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.

SARS-CoV-2 infection and the risk of depressive symptoms: a retrospective longitudinal study from the population-based CONSTANCES cohort.

BACKGROUND: Should COVID-19 have a direct impact on the risk of depression, it would suggest specific pathways for prevention and treatment. In this retrospective population-based study, we aimed to examine the association of prior SARS-CoV-2 infection with depressive symptoms, distinguishing self-reported v. biologically confirmed COVID-19. METHODS: 32 007 participants from the SAPRIS survey nested in the French CONSTANCES cohort were included. COVID-19 was measured as followed: ad hoc serologic testing, self-reported PCR or serology positive test results, and self-reported COVID-19. Depressive symptoms were measured with the Center of Epidemiologic Studies-Depression Scale (CES-D). Outcomes were depressive symptoms (total CES-D score, its four dimensions, and clinically significant depressive symptoms) and exposure was prior COVID-19 (no COVID-19/self-reported unconfirmed COVID-19/biologically confirmed COVID-19). RESULTS: In comparison to participants without COVID-19, participants with self-reported unconfirmed COVID-19 and biologically confirmed COVID-19 had higher CES-D scores (ß for one interquartile range increase [95% CI]: 0.15 [0.08-0.22] and 0.09 [0.05-0.13], respectively) and somatic complaints dimension scores (0.15 [0.09-0.21] and 0.10 [0.07-0.13]). Only those with self-reported but unconfirmed COVID-19 had higher depressed affect dimension scores (0.08 [0.01-0.14]). Accounting for ad hoc serologic testing only, the CES-D score and the somatic complaints dimension were only associated with the combination of self-reported COVID-19 and negative serology test results. CONCLUSIONS: The association between COVID-19 and depressive symptoms was merely driven by somatic symptoms of depression and did not follow a gradient consistent with the hypothesis of a direct impact of SARS-CoV-2 infection on the risk of depression.

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.

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.

Impact of breast cancer care pathways and related symptoms on the return-to-work process: results from a population-based French cohort study (CONSTANCES).

BACKGROUND: Breast cancer (BC) treatments and related symptoms may affect return to work (RTW). The objective of this study was to investigate the impact of BC care pathways (timing and sequence of treatments) and related symptoms on RTW. METHODS: The study population included working-age women with BC who were enrolled in the French CONSTANCES cohort from 2012 to 2018. BC treatments, antidepressant/anxiolytic and antalgic drug deliveries (used as proxies of depression and pain, respectively) and statutory sick pay (used to estimate RTW and time to RTW) were assessed monthly using data from the French national healthcare system database. BC care pathways were identified with the sequence analysis method. Cox models with time-dependent covariates were used to investigate the impact of BC care pathways and related symptoms on RTW and time to RTW, after adjusting for age and socioeconomic characteristics. RESULTS: 73.2% (231/303) of women returned to work within 2 years after BC diagnosis. Five BC care pathway patterns were identified: (i) BC surgery only, (ii) BC surgery and radiotherapy, (iii) BC surgery and chemotherapy, (iv) BC surgery and chemotherapy and radiotherapy, and (v) BC surgery and long-term alternative chemotherapy/radiotherapy. The hazards ratios of non-RTW were significantly higher for women who received BC surgery and long-term alternative chemotherapy/radiotherapy and for > 55-year-old women. Time to RTW was significantly longer in women who received chemotherapy (patterns iii to v) and in women with antidepressant/anxiolytic and antalgic drug deliveries. CONCLUSION: This study highlights the value of considering the dynamic, cumulative and temporal features of BC care pathways and related symptoms to facilitate the RTW of women with BC.

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.

Health behaviours of teachers and other education professionals in France: can we do better?

Education professionals play a critical role in health education, both as knowledge providers and as role-models. Drawing on the CONSTANCES French cohort (baseline 2012-19) and adjusting for important confounders, we compared education professionals (n = 14 730) with a random sample of non-education sector employees (n = 34 244) on three indicators of high-risk behaviour (at-risk drinking, current smoking, past-year cannabis use) and three indicators of unhealthy lifestyle (low physical activity, poor adherence to nutritional guidelines, overweight/obesity). Among education professionals, we distinguished between teachers (n = 12 820), school principals (n = 372), senior education advisers (n = 189), school health professionals (n = 128) and school service staff (n = 1221). Compared with non-education sector employees with similar demographic and socioeconomic profiles, teachers were less likely to be at-risk drinkers, to smoke, to have used cannabis in the past year and to be overweight/obese. Other non-teaching education professionals were also less involved in high-risk behaviours than non-education employees, but results were more mixed concerning some lifestyle indicators, with certain non-teaching education professional groups showing a higher likelihood of being physically inactive or overweight/obese. In this nationwide French study, our results suggest a window of opportunity to promote school staff health but also indirectly, that of the youth with whom they interact daily. We suggest that school staff should be supported in health matters not only through the provision of health information but also most importantly, through the development of a favourable and supportive environment enabling them to put health knowledge into practice.

Education professionals play a crucial role in health education, notably as role-models, since they come into contact with students on a daily basis. Therefore, examining their health behaviours may be instructive. In this nationwide French study, teachers appeared to behave more healthily compared with non-education sector employees in important domains such as alcohol consumption or tobacco use. However, certain non-teaching education professional groups were more likely to be physically inactive or overweight/obese. Our results highlight opportunities for interventions aimed at raising health awareness and empowerment among school staff. A comprehensive health promotion approach integrating our findings would draw less on a vertical or top-down transfer of knowledge and depend more on participation and exchange among school staff, on teachers leading by example, as well as on the development of a supportive school environment.

Evidence of early circulation of SARS-CoV-2 in France: findings from the population-based "CONSTANCES" cohort.

Using serum samples routinely collected in 9144 adults from a French general population-based cohort, we identified 353 participants with a positive anti-SARS-CoV-2 IgG test, among whom 13 were sampled between November 2019 and January 2020 and were confirmed by neutralizing antibodies testing. Investigations in 11 of these participants revealed experience of symptoms possibly related to a SARS-CoV-2 infection or situations at risk of potential SARS-CoV-2 exposure. This suggests early circulation of SARS-CoV-2 in Europe.

Pesticides expenditures by farming type and incidence of Parkinson disease in farmers: A French nationwide study.

BACKGROUND: Professional pesticides exposure is associated with PD risk, but it remains unclear whether specific products, which strongly depend on farming type, are specifically involved. We performed a nationwide ecological study to examine the association of pesticides expenditures for the main farming types with PD incidence in French farmers. METHODS: We used the French National Health Insurance database to identify incident PD cases in farmers (2010-2015). We combined data on pesticides expenditures with the agricultural census to compute pesticides expenditures for nine farming types in 2000 in 3571 French cantons. The association between pesticides expenditures and PD age/sex standardized incidence was examined using multilevel Poisson regression, adjusted for smoking, neurologists' density, and deprivation index. RESULTS: 10,282 incident PD cases were identified. Cantons with the highest pesticides expenditures for vineyards without designation of origin were characterized by 16% (95% CI = 6-28%) higher PD incidence (p-trend corrected for multiple testing = 0.006). This association was significant in men and older farmers. There was no association with pesticides expenditures for other farming types, including vineyards with designation of origin. CONCLUSIONS: PD incidence increased significantly with pesticides expenditures in vineyards without designation of origin characterized by high fungicide use. This result suggests that agricultural practices and pesticides used in these vineyards may play a role in PD and that farmers in these farms should benefit from preventive measures aiming at reducing exposure. Our study highlights the importance of considering farming type in studies on pesticides and PD and the usefulness of pesticides expenditures for exposure assessment.

Association of Parkinson's disease with industry sectors: a French nationwide incidence study.

In order to identify working environments at risk for Parkinson's disease (PD), we investigated the relation between the importance of industry sectors, used as a surrogate for occupational exposures, and PD incidence in French cantons. The number of incident PD cases (2010-2014) in 3689 cantons of metropolitan France was determined using drug claims from French National Health Insurance databases. The proportions of workers in 38 industry sectors in 2006 were calculated for each canton. Associations between the proportions of workers in industry sectors and PD age/sex-standardized incidence ratios were examined using incidence rate ratios (IRR) and 95% confidence intervals (CI) estimated with multilevel negative binomial regressions with a random intercept at the canton-level and adjusted for smoking, deprivation index, and density of neurologists. We then used two-step semi-Bayes hierarchical regression (HR) to include prior information about exposure to pesticides, metals, and solvents in each industry sector. We identified 112,625 incident cases. PD incidence was higher in areas characterized by high proportions of workers in "Agriculture, forestry and fishing" (IRRHR = 1.042; CI 95% = 1.014-1.070; p-TrendHR = 0.004), "Manufacture of textiles, wearing apparel, leather and related products" (IRRHR = 1.024; CI 95% = 1.005-1.044; p-TrendHR = 0.010), and "Manufacture of basic metals and fabricated metal products, except machinery and equipment" (IRRHR = 1.024; CI 95% = 1.003-1.046; p-TrendHR = 0.071). This nationwide study, based on a comprehensive analysis of industry sectors, shows significant associations between high proportions of workers in specific industry sectors (agriculture, metallurgy, textile) and PD incidence that may be targeted in further epidemiological studies to replicate and better understand these associations.

Agricultural activities and the incidence of Parkinson's disease in the general French population.

Most studies on pesticides and Parkinson's disease (PD) focused on occupational exposure in farmers. Whether non-occupational exposure is associated with PD has been little explored. We investigated the association between agricultural characteristics and PD incidence in a French nationwide ecologic study. We hypothesized that persons living in regions with agricultural activities involving more intensive pesticide use would be at higher risk. We identified incident PD cases from French National Health Insurance databases (2010-2012). The proportion of land dedicated to 18 types of agricultural activities was defined at the canton of residence level. We examined the association between agricultural activities and PD age/sex-standardized incidence ratios using multivariable multilevel Poisson regression adjusted for smoking, deprivation index, density of neurologists, and rurality (proportion of agricultural land); we used a false discovery rate approach to correct for multiple comparisons and compute q-values. We also compared incidence in clusters of cantons with similar agricultural characteristics (k-means algorithm). We identified 69,010 incident PD cases. Rurality was associated with higher PD incidence (p < 0.001). Cantons with higher density of vineyards displayed the strongest association (RRtop/bottom quartile = 1.102, 95% CI = 1.049-1.158; q-trend = 0.040). This association was similar in men, women, and non-farmers, stronger in older than younger persons, and present in all French regions. Persons living in the cluster with greatest vineyards density had 8.5% (4.4-12.6%) higher PD incidence (p < 0.001). In France, vineyards rank among the crops that require most intense pesticide use. Regions with greater presence of vineyards are characterized by higher PD risk; non-professional pesticides exposure is a possible explanation.

Association of UV radiation with Parkinson disease incidence: A nationwide French ecologic study.

BACKGROUND: Vitamin D is thought to contribute to brain health, but it is unclear whether low vitamin D levels are associated with increased incidence of Parkinson's disease (PD). Using ultraviolet B (UV-B) as a surrogate for vitamin D levels, we conducted a nationwide ecologic study in France in order to examine the association of UV-B with PD incidence. METHODS: We used French national drug claims databases to identify PD cases using a validated algorithm. UV-B data from the solar radiation database were derived from satellite images. We estimated PD incidence (2010-2012) at the canton level (small administrative French unit) and used multilevel Poisson regression to examine its association with UV-B (2005 annual average), after adjustment for age, sex, deprivation index, density of neurologists, smoking, proportion of agricultural land, and vitamin D supplementation. RESULTS: Analyses are based on 69,010 incident PD patients. The association between UV-B and PD incidence was quadratic (P<0.001) and modified by age (P<0.001). Below 70y, incidence was higher in the bottom quintile (relative risk, RRQ1:45-49y=1.18, 95% CI=1.08-1.29) compared with the middle UV-B quintile, and lower in the top quintile (RRQ5:45-49y=0.85 [0.77-0.94]). An opposite pattern was observed in older subjects (RRQ1:85-89y=0.92 [0.89-0.96]; RRQ5:85-89y=1.06 [1.02-1.11]). Analysis based on continuous UV-B yielded similar conclusions. CONCLUSIONS: In this nationwide study, there was an age-dependent quadratic association between UV-B and PD incidence. This study suggests that reasonable UV-B exposure is associated with lower PD risk in younger persons and that future studies should examine dose-response relations and take age into account.

Parkinson disease male-to-female ratios increase with age: French nationwide study and meta-analysis.

BACKGROUND: Parkinson's disease (PD) is 1.5 times more frequent in men than women. Whether age modifies this ratio is unclear. We examined whether male-to-female (M-F) ratios change with age through a French nationwide prevalence/incidence study (2010) and a meta-analysis of incidence studies. METHODS: We used French national drug claims databases to identify PD cases using a validated algorithm. We computed M-F prevalence/incidence ratios overall and by age using Poisson regression. Ratios were regressed on age to estimate their annual change. We identified all PD incidence studies with age/sex-specific data, and performed a meta-analysis of M-F ratios. RESULTS: On the basis of 149 672 prevalent (50% women) and 25 438 incident (49% women) cases, age-standardised rates were higher in men (prevalence=2.865/1000; incidence=0.490/1000 person-years) than women (prevalence=1.934/1000; incidence=0.328/1000 person-years). The overall M-F ratio was 1.48 for prevalence and 1.49 for incidence. Prevalence and incidence M-F ratios increased by 0.05 and 0.14, respectively, per 10 years of age. Incidence was similar in men and women under 50 years (M-F ratio <1.2, p>0.20), and over 1.6 (p<0.001) times higher in men than women above 80 years (p trend <0.001). A meta-analysis of 22 incidence studies (14 126 cases, 46% women) confirmed that M- F ratios increased with age (0.26 per 10 years, p trend=0.005). CONCLUSIONS: Age-increasing M-F ratios suggest that PD aetiology changes with age. Sex-related risk/protective factors may play a different role across the continuum of age at onset. This finding may inform aetiological PD research.

Risk factors for uncontrolled blood pressure among individuals with hypertension on treatment: the CONSTANCES population-based study.

BACKGROUND: We aimed to assess factors associated with uncontrolled blood pressure (BP) among individuals with hypertension on treatment, by sex. METHODS: We conducted a nested cross-sectional analysis using data from the population-based cohort study CONSTANCES, designed as a randomly selected sample of French adults aged 18-69 years at study inception. We included 11 760 participants previously diagnosed with hypertension and taking antihypertensive medications. Uncontrolled BP was defined as mean systolic BP ≥140 mmHg and/or mean diastolic BP ≥90 mmHg. Sex-specific age-adjusted multivariable analyses were performed using logistic regression models stratified by stages of uncontrolled hypertension. RESULTS: The mean age of participants was 59.4 years. The prevalence of uncontrolled BP was 51.4%, and it was higher in men than in women [adjusted odds ratio (aOR), 1.80; 95% CI, 1.67-1.94]. In both sexes, the lower the age, the lower the prevalence of uncontrolled hypertension. Low level of education and history of cardiovascular events had, respectively, higher and lower odds of uncontrolled BP. In men, additional risk factors included overweight and obesity (aOR, 1.15; 95% CI, 1.00-1.32; and aOR, 1.45; 95% CI, 1.23-1.70, respectively), lack of physical activity (aOR, 1.20; 95% CI, 1.04-1.40), low adherence to a Dietary Approach to Stop Hypertension diet (aOR, 1.21; 95% CI, 1.05-1.40) and heavy alcohol consumption (aOR, 1.33; 95% CI, 1.08-1.63), with the last two factors persisting across different stages of uncontrolled BP. CONCLUSIONS: From a population-based perspective, socio-economic and behavioural characteristics were risk factors for uncontrolled hypertension, but they differed by sex and by stage of uncontrolled hypertension. Modifiable risk factors, such as weight, diet, physical activity and alcohol consumption, have an important role in the control of hypertension.

Association of Snoring and Daytime Sleepiness With Subsequent Incident Hypertension: A Population-Based Cohort Study.

BACKGROUND: There is a strong association between obstructive sleep apnea and hypertension, but the effects of obstructive sleep apnea symptoms on the risk of incident hypertension are not well documented. The aim of this prospective study was to examine whether snoring and sleepiness are associated with incident hypertension. METHODS: Data from the French population-based CONSTANCES cohort were analyzed. Normotensive participants, aged 18 to 69 years, were included between 2012 and 2016 and screened for snoring, morning fatigue, and daytime sleepiness in 2017 using items of the Berlin Questionnaire. We used Cox models, adjusted for multiple potential confounders, including body mass index, baseline blood pressure, sleep duration, and depressive symptoms, to compute hazards ratios of incidentally treated hypertension. RESULTS: Among 34 727 subjects, the prevalence of self-reported habitual snoring, morning fatigue, and excessive daytime sleepiness (≥3× a week for each) was 23.6%, 16.6%, and 19.1%, respectively. During a median follow-up of 3.1 years (interquartile range, 3.0-3.5), the incidence of treated hypertension was 3.8%. The risk of de novo treated hypertension was higher in participants who reported habitual snoring (adjusted hazard ratio, 1.17 [95% CI, 1.03-1.32]) and excessive daytime sleepiness (adjusted hazard ratio, 1.42 [95% CI, 1.24-1.62]), and increased with the weekly frequency of symptoms, with a dose-dependent relationship (Ptrend≤0.02 for all symptoms). CONCLUSIONS: Self-reported snoring and excessive daytime sleepiness are associated with an increased risk of developing hypertension. Identification of snoring and daytime sleepiness may be a useful public health screening tool in primary care for hypertension prevention.

Somatic Symptom Disorder-B criteria scale (SSD-12): Psychometric properties of the French version and associations with health outcomes in a population-based cross-sectional study.

OBJECTIVE: The 12-item Somatic Symptom Disorder-B Criteria Scale (SSD-12) is a self-reported questionnaire designed to assess the B criteria of the DSM-5 somatic symptom disorder. In this cross-sectional study, we aimed to examine the psychometric properties of the SSD-12 French version and associated health outcomes. METHODS: Participants were volunteers from the population-based CONSTANCES cohort who reported at least one new symptom that occurred between March 2020 and January 2021. Depressive symptoms were measured with the Center for Epidemiologic Studies-Depression scale (CES-D). RESULTS: A total of 18,796 participants completed the SSD-12. The scree plot was consistent with a 1-factor structure, while goodness-of-fit indices of the confirmatory factorial analyses and clinical interpretability were consistent with a 3-factor structure (excluding the item 7): 'Perceived severity', 'Perceived impairment', 'Negative expectations'. The Cronbach's α coefficients of the total and factors scores were 0.90, 0.88, 0.84 and 0.877, respectively. The total score was associated with depressive symptoms (Spearmann's rho: 0.32), self-rated health (-0.46), the number of persistent symptoms (0.32), and seeking medical consultation (odds ratio [95% confidence interval] for one interquartile range increase: 1.51 [1.48-1.54]). Among participants seeking medical consultation, those with higher SSD-12 scores were more likely to have their symptoms attributed to "stress/anxiety/depression" (1.32 [1.22-1.43]) and "psychosomatic origin" (1.25 [1.20-1.29]), and less to "COVID-19" (0.89 [0.85-0.93]). CONCLUSION: While the SSD-12 French version can be used as a unidimensional tool, it also has a 3-factor structure, somewhat different from the DSM-5 theoretical structure, with high internal consistency and clinically meaningful associations with other health outcomes.

Psychological burden associated with incident persistent symptoms and their evolution during the COVID-19 pandemic: a prospective population-based study.

BACKGROUND: Identifying factors that predict the course of persistent symptoms that occurred during the COVID-19 pandemic is a public health issue. Modifiable factors could be targeted in therapeutic interventions. OBJECTIVE: This prospective study based on the population-based CONSTANCES cohort examined whether the psychological burden associated with incident persistent symptoms (ie, that first occurred from March 2020) would predict having ≥1 persistent symptom 6-10 months later. METHODS: A total of 8424 participants (mean age=54.6 years (SD=12.6), 57.2% women) having ≥1 incident persistent symptom at baseline (ie, between December 2020 and February 2021) were included. The psychological burden associated with these persistent symptoms was assessed with the Somatic Symptom Disorder-B Criteria Scale (SSD-12). The outcome was having ≥1 persistent symptom at follow-up. Adjusted binary logistic regression models examined the association between the SSD-12 score and the outcome. FINDINGS: At follow-up, 1124 participants (13.3%) still had ≥1 persistent symptom. The SSD-12 score at baseline was associated with persistent symptoms at follow-up in both participants with (OR (95% CI) for one IQR increase: 1.42 (1.09 to 1.84)) and without SARS-CoV-2 infection prior to baseline (1.39 (1.25 to 1.55)). Female gender, older age, poorer self-rated health and infection prior to baseline were also associated with persistent symptoms at follow-up. CONCLUSIONS: The psychological burden associated with persistent symptoms at baseline predicted the presence of ≥1 persistent symptom at follow-up regardless of infection prior to baseline. CLINICAL IMPLICATIONS: Intervention studies should test whether reducing the psychological burden associated with persistent symptoms could improve the course of these symptoms.

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.