS: A total of 94,113 participants from the NutriNet-Santé cohort were followed between 2009 and 2018. The participants have completed at least three 24 h dietary records during the first two-years of follow-up to compute nutritional scores reflecting adherence to the Mediterranean diet (MEDI-LITE), American dietary guidelines (AHEI-2010) and French dietary guidelines (mPNNS-GS). Sex-specific quartiles (Q) of scores were computed. Multivariable Cox proportional hazards models were used to estimate the associations between scores and incidence of CVD, documented using Hazard Ratio (HR) and 95% confidence intervals (95%CI). Thus, 1399 incident CVD events occurred during the follow-up (mean follow-up = 5.4 years). Comparing Q4 versus Q1 quartile, HR for the MEDI-LITE and AHEI-2010 were 0.79 (95% CI: 0.67-0.93, P-trend = .004) and 0.75 (95% CI: 0.63-0.89, P-trend = .002) respectively. These associations remained similar when removing early cases of CVD, when analyses were restricted to participants with >6 dietary records and when considering transient ischemic attacks. In this last case, association between CVD' risk and mPNNS-GS become significant. CONCLUSIONS: A better nutritional quality of diet is overall associated with lower risk of CVD. The future version of the PNNS-GS, based on the updated version of the French dietary guidelines, should strengthen the CVD protective effect of French recommendations.

A genome wide association study identifies new genes potentially associated with eyelid sagging.

Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10-10 ) and rs4746957 (P = 1.06 × 10-8 ), were significantly associated with eyelid sagging severity. The rs16927253-T and rs4746957-A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity.

Association Between Alexithymia and Risk of Incident Cardiovascular Diseases in the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) Cohort.

OBJECTIVE: Although it has been suggested that alexythymia is associated with cardiovascular diseases, studies are scarce and a causal relationship is questionable. This study explored the prospective association between alexithymia and cardiovascular events in middle-aged participants without cardiovascular history at baseline. METHODS: The 26-item Toronto Alexithymia Scale (TAS-26) was completed by 5586 participants of the French SUpplémentation en VItamines et Minéraux AntioXydants cohort (41.4% of men, M [SD] age = 52.2 [6.3] years) in 1996-1997. Covariates measured at baseline included age, occupational status, depressive symptoms, smoking status, body mass index, hypertension, diabetes, hypercholesterolemia, and hypertriglyceridemia. The follow-up ran from January 1, 1998, to the date of the first cardiovascular event, the date of death or September 1, 2007, whichever occurred first. Cardiovascular events were validated by an independent expert committee. Hazard ratios and 95% confidence intervals were computed with Cox regressions. RESULTS: During an average of 8.9 years of follow-up, 171 first cardiovascular events were validated. After adjustment for age, sex, and occupational status, there was no association between baseline alexithymia and cardiovascular events at follow-up (hazard ratio [95% confidence interval] for 15 points of TAS-26 = 1.00 [0.81-1.23], p > .99). Adjusting for all covariates, using binary TAS-26 cut-offs or TAS-26 subscores yielded similar nonsignificant results. CONCLUSIONS: In this large prospective study, alexithymia and cardiovascular events were not associated among a nonclinical population. This casts some doubt on whether alexithymia could be a meaningful target in the prevention of cardiovascular diseases. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov (NCT00272428).

Obesity and Migraine: Effect Modification by Gender and Perceived Stress.

BACKGROUND: The association between obesity and migraine has been established; however, it is unclear whether it varies by perceived stress within each gender. METHODS: This cross-sectional study used data from the ongoing NutriNet-Santé e-cohort with enrollees from the general population. Anthropometric and migraine data were provided via self-report questionnaires (2013-2016). Migraine was defined using established criteria. Perceived stress was assessed with Cohen's Perceived Stress Scale-10. Associations were estimated via gender- and stress-stratified multivariable polytomous logistic regression models. RESULTS: Among 32,835 participants with complete data (75% women; mean age = 51.9 ± 13.8 years), 34% reported no headache, 44% non-migraine headache, and 22% migraine with or without aura during one's lifetime. In these groups, obesity was present in 8.6, 9.9, and 11.6%, respectively. Stress was a significant moderator of the obesity-migraine association only among women. The largest significant adjusted odds ratio (aOR) was found between obesity and migraine in women with high stress (aOR 1.61, 95% CI 1.35-1.91). CONCLUSIONS: We found support for gender- and stress-dependent associations between obesity and migraine using a large, heterogeneous adult sample. This underscores the need for evidence-based strategies for weight loss and stress reduction for female migraineurs.

Two decades of tobacco use prevention and control policies in Cameroon: results from the analysis of non-communicable disease prevention policies in Africa.

BACKGROUND: Tobacco use is the leading cause of preventable death in the world today. In 2010, the World Health Organization (WHO) proposed efficient and inexpensive "best buy" interventions for prevention of tobacco use including: tax increases, smoke-free indoor workplaces and public places, bans on tobacco advertising, promotion and sponsorship, and health information and warnings. This paper analyzes the extent to which tobacco use prevention policies in Cameroon align with the WHO tobacco "best buy" interventions. It further explores the context, content, formulation and implementation level of these policies. METHODS: This was a case study combining a structured review of 19 government policy documents related to tobacco use and prevention, in-depth interviews with 38 key stakeholders and field observations. The Walt and Gilson's policy analysis triangle was used to describe and interpret the context, content, processes and actors during the formulation and implementation of tobacco prevention and control policies. Direct observations ascertained the level of implementation of some selected policies. RESULTS: Twelve out of 19 policies for tobacco use and prevention address the WHO "best buy" interventions. Cameroon policy formulation was driven locally by the social context of non-communicable diseases, and globally by the adoption of the WHO Framework Convention on Tobacco Control. These policies incorporated at a certain level all four domains of tobacco use "best buy" interventions. Formulating policy on smoke-free areas was single-sector oriented, while determining tobacco taxes and health warnings was more complex utilizing multisectoral approaches. The main actors involved were ministerial departments of Health, Education, Finances, Communication and Social Affairs. The level of implementation varied widely from one policy to another and from one region to another. Political will, personal motivation and the existence of formal exchange platforms facilitated policy formulation and implementation, while poor resource allocation and lack of synergy constituted barriers. CONCLUSIONS: Despite actions made by the Government, there is no real political will to control tobacco use in Cameroon. Significant shortcomings still exist in developing and/or implementing comprehensive tobacco use and prevention policies. These findings highlight major gaps as well as opportunities that can be harnessed to improve tobacco control in Cameroon.