The association of overweight, obesity, and long-term obesity with SARS-CoV-2 infection: a meta-analysis of 9 population-based cohorts from the Netherlands Cohorts Consortium.

BACKGROUND: Obesity may affect an individual's immune response and subsequent risk of infection, such as a SARS-CoV-2 infection. It is less clear whether overweight and long-term obesity also constitute risk factors. We investigated the association between the degree and duration of overweight and obesity and SARS-CoV-2 infection. METHODS: We analyzed data from nine prospective population-based cohorts of the Netherlands Cohorts Consortium, with a total of 99,570 participants, following a standardized procedure. Body mass index (BMI) and waist circumference (WC) were assessed two times before the pandemic, with approximately 5 years between measurements. SARS-CoV-2 infection was defined by self-report as a positive PCR or rapid-antigen test or as COVID-19 ascertained by a physician between March 2020 and January 2023. For three cohorts, information on SARS-CoV-2 infection by serology was available. Results were pooled using random-effects meta-analyses and adjusted for age, sex, educational level, and number of SARS-CoV-2 infection measurements. RESULTS: Individuals with overweight (25 ≤ BMI < 30 kg/m2) (odds ratio (OR) = 1.08, 95%-confidence interval (CI) 1.04-1.13) or obesity (BMI ≥ 30 kg/m2) (OR = 1.43, 95%-CI 1.18-1.75) were more likely to report SARS-CoV-2 infection than individuals with a healthy body weight. We observed comparable ORs for abdominal overweight (men: 94 cm≤WC < 102 cm, women: 80 cm≤WC < 88 cm) (OR = 1.09, 95%-CI 1.04-1.14, I2 = 0%) and abdominal obesity (men: WC ≥ 102 cm, women: WC ≥ 88 cm) (OR = 1.24, 95%-CI 0.999-1.55, I2 = 57%). Individuals with obesity long before the pandemic, but with a healthy body weight or overweight just before the pandemic, were not at increased risk. CONCLUSION: Overweight and obesity were associated with increased risk of SARS-CoV-2 infection with stronger associations for obesity. Individuals with a healthier weight prior to the pandemic but previous obesity did not have an increased risk of SARS-CoV-2, suggesting that weight loss in those with obesity reduces infection risk. These results underline the importance of obesity prevention and weight management for public health.

Association of circulating fatty acids with cardiovascular disease risk: Analysis of individual-level data in three large prospective cohorts and updated meta-analysis.

BACKGROUND: Associations of saturated and unsaturated fatty acids (FAs) with cardiovascular disease (CVD) remain controversial. We therefore aimed to investigate the prospective associations of objectively measured FAs with CVD, including incident coronary heart disease (CHD) and stroke, as well as CVD mortality. METHODS: Circulating FA concentrations expressed as the percentage of total FAs were assayed in 172,891 participants without prior vascular disease at baseline from the European Prospective Investigation into Cancer and Nutrition-CVD (EPIC-CVD) (7,343 CHD; 6,499 stroke), UK Biobank (1,825; 1,474), and INTERVAL (285; 209) cohort studies. Hazard ratio (HR) per 1-standard deviation (SD) higher FA concentrations was estimated using Cox regression models and pooled by random-effects meta-analysis. Systematic reviews with meta-analysis published by 6 May 2023 on associations between FAs and CVDs were systematically searched and updated meta-analyses using random-effects model were conducted. Evidence from randomized controlled trials (RCTs) was also summarized. RESULTS: Higher concentrations of total saturated FAs (SFAs) were associated with higher cardiovascular risks in the combined analysis, with differential findings noted for SFA subtypes in further analysis restricted to EPIC-CVD: positive associations for even-chain SFA [HR for CHD 1.24 (95% CI: 1.18-1.32); stroke 1.23 (1.10-1.38)] and negative associations for odd-chain [0.82 (0.76-0.87); 0.73 (0.67-0.78)] and longer-chain [0.95 (0.80-1.12); 0.84 (0.72-0.99)] SFA. In the combined analysis, total n-3 polyunsaturated FA (PUFA) [0.91 (0.85-0.97)], including docosahexaenoic acid (DHA) [0.91 (0.84-0.98)], was negatively associated with incident CHD risk. Similarly, total n-6 PUFA [0.94 (0.91-0.98)], including linoleic acid (LA) [0.89 (0.83-0.95)], was negatively associated with incident stroke risk. By contrast, more detailed analyses in EPIC-CVD revealed that several downstream n-6 PUFAs of LA were positively associated with CHD risk. Updated meta-analyses of 37 FAs including 49 non-overlapping studies, involving between 7,787 to 22,802 CHD and 6,499 to 14,221 stroke cases, showed broadly similar results as our combined empirical analysis and further suggested significant inverse associations of individual long-chain n-3 PUFAs and LA on both CHD and stroke. The findings of long-chain n-3 PUFAs were consistent with those from published RCTs on CHD despite insufficient evidence in monotherapy, while RCT evidence remained unclear for the rest of the explored FAs. CONCLUSIONS: Our study provides an overview of the most recent evidence on the associations between objectively measured FAs and CVD outcomes. Collectively, the data reveals notable differences in associations by SFA subtypes and calls for further studies, especially RCTs, to explore these links.

We conducted the largest analysis to date to examine the association of circulating saturated and unsaturated fatty acids, either individually or in combination, with incident cardiovascular disease outcomes. Our study reinforces that cardiovascular disease associations vary importantly across saturated fatty acid subtypes, with positive associations for even-chain saturated fatty acids but negative associations for odd-chain and longer-chain saturated fatty acids, challenging the current broad dietary recommendations focused solely on lowering overall saturated fat intake.Marine-derived n-3 polyunsaturated fatty acids and linoleic acid were negatively associated with both coronary heart disease and stroke, except for eicosapentaenoic acid which was null for stroke. It supports the potential cardiovascular benefits of individual marine-derived n-3 polyunsaturated fatty acids and linoleic acid and provides evidence to help inform currently inconsistent and insufficient trial evidence.

Socioeconomic Inequalities in the External Exposome in European Cohorts: The EXPANSE Project.

Socioeconomic inequalities in the exposome have been found to be complex and highly context-specific, but studies have not been conducted in large population-wide cohorts from multiple countries. This study aims to examine the external exposome, encompassing individual and environmental factors influencing health over the life course, and to perform dimension reduction to derive interpretable characterization of the external exposome for multicountry epidemiological studies. Analyzing data from over 25 million individuals across seven European countries including 12 administrative and traditional cohorts, we utilized domain-specific principal component analysis (PCA) to define the external exposome, focusing on air pollution, the built environment, and air temperature. We conducted linear regression to estimate the association between individual- and area-level socioeconomic position and each domain of the external exposome. Consistent exposure patterns were observed within countries, indicating the representativeness of traditional cohorts for air pollution and the built environment. However, cohorts with limited geographical coverage and Southern European countries displayed lower temperature variability, especially in the cold season, compared to Northern European countries and cohorts including a wide range of urban and rural areas. The individual- and area-level socioeconomic determinants (i.e., education, income, and unemployment rate) of the urban exposome exhibited significant variability across the European region, with area-level indicators showing stronger associations than individual variables. While the PCA approach facilitated common interpretations of the external exposome for air pollution and the built environment, it was less effective for air temperature. The diverse socioeconomic determinants suggest regional variations in environmental health inequities, emphasizing the need for targeted interventions across European countries.

Association of body shape phenotypes and body fat distribution indexes with inflammatory biomarkers in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank.

BACKGROUND: The allometric body shape index (ABSI) and hip index (HI), as well as multi-trait body shape phenotypes, have not yet been compared in their associations with inflammatory markers. The aim of this study was to examine the relationship between novel and traditional anthropometric indexes with inflammation using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts. METHODS: Participants from EPIC (n = 17,943, 69.1% women) and UK Biobank (n = 426,223, 53.2% women) with data on anthropometric indexes and C-reactive protein (CRP) were included in this cross-sectional analysis. A subset of women in EPIC also had at least one measurement for interleukins, tumour necrosis factor alpha, interferon gamma, leptin, and adiponectin. Four distinct body shape phenotypes were derived by a principal component (PC) analysis on height, weight, body mass index (BMI), waist (WC) and hip circumferences (HC), and waist-to-hip ratio (WHR). PC1 described overall adiposity, PC2 tall with low WHR, PC3 tall and centrally obese, and PC4 high BMI and weight with low WC and HC, suggesting an athletic phenotype. ABSI, HI, waist-to-height ratio and waist-to-hip index (WHI) were also calculated. Linear regression models were carried out separately in EPIC and UK Biobank stratified by sex and adjusted for age, smoking status, education, and physical activity. Results were additionally combined in a random-effects meta-analysis. RESULTS: Traditional anthropometric indexes, particularly BMI, WC, and weight were positively associated with CRP levels, in men and women. Body shape phenotypes also showed distinct associations with CRP. Specifically, PC2 showed inverse associations with CRP in EPIC and UK Biobank in both sexes, similarly to height. PC3 was inversely associated with CRP among women, whereas positive associations were observed among men. CONCLUSIONS: Specific indexes of body size and body fat distribution showed differential associations with inflammation in adults. Notably, our results suggest that in women, height may mitigate the impact of a higher WC and HC on inflammation. This suggests that subtypes of adiposity exhibit substantial variation in their inflammatory potential, which may have implications for inflammation-related chronic diseases.

The role of ultra-processed foods in plant-based diets: associations with human health and environmental sustainability.

PURPOSE: Investigate the associations of ultra-processed foods (UPF) in healthful (hPDI) and unhealthful (uPDI) plant-based diets with all-cause mortality, greenhouse gas emissions (GHGE), and blue water consumption (BWC). METHODS: Analyses were based on 35,030 participants (20-70 years; 74% females) from the EPIC-NL cohort who were followed up from 1993 to 1997 through 2014. Plant-based diet indices (hPDI and uPDI) and UPF consumption were calculated from a validated FFQ, assessed at baseline. Cox proportional hazard and multiple linear regression models were used to estimate associations between combined quartiles of the PDI indices and UPF consumption. RESULTS: With lower hPDI and higher UPF diets as the reference, we observed the following. Risk estimates of all-cause mortality were 0.98 (95% CI: 0.83, 1.16) for lower UPF consumption, 0.86 (95% CI: 0.68, 1.08) for higher hPDI, and 0.78 (95% CI: 0.66, 0.89) for combined higher hPDI and lower UPF consumption. Results with the uPDI were inconclusive. Mean differences in GHGE and BWC were 1.4% (95% CI: 0.3, 2.4) and 1.6% (95% CI: -0.5, 3.7) for lower UPF consumption, -7.4% (95% CI: -8.6, -6.4) and 9.6% (95% CI: 7.2, 12.0) for higher hPDI, and - 6.8% (95% CI: -7.4, -6.1) and 13.1% (95% CI: 11.6, 14.8) for combined higher hPDI and lower UPF consumption. No apparent conflict between environmental impacts was observed for the uPDI; GHGE and BWC were lower for higher uPDI scores. CONCLUSION: Mortality risk and environmental impacts were mostly associated with the amount of plant-based foods and to a lesser extent UPF in the diet. Shifting to a more healthful plant-based diet could improve human health and reduce most aspects of environmental impact (GHGE, but not BWC) irrespective of UPF consumption.

Physical activity, sedentary behaviour, and childhood asthma: a European collaborative analysis.

OBJECTIVES: To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study. DESIGN: Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined. SETTING: Children aged 0-18 years from 26 European birth cohorts. PARTICIPANTS: 136 071 individual children from 26 cohorts, with information on PA and/or sedentary behaviour in early childhood and asthma assessment in later childhood. MAIN OUTCOME MEASURE: Questionnaire-based current asthma and lung function measured by spirometry (forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity) at age 6-18 years. RESULTS: Questionnaire-based and accelerometry-based PA and sedentary behaviour at age 3-5 years was not associated with asthma at age 6-18 years (PA in hours/day adjusted OR 1.01, 95% CI 0.98 to 1.04; sedentary behaviour in hours/day adjusted OR 1.03, 95% CI 0.99 to 1.07). PA was not associated with lung function at any age. Analyses of sedentary behaviour and lung function showed inconsistent results. CONCLUSIONS: Reduced PA and increased sedentary behaviour before 6 years of age were not associated with the presence of asthma later in childhood.

Prediction of individual lifetime cardiovascular risk and potential treatment benefit: development and recalibration of the LIFE-CVD2 model to four European risk regions.

AIMS: The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals. METHODS AND RESULTS: The updated LIFE-CVD (i.e. LIFE-CVD2) models were derived using individual participant data from 44 cohorts in 13 countries (687 135 individuals without established CVD, 30 939 CVD events in median 10.7 years of follow-up). LIFE-CVD2 uses sex-specific functions to estimate the lifetime risk of fatal and non-fatal CVD events with adjustment for the competing risk of non-CVD death and is systematically recalibrated to four distinct European risk regions. The updated models showed good discrimination in external validation among 1 657 707 individuals (61 311 CVD events) from eight additional European cohorts in seven countries, with a pooled C-index of 0.795 (95% confidence interval 0.767-0.822). Predicted and observed CVD event risks were well calibrated in population-wide electronic health records data in the UK (Clinical Practice Research Datalink) and the Netherlands (Extramural LUMC Academic Network). When using LIFE-CVD2 to estimate potential gain in CVD-free life expectancy from preventive therapy, projections varied by risk region reflecting important regional differences in absolute lifetime risk. For example, a 50-year-old smoking woman with a systolic blood pressure (SBP) of 140 mmHg was estimated to gain 0.9 years in the low-risk region vs. 1.6 years in the very high-risk region from lifelong 10 mmHg SBP reduction. The benefit of smoking cessation for this individual ranged from 3.6 years in the low-risk region to 4.8 years in the very high-risk region. CONCLUSION: By taking into account geographical differences in CVD incidence using contemporary representative data sources, the recalibrated LIFE-CVD2 model provides a more accurate tool for the prediction of lifetime risk and CVD-free life expectancy for individuals without previous CVD, facilitating shared decision-making for cardiovascular prevention as recommended by 2021 European guidelines.

The study introduces LIFE-CVD2, a new tool that helps predict the risk of heart disease over a person's lifetime, and highlights how where you live in Europe can affect this risk.Using health information from over 687 000 people, LIFE-CVD2 looks at things like blood pressure and whether someone smokes to figure out their chance of having heart problems later in life. Health information from another 1.6 million people in seven different European countries was used to show that it did a good job of predicting who might develop heart disease.Knowing your heart disease risk over your whole life helps doctors give you the best advice to keep your heart healthy. Let us say there is a 50-year-old woman who smokes and has a bit high blood pressure. Right now, she might not look like she is in danger. But with the LIFE-CVD2 tool, doctors can show her how making changes today, like lowering her blood pressure or stopping smoking, could mean many more years without heart problems. These healthy changes can make a big difference over many years.

Clinical implications of airway obstruction with normal or low FEV1 in childhood and adolescence.

BACKGROUND: Airway obstruction is defined by spirometry as a low forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio. This impaired ratio may originate from a low FEV1 (classic) or a normal FEV1 in combination with a large FVC (dysanaptic). The clinical implications of dysanaptic obstruction during childhood and adolescence in the general population remain unclear. AIMS: To investigate the association between airway obstruction with a low or normal FEV1 in childhood and adolescence, and asthma, wheezing and bronchial hyperresponsiveness (BHR). METHODS: In the BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology; Sweden) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy; the Netherlands) birth cohorts, obstruction (FEV1:FVC ratio less than the lower limit of normal, LLN) at ages 8, 12 (PIAMA only) or 16 years was classified as classic (FEV1

Impact of COVID-19 containment measures on perceived health and health-protective behavior: a longitudinal study.

This longitudinal study aimed to assess the impact of COVID-19 containment measures on perceived health, health protective behavior and risk perception, and investigate whether chronic disease status and urbanicity of the residential area modify these effects. Participants (n = 5420) were followed for up to 14 months (September 2020-October 2021) by monthly questionnaires. Chronic disease status was obtained at baseline. Urbanicity of residential areas was assessed based on postal codes or neighborhoods. Exposure to containment measures was assessed using the Containment and Health Index (CHI). Bayesian multilevel-models were used to assess effect modification of chronic disease status and urbanicity by CHI. CHI was associated with higher odds for worse physical health in people with chronic disease (OR = 1.09, 95% credibility interval (CrI) = 1.01, 1.17), but not in those without (OR = 1.01, Crl = 0.95, 1.06). Similarly, the association of CHI with higher odds for worse mental health in urban dwellers (OR = 1.31, Crl = 1.23, 1.40) was less pronounced in rural residents (OR = 1.20, Crl = 1.13, 1.28). Associations with behavior and risk perception also differed between groups. Our study suggests that individuals with chronic disease and those living in urban areas are differentially affected by government measures put in place to manage the COVID-19 pandemic. This highlights the importance of considering vulnerable subgroups in decision making regarding containment measures.

Dietary amino acids and risk of stroke subtypes: a prospective analysis of 356,000 participants in seven European countries.

PURPOSE: Previously reported associations of protein-rich foods with stroke subtypes have prompted interest in the assessment of individual amino acids. We examined the associations of dietary amino acids with risks of ischaemic and haemorrhagic stroke in the EPIC study. METHODS: We analysed data from 356,142 participants from seven European countries. Dietary intakes of 19 individual amino acids were assessed using validated country-specific dietary questionnaires, calibrated using additional 24-h dietary recalls. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischaemic and haemorrhagic stroke in relation to the intake of each amino acid. The role of blood pressure as a potential mechanism was assessed in 267,642 (75%) participants. RESULTS: After a median follow-up of 12.9 years, 4295 participants had an ischaemic stroke and 1375 participants had a haemorrhagic stroke. After correction for multiple testing, a higher intake of proline (as a percent of total protein) was associated with a 12% lower risk of ischaemic stroke (HR per 1 SD higher intake 0.88; 95% CI 0.82, 0.94). The association persisted after mutual adjustment for all other amino acids, systolic and diastolic blood pressure. The inverse associations of isoleucine, leucine, valine, phenylalanine, threonine, tryptophan, glutamic acid, serine and tyrosine with ischaemic stroke were each attenuated with adjustment for proline intake. For haemorrhagic stroke, no statistically significant associations were observed in the continuous analyses after correcting for multiple testing. CONCLUSION: Higher proline intake may be associated with a lower risk of ischaemic stroke, independent of other dietary amino acids and blood pressure.

Associations of Anti-COVID-19 Measures and Lifestyle Changes During the COVID-19 Pandemic With Sleep Patterns in the Netherlands: A Longitudinal Study.

Although there is scientific evidence for an increased prevalence of sleep disorders during the coronavirus disease 2019 (COVID-19) pandemic, there is still limited information on how lifestyle factors might have affected sleep patterns. Therefore, we followed a large cohort of participants in the Netherlands (n = 5,420) for up to 1 year (September 2020-2021) via monthly Web-based questionnaires to identify lifestyle changes (physical activity, cigarette smoking, alcohol consumption, electronic device use, and social media use) driven by anti-COVID-19 measures and their potential associations with self-reported sleep (latency, duration, and quality). We used the Containment and Health Index (CHI) to assess the stringency of anti-COVID-19 measures and analyzed associations through multilevel ordinal response models. We found that more stringent anti-COVID-19 measures were associated with higher use of electronic devices (per interquartile-range increase in CHI, odds ratio (OR) = 1.47, 95% confidence interval (CI): 1.40, 1.53), less physical activity (OR = 0.94, 95% CI: 0.90, 0.98), lower frequency of alcohol consumption (OR = 0.63, 95% CI: 0.60, 0.66), and longer sleep duration (OR = 1.11, 95% CI: 1.05, 1.16). Lower alcohol consumption frequency and higher use of electronic devices and social media were associated with longer sleep latency. Lower physical activity levels and higher social media and electronic device use were related to poorer sleep quality and shorter sleep duration.

Consumption of ultra-processed foods and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study.

Background: It is currently unknown whether ultra-processed foods (UPFs) consumption is associated with a higher incidence of multimorbidity. We examined the relationship of total and subgroup consumption of UPFs with the risk of multimorbidity defined as the co-occurrence of at least two chronic diseases in an individual among first cancer at any site, cardiovascular disease, and type 2 diabetes. Methods: This was a prospective cohort study including 266,666 participants (60% women) free of cancer, cardiovascular disease, and type 2 diabetes at recruitment from seven European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Foods and drinks consumed over the previous 12 months were assessed at baseline by food-frequency questionnaires and classified according to their degree of processing using Nova classification. We used multistate modelling based on Cox regression to estimate cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations of total and subgroups of UPFs with the risk of multimorbidity of cancer and cardiometabolic diseases. Findings: After a median of 11.2 years of follow-up, 4461 participants (39% women) developed multimorbidity of cancer and cardiometabolic diseases. Higher UPF consumption (per 1 standard deviation increment, ∼260 g/day without alcoholic drinks) was associated with an increased risk of multimorbidity of cancer and cardiometabolic diseases (HR: 1.09, 95% CI: 1.05, 1.12). Among UPF subgroups, associations were most notable for animal-based products (HR: 1.09, 95% CI: 1.05, 1.12), and artificially and sugar-sweetened beverages (HR: 1.09, 95% CI: 1.06, 1.12). Other subgroups such as ultra-processed breads and cereals (HR: 0.97, 95% CI: 0.94, 1.00) or plant-based alternatives (HR: 0.97, 95% CI: 0.91, 1.02) were not associated with risk. Interpretation: Our findings suggest that higher consumption of UPFs increases the risk of cancer and cardiometabolic multimorbidity. Funding: Austrian Academy of Sciences, Fondation de France, Cancer Research UK, World Cancer Research Fund International, and the Institut National du Cancer.

Corrigendum: Characterization of the degree of food processing in the European Prospective Investigation into Cancer and Nutrition: application of the Nova classification and validation using selected biomarkers of food processing.

[This corrects the article DOI: 10.3389/fnut.2022.1035580.].

Associations between dietary inflammatory scores and biomarkers of inflammation in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BACKGROUND: Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation. OBJECTIVE: We aimed to investigate the relationship between four dietary inflammatory scores [DII, two energy-adjusted derivatives (E-DII and E-DIIr), and the Inflammatory Score of the Diet (ISD)], and circulating levels of several inflammatory markers and adipokines. METHODS: This study included 17 637 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with at least one marker of inflammation measured in blood. Associations between the four scores and C-reactive protein (CRP), interleukin (IL)6, IL10, IL1RA, tumor necrosis factor-α (TNFα), soluble tumor necrosis factor receptor-1 (sTNFR1), sTNFR2, leptin, soluble leptin receptor (sLeptin R), adiponectin, and High Molecular Weight (HMW) adiponectin were evaluated using multivariable linear regressions adjusted for potential confounders. RESULTS: Positive associations were observed between the four dietary inflammatory scores and levels of CRP, IL6, sTNFR1, sTNFR2 and leptin. However, only the DII and the ISD were positively associated with IL1RA levels and only the DII and the E-DIIr were positively associated with TNFα levels. The proportion of variance of each biomarker explained by the scores was lower than 2%, which was equivalent to the variance explained by smoking status but much lower than that explained by body mass index. CONCLUSIONS: Our results suggest that the four dietary inflammatory scores were associated with some biomarkers of inflammation and could be used to assess the inflammatory potential of diet in European adults but are not sufficient to capture the inflammatory status of an individual. These findings can help to better understand the inflammatory potential of diet, but they need to be replicated in studies with repeated dietary measurements.

Adherence to the EAT-Lancet Healthy Reference Diet in Relation to Risk of Cardiovascular Events and Environmental Impact: Results From the EPIC-NL Cohort.

Background The Healthy Reference Diet (HRD) was created to formulate dietary guidelines that would be healthy and sustainable. We aimed to construct a diet score measuring adherence to the HRD and to explore its association with cardiovascular events and environmental impact. Methods and Results We included 35 496 participants from the population-based EPIC-NL (European Prospective Investigation into Cancer and Nutrition-Netherlands) study. HRD scores were calculated using data from food frequency questionnaires (0-140). Data on morbidity and mortality were retrieved through linkage with national and death registries. Data on environmental impact indicators were obtained from life cycle assessments. Associations between adherence to the HRD and cardiovascular events were estimated with Cox proportional hazard models. Linear regression analysis was conducted for the adherence to the HRD and each environmental indicator. High adherence to the HRD was associated with 14%, 12%, and 11% lower risks of cardiovascular disease (hazard ratio [HR]Q4vsQ1, 0.86 [95% CI, 0.78-0.94]), coronary heart disease (HRQ4vsQ1, 0.88 [95% CI, 0.78-1.00]), and total stroke (HRQ4vsQ1, 0.89 [95% CI, 0.72-1.10]), respectively. High HRD adherence was associated with 2.4% (95% CI, -5.0 to 0.2) lower greenhouse gas emissions, 3.9% (95% CI, -5.2 to -2.6) less land use, 0.5% (95% CI, -2.6 to 1.6), less freshwater eutrophication, 3.3% (95% CI, -5.8 to -0.8), less marine eutrophication, 7.7% (95% CI, -10.8 to -4.6), less terrestrial acidification, and 32.1 % (95% CI, 28.5-35.7) higher blue water use. Conclusions High adherence to the HRD was associated with lower risk of cardiovascular disease, coronary heart disease, and modestly lower levels of most environmental indicators but a higher level of blue water use.

Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study.

BACKGROUND: Observational studies have linked childhood obesity with elevated risk of colorectal cancer; however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk. METHODS: We conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size (thinner, plumper, or about average) in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants. RESULTS: Genetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98-1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00-1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04-1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77-1.22) and colon cancer (OR: 0.97, 95% CI: 0.76-1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90-1.77). Genetically predicted adult life body size was estimated to increase odds of colorectal (OR: 1.27, 95% CI: 1.03, 1.57), colon (OR: 1.32, 95% CI: 1.05, 1.67), and proximal colon (OR: 1.57, 95% CI: 1.21, 2.05). CONCLUSIONS: Our findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood.

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Ambient ultrafine particles and asthma onset until age 20: The PIAMA birth cohort.

RATIONALE: Evidence regarding the role of long-term exposure to ultrafine particles (<0.1 µm, UFP) in asthma onset is scarce. OBJECTIVES: We examined the association between exposure to UFP and asthma development in the Dutch PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort and assessed whether there is an association with UFP, independent of other air pollutants. METHODS: Data from birth up to age 20 years from 3687 participants were included. Annual average exposure to UFP at the residential addresses was estimated with a land-use regression model. Overall and age-specific associations of exposure at the birth address and current address at the time of follow-up with asthma incidence were assessed using discrete-time hazard models adjusting for potential confounders. We investigated both single- and two-pollutant models accounting for co-exposure to other air pollutants (PM2.5 and PM10 mass concentrations, nitrogen dioxide, and PM2.5 absorbance). MEASUREMENTS AND MAIN RESULTS: A total of 812 incident asthma cases were identified. Overall, we found that higher UFP exposure was associated with higher asthma incidence (adjusted odds ratio (95% confidence interval) 1.08 (1.02,1.14) and 1.06 (1.00, 1.12) per interquartile range increase in exposure at the birth address and current address at the time of follow-up, respectively). Age-specific associations were not consistent. The association was no longer significant after adjustment for other traffic-related pollutants (nitrogen dioxide and PM2.5 absorbance). CONCLUSIONS: Our findings support the importance of traffic-related air pollutants for asthma development through childhood and adolescence, but provide little support for an independent effect of UFP.

The association of pure fruit juice, sugar-sweetened beverages and fruit consumption with asthma prevalence in adolescents growing up from 11 to 20 years: The PIAMA birth cohort study.

Pure fruit juice is comparable to sugar-sweetened beverages (SSBs) with respect to its sugar and fructose content. However, it also contains favorable components like polyphenols. From this perspective, pure fruit juice is more comparable with whole fruit. SSBs have been associated with higher asthma risk, while whole fruit consumption has been associated with lower prevalence of asthma (symptoms). Associations with pure fruit juice have been rarely studied. Therefore, we studied the associations of consumption of pure fruit juice, SSBs and whole fruit with asthma prevalence in 3046 children of the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort growing up from 11 to 20 years. Consumption of pure fruit juice, SSBs and fruit was self-reported at the ages of 11, 14, 17 and 20 years. Presence of asthma was defined based on parental reports of asthma diagnosis ever, and wheezing and asthma medication in the last 12 months. Odds ratios (OR) were estimated using generalized linear mixed models accounting for correlation between repeated measurements within subjects. No associations were found between pure fruit juice, SSBs and fruit consumption and the overall prevalence of asthma from 11 to 20 years. An earlier reported association of low pure fruit juice consumption with higher asthma prevalence at the age of 11 years in the PIAMA population was confirmed, but no associations were found at the ages of 14, 17 and 20 years.