Primary hypocholesterolemia is associated with an increased risk of hepatic complications in the general population.

BACKGROUND & AIMS: Beyond cardiovascular disease protection, the health consequences of very low concentrations of low-density lipoprotein-cholesterol (LDL-C) remain a matter of debate. In primary hypobetalipoproteinemia (HBL), liver steatosis and cirrhosis have occasionally been reported. Here, we aimed to investigate the association between HBL and the risk of hepatic complications (cirrhosis complications and/or primary liver cancer) in the general population. METHODS: A cohort study was conducted in the French population-based cohort CONSTANCES. Participants with primary HBL (LDL-C <5th percentile for age and sex, [HBL]) were compared with those with normal LDL-C concentrations (40th-60th percentile, [Control]). Participants on lipid-lowering therapies were excluded. For hepatic complications, follow-up events were compared by calculating the incidence density ratio (IDR). The same analyses were replicated in the UK Biobank (UKBB) cohort. RESULTS: In the CONSTANCES and UKBB cohorts, 34,653 and 94,666 patients were analyzed, with median ages of 45 and 56 years, mean LDL-C concentrations (HBL vs. control) of 71 vs. 128 mg/dl and 86 vs. 142 mg/dl, and mean follow-up durations of 5.0 and 11.5 years, respectively. The HBL group presented a higher incidence of hepatic complications than the control group: 0.32/ vs. 0.07/1,000 person-years (IDR = 4.50, 95% CI 1.91-10.6) in CONSTANCES, and 0.69/ vs. 0.21/1,000 person-years (IDR = 3.27, 95% CI 2.63-4.06) in the UKBB. This risk proved to be independent of classic risk factors for liver disease (obesity, alcohol consumption, diabetes, viral hepatitis), including in a 5-year landmark analysis excluding early events. Sensitivity analyses based on apoliprotein-B levels (instead of LDL-C levels) or genetically defined HBL showed similar results. CONCLUSIONS: HBL is associated with a markedly increased risk of hepatic complications. HBL must be considered as a substantial independent risk factor for liver diseases which justifies specific prevention and screening. IMPACT AND IMPLICATIONS: Hypobetalipoproteinemia (HBL) is a lipid disorder characterized by permanent, inherited low levels (below the 5th percentile) of low-density lipoprotein-cholesterol. While HBL is associated with a lower risk of cardiovascular events, some studies suggest that it may be associated with a potential risk of hepatic steatosis and hepatic complications. Here, we studied the association between HBL and hepatic complications (defined as cirrhosis complications and/or primary liver cancer) in two populations of several hundred thousand people, both in France (CONSTANCES cohort) and the United Kingdom (UKBB). The results show that HBL is associated with a significant and independent excess risk of hepatic complications, including primary liver cancer. Thus, in people with HBL, the value of regular liver monitoring must be studied.

Lean individuals with NAFLD have more severe liver disease and poorer clinical outcomes (NASH-CO Study).

BACKGROUND AND AIMS: The severity of liver injury and clinical outcomes in lean individuals with NAFLD is a subject of debate and very few studies have been performed in the general population. The aim of this study was to compare subject characteristics and mortality between lean and nonlean NAFLD in a community setting. APPROACH AND RESULTS: The study population included 169,303 participants from the nationwide Constances cohort. Subjects with excessive alcohol consumption, viral hepatitis, or other liver diseases were excluded and 137,206 subjects were analyzed. The diagnosis of NAFLD and fibrosis was performed using the Fatty Liver Index and the Forns Index. The median follow-up was 3.58 years. The prevalence of NAFLD was 5.3% (95% CI: 5.2-5.4) in lean subjects, while 16.3% (95% CI: 15.7-16.8) of NAFLD subjects were lean. Despite their better metabolic profile, the prevalence of advanced fibrosis was significantly higher in lean than in nonlean NAFLD (3.7% vs. 1.7%, respectively, p < 0.01). Among NAFLD subjects and after adjustment for demographics, metabolic risk factors and lifestyle, lean status was associated with advanced fibrosis (OR=1.26, 95% CI: 1.20-1.65, p = 0.005), an increased risk of liver-related events (adjusted HR=5.84, 95% CI: 4.03-8.46), chronic kidney disease (adjusted HR=2.49, 95% CI: 1.49-4.16), and overall mortality (adjusted HR=3.01, 95% CI: 2.21-4.11). Liver-related events and overall mortality were related to the severity of fibrosis, both in lean and nonlean NAFLD subjects, whatever the usual risk factors. CONCLUSION: This study in a large community-based cohort confirms that NAFLD in lean subjects is more severe for fibrosis, the progression of liver disease, chronic kidney disease, and overall mortality.

Depression and anxiety before and at the beginning of the COVID-19 pandemic and incident persistent symptoms: a prospective population-based cohort study.

Many patients affected by COVID-19 suffer from debilitating persistent symptoms whose risk factors remained poorly understood. This prospective study examined the association of depression and anxiety symptoms measured before and at the beginning of the COVID-19 pandemic with the incidence of persistent symptoms. Among 25,114 participants [mean (SD) age, 48.72 years (12.82); 51.1% women] from the SAPRIS and SAPRIS-Sérologie surveys nested in the French CONSTANCES population-based cohort, depression and anxiety symptoms were measured with the Center for Epidemiologic Studies-Depression scale and the 12-item General Health Questionnaire before the pandemic, and with the 9-item Patient Health Questionnaire and the 7-Item Generalized Anxiety Disorder scale at the beginning of the pandemic (i.e., between April 6, 2020 and May 4, 2020). Incident persistent symptoms were self-reported between December 2020 and January 2021. The following variables were also considered: gender, age, educational level, household income, smoking status, BMI, hypertension, diabetes, self-rated health, and SARS-CoV-2 infection according to serology/PCR test results. After a follow-up of seven to ten months, 2329 participants (9.3%) had been infected with SARS-CoV-2 and 4262 (17.0%) reported at least one incident persistent symptom that emerged from March 2020, regardless of SARS-CoV-2 infection. In multi-adjusted logistic regression models, participants in the highest (versus the lowest) quartile of depressive or anxiety symptom levels before or at the beginning of the pandemic were more likely to have at least one incident persistent symptom (versus none) at follow-up [OR (95%CI) ranging from 2.10 (1.89-2.32) to 3.01 (2.68-3.37)], with dose-response relationships (p for linear trend <0.001). Overall, these associations were significantly stronger in non-infected versus infected participants, except for depressive symptoms at the beginning of the pandemic. Depressive symptoms at the beginning of the pandemic were the strongest predictor of incident persistent symptoms in both infected and non-infected participants [OR (95%CI): 2.88 (2.01-4.14) and 3.03 (2.69-3.42), respectively]. In exploratory analyses, similar associations were found for each symptom taken separately in different models. Depression and anxiety symptoms should be tested as a potential target for preventive interventions against persistent symptoms after an infection with SARS-CoV-2.

Long-term health in individuals born preterm or with low birth weight: A cohort study.

BACKGROUND: To measure the association of prematurity and non-preterm low birth weight (LBW) with several long-term health outcomes. METHODS: We selected adult participants from the Constances cohort. Associations between preterm birth (<37 weeks versus ≥37 weeks) and outcomes were measured using modified Poisson regression with adjustment for participant age and parental history. We used the same modeling methods to measure the association between LBW (i.e.,

Chronic occupational exposures to irritants and asthma in the CONSTANCES cohort.

OBJECTIVES: The impact of chronic occupational exposures to irritants on asthma remains discussed. We studied the associations between occupational exposures and asthma, with specific interest for chronic exposure to irritants, including disinfectants and cleaning products (DCPs) and solvents. METHODS: Cross-sectional analyses included 115 540 adults (55% women, mean age 43 years, 10% current asthma) working at inclusion in the French population-based CONSTANCES cohort (2012-2020). Current asthma was defined by ever asthma with symptoms, medication or asthma attacks (past 12 months), and the asthma symptom score by the sum of 5 respiratory symptoms (past 12 months). Both lifetime and current occupational exposures were assessed by the Occupational Asthma-specific Job-Exposure Matrix. Associations were evaluated by gender using logistic and binomial negative regressions adjusted for age, smoking status and body mass index. RESULTS: In women, associations were observed between current asthma and lifetime exposure to irritants (OR 1.05, 95% CI 1.00 to 1.11), DCPs (1.06, 95% CI 1.00 to 1.12) and solvents (1.06, 95% CI 0.98 to 1.14). In men, only lifetime exposure to DCPs (1.10, 95% CI 1.01 to 1.20) was associated with current asthma. Lifetime exposure to irritants was associated with higher asthma symptom score both in women (mean score ratio: 1.08, 95% CI 1.05 to 1.11) and men (1.11, 95% CI 1.07 to 1.15), especially for DCPs (women: 1.09, 95% CI 1.06 to 1.13, men: 1.21, 95% CI 1.15 to 1.27) and solvents (women 1.14, 95% CI 1.10 to 1.19, men: 1.10, 95% CI 1.05 to 1.15). For current exposures, no consistent associations were observed with current asthma and asthma symptom score. CONCLUSIONS: Lifetime occupational exposures to irritants were associated with current asthma and higher asthma symptom score. These exposures should be carefully considered in asthma management.

Chronic exposure to drinking water nitrate and trihalomethanes in the French CONSTANCES cohort.

Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water. Chronic exposure has been associated with increased cancer risk despite inconclusive evidence, partly due to the challenges in long-term exposure assessment and potential exposure misclassification. We estimated concentrations of nitrate and THMs in drinking water using a public regulatory monitoring database (SISE-Eaux) for CONSTANCES, a French population-based prospective cohort. We obtained 26,322,366 measurements of drinking water parameters from 2000 to 2020. We excluded missing, implausible and duplicated measurements; we corrected or imputed missing geocodes of sampling locations; we calculated the annual median concentration of nitrate and THMs by surveillance area. To predict missing annual median concentrations, linear mixed models with random intercept using surveillance area as a clustering variable were developed for each region for nitrate and the four THM components (chloroform, chlorodibromomethane, bromodichloromethane and bromoform) separately. Concentrations in the nearest surveillance area from the household were merged per year among 75,462 participants with residential history geocoded for 2000-2020. Estimated concentrations resulting from this approach were compared with measured concentrations in 100 samples collected in Paris, Rennes and Saint-Brieuc in 2021. Median annual concentrations of total THMs and nitrate at study participants' homes for 2000-2020 were, respectively, 15.7 µg/l (IQR: 15.2) and 15.2 mg/l (IQR: 20.8). Among these, 35% were based on measurements for nitrate (16% for THMs), 44% (46%) were predicted using on linear mixed models, and 21% (38%) were based on distribution unit median values. Conditional R2 predictive models ranged from 0.71 to 0.91 (median: 0.85) for nitrate, and from 0.48 to 0.80 for THMs (median: 0.68). These concentrations will allow future association analyses with risk of breast and colorectal cancer. Our cleaning process introduced here could be adapted to other large drinking water monitoring data.

Prevalence of self-reported severe periodontitis: Data from the population-based CONSTANCES cohort.

AIM: To assess the prevalence of severe periodontitis based on the population-based CONSTANCES cohort using a validated self-reported questionnaire. MATERIALS AND METHODS: Individuals were selected from the adult population in France using a random sampling scheme. Analyses were restricted to those invited in 2013-2014 who completed the periodontal health questionnaire at the 2017 follow-up. The risk of severe periodontitis was assessed using the periodontal screening score (PESS) and weighting coefficients were applied to provide representative results in the general French population. RESULTS: The study included 19,859 participants (9204 men, mean age: 52.8 ± 12.6 years). Based on a PESS ≥ 5, 7106 participants were at risk of severe periodontitis, corresponding to a weighted prevalence of 31.6% (95% confidence interval: 30.6%-32.7%). This prevalence was higher among participants aged 55 and over, those with lower socio-economic status as well as current smokers, e-cigarette users and heavy drinkers. Among individuals at risk of severe periodontitis, only 18.8% (17.3%-20.4%) thought they had gum disease, although 50.5% (48.6%-52.5%) reported that their last dental visit was less than 6 months. CONCLUSIONS: The present survey indicates that (1) self-reported severe periodontitis is highly prevalent with marked disparities between groups in the general French adult population, and (2) periodontitis could frequently be under-diagnosed given the low awareness.

Tobacco use and employment status: A cross-sectional analysis of the CONSTANCES cohort / Liens entre le statut tabagique et la situation vis-à-vis de l'emploi : analyse transversale de la cohorte CONSTANCES

This study aims to estimate the prevalence of tobacco use in 2017 and 2019 in the French population covered by the Régime Général d'Assurance Maladie according to employment status. From the French national CONSTANCES cohort, 18,008 randomly recruited volunteers aged between 18 and 69 years, affiliated to the Régime Général d'Assurance Maladie and enrolled in 2017, were included in the analysis. The prevalence of tobacco use according to employment status was estimated. Estimates of these prevalence data were calculated in 2017 and 2019 after correction for selection bias at inclusion and non-response at follow-up. In 2019, smoking prevalence was higher among unemployed people (29.2% among men and 20.7% among women) than among employed people (16.5% among men and 13.8% among women). Smoking prevalence was highest among those not in work for health reasons (38.5% among men and 35.8% among women). Smokers were more likely to be unemployed than non-smokers (OR 2.63 [95% confidence interval (CI): 1.79; 3.85] in men and OR 1.55 [95% CI: 1.08; 2.22] in women). Among men, the prevalence of employed people among light smokers (<10 cigarettes/day) significantly decreased between 2017 (87.1%) and 2019 (74.8%). These results underline the importance of reinforcing smoking prevention campaigns among the unemployed, particularly for health reasons.

Estimer les prévalences d'usage de tabac en 2017 et en 2019 en population française couverte par le Régime Général d'Assurance Maladie en fonction du statut vis-à-vis de l'emploi. À partir d'un échantillon de 18 008 volontaires inclus en 2017 dans CONSTANCES, une cohorte nationale en population générale française ayant recruté de manière aléatoire des volontaires de 18-69 ans affiliés au Régime Général d'Assurance Maladie, les prévalences d'usage du tabac en fonction de du statut vis-à-vis de l'emploi ont été estimées en 2017 et en 2019 après correction pour les biais de sélection à l'inclusion et de non-réponse au suivi. En 2019, la prévalence du tabagisme était plus élevée chez les actifs inoccupés (29,2 % chez les hommes et 20,7 % chez les femmes) par rapport aux actifs occupés (16,5 % chez les hommes et 13,8 % chez les femmes). La prévalence du tabagisme la plus élevée concernait les personnes sans activité professionnelle pour raisons de santé (38,5 % chez les hommes et 35,8 % chez les femmes). Les fumeurs étaient plus à risque d'être actifs inoccupés comparativement aux non-fumeurs (OR 2,63 [95 % Intervalle de confiance [IC] : 1,79 ; 3,85] chez les hommes et OR 1,55 [95 % IC : 1,08 ; 2,22] chez les femmes). Chez les hommes, la prévalence d'actifs occupés parmi les petits fumeurs (<10 cigarettes/jour) a baissé entre 2017 (87,1 %) et 2019 (74,8 %). Ces analyses soulignent l'importance d'intensifier les campagnes de prévention sur le tabagisme parmi les actifs inoccupés et les inactifs, en particulier pour raisons de santé.

Long-term exposure to ambient air pollution and asthma symptom score in the CONSTANCES cohort.

BACKGROUND: The asthma symptom score allows to consider asthma as a continuum and to investigate its risk factors. One previous study has investigated the association between asthma score and air pollution and only for nitrogen dioxide (NO2). We aimed to study the associations between particulate matter with an aerodynamic diameter lower than 2.5 µm (PM2.5), black carbon (BC) and NO2 and the asthma symptom score in adults from CONSTANCES, a French population-based cohort. METHODS: Asthma symptom score (range: 0-5) was based on the number of five self-reported symptoms of asthma in the last 12 months. Annual individual exposure to PM2.5, BC and NO2 was estimated at participants' residential address using hybrid land-use regression models. Cross-sectional associations of each pollutant with asthma symptom score were estimated using negative binomial regressions adjusted for age, sex, smoking status and socioeconomic position. Associations with each symptom were estimated using logistic regression. The effect of BC independent of total PM2.5 was investigated with a residual model. RESULTS: Analyses were conducted on 135 165 participants (mean age: 47.2 years, 53.3% women, 19.0% smokers, 13.5% ever asthma). The ratio of mean score was 1.12 (95% CI 1.10 to 1.14), 1.14 (95% CI 1.12 to 1.16) and 1.12 (95% CI 1.10 to 1.14) per one IQR increase of PM2.5 (4.86 µg/m3), BC (0.88 10-5 m-1) and NO2 (17.3 µg/m3). Positive and significant associations were also found for each asthma symptom separately. BC effect persisted independently of total PM2.5. CONCLUSION: Exposure to each pollutant was associated with increased asthma symptom score in adults. This study highlights that BC could be one of the most harmful particulate matter components.

Rhinitis phenotypes and multimorbidities in the general population: the CONSTANCES cohort.

BACKGROUND: Scarce epidemiological studies have characterised allergic rhinitis (AR) and non-allergic rhinitis (NAR) in adults. In a population-based cohort, our aims were to 1) describe rhinitis, AR and NAR, and 2) explore how asthma and conjunctivitis may lead to the identification of novel rhinitis phenotypes. METHODS: In this cross-sectional analysis, current rhinitis was defined as present in the last 12 months using a questionnaire from the French CONSTANCES cohort. Participants with current rhinitis reporting nasal allergies were considered as AR, otherwise as NAR. We described AR and NAR phenotypes, and their phenotypes including co-occurrence with ever-asthma and ever-conjunctivitis. RESULTS: Among the 20 772 participants included in this analysis (mean±sd age 52.6±12.6 years; 55.2% female), crude prevalences of AR and NAR were 28.0% and 10.9%. AR participants more frequently reported persistent rhinitis (31.6% versus 25.1%) and moderate-to-severe rhinitis (40.1% versus 24.2%) than NAR participants. Among AR or NAR participants, those with ever-asthma reported more moderate-to-severe rhinitis. Participants with AR, ever-asthma and ever-conjunctivitis had an earlier age of rhinitis onset, more severe rhinitis and higher eosinophil counts than participants in other groups. Results were replicated in another cohort. CONCLUSIONS: In this large population-based cohort, 40% reported current rhinitis, with a lower prevalence of moderate-to-severe rhinitis than in clinical practice. For the first time in a general adult population, we showed that AR and NAR alone or in combination with asthma or in combination with asthma and conjunctivitis are different phenotypes. These results provide new insights on how best to manage rhinitis and its multimorbidities.

Association between birth weight, preterm birth, and nonalcoholic fatty liver disease in a community-based cohort.

BACKGROUND AND AIMS: The association between birth weight (BW) and metabolic outcomes has been described since the 1980s but NAFLD has been rarely studied. This study aimed to investigate the association between BW and NAFLD occurrence in adult subjects. APPROACH AND RESULTS: The study population consisted of participants from the French nationwide Constances cohort from 2012 to 2019. Participants with a history of chronic viral hepatitis or excessive alcohol consumption were excluded. Noninvasive diagnosis of NAFLD and fibrosis was performed using a combination of the Fatty Liver Index (FLI) and the Forns Index. The relationship between BW and NAFLD was analyzed with a sex-stratified logistic regression model adjusted for sociodemographic parameters, lifestyle, and birth term, whereas liver fibrosis was analyzed with a sex-stratified linear regression model. In total, 55,034 individuals with reliable BW were included (43% men, mean age: 38 years). NAFLD (FLI ≥ 60) was present in 5530 individuals (10%). Multivariate logistic regression showed a significant U-shaped relationship between BW and NAFLD, with no significant interaction with sex. A significant and slightly decreasing association was found between BW and Forns Index (ß = -0.05; p = 0.04). Premature birth (OR, 1.23; 95% CI, 1.03-1.48 for birth between 33 and 37 weeks versus ≥ 37 weeks) was associated with NAFLD, with a significant direct effect of premature birth, and without an indirect effect of low BW in mediation analysis. Forns Index was not significantly higher in participants with preterm birth compared to full-term birth. CONCLUSIONS: This large prospective adult-based cohort confirms the relationship between BW and NAFLD occurrence.

The NAFLD burden on mortality and morbidities in general population: A community-based longitudinal study (NASH-CO study).

BACKGROUND: The impact of non-alcoholic fatty liver disease (NAFLD) on morbidity and mortality has yet to be documented at the general population level. This study aimed to assess whether NAFLD was associated with morbidities and mortality and to estimate its impact on health status and mortality. METHODS: The study population consisted of 137 206 participants from Constances cohort. Non-invasive diagnosis of NAFLD and advanced fibrosis was performed using the fatty liver index and Forns index, respectively. Constances data were linked to health care and hospitalization data to identify liver-related events, cardiovascular diseases (CVD), extrahepatic cancers (EHC), chronic kidney disease (CKD) and all-cause mortality. RESULTS: The prevalence of NAFLD was 18.3% in subjects without other chronic liver diseases, among whom 2.7% had fibrosis. NAFLD after IPTW-weighted remained associated with an increased risk of death (HR 1.26, 95% CI 1.01-1.57), hepatic-related complications (HR 2.48, 95% CI 1.99-3.29), CVD (HR 1.42, 95% CI 1.30-1.55), EHC (HR 1.11, 95% CI 1.01-1.28) and CKD (HR 1.81, 95% CI 1.53-2.07) compared to those without chronic liver diseases risk factors (Non-NAFLD). In the trend analysis over the study period of inclusion and compared to Non-NAFLD, NAFLD has shown a fastest growing cause of hepatic events (HR 1.38, 95% CI 1.07-1.76 per year), CVD (HR 1.08, 95% CI 1.03-1.12), CKD (HR 1.16, 95% CI 1.07-1.25), and death (HR 1.39, 95% CI 1.39-1.50). CONCLUSION: This large community-based cohort showed that NAFLD was associated with excess morbidity and mortality and demonstrated a fastest-growing trend.

Antibody response, associated symptoms and profile of patients presumably infected by SARS-CoV-2 with taste or smell disorders in the SAPRIS multicohort study.

BACKGROUND: Taste or smell disorders have been reported as strongly associated with COVID-19 diagnosis. We aimed to identify subject characteristics, symptom associations, and antibody response intensity associated with taste or smell disorders. METHODS: We used data from SAPRIS, a study based on a consortium of five prospective cohorts gathering 279,478 participants in the French general population. In the analysis, we selected participants who were presumably infected by SARS-CoV-2 during the first epidemic wave. RESULTS: The analysis included 3,439 patients with a positive ELISA-Spike. Sex (OR = 1.28 [95% CI 1.05-1.58] for women), smoking (OR = 1.54 [95% CI 1.13-2.07]), consumption of more than 2 drinks of alcohol a day (OR = 1.37 [95% CI 1.06-1.76]) were associated with a higher probability of taste or smell disorders. The relationship between age and taste or smell disorders was non-linear. Serological titers were associated with taste or smell disorders: OR = 1.31 [95% CI 1.26-1.36], OR = 1.37 [95% CI 1.33-1.42] and OR = 1.34 [95% CI 1.29-1.39] for ELISA-Spike, ELISA-Nucleocapsid and seroneutralization, respectively. Among participants with taste or smell disorders, 90% reported a wide variety of other symptoms whereas 10% reported no other symptom or only rhinorrhea. CONCLUSIONS: Among patients with a positive ELISA-Spike test, women, smokers and people drinking more than 2 drinks a day were more likely to develop taste or smell disorders. This symptom was strongly associated with an antibody response. The overwhelming majority of patients with taste or smell disorders experienced a wide variety of symptoms.

Social inequalities, stressful work and non-fatal cardiovascular disease: follow-up findings from the CONSTANCES Study.

BACKGROUND: Studies show that a disadvantaged socioeconomic position (SEP) and psychosocial stress at work are both independently associated with an increased risk of cardiovascular disease (CVD). But it is not clear if the effect of stress at work on CVD varies by SEP. METHODS: We used baseline and follow-up data from the French population-based cohort study CONSTANCES, including 48 383 employed women and men aged 30-70 years. Three SEP indicators (education, income, occupation), stressful psychosocial work as measured by effort-reward imbalance, pre-existing CVD and confounders were assessed at baseline, and incident non-fatal CVD events reported during annual follow-up (up to five follow-ups) were used as outcomes. The effect modification hypothesis was both investigated on an additive and multiplicative scale. RESULTS: SEP was inversely associated with CVD risk (eg, for low vs high income, OR 1.28 (95% CI 1.12 to 1.46)), and for all three components of stressful work CVD risks were significantly increased (eg, for effort-reward ratio OR 1.26 (95% CI 1.17 to 1.36)). Employees with a disadvantaged SEP showed moderately increased effect sizes of stressful work on CVD. However, no clear evidence of an effect modification was found. CONCLUSIONS: Disadvantaged SEP and stressful work contribute to higher CVD risk in this cohort. Despite moderately increased effect sizes for disadvantaged SEP groups, no evidence was found to support an effect modification hypothesis.

Women with type 2 diabetes have LDL cholesterol levels higher than those of men, regardless of their treatment and their cardiovascular risk level.

BACKGROUND AND AIMS: Several works have shown that control of the principal cardiovascular risk factors, especially LDL-C, is poorer among women with type 2 diabetes than men with this disease. Our objectives were to compare the statin treatments and LDL-C levels between men and women with type 2 diabetes, according to the potency of the statin they take, while taking their cardiovascular risk level into account. METHOD AND RESULTS: This is a descriptive cross-sectional study within the French CONSTANCES cohort. At inclusion, each individual completed several self-administered questionnaires. Data were then matched to their health insurance fund reimbursement data. The study population comprises cohort members with pharmacologically treated type 2 diabetes. We identified 2541 individuals with type 2 diabetes; 2214 had an available LDL-C value. In the total sample, treatment by statins did not differ between men and women, while the women had a higher mean LCL-C level than men. The analyses stratified by cardiovascular risk showed that women at very high cardiovascular risk received significantly less frequent statin delivery than men (OR = 0.72 [0.56-0.92]; p = 0.01). At the same time, women received the same rate of high-potency statins as men. Women taking equivalently potent statins had significantly higher LDL-C levels than men did. CONCLUSION: For the same cardiovascular risk level and the same statin treatment, women had an LDL-C level higher than that of men. They thus present a residual cardiovascular risk that justifies intensification of their statin treatment if tolerance allows.

The association between substance use and subsequent employment among students: prospective findings from the CONSTANCES cohort.

PURPOSE: To examine prospectively associations between substance use and subsequent employment among young students. METHODS: From the French population-based CONSTANCES cohort, 1427 students who never worked were included between 2012 and 2018 and followed up for 2.1 years on average. Generalized estimating equations computed the odds of being unemployed versus employed according to substance use at baseline controlling for sociodemographic factors and depressive state. Tobacco use (smoking status and number of cigarettes), cannabis use frequency, and at-risk alcohol use according to the Alcohol Use Disorder Identification Test (total score > 7) were introduced separately in the models. RESULTS: Tobacco use was not significantly associated with employment. Cannabis use at least weekly was associated with increased odds of being unemployed OR 1.73 (1.16-2.57). At-risk alcohol use was no longer significantly associated with employment after adjustment for depressive state, while analyses on sub-scores of alcohol use suggested that alcohol dependence was associated with increased odds of being unemployed OR 1.65 (1.16-2.34). CONCLUSION: Public health campaigns targeting youth should include lower chances of getting employed among the detrimental roles of regular cannabis use and at-risk alcohol use.

Liens entre le statut tabagique et la situation vis-à-vis de l'emploi : analyse transversale de la cohorte CONSTANCES.

This study aims to estimate the prevalence of tobacco use in 2017 and 2019 in the French population covered by the Régime Général d'Assurance Maladie according to employment status. From the French national CONSTANCES cohort, 18,008 randomly recruited volunteers aged between 18 and 69 years, affiliated to the Régime Général d'Assurance Maladie and enrolled in 2017, were included in the analysis. The prevalence of tobacco use according to employment status was estimated. Estimates of these prevalence data were calculated in 2017 and 2019 after correction for selection bias at inclusion and non-response at follow-up. In 2019, smoking prevalence was higher among unemployed people (29.2% among men and 20.7% among women) than among employed people (16.5% among men and 13.8% among women). Smoking prevalence was highest among those not in work for health reasons (38.5% among men and 35.8% among women). Smokers were more likely to be unemployed than non-smokers (OR 2.63 [95% confidence interval (CI): 1.79; 3.85] in men and OR 1.55 [95% CI: 1.08; 2.22] in women). Among men, the prevalence of employed people among light smokers (<10 cigarettes/day) significantly decreased between 2017 (87.1%) and 2019 (74.8%). These results underline the importance of reinforcing smoking prevention campaigns among the unemployed, particularly for health reasons.

Evaluation of saliva as a source of accurate whole-genome and microbiome sequencing data.

This study sets out to establish the suitability of saliva-based whole-genome sequencing (WGS) through a comparison against blood-based WGS. To fully appraise the observed differences, we developed a novel technique of pseudo-replication. We also investigated the potential of characterizing individual salivary microbiomes from non-human DNA fragments found in saliva. We observed that the majority of discordant genotype calls between blood and saliva fell into known regions of the human genome that are typically sequenced with low confidence; and could be identified by quality control measures. Pseudo-replication demonstrated that the levels of discordance between blood- and saliva-derived WGS data were entirely similar to what one would expect between technical replicates if an individual's blood or saliva had been sequenced twice. Finally, we successfully sequenced salivary microbiomes in parallel to human genomes as demonstrated by a comparison against the Human Microbiome Project.

The burden of NAFLD in type 2 diabetic subjects from the general population: A Nationwide population-based follow-up study (NASHCO).

BACKGROUND: The epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD) in diabetes have been mainly investigated in the hospital setting. The goal of this study was to evaluate the characteristics of NAFLD and its impact on morbidity and mortality in type 2 diabetic subjects in a community setting. METHOD: This study included 199 341 participants in the nationwide Constances cohort. After patients with excessive alcohol consumption, viral hepatitis or other causes of liver disease were excluded, 164 285 were analysed and 8386 (5.3%) were considered to have type 2 diabetes. The non-invasive diagnosis of NAFLD and advanced fibrosis was made using a combination of the fatty liver index and Forns index. Median follow-up was 2.5 years. RESULTS: Diabetes increased the risk of NAFLD by sixfold (adjusted OR 6.05, 95% CI 5.68-6.45) and the risk of advanced fibrosis by 3.76-fold (aOR 3.76, 95% CI 2.87-4.91) in NAFLD subjects. After controlling for confounders, the presence of NAFLD in diabetic subjects was associated with an increased risk of severe liver-related events (aHR 2.53, 95% CI 1.36-4.69), cardiovascular disease (CVD, aHR 2.71, 95% CI 1.72-4.26) and overall mortality (aHR 2.91, 95% CI 1.53-5.53). The risk of hepatic and extrahepatic complications in diabetic subjects with NAFLD significantly increased with the severity of fibrosis (P < .05). CONCLUSION: This prospective, longitudinal study in a large community-based cohort provides real-world evidence of the risk for NAFLD and advanced fibrosis in diabetes, and its impact on liver disease progression, diabetes-related complications such as CVD, and overall mortality. These data could be used to estimate real clinical and economic burden of NAFLD in diabetic subjects.

The association of substance use with attaining employment among unemployed job seeking adults: Prospective findings from the French CONSTANCES cohort.

This study aimed to examine the prospective association between tobacco, alcohol and cannabis use with attaining employment among unemployed job seekers. Data from the French population-based CONSTANCES cohort on 5114 unemployed job seeking adults enrolled from 2012 to 2018 were analyzed. Binary logistic regressions were computed. Odds ratio (OR) and 95%CI of remaining unemployed at one-year of follow-up (versus attaining employment) according to substance use at baseline were obtained. The following independent variables were introduced into separate models: tobacco use (non-smoker, former smoker, light (<10cig/day), moderate (10-19cig/day) and heavy smoker (>19cig/day)), alcohol use according to the Alcohol Use Disorder Identification Test (non-users (0), low (<7), moderate (7-15) and high or very high-risk (>15)) and cannabis use (never used, no use in the previous 12 months, less than once a month, at least once a month but less than once per week, once per week or more). Analyses were adjusted for age, gender and education. At follow-up, 2490 participants (49.7%) were still unemployed. Compared to non-smokers, moderate and heavy smokers were more likely to remain unemployed, with ORs (95%CI) of 1.33 (1.08-1.64) and 1.42 (1.04-1.93), respectively. Compared to low-risk alcohol users, no alcohol users and high or very high-risk alcohol users were more likely to remain unemployed, with ORs (95% CI) of 1.40 (1.03-1.83) and 2.10 (1.53-2.87), respectively. Compared to participants who never used cannabis, participants who use cannabis once a week or more were more likely to remain unemployed, OR (95%CI) of 1.63 (1.33-2.01). Substance use may play an important role in difficulty attaining employment.