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BACKGROUND: Cardiovascular disease (CVD) is a major cause of disability and premature death. Despite European guidelines advocating the use of medical therapies in CVD, many patients still do not achieve the guideline-recommended treatment, which highlights the need for change and innovations in this field. This requirement has been widely recognised by the national ministries of health, several European cardiology societies, and the European Parliament, who support the initiation of strategies to improve and promote cardiovascular health. DISCUSSION: One of the key risk factors to recurrent cardiovascular events is the lack of adherence to medication and this has been added to the agenda of the European Commission. With the intention to improve treatment adherence in CVD, polypills have been investigated and numerous studies demonstrate that they significantly improve medication adherence, which contributes to the improvement of health outcomes. In Europe, the first cardiovascular polypill, developed by a public-private partnership (CNIC-Ferrer), recently became available for general prescription as a therapy for CVD prevention. This polypill significantly improves adherence, preventing fatal and non-fatal cardiovascular events, and appears to be a cost-effective strategy to improve sustainability of the health care systems in CVD. CONCLUSIONS: Given the importance of urgent and simple solutions to restraining the pandemic nature of CVD, the polypill approach should therefore be considered by physicians and public health systems as an available and innovative option to improve cardiovascular health.

Background: Cardiovascular disease (CVD) is a major cause of disability and premature death. Despite European guidelines advocating the use of medical therapies in CVD, many patients still do not achieve the guideline-recommended treatment, which highlights the need for change and innovations in this field. This requirement has been widely recognised by the national ministries of health, several European cardiology societies, and the European Parliament, who support the initiation of strategies to improve and promote cardiovascular health. Discussion: One of the key risk factors to recurrent cardiovascular events is the lack of adherence to medication and this has been added to the agenda of the European Commission. With the intention to improve treatment adherence in CVD, polypills have been investigated and numerous studies demonstrate that they significantly improve medication adherence, which contributes to the improvement of health outcomes. In Europe, the first cardiovascular polypill, developed by a public-private partnership (CNIC-Ferrer), recently became available for general prescription as a therapy for CVD prevention. This polypill significantly improves adherence, preventing fatal and non-fatal cardiovascular events, and appears to be a cost-effective strategy to improve sustainability of the health care systems in CVD. Conclusions: Given the importance of urgent and simple solutions to restraining the pandemic nature of CVD, the polypill approach should therefore be considered by physicians and public health systems as an available and innovative option to improve cardiovascular health. ; Financial support for the creation of this paper was provided by Ferrer Internacional. All content and opinions expressed in the article reflect those of the authors and were not influenced by Ferrer. ; Sí

Highlights: - Despite clinical evidence of its effectiveness in secondary prevention of cardiovascular disease, uptake of fixed dose combination therapy (FDCs) for CVD has been poor.- A symposium was held bringing together stakeholders on this issue, including from academia, government and NGOs.- The conclusion made was that what is now needed to improve implementation of FDCs is country-specific health systems analyses to design appropriate implementation strategies.- Implementation strategies must look beyond listing on the WHO Essential Medicines List to consider approaches to improving FDC availability, accessibility, affordability, and adherence.- Strategies might include incorporation of FDCs into the WHO HEARTS technical package, simplified treatment and monitoring algorithms, decentralisation of medicine dispensing and task-sharing for treatment management.

Background: The comparative performance of existing models for prediction of type 2 diabetes across populations has not been investigated. We validated existing non-laboratory-based models and assessed variability in predictive performance in European populations. Methods: We selected non-invasive prediction models for incident diabetes developed in populations of European ancestry and validated them using data from the EPIC-InterAct case-cohort sample (27 779 individuals from eight European countries, of whom 12 403 had incident diabetes). We assessed model discrimination and calibration for the first 10 years of follow-up. The models were first adjusted to the country-specific diabetes incidence. We did the main analyses for each country and for subgroups defined by sex, age (0·05) except for three models. However, two models overestimated risk, DPoRT by 34% (95% CI 29-39%) and Cambridge by 40% (28-52%). Discrimination was always better in individuals younger than 60 years or with a low waist circumference than in those aged at least 60 years or with a large waist circumference. Patterns were inconsistent for BMI. All models overestimated risks for individuals with a BMI of <25 kg/m 2 . Calibration patterns were inconsistent for age and waist-circumference subgroups. Interpretation: Existing diabetes prediction models can be used to identify individuals at high risk of type 2 diabetes in the general population. However, the performance of each model varies with country, age, sex, and adiposity. Funding: The European Union.

BACKGROUND: The comparative performance of existing models for prediction of type 2 diabetes across populations has not been investigated. We validated existing non-laboratory-based models and assessed variability in predictive performance in European populations. METHODS: We selected non-invasive prediction models for incident diabetes developed in populations of European ancestry and validated them using data from the EPIC-InterAct case-cohort sample (27,779 individuals from eight European countries, of whom 12,403 had incident diabetes). We assessed model discrimination and calibration for the first 10 years of follow-up. The models were first adjusted to the country-specific diabetes incidence. We did the main analyses for each country and for subgroups defined by sex, age (0·05) except for three models. However, two models overestimated risk, DPoRT by 34% (95% CI 29-39%) and Cambridge by 40% (28-52%). Discrimination was always better in individuals younger than 60 years or with a low waist circumference than in those aged at least 60 years or with a large waist circumference. Patterns were inconsistent for BMI. All models overestimated risks for individuals with a BMI of <25 kg/m(2). Calibration patterns were inconsistent for age and waist-circumference subgroups. INTERPRETATION: Existing diabetes prediction models can be used to identify individuals at high risk of type 2 diabetes in the general population. However, the performance of each model varies with country, age, sex, and adiposity. FUNDING: The European Union.

Background: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. Methods: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies. Findings: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10–1·17), coronary disease excluding myocardial infarction (1·06, 1·00–1·11), heart failure (1·09, 1·03–1·15), fatal hypertensive disease (1·24, 1·15–1·33); and fatal aortic aneurysm (1·15, 1·03–1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91–0·97). In comparison to those who reported drinking >0–≤100 g per week, those who reported drinking >100–≤200 g per week, >200–≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1–2 years, or 4–5 years, respectively. Interpretation: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. Funding: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.

BACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. METHODS: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th-95th percentile 1·04-13·5]) from 71 011 participants from 37 studies. FINDINGS: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10-1·17), coronary disease excluding myocardial infarction (1·06, 1·00-1·11), heart failure (1·09, 1·03-1·15), fatal hypertensive disease (1·24, 1·15-1·33); and fatal aortic aneurysm (1·15, 1·03-1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91-0·97). In comparison to those who reported drinking >0-≤100 g per week, those who reported drinking >100-≤200 g per week, >200-≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively. INTERPRETATION: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. FUNDING: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.