Moderate associations between the use of levonorgestrel-releasing intrauterine device and metabolomics profile.

CONTEXT: Use of levonorgestrel-releasing intrauterine device (LNG-IUD) has become common irrespective of age and parity. To date, only a few studies have examined its possible metabolic changes and large-scale biomarker profiles in detail and in a longitudinal design. OBJECTIVE: To apply the metabolomics technique to examine the metabolic profile associated with the use of LNG-IUD both in a cross-sectional and in a longitudinal design. DESIGN: The study consists of cross-sectional and longitudinal analyses of a population-based survey (Health 2000) and its 11-year follow-up (Health 2011). All participants aged 18-49 years with available information on hormonal contraceptive use and metabolomics data (n=1767) were included. Altogether 212 metabolic measures in LNG-IUD users (n=341) were compared to those in non-users of hormonal contraception (n=1426) via multivariable linear regression models. Participants with complete longitudinal information (n=240) were divided into continuers, stoppers, starters, and never-user groups, and 11-year changes in levels of each metabolite were compared. RESULTS: After adjustment for covariates, levels of 102 metabolites differed in LNG-IUD current users compared to non-users of hormonal contraception (median difference in biomarker concentration: -0.12 SD): lower levels of fatty acids concentrations and ratios, cholesterol, triglycerides and other lipids, as well as particle concentration, cholesterol, total lipids and phospholipids in lipoproteins. The 11-year metabolic changes did not differ in relation to changes in LNG-IUD use. CONCLUSIONS: The use of LNG-IUD was associated with several moderate metabolic changes, mostly suggestive of a reduced arterial cardiometabolic risk. Changes in LNG-IUD use were not related to long-term metabolic changes.

Genome-wide characterization of circulating metabolic biomarkers.

Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1-7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8-11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.

Integration of polygenic and gut metagenomic risk prediction for common diseases.

Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18 years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.

Pulmonary primary oxysterol and bile acid synthesis as a predictor of outcomes in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare and fatal vascular disease with heterogeneous clinical manifestations. To date, molecular determinants underlying the development of PAH and related outcomes remain poorly understood. Herein, we identify pulmonary primary oxysterol and bile acid synthesis (PPOBAS) as a previously unrecognized pathway central to PAH pathophysiology. Mass spectrometry analysis of 2,756 individuals across five independent studies revealed 51 distinct circulating metabolites that predicted PAH-related mortality and were enriched within the PPOBAS pathway. Across independent single-center PAH studies, PPOBAS pathway metabolites were also associated with multiple cardiopulmonary measures of PAH-specific pathophysiology. Furthermore, PPOBAS metabolites were found to be increased in human and rodent PAH lung tissue and specifically produced by pulmonary endothelial cells, consistent with pulmonary origin. Finally, a poly-metabolite risk score comprising 13 PPOBAS molecules was found to not only predict PAH-related mortality but also outperform current clinical risk scores. This work identifies PPOBAS as specifically altered within PAH and establishes needed prognostic biomarkers for guiding therapy in PAH.

Pairwise association of key lifestyle factors and risk of solid cancers - A prospective pooled multi-cohort register study.

Smoking, alcohol consumption, obesity, and physical inactivity are key lifestyle risk factors for cancer. Previously these have been mostly examined singly or combined as an index, assuming independent and equivalent effects to cancer risk. The aim of our study was to systematically examine the joint pairwise and interactive effects of these lifestyle factors on the risk of a first solid primary cancer in a multi-cohort prospective setting. We used pooled data from seven Finnish health survey studies during 1972-2015, with 197,551 participants diagnosed with 16,373 solid malignant primary tumors during follow-up. Incidence of any cancer was analyzed separately without and with lung cancers using Poisson regression with main and interaction effects of key lifestyle factors. When excluding lung cancer, the highest risk of any cancer in men was observed for smokers with a BMI of ≥25 kg/m2 (HR 1.36, 95 % CI 1.25-1.48) and in women for smokers consuming alcohol (HR 1.22, 1.14-1.30). No statistically significant interactions between any studied risk factor pairs were observed. When including lung cancer, the highest HRs among men were observed for smokers who consume alcohol (HR 1.72, 1.57-1.89) and among women for smokers who were physically inactive (HR 1.38, 1.27-1.49). Smoking combined with other lifestyle factors at any exposure level resulted in highest pairwise risks, both in men and women. These results highlight the importance of smoking prevention, but also the importance of preventing obesity and reducing alcohol consumption.

C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project.

BACKGROUND AND AIMS: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population. METHODS: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L). RESULTS: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024). CONCLUSIONS: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.

Partial substitution of red meat or processed meat with plant-based foods and the risk of colorectal cancer.

OBJECTIVES: Shifting from animal-based to plant-based diets could reduce colorectal cancer (CRC) incidence. Currently, the impacts of these dietary shifts on CRC risk are ill-defined. Therefore, we examined partial substitutions of red or processed meat with whole grains, vegetables, fruits or a combination of these in relation to CRC risk in Finnish adults. METHODS: We pooled five Finnish cohorts, resulting in 43 788 participants aged ≥ 25 years (79% men). Diet was assessed by validated food frequency questionnaires at study enrolment. We modelled partial substitutions of red (100 g/week) or processed meat (50 g/week) with corresponding amounts of plant-based foods. Cohort-specific hazard ratios (HR) for CRC were calculated using Cox proportional hazards models and pooled together using random-effects models. Adjustments included age, sex, energy intake and other relevant confounders. RESULTS: During the median follow-up of 28.8 years, 1124 CRCs were diagnosed. We observed small risk reductions when red meat was substituted with vegetables (HR 0.97, 95% CI 0.95 - 0.99), fruits (0.97, 0.94 - 0.99), or whole grains, vegetables and fruits combined (0.97, 0.95 - 0.99). For processed meat, these substitutions yielded 1% risk reductions. Substituting red or processed meat with whole grains was associated with a decreased CRC risk only in participants with < median whole grain intake (0.92, 0.86 - 0.98; 0.96, 0.93 - 0.99, respectively; pinteraction=0.001). CONCLUSIONS: Even small, easily implemented substitutions of red or processed meat with whole grains, vegetables or fruits could lower CRC risk in a population with high meat consumption. These findings broaden our insight into dietary modifications that could foster CRC primary prevention.

Every tenth malignant solid tumor attributed to overweight and alcohol consumption: A population-based cohort study.

BACKGROUND: Recent studies have shown that some four in ten cancers are attributable to a few key risk factors. The aim of this study was to estimate cohort-based population attributable fractions (PAFs) in Finland for potentially modifiable cancer risk factors. METHODS: Data from eight health studies including 253,953 subjects with 29,802 incident malignant solid tumors were analysed using Bayesian multivariate regression model with multiplicative risk factor effects. We estimated the effects of smoking, excess body weight, alcohol consumption, physical activity, parity and education on cancer incidence and related PAFs by cancer site, accounting for competing mortality. RESULTS: PAF for all cancer sites and exposures combined was 34% (95% credible interval 29%-39%) in men and 24% (19%-28%) in women. In men, 23% (21%-27%) and in women 8% (6%-9%) of all cancers were attributed to smoking. PAF related to excess body weight was 4% (2%-6%) in men and 5% (2%-7%) in women, to alcohol 7% (3%-10%) in men and 4% (0%-7%) in women, and to excess body weight and alcohol combined 10% (6%-15%) in men and 9% (4%-13%) in women. CONCLUSION: Smoking was the most important factor contributing to cancer burden in Finnish men and women over the last 40 years. The contribution of excess body weight and alcohol consumption together outweighed the role of smoking in women. As the prevalence of overweight is expected to increase, more efficient public health measures supporting adherence to healthy weight are essential to reduce cancer burden.

Association between active commuting and low-grade inflammation: a population-based cross-sectional study.

BACKGROUND: Prior studies suggest that physical activity lowers circulating C-reactive protein (CRP) levels. However, little is known about the association between regular active commuting, i.e. walking or cycling to work, and CRP concentrations. This study examines whether active commuting is associated with lower CRP. METHODS: We conducted a cross-sectional study using population-based FINRISK data from 1997, 2002, 2007 and 2012. Participants were working adults living in Finland (n = 6208; mean age = 44 years; 53.6% women). We used linear and additive models adjusted for potential confounders to analyze whether daily active commuting, defined as the time spent walking or cycling to work, was associated with lower high-sensitivity (hs-) CRP serum concentrations compared with passive commuting. RESULTS: We observed that daily active commuting for 45 min or more (vs. none) was associated with lower hs-CRP [% mean difference in the main model: -16.8%; 95% confidence interval (CI) -25.6% to -7.0%), and results were robust to adjustment for leisure-time and occupational physical activity, as well as diet. Similarly, active commuting for 15-29 min daily was associated with lower hs-CRP in the main model (-7.4; 95% CI -14.1 to -0.2), but the association attenuated to null after further adjustments. In subgroup analyses, associations were only observed for women. CONCLUSIONS: Active commuting for at least 45 min a day was associated with lower levels of low-grade inflammation. Promoting active modes of transport may lead not only to reduced emissions from motorized traffic but also to population-level health benefits.

Regional and temporal differences in the associations between cardiovascular disease and its classic risk factors: an analysis of 49 cohorts from 11 European countries.

AIMS: The regional and temporal differences in the associations between cardiovascular disease (CVD) and its classic risk factors are unknown. The current study examined these associations in different European regions over a 30-year period. METHODS AND RESULTS: The study sample comprised 553 818 individuals from 49 cohorts in 11 European countries (baseline: 1982-2012) who were followed up for a maximum of 10 years. Risk factors [sex, smoking, diabetes, non-HDL cholesterol, systolic blood pressure (BP), and body mass index (BMI)] and CVD events (coronary heart disease or stroke) were harmonized across cohorts. Risk factor-outcome associations were analysed using multivariable-adjusted Cox regression models, and differences in associations were assessed using meta-regression. The differences in the risk factor-CVD associations between central Europe, northern Europe, southern Europe, and the UK were generally small. Men had a slightly higher hazard ratio (HR) in southern Europe (P = 0.043 for overall difference), and those with diabetes had a slightly lower HR in central Europe (P = 0.022 for overall difference) compared with the other regions. Of the six CVD risk factors, minor HR decreases per decade were observed for non-HDL cholesterol [7% per mmol/L; 95% confidence interval (CI), 3-10%] and systolic BP (4% per 20 mmHg; 95% CI, 1-8%), while a minor HR increase per decade was observed for BMI (7% per 10 kg/m2; 95% CI, 1-13%). CONCLUSION: The results demonstrate that all classic CVD risk factors are still relevant in Europe, irrespective of regional area. Preventive strategies should focus on risk factors with the greatest population attributable risk.

All classic cardiovascular disease (CVD) risk factors are still relevant in Europe, irrespective of regional area. The differences in the associations of CVD risk factors with overt CVD between regions of Europe are generally small. Minor temporal hazard decreases were observed for non-HDL cholesterol and systolic blood pressure, while a minor hazard increase was observed for body mass index.

Role of Gut Microbiota in Statin-Associated New-Onset Diabetes-A Cross-Sectional and Prospective Analysis of the FINRISK 2002 Cohort.

BACKGROUND: Dyslipidemia is treated effectively with statins, but treatment has the potential to induce new-onset type-2 diabetes. Gut microbiota may contribute to this outcome variability. We assessed the associations of gut microbiota diversity and composition with statins. Bacterial associations with statin-associated new-onset type-2 diabetes (T2D) risk were also prospectively evaluated. METHODS: We examined shallow-shotgun-sequenced fecal samples from 5755 individuals in the FINRISK-2002 population cohort with a 17+-year-long register-based follow-up. Alpha-diversity was quantified using Shannon index and beta-diversity with Aitchison distance. Species-specific differential abundances were analyzed using general multivariate regression. Prospective associations were assessed with Cox regression. Applicable results were validated using gradient boosting. RESULTS: Statin use associated with differing taxonomic composition (R2, 0.02%; q=0.02) and 13 differentially abundant species in fully adjusted models (MaAsLin; q<0.05). The strongest positive association was with Clostridium sartagoforme (ß=0.37; SE=0.13; q=0.02) and the strongest negative association with Bacteroides cellulosilyticus (ß=-0.31; SE=0.11; q=0.02). Twenty-five microbial features had significant associations with incident T2D in statin users, of which only Bacteroides vulgatus (HR, 1.286 [1.136-1.457]; q=0.03) was consistent regardless of model adjustment. Finally, higher statin-associated T2D risk was seen with [Ruminococcus] torques (ΔHRstatins, +0.11; q=0.03), Blautia obeum (ΔHRstatins, +0.06; q=0.01), Blautia sp. KLE 1732 (ΔHRstatins, +0.05; q=0.01), and beta-diversity principal component 1 (ΔHRstatin, +0.07; q=0.03) but only when adjusting for demographic covariates. CONCLUSIONS: Statin users have compositionally differing microbiotas from nonusers. The human gut microbiota is associated with incident T2D risk in statin users and possibly has additive effects on statin-associated new-onset T2D risk.

Dietary inflammatory index in relation to salivary cytokine concentrations and periodontitis: A cross-sectional analysis.

AIM: To examine the associations of dietary inflammatory index (DII) with salivary cytokine concentrations and periodontitis after controlling for body mass index (BMI), socio-demographic factors and lifestyle. MATERIALS AND METHODS: Subgroups from two Finnish surveys, DILGOM 2007 and Health 2000, were included (total n = 727). The DII scores were calculated based on a food frequency questionnaire. Periodontal status was assessed with a cumulative risk score in DILGOM 2007 and by pocket depth measurement in Health 2000. From saliva, interleukin (IL)-1ß, IL-1 receptor antagonist, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α concentrations were measured. RESULTS: The DII scores did not differ between non-periodontitis and periodontitis participants in pairwise comparison. After adjusting for energy intake, periodontal status, BMI, age, education level, smoking habit and physical activity, DII was not associated with salivary cytokine concentrations. After adjusting for salivary cytokine levels and other confounding factors, DII was associated with periodontitis in the Health 2000 subgroup but not in the DILGOM 2007 subgroup. CONCLUSIONS: The current data support the evidence that diet is not associated with salivary cytokine levels but may be associated with periodontitis. The association observed between diet and periodontitis is related to factors other than diet-dependent inflammatory tendency in the oral cavity.

Associations of EAT-Lancet Planetary Health Diet or Finnish Nutrition Recommendations with changes in obesity measures: a follow-up study in adults.

Background: Knowledge on the association between the EAT-Lancet Planetary Health Diet (PHD) or the Finnish Nutrition recommendations (FNR) and anthropometric changes is scarce. Especially, the role of the overall diet quality, distinct from energy intake, on weight changes needs further examination. Objectives: To examine the association between diet quality and weight change indicators and to develop a dietary index based on the PHD adapted for the Finnish food culture. Methods: The study population consisted of participants of two Finnish population-based studies (n = 4,371, 56% of women, aged 30-74 years at baseline). Dietary habits at the baseline were assessed with a validated food frequency questionnaire including 128-130 food items. We developed a Planetary Health Diet Score (PHDS) (including 13 components) and updated the pre-existing Recommended Finnish Diet Score (uRFDS) (including nine components) with energy density values to measure overall diet quality. Weight, height, and waist circumference (WC), and the body mass index (BMI) were measured at the baseline and follow-up, and their percentual changes during a 7-year follow-up were calculated. Two-staged random effects linear regression was used to evaluate ß-estimates with 95% confidence intervals. Results: Adherence to both indices was relatively low (PHDS: mean 3.6 points (standard deviation [SD] 1.2) in the range of 0-13; uRFDS: mean 12.7 points (SD 3.9) in the range of 0-27). We did not find statistically significant associations between either of the dietary indices and anthropometric changes during the follow-up (PHDS, weight: ß -0.04 (95% CI -0.19, 0.11), BMI: ß 0.05 (-0.20, 0.10), WC: ß -0.08 (-0.22, 0.06); uRFDS, weight: ß 0.01 (-0.04, 0.06), BMI: ß 0.01 (-0.04, 0.06), WC: ß -0.02 (-0.07, 0.03)). Conclusion: No associations between overall diet quality and anthropometric changes were found, which may be at least partly explained by low adherence to the PHD and the FNR in the Finnish adult population.

Trajectories of hospitalizations after age-based statutory retirement.

Retirement years are ideally spent in good health. We aimed to produce new information using person-oriented methods by identifying groups of statutory retirees who did or did not achieve this objective and the factors that distinguish these groups from each other. Our particular focus was on the years directly after the transition into retirement, and the pre-retirement factors that explained the development of health, using a more severe health-related outcome-hospitalization. We studied the retirement, hospitalizations, education, and work characteristics of former employees of the City of Helsinki, Finland (N = 6569), from complete registers. We used group-based trajectory models and identified groups of constant low, constant high, decreasing, and temporarily occurring hospitalizations, and one group of increasing hospitalizations among women and two groups of earlier and later increasing hospitalizations among men. Multinomial regression models showed that among women, belonging to groups with less favourable health was associated with secondary education, older age at retirement, and reduced working hours. Education and work characteristics before retirement both contribute to the development of health, as indicated by hospitalizations directly after retirement. Our findings show that socioeconomic inequalities in health are persistent and should also be addressed after transition into retirement.

Microbiome-based risk prediction in incident heart failure: a community challenge.

Heart failure (HF) is a major public health problem. Early identification of at-risk individuals could allow for interventions that reduce morbidity or mortality. The community-based FINRISK Microbiome DREAM challenge (synapse.org/finrisk) evaluated the use of machine learning approaches on shotgun metagenomics data obtained from fecal samples to predict incident HF risk over 15 years in a population cohort of 7231 Finnish adults (FINRISK 2002, n=559 incident HF cases). Challenge participants used synthetic data for model training and testing. Final models submitted by seven teams were evaluated in the real data. The two highest-scoring models were both based on Cox regression but used different feature selection approaches. We aggregated their predictions to create an ensemble model. Additionally, we refined the models after the DREAM challenge by eliminating phylum information. Models were also evaluated at intermediate timepoints and they predicted 10-year incident HF more accurately than models for 5- or 15-year incidence. We found that bacterial species, especially those linked to inflammation, are predictive of incident HF. This highlights the role of the gut microbiome as a potential driver of inflammation in HF pathophysiology. Our results provide insights into potential modeling strategies of microbiome data in prospective cohort studies. Overall, this study provides evidence that incorporating microbiome information into incident risk models can provide important biological insights into the pathogenesis of HF.

Trajectories of CVD medication after statutory retirement: contributions of pre-retirement sociodemographic, work and health-related factors: a register study in Finland.

BACKGROUND: Cardiovascular diseases (CVDs) are prevalent in older people, but few studies focus on developmental patterns in CVD medication directly after transition to statutory retirement. We thus aimed to identify trajectories of CVD medication after retirement, and their sociodemographic, work and health-related determinants. METHODS: We used complete register data of former employees of the City of Helsinki, Finland. All who reached their statutory retirement in 2000-2013, with five-year follow-up data (n = 6,505, 73% women), were included. Trajectories of CVD medication were identified with group-based trajectory modelling using data from Finnish Social Insurance Institution's reimbursement register. Sociodemographic, work and health-related determinants of trajectory group membership were analysed using multinomial logistic regression. RESULTS: Six trajectories of CVD medication were distinguished: "constant low" (35%), "late increase" (6%), "early increase" (5%), "constant high" (39%), "high and decreasing " (8%), and "low and decreasing" (7%). The majority (74%) of the retirees fell into the "constant low" and "constant high" categories. Lower occupational class and increased pre-retirement sickness absence were associated with the "constant high" trajectory. Further, those with lower educational attainment were more prone to be in the "early increase" trajectory. CONCLUSIONS: Individuals in lower socioeconomic positions or with a higher number of pre-retirement sickness absence may be considered at higher risk and might benefit from early interventions, e.g. lifestyle interventions and interventions targeting working conditions, or more frequent monitoring.

Associations of food motives with red meat and legume consumption in the population-based DILGOM study.

PURPOSE: To improve human health and environmental sustainability, red meat consumption should decrease and legume consumption increase in diets. More information on food motives, however, is required when developing more tailored and effective interventions targeting legume and meat consumption. We aimed to examine the associations between food motives and red meat and legume consumption, and whether these associations differ between different subgroups (gender, age groups, marital status, education, BMI). METHODS: Ten food motives (health, mood, convenience, sensory appeal, natural content, price-cheap, price-value, weight control, familiarity and ethical concern measured with Food Choice Questionnaire) were studied in 3079 Finnish adults in the population-based DILGOM study. Food consumption was assessed with Food Frequency Questionnaire. The adjusted estimates from multivariable regression models are reported. RESULTS: Higher relative importance of natural content (ß = - 0.275, 95% CI - 0.388; - 0.162) and ethical concern (ß = - 0.462, 95% CI - 0.620; - 0.305) were associated with lower red meat consumption, and higher appreciation of sensory appeal (ß = 0.482, 95% CI 0.347; 0.616) and price-cheap (ß = 0.190, 95% CI 0.099; 0.281) with higher red meat consumption. Higher importance of health (ß = 0.608, 95% CI 0.390; 0.825) was associated with higher legume consumption, and higher appreciation of convenience (ß = - 0.401, 95% CI - 0.522; - 0.279), price-value (ß = - 0.257, 95% CI - 0.380; - 0.133) and familiarity (ß = - 0.278, 95% CI - 0.393; - 0.164) with lower legume consumption. The associations of particularly ethical concern, weight control, sensory appeal and mood varied according to gender, age, marital status or BMI. CONCLUSION: The development and implementation of actions to decrease red meat and increase legume consumption should focus on several food motives across different subgroups.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).