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.

Gonadotropic status in adult women with pituitary stalk interruption syndrome.

OBJECTIVE: Pituitary stalk interruption syndrome (PSIS) is a rare cause of congenital hypopituitarism. Limited data exist on the gonadotropic status and fertility of adult women with PSIS. Our study aims to describe pubertal development and the evolution of gonadotropic function and fertility in adult women with PSIS. DESIGN: A retrospective multicentric French study. METHODS: We described gonadotropic function in 56 adult women with PSIS from puberty onward. We compared live birth rates per woman with PSIS with age-matched controls from the large French epidemiological cohort (CONSTANCES). Additionally, we assessed height, body mass index (BMI), blood pressure, other metabolic parameters, and socioeconomic status. RESULTS AND CONCLUSIONS: Among 56 women with PSIS, 36 did not experience spontaneous puberty. Of these, 13 underwent ovarian stimulation, resulting in 7 women having a total of 11 children. In the subgroup with spontaneous puberty (n = 20), 4 had a total of 8 pregnancies, while 6 developed secondary gonadotropic deficiency. Women with PSIS had fewer children than controls (0.33 vs 0.63, P = .04). Median height was also lower (160.5 vs 165.0 cm, P < .0001). Although mean blood pressure was lower in women with PSIS compared with controls (111.3/65.9 ± 11.2/8.1 vs 118.7/72.1 ± 10.1/7.7 mmHg, P < .001), there were no significant differences in other metabolic parameters, notably BMI and lipid profile. Employment/academic status was not different in the 2 groups, but fewer women with PSIS were in relationships (42% vs 57.6% in controls, P = .02). The fertility prognosis in patients with PSIS needs optimization. Patients should be informed about the likelihood of declining gonadotropic function over time.

Development of a crosswalk to convert French PCS2003 into international ISCO88 occupational classifications. Application to the Occupational Asthma-specific Job-Exposure Matrix (OAsJEM).

INTRODUCTION: The problem of transcoding is recurrent when researchers wish to link occupational data from cohorts to Job-Exposure Matrices (JEMs) which were not set up in the same classifications. The Occupational Asthma-specific JEM (OAsJEM) is a JEM developed for assessing exposure to agents known at risk for asthma for jobs coded with ISCO88 occupation classification. To apply the OAsJEM in the CONSTANCES cohort, in which jobs and industries were coded with French PCS2003 and NAF2008 classifications respectively, we developed a crosswalk to convert jobs from PCS2003 into ISCO88 classification. METHODS: This work was carried out by 2 skilled coders and 1 novice coder who have worked independently by using different tools and transcoding strategies defined a priori. Consensus meetings were organized with skilled coders to define the final crosswalk. This work was elaborated in 2 steps: (i) for 38 ISCO88 codes classified as potentially exposed to cleaning and disinfection products by the OAsJEM, and (ii) for all jobs from the ISCO88 classification. A comparison between the 3 initial coder's crosswalk proposals and the final crosswalk was made for the 38 ISCO codes in step (i). RESULTS: The final crosswalk provided 998 matches between the 482 4-digit PCS2003 codes, 308 4-digit ISCO88 codes, and 31 3-digit ISCO88 codes. Information regarding the NAF2008 industry classification was also used in some cases to improve the final crosswalk. For the selected 38 ISCO88 codes, the final crosswalk provided 110 combinations, but the number of proposed ISCO88-PCS2003 couples by each of the 3 coders varied greatly from 68 to 153. In addition, an important variability between the 3 coders were observed among the number of common combinations between the initial coder's proposals and the final crosswalk (from 47% to 78%). DISCUSSION: We have developed a crosswalk specifically for an application of the OAsJEM in population-based surveys using the PCS2003 occupation classification. The development of this crosswalk is of great interest for the use of OAsJEM on the data of the CONSTANCES cohort and on any other survey with occupational data coded according to the French classifications. This OAsJEM crosswalk could be used by other teams to evaluate occupational exposures known to be at risk of asthma from occupational calendars coded with French classifications.

Prevalence of chronic kidney disease in France: methodological considerations and pitfalls with the use of Health claims databases.

Background: Health policy-making require careful assessment of chronic kidney disease (CKD) epidemiology to develop efficient and cost-effective care strategies. The aim of the present study was to use the RENALGO-EXPERT algorithm to estimate the global prevalence of CKD in France. Methods: An expert group developed the RENALGO-EXPERT algorithm based on healthcare consumption. This algorithm has been applied to the French National Health claims database (SNDS), where no biological test findings are available to estimate a national CKD prevalence for the years 2018-2021. The CONSTANCES cohort (+219 000 adults aged 18-69 with one CKD-EPI eGFR) was used to discuss the limit of using health claims data. Results: Between 2018 and 2021, the estimated prevalence in the SNDS increased from 8.1% to 10.5%. The RENALGO-EXPERT algorithm identified 4.5% of the volunteers in the CONSTANCES as CKD. The RENALGO-EXPERT algorithm had a positive predictive value of 6.2% and negative predictive value of 99.1% to detect an eGFR<60 ml/min/1.73 m². Half of 252 false positive cases (ALGO+, eGFR > 90) had been diagnosed with kidney disease during hospitalization, and the other half based on healthcare consumption suggestive of a 'high-risk' profile; 95% of the 1661 false negatives (ALGO-, eGFR < 60) had an eGFR between 45 and 60 ml/min, half had medication and two-thirds had biological exams possibly linked to CKD. Half of them had a hospital stay during the period but none had a diagnosis of kidney disease. Conclusions: Our result is in accordance with other estimations of CKD prevalence in the general population. Analysis of diverging cases (FP and FN) suggests using health claims data have inherent limitations. Such an algorithm can identify patients whose care pathway is close to the usual and specific CKD pathways. It does not identify patients who have not been diagnosed or whose care is inappropriate or at early stage with stable GFR.

Healthy lifestyle change and all-cause and cancer mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Healthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35-70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years). RESULTS: After the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI. CONCLUSIONS: Making healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death.

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.

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.

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.

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.

Lifetime exposure to unemployment and prior working conditions are associated with retiree's health: A retrospective study in a large population-based French cohort.

It is unclear whether unemployment exposure, as well as working conditions, can have sustained effects on the health of retirees who are no longer exposed. The aim of the present study is to investigate this issue in 29,281 French retirees from the CONSTANCES cohort in whom the prevalence of suboptimal self-rated health, disability for routine tasks, cardiovascular diseases and cancers is assessed according to lifetime exposure to unemployment and prior working conditions. The analyses are performed retrospectively using multivariable logistic regression models with adjustment for potential confounders such as sex, birth year, parental histories of cardiovascular disease and cancer, social position, retirement age and duration. High lifetime exposure to unemployment is associated with an increased prevalence of suboptimal self-rated health (adjusted odds ratio (95% CI), 1.39 (1.23-1.57)), disability for routine tasks (1.41 (1.26-1.57)) and several cardiovascular diseases including stroke (1.66 (1.19-2.31)), myocardial infarction (1.65 (1.18-2.31)) and peripheral arterial disease (2.38 (1.46-3.90)). Bad prior working conditions are associated with an increased prevalence of disability for routine tasks (1.17 (1.04-1.33)) and cancers (1.27 (1.04-1.54)), notably prostate cancer (1.60 (1.01-2.64)). These findings suggest that unemployment and working conditions have long-term health effects that may cumulate over lifetime, emphasizing that risk evaluation and preventive strategies in retirees, as in workers, should take into account the life-course of individuals in addition to traditional risk factors.

Is the number of ideal cardiovascular health metrics in midlife associated with lower risk of cancer? Evidence from 3 European prospective cohorts.

BACKGROUND: Primordial prevention may be a relevant strategy for the prevention of cancer. Given the commonality of risk factors and mechanisms between cancer and cardiovascular disease, we examined the associations between the number of ideal cardiovascular health metrics in midlife and incident cancer. METHODS: In 3 European cohorts (NutriNet-Santé and GAZEL, France; Whitehall II, United Kingdom), the number of ideal cardiovascular health metrics was determined at baseline (range 0-7). Follow-up for cancer events was until October 2020 (NutriNet-Santé), March 2017 (Whitehall II) and December 2015 (GAZEL). Cox regression was conducted in each cohort, and results were thereafter pooled using a random-effects model. RESULTS: Data were available on 39 718 participants. A total of 16 237 were from NutriNet-Santé (mean age 51.3 yr; 28% men), 9418 were from Whitehall II (mean age 44.8 yr; 68% men) and 14 063 were from GAZEL (mean age 45.2 yr; 75% men). The median follow-up was 8.1 years in NutriNet-Santé, 29.6 years in Whitehall II and 24.8 years in GAZEL, and yielded a total of 4889 cancer events. A greater number of ideal cardiovascular health metrics was associated with a lower overall cancer risk in each cohort, with an aggregate hazard ratio (HR) per 1 increment in number of ideal metrics of 0.91 (95% confidence interval [CI] 0.88-0.93). This association remained after removal of the smoking metric (aggregate HR per unit increment in number of ideal metrics: 0.94, 95% CI 0.90-0.97), and site-specific analysis demonstrated a significant association with lung cancer. INTERPRETATION: A greater number of ideal cardiovascular health metrics in midlife was associated with lower cancer risk, notably lung cancer. Primordial prevention of cardiovascular risk factors in midlife may be a complementary strategy to prevent the onset of cancer.

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.

Cardiovascular burden and unemployment: A retrospective study in a large population-based French cohort.

The specific effect of unemployment on cardiovascular health relatively to the effects of social position and work environment is still unclear. To clarify this effect, the associations between current or past unemployment and the prevalence of common cardiovascular risk factor and events were tested using multiple logistic regression models with adjustment for both social position and prior work environment. The analyses were performed in a population-based French cohort (CONSTANCES) that included 131,186 adults enrolled between 2012 and 2021. Participants who were unemployed at inclusion (n = 8278) were overexposed to non-moderate alcohol consumption, smoking, leisure-time physical inactivity and depression (odds ratios (ORs) from 1.19 to 1.58) whereas those who have been unemployed at least once in the past (n = 19,015) were additionally overexposed not only to the previous risk factors but also to obesity, diabetes and sleep disorders (ORs from 1.10 to 1.35). These latter were also more exposed to non-fatal myocardial infarction and peripheral arterial disease (ORs of 1.44 and 1.47 respectively), overexposures that persisted after further adjustment for cardiovascular risk factors (ORs of 1.36 and 1.33). The overexposures to risk factors and cardiovascular events were both dependent on the duration of past unemployment. They were equally observed in participants with low social position or bad work environment. These results suggest that unemployment increases cardiovascular risk independently from social position and work environment with a cumulative effect over time. The effect of unemployment could add up to those of low social position and bad work environment during lifetime to further increase cardiovascular risk. They also suggest that long-term unemployment increases the prevalence of cardiovascular events through pathways including but not limited to overexposure to common risk factors.

Distinct cardiovascular and cancer burdens associated with social position, work environment and unemployment: a cross-sectional and retrospective study in a large population-based French cohort.

OBJECTIVES: Distinguish the respective effects of social position, work environment and unemployment on cardiovascular and cancer risks. DESIGN: A cross-sectional and retrospective observational study. SETTING: A population-based French cohort (CONSTANCES). PARTICIPANTS: 130 197 adults enrolled between 2012 and 2021 without missing values. PRIMARY OUTCOME MEASURES: The associations of social position, work environment and unemployment exposure with the prevalence of cardiovascular events and cancers simultaneously tested using logistic regression models adjusting for common risk factors. RESULTS: While social position, work environment and unemployment exposure are strongly inter-related with each other, they are not linked to the same cardiovascular and cancer outcomes. Low social position and long unemployment duration are significantly associated with an increased prevalence of angina pectoris, myocardial infarction and peripheral arterial disease (OR=1.22 to 1.90, p<0.04 to p<0.0001) but not of stroke. In contrast, a bad work environment is associated with an increased prevalence of stroke (OR=1.29, p<0.01) but not of angina pectoris, myocardial infarction and peripheral arterial disease. Low social position is associated with an increased prevalence of cervical and lung cancers (OR=1.73 and 1.95, p<0.002 and p<0.03) and a decreased prevalence of skin cancer (OR=0.70, p<0.0001) while a bad work environment is associated with an increased prevalence of breast, skin, prostate and colon cancers (OR=1.31 to 2.91, p<0.0002 to p<0.0001). Unemployment exposure is not associated with the prevalence of any type of cancers. CONCLUSIONS: Social position, work environment and unemployment are associated with distinct cardiovascular and cancerous diseases that could add up during lifetime, they should therefore be considered all together in any preventive strategy.

Long-term exposure to airborne metals and risk of cancer in the French cohort Gazel.

BACKGROUND: The specific compounds that make ambient fine particulate matter (PM2.5) carcinogen remain poorly identified. Some metals contribute to ambient PM2.5 and possibly to its adverse effects. But the challenge of assessing exposure to airborne metals limits epidemiological studies. OBJECTIVE: To analyze the relationships between several airborne metals and risk of cancer in a large population. METHODS: We estimated the individual exposure to 12 airborne metals of âˆ¼ 12,000 semi-urban and rural participants of the French population-based Gazel cohort using moss biomonitoring data from a 20-year national program. We used principal component analyses (PCA) to derive groups of metals, and focused on six single carcinogenic or toxic metals (arsenic, cadmium, chromium, lead, nickel, and vanadium). We used extended Cox models with attained age as time-scale and time-varying weighted average exposures, adjusted for individual and area-level covariables, to analyze the association between each exposure and all-site combined, bladder, lung, breast, and prostate cancer incidence. RESULTS: We identified 2,401 cases of all-site cancer between 2001 and 2015. Over the follow-up, median exposures varied from 0.22 (interquartile range (IQR): 0.18-0.28) to 8.68 (IQR: 6.62-11.79) µg.g-1 of dried moss for cadmium and lead, respectively. The PCA yielded three groups identified as "anthropogenic", "crustal", and "marine". Models yielded positive associations between most single and groups of metal and all-site cancer, with e.g. hazard ratios of 1.08 (95% CI: 1.03, 1.13) for cadmium or 1.06 (95% CI: 1.02,1.10) for lead, per interquartile range increase. These findings were consistent across supplementary analyses, albeit attenuated when accounting for total PM2.5. Regarding specific site cancers, we estimated positive associations mostly for bladder, and generally with large confidence intervals. CONCLUSION: Most single and groups of airborne metals, except vanadium, were associated with risk of cancer. These findings may help identify sources or components of PM2.5 that may be involved in its carcinogenicity.

Prevalence of sexual dysfunction after breast cancer compared to controls, a study from CONSTANCES cohort.

PURPOSE: Sexuality, a substantial factor in quality of life, may be altered after breast cancer (BC) treatments as they intimately afflict femininity. This study aimed to assess the prevalence of sexual dysfunction in women with a history of BC and to compare it with women without a BC history. METHODS: The French general epidemiological cohort CONSTANCES includes more than 200,000 adults. All inclusion questionnaires from CONSTANCES non-virgin adult female participants were analyzed. Women reporting a history of BC were compared to controls in univariate analysis. Multivariate analysis was performed to highlight any demographic risk factor for sexual dysfunction. RESULTS: Among the 2,680 participants who had a history of BC, 34% did not engage in sexual intercourse (SI) in the month preceding the completion of the questionnaire (n = 911), 34% had pain during SI (n = 901) and 30% were not satisfied with their sex life (n = 803). Sexual dysfunction was significantly more frequent in women who had a history of BC: they had less sexual interest (OR 1.79 [1.65;1.94], p < 0.001), experienced more pain during SI (OR 1.10 [1.02;1.19], p < 0.001) and were more dissatisfied with their sex life (OR 1.58 [1.47;1.71], p < 0.001). This stayed true after adjustment on multiple demographic factors such as age, menopausal status, body mass index and depression. CONCLUSIONS: Overall, in this real-life study in a large national cohort, history of BC appeared to be a risk factor for sexual disorders. IMPLICATIONS FOR CANCER SURVIVORS: Efforts to detect sexual disorders in BC survivors and offer quality support must be pursued.

Prevalence, treatment and determinants of obstructive sleep apnoea and its symptoms in a population-based French cohort.

Background: Obstructive sleep apnoea (OSA) is associated with increased morbidity and mortality. Although the disorder has been well studied in selected high-risk populations, few data exist on its prevalence in the general population. We aimed to assess the prevalence and determinants of OSA in France. Methods: Data from participants of the French population-based CONSTANCES cohort aged 18-69 years at inclusion and being treated for sleep apnoea or screened for OSA in 2017 using the Berlin Questionnaire were analysed. Weighted analyses were performed to provide recent and representative results in the general population. Results: Among 20 151 participants, the prevalence of treated sleep apnoea was 3.5% (95% CI 3.0-3.9%). The prevalence of untreated subjects with a positive Berlin Questionnaire was 18.1% (95% CI 17.3-19.2%) for a total weighted prevalence of treated sleep apnoea or high risk of OSA of 20.9% (95% CI 20.0-21.9%). Regarding prevalence of OSA symptoms, it was 37.2% (95% CI 36.1-38.3%) for severe snoring and 14.6% (95% CI 13.8-15.5%) for hypersomnolence. In multivariable logistic regression analysis, male sex, age, previous cardiovascular events, smoking, low educational level, low physical activity and depressive symptoms were associated with having either treated sleep apnoea or a positive Berlin Questionnaire. Conclusion: In this large French population-based cohort, one in five participants had a high likelihood of OSA, whereas only 3.5% were treated for the disorder, suggesting major underdiagnosis in the general population. OSA diagnosis should be considered more often in people with risk factors such as depressive symptoms as well as unhealthy behaviours and socioeconomic conditions.

Impact of asthma on working life: an analysis of the French CONSTANCES cohort.

OBJECTIVES: Asthma has significant occupational consequences. The objective of our study was to investigate the links between asthma and the career path, taking into account gender and age at asthma onset. METHODS: Using cross-sectional data collected at inclusion in the French CONSTANCES cohort in 2013-2014, we studied the links between each career path indicator (number of job periods, total duration of employment, numbers of part-time jobs and work interruptions due to unemployment or health issues, employment status at inclusion) on the one hand, and current asthma and asthma symptom score in the last 12 months on the other hand, as reported by the participants. Multivariate analyses were performed separately for men and women using logistic and negative binomial regression models adjusted for age, smoking status, body mass index and educational level. RESULTS: When the asthma symptom score was used, significant associations were observed with all of the career path indicators studied: a high symptom score was associated with a shorter total duration of employment as well as a greater number of job periods, part-time jobs and work interruptions due to unemployment or health issues. These associations were of similar magnitude in men and women. When current asthma was used, the associations were more pronounced in women for some career path indicators. CONCLUSION: The career path of asthmatic adults is more often unfavourable than that of those without asthma. Efforts should be made to support people with asthma in the workplace, in order to maintain employment and facilitate the return to work.

Association of Midlife Cardiovascular Health and Subsequent Change in Cardiovascular Health With Incident Cancer.

Background: The commonality of risk factors between cancer and cardiovascular disease suggests that primordial prevention (preventing the onset of risk factors) is a relevant strategy for cancer prevention. Objectives: This study sought to examine the association between baseline and change in the cardiovascular health (CVH) score and incident cancer. Methods: Using serial examinations of the GAZEL (GAZ et ELECTRICITE de France) study in France, we examined the associations between the American Heart Association's Life's Simple 7 CVH score (range: 0-to 14 [poor, intermediate, and ideal level of smoking, physical activity, body mass index, diet, blood pressure, diabetes status, or lipids]) in 1989/1990, their change over 7 years, and incident cancer and cardiac events up to 2015. Results: The study population included 13,933 participants (mean age: 45.3 ± 3.4 years, 24% women). After a median follow-up of 24.8 years (Q1-Q3: 19.4-24.9 years), 2,010 participants had an incident cancer and 899 a cardiac event. The risk of cancer (any site) decreased by 9% (HR: 0.91; 95% CI: 0.88-0.93) per 1-point increase in the CVH score in 1989/1990 compared with a 20% (HR: 0.80; 95% CI: 0.77-0.83) risk reduction for cardiac events. The risk of cancer decreased by 5% (HR: 0.95; 95% CI: 0.92-0.99) per unit of change in the CVH score between 1989/1990 and 1996/1997 compared with a 7% risk reduction for cardiac events (HR: 0.93; 95% CI: 0.88-0.98). These associations remained after omitting the smoking metric from the CVH score. Conclusions: Primordial prevention is a relevant strategy for the prevention of cancer in the population.

Association of Cardiovascular Health With Risk of Clinically Relevant Depressive Symptoms.

Importance: Cardiovascular health may be used for prevention of depressive symptoms. However, data on the association of cardiovascular health across midlife with depressive symptoms are lacking. Objective: To evaluate whether better baseline cardiovascular health and improvement of cardiovascular health over time are associated with a lower risk of both incident depressive symptoms and unfavorable trajectories of depressive symptoms. Design, Setting, and Participants: Participants without depressive symptoms were included from a prospective community-based cohort in France (GAZEL cohort). Cardiovascular health examinations occurred in 1990 and 1997 and assessment of depressive symptoms in 1997 and every 3 years thereafter until 2015. Data were analyzed from January to October 2022. Exposures: Number of cardiovascular health metrics (smoking, body mass index, physical activity, diet, blood pressure, glucose, and cholesterol) at an intermediate or ideal level in 1997 (range, 0-7) and 7-year change in cardiovascular health between 1990 and 1997. Main Outcomes and Measures: Primary outcome was incident depressive symptoms (20-item Center for Epidemiologic Studies-Depression Scale [CES-D] score of 17 or greater in men or 23 or greater in women); secondary outcome was trajectories of depressive symptoms scores. Trajectories included consistently low scores, moderately elevated scores, low starting then increasing scores, moderately high starting, increasing, then remitting scores, and moderately high starting then increasing scores. Results: Of 6980 included patients, 1671 (23.9%) were women, and the mean (SD) age was 53.3 (3.5) years. During a follow-up spanning 19 years after 1997, 1858 individuals (26.5%) had incident depressive symptoms. Higher baseline cardiovascular health in 1997 and improvement in cardiovascular health over 7 years were each associated with lower risk of depressive symptoms (odds ratio [OR] per additional metric at intermediate or ideal level at baseline, 0.87; 95% CI, 0.84-0.91; OR per 1 higher metric at intermediate or ideal level over 7 years, 0.91; 95% CI, 0.86-0.96). Also, better cardiovascular health was associated with lower risk of unfavorable depressive symptoms trajectories. Compared with the consistently low score trajectory, the lowest risks were observed for the low starting then increasing score trajectory (OR per additional metric at intermediate or ideal level at baseline, 0.70; 95% CI, 0.64-0.76; OR per 1 higher metric at intermediate or ideal level over 7 years, 0.73; 95% CI, 0.68-0.79) and the moderately high starting then increasing score trajectory (OR per additional metric at intermediate or ideal level at baseline, 0.71; 95% CI, 0.64-0.79; OR per 1 higher metric at intermediate or ideal level over 7 years, 0.71; 95% CI, 0.64-0.77). Conclusions and Relevance: In this prospective community-based cohort study of adults, higher cardiovascular health was associated with a lower risk of depressive symptoms over time. Elucidating which set of cardiovascular factors may affect depression risk could be important for prevention.