The association of Obesogenic Environments with Weight Status, Blood Pressure, and Blood Lipids: A Cross-Sectional Pooled Analysis across Five Cohorts.

In this observational cross-sectional study, we investigated the relationship between combined obesogenic neighbourhood characteristics and various cardiovascular disease risk factors in adults, including BMI, systolic blood pressure, and blood lipids, as well as the prevalence of overweight/obesity, hypertension, and dyslipidaemia. We conducted a large-scale pooled analysis, comprising data from five Dutch cohort studies (n = 183,871). Neighbourhood obesogenicity was defined according to the Obesogenic Built-environmental CharacterisTics (OBCT) index. The index was calculated for 1000m circular buffers around participants' home addresses. For each cohort, the association between the OBCT index and prevalence of overweight/obesity, hypertension and dyslipidaemia was analysed using robust Poisson regression models. Associations with continuous measures of BMI, systolic blood pressure, LDL-cholesterol, HDL-cholesterol, and triglycerides were analysed using linear regression. All models were adjusted for age, sex, education level and area-level socio-economic status. Cohort-specific estimates were pooled using random-effects meta-analyses. The pooled results show that a 10 point higher OBCT index score was significantly associated with a 0.17 higher BMI (95%CI: 0.10 to 0.24), a 0.01 higher LDL-cholesterol (95% CI: 0.01 to 0.02), a 0.01 lower HDL cholesterol (95% CI: -0.02 to -0.01), and non-significantly associated with a 0.36 mmHg higher systolic blood pressure (95%CI: -0.14 to 0.65). A 10 point higher OBCT index score was also associated with a higher prevalence of overweight/obesity (PR = 1.03; 95% CI: 1.02 to 1.05), obesity (PR = 1.04; 95% CI: 1.01 to 1.08) and hypertension (PR = 1.02; 95% CI: 1.00 to 1.04), but not with dyslipidaemia. This large-scale pooled analysis of five Dutch cohort studies shows that higher neighbourhood obesogenicity, as measured by the OBCT index, was associated with higher BMI, higher prevalence of overweight/obesity, obesity, and hypertension. These findings highlight the importance of considering the obesogenic environment as a potential determinant of cardiovascular health.

The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.

BACKGROUND: Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). METHODS: Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). RESULTS: Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). CONCLUSIONS: Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Healthy ageing in a multi-ethnic population: A descriptive cross-sectional analysis from the HELIUS study.

OBJECTIVE: We investigated ethnic health disparities in the Healthy Life in an Urban Setting multi-ethnic cohort using the multidimensional Healthy Ageing Score. STUDY DESIGN: We conducted a cross-sectional analysis of the study baseline data (2011-2015) collected through questionnaires/physical examinations for 17,091 participants (54.8 % women, mean (SD) age = 44.5 (12.8) years) from South-Asian Surinamese (14.8 %), African Surinamese (20.5 %), Dutch (24.3 %), Moroccan (15.5 %), Turkish (14.9 %), and Ghanaian (10.1 %) origins, living in Amsterdam, the Netherlands. MAIN OUTCOME MEASURES: We computed the Healthy Ageing Score developed in the Rotterdam Study, which has seven biopsychosocial domains: chronic diseases, mental health, cognitive function, physical function, pain, social support, and quality of life. That score was used to discern between healthy, moderate, and poor ageing. We explored differences in healthy ageing by ethnicity, sex, and age group using multinomial logistic regression. RESULTS: The Healthy Ageing Score [overall: poor (69.0 %), moderate (24.8 %), and healthy (6.2 %)] differed between ethnicities and was poorer in women and after midlife (cut-off 45 years) across ethnicities (all p < 0.001). In the fully adjusted models in men and women, poor ageing (vs. healthy ageing) was highest in the South-Asian Surinamese [adjusted odds ratios (95 % confidence intervals)] [2.96 (2.24-3.90) and 6.88 (3.29-14.40), respectively] and Turkish [2.80 (2.11-3.73) and 7.10 (3.31-15.24), respectively] vs. Dutch, in the oldest [5.89 (3.62-9.60) and 13.17 (1.77-98.01), respectively] vs. youngest, and in the divorced [1.48 (1.10-2.01) and 2.83 (1.39-5.77), respectively] vs. married. Poor ageing was inversely associated with educational and occupational levels, mainly in men. CONCLUSIONS: Compared with those of Dutch ethnic origin, ethnic minorities displayed less healthy ageing, which was more pronounced in women, before and after midlife, and was associated with sociodemographic factors.

Ethnic variations in metabolic syndrome components and their associations with the gut microbiota: the HELIUS study.

BACKGROUND: The occurrence of metabolic syndrome (MetS) and the gut microbiota composition are known to differ across ethnicities yet how these three factors are interwoven is unknown. Also, it is unknown what the relative contribution of the gut microbiota composition is to each MetS component and whether this differs between ethnicities. We therefore determined the occurrence of MetS and its components in the multi-ethnic HELIUS cohort and tested the overall and ethnic-specific associations with the gut microbiota composition. METHODS: We included 16,209 treatment naïve participants of the HELIUS study, which were of Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Turkish, and Moroccan descent to analyze MetS and its components across ethnicities. In a subset (n = 3443), the gut microbiota composition (16S) was associated with MetS outcomes using linear and logistic regression models. RESULTS: A differential, often sex-dependent, prevalence of MetS components and their combinations were observed across ethnicities. Increased blood pressure was commonly seen especially in Ghanaians, while South-Asian Surinamese and Turkish had higher MetS rates in general and were characterized by worse lipid-related measures. Regarding the gut microbiota, when ethnic-independent associations were assumed, a higher α-diversity, higher abundance of several ASVs (mostly for waist and triglyceride-related outcomes) and a trophic network of ASVs of Ruminococcaceae, Christensenellaceae, and Methanobrevibacter (RCM) bacteria were associated with better MetS outcomes. Statistically significant ethnic-specific associations were however noticed for α-diversity and the RCM trophic network. Associations were significant in the Dutch but not always in all other ethnicities. In Ghanaians, a higher α-diversity and RCM network abundance showed an aberrant positive association with high blood pressure measures compared to the other ethnicities. Even though adjustment for socioeconomic status-, lifestyle-, and diet-related variables often attenuated the effect size and/or the statistical significance of the ethnic-specific associations, an overall similar pattern across outcomes and ethnicities remained. CONCLUSIONS: The occurrence of MetS characteristics among ethnicities is heterogeneous. Both ethnic-independent and ethnic-specific associations were identified between the gut microbiota and MetS outcomes. Across multiple ethnicities, a one-size-fits-all approach may thus be reconsidered in regard to both the definition and/or treatment of MetS and its relation to the gut microbiota.

Sex differences in blood pressure phenotypes over time - the HELIUS study.

BACKGROUND: Hypertension can be classified into different phenotypes according to systolic and diastolic blood pressure (BP). In younger adults, these phenotypical differences have different prognostic value for men and women. However, little is known about sex differences in the natural course of different BP phenotypes over time. METHODS: We used baseline and follow-up data from the multiethnic, population-based HELIUS study to assess differences in BP phenotypes over time in men and women aged < 45 years stratified according to baseline office BP into normotension (<140/<90 mmHg), isolated systolic hypertension (ISH, ≥140/<90 mmHg), isolated diastolic hypertension (IDH, <140/≥90 mmHg) or systolic diastolic hypertension (SDH, ≥140/≥90 mmHg). Logistic regression adjusted for age, ethnicity, and follow-up time was used to assess the risk of hypertension at follow-up (BP ≥140/90 mmHg or use of antihypertensive medication), stratified by sex. RESULTS: We included 4103 participants [mean age 33.5 years (SD 7.4), 43.4% men] with a median follow-up time of 6.2 years. Compared to normotensive individuals, the age-adjusted odds ratios (OR) for having hypertension at follow-up were 4.78 (95% CI 2.90; 7.76) for ISH, 6.02 (95% CI 3.70; 9.74) for IDH and 33.73 (95% CI 20.35; 58.38) for SDH in men, while in women, OR were 10.08 (95% CI 4.09; 25.56) for ISH, 27.59 (95% CI 14.68; 53.82) for IDH and 50.58 (95% CI 24.78; 114.84) for SDH. CONCLUSIONS: The risk of hypertension at follow-up was higher among women for all phenotypes compared to men, particularly in those with IDH. Findings of this study emphasize the importance of close BP monitoring in the young, especially in women.

Sex and ethnic differences in unrecognized myocardial infarctions: Observations on recognition and preventive therapies from the multiethnic population-based HELIUS cohort.

Background: Epidemiological studies suggest sex differences in the prevalence and characteristics of unrecognized and recognized myocardial infarction (uMI, rMI). Despite increasingly diverse populations, observations are limited in multiethnic contexts. Gaining better understanding may inform policy makers and healthcare professionals on populations at risk of uMI who could benefit from preventive measures. Methods: We used baseline data from the multiethnic population-based HELIUS cohort (2011-2015; Amsterdam, the Netherlands). Using logistic regressions, we studied sex differences in the prevalence and proportion of uMIs across ethnic groups. Next, we studied whether symptoms, clinical parameters, and sociocultural factors were associated with uMIs. Finally, we compared secondary preventive therapies in women and men with a uMI or rMI. We relied on pathological Q-waves on a resting electrocardiogram as the electrocardiographic signature for (past) MI. Results: Overall, and in Turkish and Moroccan subgroups, the prevalence of uMIs was higher in men than women. The proportion of uMIs was similar in women (21.0%) and men (18.4%), yet varied by ethnicity. In women and men, symptoms (chest pain, dyspnea) and clinical parameters (hypertension, hypercholesterolemia), and in women also lower educational level and diabetes were associated with lower odds of uMIs. Women (0.0%) and men (3.6%) with uMI were unlikely to receive secondary preventive therapies compared to those with rMI (28.1-40.9%). Conclusions: The prevalence of uMIs was higher in men than women, and sex differences in the proportion of uMIs varied somewhat across ethnic groups. People with uMIs did not receive adequate preventative medications, posing a risk for recurrent events.

Psychosocial factors, health behaviors and risk of cancer incidence: Testing interaction and effect modification in an individual participant data meta-analysis.

Depression, anxiety and other psychosocial factors are hypothesized to be involved in cancer development. We examined whether psychosocial factors interact with or modify the effects of health behaviors, such as smoking and alcohol use, in relation to cancer incidence. Two-stage individual participant data meta-analyses were performed based on 22 cohorts of the PSYchosocial factors and CAncer (PSY-CA) study. We examined nine psychosocial factors (depression diagnosis, depression symptoms, anxiety diagnosis, anxiety symptoms, perceived social support, loss events, general distress, neuroticism, relationship status), seven health behaviors/behavior-related factors (smoking, alcohol use, physical activity, body mass index, sedentary behavior, sleep quality, sleep duration) and seven cancer outcomes (overall cancer, smoking-related, alcohol-related, breast, lung, prostate, colorectal). Effects of the psychosocial factor, health behavior and their product term on cancer incidence were estimated using Cox regression. We pooled cohort-specific estimates using multivariate random-effects meta-analyses. Additive and multiplicative interaction/effect modification was examined. This study involved 437,827 participants, 36,961 incident cancer diagnoses, and 4,749,481 person years of follow-up. Out of 744 combinations of psychosocial factors, health behaviors, and cancer outcomes, we found no evidence of interaction. Effect modification was found for some combinations, but there were no clear patterns for any particular factors or outcomes involved. In this first large study to systematically examine potential interaction and effect modification, we found no evidence for psychosocial factors to interact with or modify health behaviors in relation to cancer incidence. The behavioral risk profile for cancer incidence is similar in people with and without psychosocial stress.

Networks of gut bacteria relate to cardiovascular disease in a multi-ethnic population: the HELIUS study.

AIMS: Gut microbiota have been linked to blood lipid levels and cardiovascular diseases (CVDs). The composition and abundance of gut microbiota trophic networks differ between ethnicities. We aim to evaluate the relationship between gut microbiotal trophic networks and CVD phenotypes. METHODS AND RESULTS: We included cross-sectional data from 3860 individuals without CVD history from 6 ethnicities living in the Amsterdam region participating in the prospective Healthy Life in Urban Setting (HELIUS) study. Genetic variants were genotyped, faecal gut microbiota were profiled, and blood and anthropometric parameters were measured. A machine learning approach was used to assess the relationship between CVD risk (Framingham score) and gut microbiota stratified by ethnicity. Potential causal relationships between gut microbiota composition and CVD were inferred by performing two-sample Mendelian randomization with hard CVD events from the Pan-UK Biobank and microbiome genome-wide association studies summary data from a subset of the HELIUS cohort (n = 4117). Microbial taxa identified to be associated with CVD by machine learning and Mendelian randomization were often ethnic-specific, but some concordance across ethnicities was found. The microbes Akkermansia muciniphila and Ruminococcaceae UCG-002 were protective against ischaemic heart disease in African-Surinamese and Moroccans, respectively. We identified a strong inverse association between blood lipids, CVD risk, and the combined abundance of the correlated microbes Christensenellaceae-Methanobrevibacter-Ruminococcaceae (CMR). The CMR cluster was also identified in two independent cohorts and the association with triglycerides was replicated. CONCLUSION: Certain gut microbes can have a potentially causal relationship with CVD events, with possible ethnic-specific effects. We identified a trophic network centred around Christensenellaceae, Methanobrevibacter, and various Ruminococcaceae, frequently lacking in South-Asian Surinamese, to be protective against CVD risk and associated with low triglyceride levels.

Comparative Analysis of Taxonomic and Functional Gut Microbiota Profiles in Relation to Seroconversion of Thyroid Peroxidase Antibodies in Euthyroid Participants.

Background: Previous studies have reported gut microbiome alterations in Hashimoto's autoimmune thyroiditis (HT) patients. Yet, it is unknown whether an aberrant microbiome is present before clinical disease onset in participants susceptible to HT or whether it reflects the effects of the disease itself. In this study, we report for the first time a comprehensive characterization of the taxonomic and functional profiles of the gut microbiota in euthyroid seropositive and seronegative participants. Our primary goal was to determine taxonomic and functional signatures of the intestinal microbiota associated with serum thyroid peroxidase antibodies (TPOAb). A secondary aim was to determine whether different ethnicities warrant distinct reference intervals for accurate interpretation of serum thyroid biomarkers. Methods: In this cross-sectional study, euthyroid participants with (N = 159) and without (N = 1309) TPOAb were selected from the multiethnic (European Dutch, Moroccan, and Turkish) HEalthy Life In an Urban Setting (HELIUS) cohort. Fecal microbiota composition was profiled using 16S rRNA sequencing. Differences between the groups were analyzed based on the overall composition (alpha and beta diversity), as well as differential abundance (DA) of microbial taxa and functional pathways using multiple DA tools. Results: Overall composition showed a substantial overlap between the two groups (p > 0.05 for alpha-diversity; p = 0.39 for beta-diversity), indicating that TPOAb-seropositivity does not significantly differentiate gut microbiota composition and diversity. Interestingly, TPOAb status accounted for only a minor fraction (0.07%) of microbiome variance (p = 0.545). Further exploration of taxonomic differences identified 138 taxa nominally associated with TPOAb status. Among these, 13 taxa consistently demonstrated nominal significance across three additional DA methods, alongside notable associations within various functional pathways. Furthermore, we showed that ethnicity-specific reference intervals for serum thyroid biomarkers are not required, as no significant disparities in serum thyroid markers were found among the three ethnic groups residing in an iodine-replete area (p > 0.05 for thyrotropin, free thyroxine, and TPOAb). Conclusion: These findings suggest that there is no robust difference in gut microbiome between individuals with or without TPOAb in terms of alpha and beta-diversity. Nonetheless, several taxa were identified with nominal significance related to TPOAb presence. Further research is required to determine whether these changes indeed imply a higher risk of overt HT.

SARS-CoV-2 vaccination uptake in six ethnic groups living in Amsterdam, the Netherlands: A registry-based study within the HELIUS cohort.

OBJECTIVE: Ethnic minority groups have experienced a disproportionate burden of COVID-19, and should therefore be especially encouraged to receive SARS-CoV-2 vaccination. This study compared first-dose uptake of the primary SARS-CoV-2 vaccination series across six ethnic groups in Amsterdam, the Netherlands in 2021. METHODS: We analyzed data from participants of the population-based HELIUS cohort. We linked their data to the SARS-CoV-2 vaccination registry data of the Public Health Service of Amsterdam. We included registry data from January 6, 2021 (the start of the Dutch vaccination campaign) until September 6, 2021 (a date by which all adults in the Netherlands could have received one or two vaccine doses). SARS-CoV-2 vaccination uptake was defined as having received at least one vaccine dose of the primary vaccination series. We examined the association between ethnicity and vaccination uptake using multivariable logistic regression, while accounting for the age and sex distribution of ethnic groups in Amsterdam. RESULTS: We included 19,006 participants (median age 53 years [interquartile range 41-62], 57% female). SARS-CoV-2 vaccination uptake was highest in the South-Asian Surinamese group (60.3%, 95%CI = 58.2-62.3%), followed by the Dutch (59.6%, 95%CI = 58.0-61.1%), Ghanaian (54.1%, 95%CI = 51.7-56.5%), Turkish (47.7%, 95%CI = 45.9-49.6%), African Surinamese (43.0%, 95%CI = 41.2-44.7%), and Moroccan (35.8%, 95%CI = 34.1-37.5%) groups. After adjusting for age, sex, perceived social support, and presence of relevant comorbidities, participants of African Surinamese, Ghanaian, Turkish and Moroccan origin were significantly less likely to be vaccinated than those of Dutch origin. CONCLUSIONS: Prevention strategies should continue tailoring to specific ethnic groups to encourage vaccination uptake and reduce barriers to vaccination.

Ethnic Differences in Carotid Intima Media Thickness and Plaque Presence - The HELIUS study.

Introduction In the Netherlands, the prevalence of cardiovascular diseases (CVD) is higher among South-Asian Surinamese and lower among Moroccans compared to the Dutch. Traditional risk factors for atherosclerotic CVD do not fully explain these disparities. We aim to assess ethnic differences in plaque presence and intima media thickness (cIMT) and explore to which extent these differences are explained by traditional risk factors. Methods We used cross-sectional data from a subgroup of participants enrolled in the multi-ethnic population-based HEalthy Life In an Urban Setting (HELIUS) study who underwent carotid ultrasonography. Logistic and linear regression models were built to assess ethnic differences in plaque presence and cIMT with the Dutch population as reference. Additional models were created to adjust for socioeconomic status, body height and cardiovascular risk factors. Results Of the 3022 participants, 1183, 1051 and 790 individuals were of Dutch, South-Asian Surinamese and Moroccan descent. Mean age was 60.9 years (SD 8.0), 52.8% was female. Compared to the Dutch, we found lower odds for plaque presence in Moroccans (0.77, 95% CI 0.62; 0.95) and no significant differences between the South-Asian Surinamese and Dutch population (0.91, 95% CI 0.76; 1.10). After adjustment for CVD risk factors, we found a lower plaque presence in South-Asian Surinamese (0.63, 95% CI 0.48; 0.82). In both Moroccan and South-Asian Surinamese individuals, adjustment for socioeconomic status did not materially change the results. cIMT was lower in South-Asian Surinamese compared to the Dutch (-17.9 µm, 95% CI -27.9; -7.9) and partly explained by ethnic differences in body height as South-Asian Surinamese individuals were, on average, shorter than the Dutch population. No differences in cIMT between Moroccans and Dutch were found. Conclusions cIMT and plaque prevalence differ between ethnic groups independent of CVD risk. Lower plaque prevalence in Moroccans was partly attributable to a lower prevalence of traditional CVD risk factors, while body height was an important contributor to differences in cIMT in South-Asians. This study emphasizes the need for ethnic-specific cut-off values for plaque presence and cIMT.

Socioeconomic Inequalities in Type 2 Diabetes: Mediation Through Status Anxiety?

Objectives: While status anxiety has received attention as a potential mechanism generating health inequalities, empirical evidence is still limited. Studies have been ecological and have largely focused on mental and not physical health outcomes. Methods: We conducted individual-level analyses to assess status anxiety (feelings of inferiority resulting from social comparisons) and resources (financial difficulties) as mediators of the relationship between socioeconomic status (SES) (education/occupation/employment status) and type 2 diabetes (T2D). We used cross-sectional data of 21,150 participants (aged 18-70 years) from the Amsterdam-based HELIUS study. We estimated associations using logistic regression models and estimated mediated proportions using natural effect modelling. Results: Odds of status anxiety were higher among participants with a low SES [e.g., OR = 2.66 (95% CI: 2.06-3.45) for elementary versus academic occupation]. Odds of T2D were 1.49 (95% CI: 1.12-1.97) times higher among participants experiencing status anxiety. Proportion of the SES-T2D relationship mediated was 3.2% (95% CI: 1.5%-7.0%) through status anxiety and 10.9% (95% CI: 6.6%-18.0%) through financial difficulties. Conclusion: Status anxiety and financial difficulties played small but consistent mediating roles. These individual-level analyses underline status anxiety's importance and imply that status anxiety requires attention in efforts to reduce health inequalities.

Depression, anxiety, and the risk of cancer: An individual participant data meta-analysis.

BACKGROUND: Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. METHODS: The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2). RESULTS: No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios [HRs], 1.06-1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04-1.23). CONCLUSIONS: Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers. PREREGISTRATION NUMBER: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=157677.

Relative contributions of pre-pandemic factors and intra-pandemic activities to differential COVID-19 risk among migrant and non-migrant populations in the Netherlands: lessons for future pandemic preparedness.

BACKGROUND: Although risk factors for differences in SARS-CoV-2 infections between migrant and non-migrant populations in high income countries have been identified, their relative contributions to these SARS-CoV-2 infections, which could aid in the preparation for future viral pandemics, remain unknown. We investigated the relative contributions of pre-pandemic factors and intra-pandemic activities to differential SARS-CoV-2 infections in the Netherlands by migration background (Dutch, African Surinamese, South-Asian Surinamese, Ghanaians, Turkish, and Moroccan origin). METHODS: We utilized pre-pandemic (2011-2015) and intra-pandemic (2020-2021) data from the HELIUS cohort, linked to SARS-CoV-2 PCR test results from Public Health Service of Amsterdam (GGD Amsterdam). Pre-pandemic factors included socio-demographic, medical, and lifestyle factors. Intra-pandemic activities included COVID-19 risk aggravating and mitigating activities such as physical distancing, use of face masks, and other similar activities. We calculated prevalence ratios (PRs) in the HELIUS population that was merged with GGD Amsterdam PCR test data using robust Poisson regression (SARS-CoV-2 PCR test result as outcome, migration background as predictor). We then obtained the distribution of migrant and non-migrant populations in Amsterdam as of January 2021 from Statistics Netherlands. The migrant populations included people who have migrated themselves as well as their offspring. We used PRs and the population distributions to calculate population attributable fractions (PAFs) using the standard formula. We used age and sex adjusted models to introduce pre-pandemic factors and intra-pandemic activities, noting the relative changes in PAFs. RESULTS: From 20,359 eligible HELIUS participants, 8,595 were linked to GGD Amsterdam PCR test data and included in the study. Pre-pandemic socio-demographic factors (especially education, occupation, and household size) resulted in the largest changes in PAFs when introduced in age and sex adjusted models (up to 45%), followed by pre-pandemic lifestyle factors (up to 23%, especially alcohol consumption). Intra-pandemic activities resulted in the least changes in PAFs when introduced in age and sex adjusted models (up to 16%). CONCLUSION: Interventions that target pre-pandemic socio-economic status and other drivers of health inequalities between migrant and non-migrant populations are urgently needed at present to better prevent infection disparities in future viral pandemics.

Emotional distress in cancer survivors from various ethnic backgrounds: Analysis of the multi-ethnic HELIUS study.

PURPOSE: Insight into emotional distress of cancer survivors from ethnic minority groups in Europe is scarce. We aimed to compare distress levels of survivors from ethnic minorities to that of the majority population, determine whether the association between having cancer (yes vs. no) and distress differs among ethnic groups and investigate sociocultural correlates of distress. METHODS: Cross-sectional data were derived from HELIUS, a multi-ethnic cohort study conducted in the Netherlands. Of 19,147 participants, 351 were diagnosed with cancer (n = 130 Dutch, n = 75 African Surinamese, n = 53 South-Asian Surinamese, n = 43 Moroccan, n = 28 Turkish, n = 22 Ghanaian). Distress (PHQ-9, MCS-12) and correlates were assessed by self-report. Cancer-related variables were derived from the Netherlands Cancer Registry. RESULTS: Survivors were on average 7 years post-diagnosis. Survivors from South-Asian Surinamese, Moroccan, Turkish and Ghanaian origin reported more distress than survivors from Dutch origin (effect sizerange : 0.44-1.17; adjusted models). The association between having cancer or not with distress differed in direction between Dutch and the non-Dutch ethnic groups: Non-Dutch cancer patients tended to have more distress than their cancer-free peers, whereas Dutch cancer patients tended to have less distress than their cancer-free peers. For Moroccan and Turkish patients, the acculturation style of separation/marginalization, compared to integration/assimilation, was associated with higher depressive symptoms. In analyses pooling data from all ethnic minorities, lower health literacy, lower emotional support satisfaction and younger age at the time of migration were associated with higher depressive symptoms. Lower health literacy, fewer emotional support transactions, and more frequent attendance at religious services were associated with worse mental health. CONCLUSION: Cancer survivors from ethnic minorities experience more distress than those from the majority population. Culturally sensitive supportive care should be considered.

Sex differences in associations of plasma metabolites with blood pressure and heart rate variability: The HELIUS study.

BACKGROUND AND AIMS: Since plasma metabolites can modulate blood pressure (BP) and vary between men and women, we examined sex differences in plasma metabolite profiles associated with BP and sympathicovagal balance. Our secondary aim was to investigate associations between gut microbiota composition and plasma metabolites predictive of BP and heart rate variability (HRV). METHODS: From the HELIUS cohort, we included 196 women and 173 men. Office systolic BP and diastolic BP were recorded, and heart rate variability (HRV) and baroreceptor sensitivity (BRS) were calculated using finger photoplethysmography. Plasma metabolomics was measured using untargeted LC-MS/MS. Gut microbiota composition was determined using 16S sequencing. We used machine learning models to predict BP and HRV from metabolite profiles, and to predict metabolite levels from gut microbiota composition. RESULTS: In women, best predicting metabolites for systolic BP included dihomo-lineoylcarnitine, 4-hydroxyphenylacetateglutamine and vanillactate. In men, top predictors included sphingomyelins, N-formylmethionine and conjugated bile acids. Best predictors for HRV in men included phenylacetate and gentisate, which were associated with lower HRV in men but not in women. Several of these metabolites were associated with gut microbiota composition, including phenylacetate, multiple sphingomyelins and gentisate. CONCLUSIONS: Plasma metabolite profiles are associated with BP in a sex-specific manner. Catecholamine derivatives were more important predictors for BP in women, while sphingomyelins were more important in men. Several metabolites were associated with gut microbiota composition, providing potential targets for intervention.

Gut microbiome transitions across generations in different ethnicities in an urban setting-the HELIUS study.

BACKGROUND: During the course of history, various important lifestyle changes have caused profound transitions of the gut microbiome. These include the introduction of agriculture and animal husbandry, a shift from a nomadic to a more sedentary lifestyle, and recently increased levels of urbanization and a transition towards a more Western lifestyle. The latter is linked with shifts in the gut microbiome that have a reduced fermentative capability and which are commonly associated with diseases of affluence. In this study, in which 5193 subjects are included, we investigated the direction of microbiome shifts that occur in various ethnicities living in Amsterdam by comparing 1st and 2nd generation participants. We furthermore validated part of these findings with a cohort of subjects that moved from rural Thailand to the USA. RESULTS: The abundance of the Prevotella cluster, which includes P. copri and the P. stercorea trophic network, diminished in the 2nd generation Moroccans and Turks but also in younger Dutch, whilst the Western-associated Bacteroides/Blautia/Bifidobacterium (BBB) cluster, which has an inverse correlation with α-diversity, increased. At the same time, the Christensenellaceae/Methanobrevibacter/Oscillibacter trophic network, which is positively associated with α-diversity and a healthy BMI, decreased in younger Turks and Dutch. Large compositional shifts were not observed in South-Asian and African Surinamese, in whom the BBB cluster is already dominant in the 1st generation, but ASV-level shifts towards certain species, associated amongst others with obesity, were observed. CONCLUSION: The Moroccan and Turkish populations, but also the Dutch population are transitioning towards a less complex and fermentative less capable configuration of the gut microbiota, which includes a higher abundance of the Western-associated BBB cluster. The Surinamese, whom have the highest prevalence of diabetes and other diseases of affluence, are already dominated by the BBB cluster. Given the continuous increase in diseases of affluence, this devolution towards low-diversity and fermentatively less capable gut microbiome compositions in urban environments is a worrying development. Video Abstract.

The COVID-19 pandemic and temporal change in metabolic risk factors for cardiovascular disease: A natural experiment within the HELIUS study.

The coronavirus disease 2019 (COVID-19) pandemic, including the restrictive measures taken to reduce the spread of the virus, negatively affected people's health behavior. We explored whether the pandemic also had an effect on metabolic risk factors for cardiovascular disease (CVD) in women and men. We conducted a natural experiment, using data from 6962 participants without CVD at baseline (2011-2015) of six ethnic groups of the HELIUS study in Amsterdam, the Netherlands. We studied whether participants whose follow-up measurements were taken within the 11 months before the pandemic (control group) differed from those whose measurements were taken taken within 6 months after the first lockdown (exposed group). Using sex-stratified linear regressions with inverse probability weighting, we compared changes in baseline- and follow-up data between the control and exposed group in six metabolic risk factors: systolic and diastolic blood pressure (SBP, DBP), total cholesterol (TC), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR). Next, we explored the mediating effect of changes in body-mass index (BMI), alcohol, smoking, depressive symptoms and negative life events at follow-up. We observed less favorable changes in SBP (+1.12mmHg for women, +1.38mmHg for men), DBP (+0.85mmHg, +0.80mmHg) and FPG (only in women, +0.12 mmol/L) over time in the exposed group relative to the control group. Conversely, changes in HbA1c (-0.65 mmol/mol, -0.84 mmol/mol) and eGFR (+1.06 mL/min, +1.04 mL/min) were more favorable in the exposed compared to the control group, respectively. Changes in SBP, DBP, and FPG were partially mediated by changes in behavioral factors, in particular BMI and alcohol consumption. Concluding, the COVID-19 pandemic, in particular behavioral changes associated with restrictive lockdown measures, may have negatively affected several CVD risk factors, in both women and men.

Psychosocial factors may serve as additional eligibility criteria for cardiovascular risk screening in women and men in a multi-ethnic population: The HELIUS study.

Cardiovascular disease (CVD) prevention strategies include identifying and managing high risk individuals. Identification primarily occurs through screening or case finding. Guidelines indicate that psychosocial factors increase CVD risk, but their use for screening is not yet recommended. We studied whether psychosocial factors may serve as additional eligibility criteria in a multi-ethnic population without prior CVD. We performed a cross-sectional analysis using baseline data of 10,226 participants of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin aged 40-70 years, living in Amsterdam, the Netherlands. Using logistic regressions and Akaike Information Criteria, we analyzed whether psychosocial factors (educational level, employment status, occupational level, financial stress, primary earner status, mental health, stress, depression, and social isolation) improved prediction of high CVD risk (SCORE-estimated fatal and non-fatal CVD risk ≥5%) beyond eligibility criteria from history taking (smoking, obesity, family history of CVD). Next, we compared the additional predictive value of psychosocial eligibility criteria in women and men across ethnic groups, using the area under the curve (AUC). Of our sample, 32.7% had a high CVD risk. Only socioeconomic eligibility criteria (employment status and educational level) improved high CVD risk prediction (p < .001 for likelihood-ratio tests). These increased AUCs in women (from 0.563 to 0.682) and men (from 0.610 to 0.664), particularly in Dutch, South-Asian Surinamese, African Surinamese and Moroccan women, and Dutch and Moroccan men. Concluding, socioeconomic eligibility criteria may be considered as additional eligibility criteria for CVD risk screening, as they improve detection of women and men at high CVD risk.

Ancestral and environmental patterns in the association between triglycerides and other cardiometabolic risk factors.

BACKGROUND: West Africans and African Americans with substantial (∼80%) West African ancestry are characterized by low levels of triglycerides (TG) compared to East Africans and Europeans. The impact of these varying TG levels on other cardiometabolic risk factors is unclear. We compared the strength of association between TG with hypertension, blood pressure, BMI, waist circumference, type 2 diabetes (T2D), and fasting glucose across West African (WA), East African (EA), and European (EU) ancestry populations residing in three vastly different environmental settings: sub-Saharan Africa, United States, and Europe. METHODS: We analysed data from four cross-sectional studies that included WA in sub-Saharan Africa (n = 7201), the U.S. (n = 4390), and Europe (n = 6436), EA in sub-Saharan Africa (n = 781), and EU in the U.S. (n = 8670) and Europe (n = 4541). Linear regression analyses were used to test the association between TG and cardiometabolic risk factors. FINDINGS: Higher adjusted regression coefficients were observed in EU compared with WA ancestry for TG on hypertension (EU ß [95% CI]: 0.179 [0.156, 0.203], WA ß [95% CI]: 0.102 [0.086, 0.118]), BMI (EU ß [95% CI]: 0.028 [0.027, 0.030], WA ß [95% CI]: 0.015 [0.014, 0.016]), and waist circumference (EU ß [95% CI]: 0.013 [0.013, 0.014], WA ß [95% CI]: 0.009 [0.008, 0.009) (all ancestry × trait interaction P-values <0.05), irrespective of environmental differences within ancestry groups. Less consistency was observed among EA. Associations of TG with T2D did not follow ancestry patterns, with substantial variation observed between environments. INTERPRETATION: TG may not be an equally strong associated with other established cardiometabolic risk factors in West and East Africans in contrast to European ancestry populations. The value of TG for identifying individuals at high risk for developing metabolic disorders needs to be re-evaluated for African ancestry populations. FUNDING: National Institutes of Health, European Commission, Dutch Heart Foundation, Netherlands Organization for Health Research and Development, Centers for Disease Control and Prevention.