Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40–69 years in Europe. Methods and results  We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65–0.68) to 0.81 (0.76–0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low-risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion  SCORE2—a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations—enhances the identification of individuals at higher risk of developing CVD across Europe.

Key Points Question To what extent are established cardiovascular risk factors associated with risk of venous thromboembolism (VTE)? Findings In this analysis of individual participant data from the Emerging Risk Factors Collaboration and the UK Biobank including 1.1 million participants, among a panel of several established cardiovascular risk factors, older age, smoking, and greater adiposity were consistently associated with higher VTE risk. Meaning There is overlap in at least some of the major population determinants of important venous and arterial thrombotic diseases.

The association of glycemic index (GI) and glycemic load (GL) with the risk of type 2 diabetes remains unclear. We investigated associations of dietary GI, GL, and digestible carbohydrate with incident type 2 diabetes. We performed a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition Study, including a random subcohort (n = 16,835) and incident type 2 diabetes cases (n = 12,403). The median follow-up time was 12 y. Baseline dietary intakes were assessed using country-specific dietary questionnaires. Country-specific HR were calculated and pooled using random effects meta-analysis. Dietary GI, GL, and digestible carbohydrate in the subcohort were (mean ± SD) 56 ± 4, 127 ± 23, and 226 ± 36 g/d, respectively. After adjustment for confounders, GI and GL were not associated with incident diabetes [HR highest vs. lowest quartile (HR(Q4)) for GI: 1.05 (95% CI = 0.96, 1.16); HR(Q4) for GL: 1.07 (95% CI = 0.95, 1.20)]. Digestible carbohydrate intake was not associated with incident diabetes [HR(Q4): 0.98 (95% CI = 0.86, 1.10)]. In additional analyses, we found that discrepancies in the GI value assignment to foods possibly explain differences in GI associations with diabetes within the same study population. In conclusion, an expansion of the GI tables and systematic GI value assignment to foods may be needed to improve the validity of GI values derived in such studies, after which GI associations may need reevaluation. Our study shows that digestible carbohydrate intake is not associated with diabetes risk and suggests that diabetes risk with high-GI and -GL diets may be more modest than initial studies suggested.

Genome-Wide Association Study (GWAS) Higher Blood pressure Arthritides Neuropsychiatric conditions Malignancies Lower Anaemias Lipidaemias Ischaemic heart disease Genetically higher central obesity Highlights Variants in HFE and TMPRSS6 are associated with higher liver iron. There is genetic evidence that higher central obesity causes higher liver iron. Liver iron variants are not organ specific and associate with multiple diseases.

Background Walkability indices have been developed and linked to behavioural and health outcomes elsewhere in the world, but not comprehensively for Europe. We aimed to 1) develop a theory-based and evidence-informed Dutch walkability index, 2) examine its cross-sectional associations with total and purpose-specific walking behaviours of adults across socioeconomic (SES) and urbanisation strata, 3) explore which walkability components drive these associations. Methods Components of the index included: population density, retail and service density, land use mix, street connectivity, green space, sidewalk density and public transport density. Each of the seven components was calculated for three Euclidean buffers: 150 m, 500 m and 1000 m around every 6-digit postal code location and for every administrative neighbourhood in GIS. Componential z-scores were averaged, and final indices normalized between 0 and 100. Data on self-reported demographic characteristics and walking behaviours of 16,055 adult respondents (aged 18–65) were extracted from the Dutch National Travel Survey 2017. Using Tobit regression modelling adjusted for individual- and household-level confounders, we assessed the associations between walkability and minutes walking in total, for non-discretionary and discretionary purposes. By assessing the attenuation in associations between partial indices and walking outcomes, we identified which of the seven components drive these associations. We also tested for effect modification by urbanization degree, SES, age and sex. Results In fully adjusted models, a 10% increase in walkability was associated with a maximum increase of 8.5 min of total walking per day (95%CI: 7.1–9.9). This association was consistent across buffer sizes and purposes of walking. Public transport density was driving the index’s association with walking outcomes. Stratified results showed that associations with minutes of non-discretionary walking were stronger in rural compared to very urban areas, in neighbourhoods with low SES compared to high SES, and in middle-aged (36–49 years) compared to young (18–35 years old) and older adults (50–65 years old). Conclusions The walkability index was cross-sectionally associated with Dutch adult’s walking behaviours, indicating its validity for further use in research.

We aimed to systematically assess the measurement properties of diabetes-specific patient-reported outcome measures (PROMs) for measuring physical functioning, one of the core outcomes, in adults with type 2 diabetes.We performed a systematic literature search for PROMs or subscales measuring physical function that were validated to at least some extent in EMBASE and MEDLINE. Measurement properties were evaluated according to the COSMIN guideline for systematic reviews of PROMs.In total 21 articles were included, describing 12 versions of 7 unique diabetes-specific PROMs or subscales measuring physical functioning. In general, there were few high-quality studies on measurement properties of PROMs measuring physical functioning in adults with type 2 diabetes. The Dependence/Daily Life subscale of the Diabetic Foot Ulcer Scale—Short Form (DFS-SF) and the Impact of Weight on Activities of Daily Living Questionnaire (IWADL) were most extensively evaluated. Both had sufficient ratings for aspects of content validity, although with mostly very low-quality evidence. Sufficient ratings for structural validity, internal consistency, and reliability were also found for both instruments, but responsiveness was rated inconsistent for both instruments. The other PROMs or subscales often had insufficient aspects of content validity, or their unidimensionality could not be confirmed.This systematic review showed that the Dependence/Daily Life subscale of the DFS-SF and the IWADL could be used to measure physical functioning in people with type 2 diabetes in research or clinical practice, while keeping the limitations of these instruments in mind. The measurement properties that have not been evaluated extensively for these PROMs should be evaluated in future studies.The study protocol was registered in the PROSPERO database, number CRD42021234890.

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Moderate alcohol consumption increases HDL cholesterol, which is involved in reverse cholesterol transport (RCT). The aim of this study was to investigate the effect of moderate alcohol consumption on cholesterol efflux, using J774 mouse macrophages and Fu5AH cells, and on other parameters in the RCT pathway. Twenty-three healthy men (45-65 years) participated in a randomized, partially diet-controlled, crossover trial. They consumed four glasses of whisky (40 g of alcohol) or water daily for 17 days. After 17 days of whisky consumption, serum capacity to induce ABCA1-dependent cholesterol efflux from J774 mouse macrophages was increased by 17.5% ( P ‫؍‬ 0.027) compared with water consumption. Plasma capacity to induce cholesterol efflux from Fu5AH cells increased by 4.6% ( P ‫؍‬ 0.002). Pre ␤ -HDL, apolipoprotein A-I (apoA-I), and lipoprotein A-I:A-II also increased by 31.6, 6.2, and 5.7% ( P Ͻ 0.05), respectively, after whisky consumption compared with water consumption. Changes of cAMP-stimulated cholesterol efflux correlated ( r ‫؍‬ 0.65, P Ͻ 0.05) with changes of apoA-I but not with changes of pre ␤ -HDL ( r ‫؍‬ 0.30, P ‫؍‬ 0.18). Cholesterol efflux capacities from serum of lean men were higher than those from overweight men.In conclusion, this study shows that moderate alcohol consumption increases the capacity of serum to induce cholesterol efflux from J774 mouse macrophages, which may be mediated by ABCA1.