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.

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.

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.].

Different Levels of Ultraprocessed Food and Beverage Consumption and Associations with Environmental Sustainability and All-cause Mortality in EPIC-NL.

BACKGROUND: The adverse health effects of high ultraprocessed food and drink (UPFD) consumption are well documented. However, the environmental impact remains unclear, and the separate effects of ultraprocessed foods (UPFs) and drinks (UPDs) on all-cause mortality have not been studied previously. OBJECTIVES: To assess the association between levels of UPFD, UPF, and UPD consumption and diet-related environmental impacts and all-cause mortality in Dutch adults. METHODS: Habitual diets were assessed by a Food Frequency Questionnaire (FFQ) from 1993-1997 in 38,261 participants of the Dutch European Prospective Investigation into Cancer and Nutrition cohort. The mean follow-up time was 18.2 y (SD = 4.1); 4,697 deaths occurred. FFQ items were categorized according to the NOVA classification. Associations between quartiles of UPFD, UPF, and UPD consumption and environmental impact indicators were analyzed using general linear models and all-cause mortality by Cox proportional hazard models. The lowest UPFD, UPF, and UPD consumption quartiles were used as comparator. RESULTS: The average UPFD consumption was 181 (SD = 88) g/1000 kcal. High UPF consumption was statistically significantly inversely associated with all environmental impact indicators (Q4vsQ1: -13.6% to -3.0%), whereas high UPD consumption was, except for land use, statistically significant positively associated with all environmental impact indicators (Q4vsQ1: 1.2% to 5.9%). High UPFD consumption was heterogeneously associated with environmental impacts (Q4vsQ1: -4.0% to 2.6%). After multivariable adjustment, the highest quartiles of UPFD and UPD consumption were significantly associated with all-cause mortality (HRQ4vsQ1: 1.17, 95%CI: 1.08, 1.28 and HRQ4vsQ1: 1.16, 95%CI: 1.07, 1.26, respectively). UPF consumption of Q2 and Q3 were associated with a borderline significant lower risk of all-cause mortality (HRQ2vsQ1: 0.93, 95% CI: 0.85, 1.00; HRQ3vsQ1: 0.91, 95% CI: 0.84, 0.99) whereas Q4 was not statistically significant (HRQ4vsQ1: 1.06, 95% CI: 0.97, 1.15). CONCLUSIONS: Reducing UPD consumption may lower environmental impact and all-cause mortality risk; however, this is not shown for UPFs. When categorizing food consumption by their degree of processing, trade-offs are observed for human and planetary health aspects.

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.

Residential exposure to livestock farms and lung function in adolescence - The PIAMA birth cohort study.

BACKGROUND: There is a growing interest in the impact of air pollution from livestock farming on respiratory health. Studies in adults suggest adverse effects of livestock farm emissions on lung function, but so far, studies involving children and adolescents are lacking. OBJECTIVES: To study the association of residential proximity to livestock farms and modelled particulate matter ≤10 µm (PM10) from livestock farms with lung function in adolescence. METHODS: We performed a cross-sectional study among 715 participants of the Dutch prospective PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort study. Relationships of different indicators of residential livestock farming exposure (distance to farms, distance-weighted number of farms, cattle, pigs, poultry, horses and goats within 3 km; modelled atmospheric PM10 concentrations from livestock farms) with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at age 16 were assessed by linear regression taking into account potential confounders. Associations were expressed per interquartile range increase in exposure. RESULTS: Higher exposure to livestock farming was consistently associated with a lower FEV1, but not with FVC among participants living in less urbanized municipalities (<1500 addresses/km2, N = 402). Shorter distances of homes to livestock farms were associated with a 1.4% (0.2%; 2.7%) lower FEV1. Larger numbers of farms within 3 km and higher concentrations of PM10 from livestock farming were associated with a 1.8% (0.8%, 2.9%) and 0.9% (0.4%,1.5%) lower FEV1, respectively. CONCLUSIONS: Our findings suggest that higher exposure to livestock farming is associated with a lower FEV1 in adolescents. Replication and more research on the etiologic agents involved in these associations and the underlying mechanisms is needed.

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.

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.

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 distribution of covert microbial natural enemies of a globally invasive crop pest, fall armyworm, in Africa: Enemy release and spillover events.

Invasive species pose a significant threat to biodiversity and agriculture world-wide. Natural enemies play an important part in controlling pest populations, yet we understand very little about the presence and prevalence of natural enemies during the early invasion stages. Microbial natural enemies of fall armyworm Spodoptera frugiperda are known in its native region, however, they have not yet been identified in Africa where fall armyworm has been an invasive crop pest since 2016. Larval samples were screened from Malawi, Rwanda, Kenya, Zambia, Sudan and Ghana for the presence of four different microbial natural enemies; two nucleopolyhedroviruses, Spodoptera frugiperda NPV (SfMNPV) and Spodoptera exempta NPV (SpexNPV); the fungal pathogen Metarhizium rileyi; and the bacterium Wolbachia. This study aimed to identify which microbial pathogens are present in invasive fall armyworm, and determine the geographical, meteorological and temporal variables that influence prevalence. Within 3 years of arrival, fall armyworm was exposed to all four microbial natural enemies. SfMNPV probably arrived with fall armyworm from the Americas, but this is the first putative evidence of host spillover from Spodoptera exempta (African armyworm) to fall armyworm for the endemic pathogen SpexNPV and for Wolbachia. It is also the first confirmed incidence of M. rileyi infecting fall armyworm in Africa. Natural enemies were localised, with variation being observed both nationally and temporally. The prevalence of SfMNPV (the most common natural enemy) was predominantly explained by variables associated with the weather; declining with increasing rainfall and increasing with temperature. However, virus prevalence also increased as the growing season progressed. The infection of an invasive species with a natural enemy from its native range and novel pathogens specific to its new range has important consequences for understanding the population ecology of invasive species and insect-pathogen interactions. Additionally, while it is widely known that temporal and geographic factors affect insect populations, this study reveals that these are important in understanding the distribution of microbial natural enemies associated with invasive pests during the early stages of invasion, and provide baseline data for future studies.

Physical activity attenuates but does not eliminate coronary heart disease risk amongst adults with risk factors: EPIC-CVD case-cohort study.

AIMS: This study aimed to evaluate the association between physical activity and the incidence of coronary heart disease (CHD) in individuals with and without CHD risk factors. METHODS AND RESULTS: EPIC-CVD is a case-cohort study of 29 333 participants that included 13 582 incident CHD cases and a randomly selected sub-cohort nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Self-reported physical activity was summarized using the Cambridge physical activity index (inactive, moderately inactive, moderately active, and active). Participants were categorized into sub-groups based on the presence or the absence of the following risk factors: obesity (body mass index ≥30 kg/m2), hypercholesterolaemia (total cholesterol ≥6.2 mmol/L), history of diabetes, hypertension (self-reported or ≥140/90 mmHg), and current smoking. Prentice-weighted Cox regression was used to assess the association between physical activity and incident CHD events (non-fatal and fatal).Compared to inactive participants without the respective CHD risk factor (referent), excess CHD risk was highest in physically inactive and lowest in moderately active participants with CHD risk factors. Corresponding excess CHD risk estimates amongst those with obesity were 47% [95% confidence interval (CI) 32-64%] and 21% (95%CI 2-44%), with hypercholesterolaemia were 80% (95%CI 55-108%) and 48% (95%CI 22-81%), with hypertension were 80% (95%CI 65-96%) and 49% (95%CI 28-74%), with diabetes were 142% (95%CI 63-260%), and 100% (95%CI 32-204%), and amongst smokers were 152% (95%CI 122-186%) and 109% (95%CI 74-150%). CONCLUSIONS: In people with CHD risk factors, moderate physical activity, equivalent to 40 mins of walking per day, attenuates but does not completely offset CHD risk.

Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization.

BACKGROUND: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. OBJECTIVES: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men. DESIGN: Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard inverse-variance weighted (IVW) regression, and MR-Egger regression. PARTICIPANTS: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were pooled for the different analyses. MAIN OUTCOME MEASURES: CHD, CHD risk factors, and ANM. RESULTS: Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging. CONCLUSION: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men.

Substitution of pure fruit juice for fruit and sugar-sweetened beverages and cardiometabolic risk in European Prospective Investigation into Cancer and Nutrition (EPIC)-NL: a prospective cohort study.

OBJECTIVE: Dietary guidelines on pure fruit juice differ between countries regarding the question whether pure fruit juice (without added sugars) is an acceptable substitute for fruit or should be avoided because of its comparable sugar content with that of sugar-sweetened beverages (SSB). We modelled whether substituting pure fruit juice for fruit or SSB was associated with cardiometabolic risk. DESIGN: Prospective cohort study. SETTING: Based on a validated FFQ at baseline, we calculated the relative contribution of pure fruit juice to total consumption of fruit and pure fruit juice (${{{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\;\left( {{\rm{g}}/{\rm{day}}} \right)} \over {{\rm{fruit}}\; + \;{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\left( {{\rm{g}}/{\rm{day}}} \right)}}$) and to total consumption of SSB and pure fruit juice (${{{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\;\left( {{\rm{g}}/{\rm{day}}} \right)} \over {{\rm{SSBs}}\; + \;{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\left( {{\rm{g}}/{\rm{day}}} \right)}}$). In multivariate analyses (Cox regression), we assessed associations with incidence of type 2 diabetes, CVD, CHD and stroke after an average follow-up of 14·6 years. PARTICIPANTS: About 35 000 participants from the EPIC-NL study, aged 20-70 years at enrolment. RESULTS: Substitution of pure fruit juice for SSB was associated with lower risk of all endpoints. For type 2 diabetes and CHD, for example, drinking 75-100 % (as compared with 0-<25 %) of total SSB + pure fruit juice as pure fruit juice showed hazard ratio (95 % CI) of 0·74 (95 % CI 0·64, 0·85) and 0·85 (95 % CI 0·76, 0·96), respectively. Substitution of pure fruit juice for fruit was not associated with the risk of type 2 diabetes, CVD, CHD and stroke. CONCLUSIONS: Substituting pure fruit juice for SSB was associated with lower cardiometabolic risk, whereas substituting pure fruit juice for fruit was not associated with cardiometabolic risk.