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This report from the European Society of Cardiology (ESC) Atlas Project updates and expands upon the 2021 report in presenting cardiovascular disease (CVD) statistics for the ESC member countries. This paper examines inequalities in cardiovascular healthcare and outcomes in ESC member countries utilizing mortality and risk factor data from the World Health Organization and the Global Burden of Disease study with additional economic data from the World Bank. Cardiovascular healthcare data were collected by questionnaire circulated to the national cardiac societies of ESC member countries. Statistics pertaining to 2022, or latest available year, are presented. New material in this report includes contemporary estimates of the economic burden of CVD and mortality statistics for a range of CVD phenotypes. CVD accounts for 11% of the EU's total healthcare expenditure. It remains the most common cause of death in ESC member countries with over 3 million deaths per year. Proportionately more deaths from CVD occur in middle-income compared with high-income countries in both females (53% vs. 34%) and males (46% vs. 30%). Between 1990 and 2021, median age-standardized mortality rates (ASMRs) for CVD decreased by median >50% in high-income ESC member countries but in middle-income countries the median decrease was <12%. These inequalities between middle- and high-income ESC member countries likely reflect heterogeneous exposures to a range of environmental, socioeconomic, and clinical risk factors. The 2023 survey suggests that treatment factors may also contribute with middle-income countries reporting lower rates per million of percutaneous coronary intervention (1355 vs. 2330), transcatheter aortic valve implantation (4.0 vs. 153.4) and pacemaker implantation (147.0 vs. 831.9) compared with high-income countries. The ESC Atlas 2023 report shows continuing inequalities in the epidemiology and management of CVD between middle-income and high-income ESC member countries. These inequalities are exemplified by the changes in CVD ASMRs during the last 30 years. In the high-income ESC member countries, ASMRs have been in steep decline during this period but in the middle-income countries declines have been very small. There is now an important need for targeted action to reduce the burden of CVD, particularly in those countries where the burden is greatest., (© European Society of Cardiology 2024.)

This Review provides an epidemiological overview of global mortality from acute coronary syndromes (ACS). Across the regions of the world where data are available, mortality from ACS - including premature (age <70 years) mortality from ACS - was higher in men than in women. In both sexes, age-standardized mortality rates (ASMRs) for ACS in 2020 were highest in lower-income global regions. However, 20 years earlier, ASMRs for ACS were highest in higher-income global regions, including Europe, Northern America and Oceania. These higher-income regions have seen progressive reductions in mortality from ACS during the past 20 years, which is in contrast to the more stable levels of mortality from ACS in Asia and in Latin America and the Caribbean. In the seven African countries with data available, a small upwards trend in ASMRs for ACS was observed, reflecting an epidemiological transition that is already well advanced in these regions. Consistent with these changes during the past 20 years were >50% reductions in ASMRs for ACS in the high-income countries of the world compared with <15% reductions in lower-middle-income countries. Policymakers need more complete epidemiological data across and within global regions to identify those countries in which the burden of death from ACS is greatest and the need to implement preventive strategies is most pressing., (© 2023. Springer Nature Limited.)

Variations in cardiovascular disease (CVD) burden between West and South European countries are rarely reported. To address this knowledge gap, The Lancet Regional Health-Europe convened experts from a broad range of countries to assess the current state of knowledge of cardiovascular disease inequalities across Europe. This Review is specifically focused on West and South European countries. Mortality, risk factor and economic data for nine West European and six South European countries were sourced from the World Health Organisation, the Global Burden of Disease study and the World Bank. Healthcare data were collected by survey of participating countries. A key finding was of declines in age-standardised mortality rates (ASMRs) across all countries since 1990. In 2019 rates per 100,000 were lower in West European countries in males (279.7 (264.1-335.9) vs 337.2 (323.7-367.2)) and females (196.2 (183.3-228.8) vs 247.3 (232.2-268.3)). Differences in risk factor exposures were small, with the exception of physical activity and dietary factors, but across all countries the prevalence of obesity has increased, affecting >20% of adults in 2019. Healthcare delivery in 2019 showed inequalities with cardiovascular procedure rates lower in South compared with West European countries. Further declines in ASMRs in West and South European countries will require population strategies to reduce obesity and address inequalities in physical activity and dietary factors. Reducing the gap in procedure rates is unlikely to match the beneficial effects of population strategies for reducing CVD burden in South European countries., Competing Interests: Timmis owns stock in HD Clinical (Electronic health record systems) and RE-COGNITION Health (Dementia care). Torbica has a consulting contract with the European Society of Cardiology. Aboyans has an unpaid leadership role in the European Heart Health Institute and has received consulting fees from Bayer, Amarin, Boehringer-Ingelheim and NovoNordisk. Vardas has received consulting fees from Hygeia Hospital Group., (© 2023 The Author(s).)

Aims: This report from the European Society of Cardiology (ESC) Atlas Project updates and expands upon the widely cited 2019 report in presenting cardiovascular disease (CVD) statistics for the 57 ESC member countries., Methods and Results: Statistics pertaining to 2019, or the latest available year, are presented. Data sources include the World Health Organization, the Institute for Health Metrics and Evaluation, the World Bank, and novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery. New material in this report includes sociodemographic and environmental determinants of CVD, rheumatic heart disease, out-of-hospital cardiac arrest, leftsided valvular heart disease, the advocacy potential of these CVD statistics, and progress towards World Health Organization (WHO) 2025 targets for non-communicable diseases. Salient observations in this report: (i) Females born in ESC member countries in 2018 are expected to live 80.8 years and males 74.8 years. Life expectancy is longer in high income (81.6 years) compared with middle-income (74.2 years) countries. (ii) In 2018, high-income countries spent, on average, four times more on healthcare than middle-income countries. (iii) The median PM2.5 concentrations in 2019 were over twice as high in middle-income ESC member countries compared with high-income countries and exceeded the EU air quality standard in 14 countries, all middle-income. (iv) In 2016, more than one in five adults across the ESC member countries were obese with similar prevalence in high and low-income countries. The prevalence of obesity has more than doubled over the past 35 years. (v) The burden of CVD falls hardest on middle-income ESC member countries where estimated incidence rates are ∼30% higher compared with high-income countries. This is reflected in disability-adjusted life years due to CVD which are nearly four times as high in middle-income compared with high-income countries. (vi) The incidence of calcific aortic valve disease has increased seven-fold during the last 30 years, with age-standardized rates four times as high in high-income compared with middle-income countries. (vii) Although the total number of CVD deaths across all countries far exceeds the number of cancer deaths for both sexes, there are 15 ESC member countries in which cancer accounts for more deaths than CVD in males and five-member countries in which cancer accounts for more deaths than CVD in females. (viii) The under-resourced status of middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, ablation procedures, device implantation, and cardiac surgical procedures., Conclusion: Risk factors and unhealthy behaviours are potentially reversible, and this provides a huge opportunity to address the health inequalities across ESC member countries that are highlighted in this report. It seems clear, however, that efforts to seize this opportunity are falling short and present evidence suggests that most of the WHO NCD targets for 2025 are unlikely to be met across ESC member countries., (© The European Society of Cardiology 2022.)

This Review presents data describing the health burden of cardiovascular disease (CVD) within and across the WHO European Region. CVD remains the most common cause of death in the region. Deaths from CVD in those aged <70 years, commonly referred to as premature, are a particular concern, with >60 million potential years of life lost to CVD in Europe annually. Although more women than men die from CVD, age-standardized rates of both morbidity and death are higher in men, and these differences in rates are greatest in individuals aged <70 years. Large inequalities in all measures of morbidity, treatment and mortality can be found between countries across the continent and must be a focus for improving health. Large differences also exist in the data available between countries. The development and implementation of evidence-based preventive and treatment approaches must be supported in all countries by consistent surveillance and monitoring, such that we can quantify the health burden of CVD as well as target interventions and provide impetus for action across Europe., (© 2021. Springer Nature Limited.)

Aims: The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) developed the HFA Atlas to provide a contemporary description of heart failure (HF) epidemiology, resources, reimbursement of guideline-directed medical therapy (GDMT) and activities of the National Heart Failure Societies (NHFS) in ESC member countries., Methods and Results: The HFA Atlas survey was conducted in 2018-2019 in 42 ESC countries. The quality and completeness of source data varied across countries. The median incidence of HF was 3.20 [interquartile range (IQR) 2.66-4.17] cases per 1000 person-years, ranging from ≤2 in Italy and Denmark to >6 in Germany. The median HF prevalence was 17.20 (IQR 14.30-21) cases per 1000 people, ranging from ≤12 in Greece and Spain to >30 in Lithuania and Germany. The median number of HF hospitalizations was 2671 (IQR 1771-4317) per million people annually, ranging from <1000 in Latvia and North Macedonia to >6000 in Romania, Germany and Norway. The median length of hospital stay for an admission with HF was 8.50 (IQR 7.38-10) days. Diagnostic and management resources for HF varied, with high-income ESC member countries having substantially more resources compared with middle-income countries. The median number of hospitals with dedicated HF centres was 1.16 (IQR 0.51-2.97) per million people, ranging from <0.10 in Russian Federation and Ukraine to >7 in Norway and Italy. Nearly all countries reported full or partial reimbursement of standard GDMT, except ivabradine and sacubitril/valsartan. Almost all countries reported having NHFS or working groups and nearly half had HF patient organizations., Conclusions: The first report from the HFA Atlas has shown considerable heterogeneity in HF disease burden, the resources available for its management and data quality across ESC member countries. The findings emphasize the need for a systematic approach to the capture of HF statistics so that inequalities and improvements in care may be quantified and addressed., (© 2021 European Society of Cardiology.)

Aims: The European Association of Percutaneous Cardiovascular Interventions (EAPCI) Atlas of Interventional Cardiology has been developed to map interventional practice across European Society of Cardiology (ESC) member countries. Here we present the main findings of a 16-country survey in which we examine the national availability of interventional infrastructure, human resource, and procedure volumes., Methods and Results: Sixteen ESC member countries participated in the EAPCI Atlas survey. Interventional data were collected by the National Cardiac Society of each participating country. An annual median of 5131 [interquartile range (IQR) 4013-5801] diagnostic heart procedures per million people were reported, ranging from <2500 in Egypt and Romania to >7000 in Turkey and Germany. Procedure rates showed significant correlation (r = 0.67, P = 0.013) with gross national income (GNI) per capita. An annual median of 2478 (IQR 1690-2633) percutaneous coronary interventions (PCIs) per million people were reported, ranging from <1000 in Egypt and Romania to >3000 in Switzerland, Poland, and Germany. Procedure rates showed significant correlation with GNI per capita (r = 0.62, P = 0.014). An annual median of 48.2 (IQR 29.1-105.2) transcatheter aortic valve implantation procedures per million people were performed, varying from <25 per million people in Egypt, Romania, Turkey, and Poland to >100 per million people in Denmark, France, Switzerland, and Germany. Procedure rates showed significant correlation with national GNI per capita (r = 0.92, P < 0.001)., Conclusion: The first report from the EAPCI Atlas has shown considerable international heterogeneity in interventional cardiology procedure volumes. The heterogeneity showed association with national economic resource, a reflection no doubt of the technological costs of developing an interventional cardiology service., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Experimental designs such as matched-pair or longitudinal studies yield mRNA sequencing (mRNA-Seq) counts that are correlated across samples. Most of the approaches for the analysis of correlated mRNA-Seq data are restricted to a specific design and/or balanced data only (with the same number of samples in each group). We propose a model that is applicable to the analysis of correlated mRNA-Seq data of different types: paired, clustered, longitudinal, or others. Any combination of explanatory variables, as well as unbalanced data, can be processed within the proposed modeling framework. The model assumes that exon counts of a particular gene of an individual sample jointly follow a multivariate negative-binomial distribution. Additional correlation between exon counts obtained for, for example, individual samples within the same pair or cluster, is taken into account by including into the model a cluster-level normally distributed random effect. An interesting feature of the model is that it provides explicit expression for marginal correlation between exon counts at different levels. The performance of the model is evaluated by using a simulation study and an analysis of two real-life data sets: a paired mRNA-Seq experiment for 24 patients with clear-cell renal-cell carcinoma and a longitudinal mRNA-Seq experiment for 29 patients with Lyme disease.

Objective: Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate comprehensive models of complex cells., Methods: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in the Systems Biology Markup Language., Results: Our analysis revealed several challenges to representing WC models using the current standards., Conclusion: We, therefore, propose several new WC modeling standards, software, and databases., Significance: We anticipate that these new standards and software will enable more comprehensive models.

Bacteria are increasingly resistant to existing antibiotics, which target a narrow range of pathways. New methods are needed to identify targets, including repositioning targets among distantly related species. We developed a novel combination of systems and structural modeling and bioinformatics to reposition known antibiotics and targets to new species. We applied this approach to Mycoplasma genitalium, a common cause of urethritis. First, we used quantitative metabolic modeling to identify enzymes whose expression affects the cellular growth rate. Second, we searched the literature for inhibitors of homologs of the most fragile enzymes. Next, we used sequence alignment to assess that the binding site is shared by M. genitalium, but not by humans. Lastly, we used molecular docking to verify that the reported inhibitors preferentially interact with M. genitalium proteins over their human homologs. Thymidylate kinase was the top predicted target and piperidinylthymines were the top compounds. Further work is needed to experimentally validate piperidinylthymines. In summary, combined systems and structural modeling is a powerful tool for drug repositioning., (Copyright © 2015 Elsevier Ltd. All rights reserved.)