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The prevalence of cardiovascular diseases (CVDs) is well known. According to the World Health Organization (WHO), almost 18 million people die from CVDs worldwide every year, accounting for 31% of all causes of death [1]. CVDs often develop concomitantly with diabetes mellitus (DM), with approximately 20% of cardiovascular deaths attributed to elevated blood glucose levels [2]. Notably, CVDs are the leading cause of death among patients with type 2 diabetes (T2DM). Based on data from the Federal Register of Diabetes 2022 in Russia, chronic heart failure was the direct cause of death in 24.2% of T2DM cases, followed by acute heart failure (13.1%), cerebrovascular events (10.0%), and myocardial infarction (3.7%) [3].The pathophysiological interplay between atherosclerotic cardiovascular disease and DM has led to a situation where cardiologists are increasingly involved in the treatment of patients with DM, while endocrinologists are encountering a growing number of patients with CVDs. This association has become so apparent that in a recent article published in the European Journal of Cardiology, Yu. Braunwald speculated about the emergence of a new subspecialty - diabetocardiology [4]. Unfortunately, experts predict that the global number of diabetic patients will reach 783 million [5].Recent data on the CV benefits of certain hypoglycemic drugs (primarily, certain SGLT2 inhibitors, several GLP-1 receptor agonists, and a novel non-steroidal mineralocorticoid receptor antagonist finerenone) prove the need for a unified interdisciplinary approach to managing CVDs and DM.Given the importance of integrated and coordinated efforts in managing patients with CVD and DM, the Task Force of the -European Society of Cardiology (ESC) updated, formulated, and published clinical guidelines on the treatment of CVD in diabetic patients in 2023 [6]. This article provides a concise overview of the key provisions outlined in the guidelines.

Cardiovascular (CV) diseases account for over 4 million deaths every year in Europe and over 220 000 deaths in Italy, representing the leading cause of morbidity and mortality worldwide. The European Society of Cardiology (ESC) guidelines have visionary included in the at very high CV risk group patients without previous acute ischemic events, such as those with subclinical atherosclerosis, chronic coronary syndrome or peripheral arterial disease, familial hypercholesterolemia, diabetes mellitus with target organ damage or multiple associated risk factors, and those with high calculated CV risk score, recommending to consider them and to achieve the same LDL-cholesterol targets as for secondary prevention patients. The aim of this position paper is to provide an updated overview of ESC guidelines that focuses on these patient categories to raise awareness within the clinical community regarding CV risk reduction in this specific epidemiological context.

Background: Prospective observational data revealed lower cardiovascular disease (CVD) incidence with modeled replacement of saturated fatty acids (SFA) from total meat by total dairy, but it is unknown what the associations are of replacing SFA from types of meat by types of dairy with CVD incidence., Objectives: This study aimed to investigate the associations of replacing SFA from total, red, processed, and poultry meat by SFA from total dairy, milk, cheese, and yogurt with the incidence of CVD., Methods: We analyzed longitudinal data from 21,841 participants of the European Prospective Investigation into Cancer and Nutrition-Norfolk study (56.4% female; age, 40-79 years). Dietary data were collected by food frequency questionnaires at baseline (1993-1997). Incident fatal or nonfatal CVD (n = 5902), coronary artery disease (CAD; n = 4215), stroke (total: n = 2544; ischemic: n = 1113; hemorrhagic: n = 449) were identified up to 2018. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression for the risk associated with replacement of 2.5% of energy from SFA from meat by dairy, adjusted for sociodemographic, lifestyle, energy, dietary, and cardiometabolic factors., Results: Replacing SFA from total meat by total dairy was associated with a lower CVD incidence (HR: 0.89; 95% CI: 0.82, 0.96) and CAD (HR: 0.88; 95% CI: 0.80, 0.96). Replacing SFA from processed meat by cheese was associated with lower CVD (HR: 0.77; 95% CI: 0.68, 0.88); CAD (HR: 0.77; 95% CI: 0.66, 0.90), and stroke (HR: 0.81; 95% CI: 0.67, 0.99). Similarly, replacing SFA from red meat by cheese was associated with lower CVD (HR: 0.86; 95% CI: 0.76, 0.97). Higher incidence of stroke was found with replacement of SFA from poultry by milk (HR: 2.06; 95% CI: 1.09, 3.89), yogurt (HR: 2.55; 95% CI: 1.27, 5.13), or cheese (HR: 1.96; 95% CI: 1.04, 3.70), but the CI were relatively large, owing to low, narrow range of poultry SFA intake., Conclusions: Findings indicate that different SFA-rich foods at baseline have differential associations with CVD risk. If confirmed by further studies, these findings could be used to inform specific food-based dietary guidance., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict of interest: M.W. has done consultancy work for Amgen and Freeline in the last 3 years. V.S. has had research collaboration with Bayer Ltd (unrelated to the present study). All other authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe., Methods and Results: SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively., Conclusion: SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe., Competing Interests: Conflict of interest A.W. reports institutional grants from an Alan Turing Institute, British Heart Foundation, NIHR, and Innovative Medicines Initiative. A.T. reports receiving payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events made to him from European Heart Journal: Quality of Care and Clinical Outcomes for being an Editor, reports leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for being a member of Trial Steering Committees for SCOT HEART 2 and DUAL ACS 2, and reports owning two shares in two start-up companies called HD Clinical and RE-COGNITION Health Ltd. B.A.F. reports grants or contracts from Novartis, Amgen, Pfizer and Esperion, consulting fees from Novartis, Amgen, Regeneron, Eli Lilly, Sanofi, Merck, AstraZeneca, Pfizer, Viatris, Novo Nordisk, New Amsterdam, Mylan, Daiichi Sankyo, Ionis Pharmaceuticals, dalCOR, CiVi Pharmaceuticals, KrKa Pharmaceuticals, American College of Cardiology, European Atherosclerosis Society and European Society of Cardiology, payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, Amgen, Regeneron, Eli Lilly, Sanofi, Merck, AstraZeneca, Pfizer, Viatris, Novo, Nordisk, New Amsterdam, Mylan, Daiichi Sankyo, Ionis Pharmaceuticals and dalCOR, patents planned, issued or pending from Novartis, Amgen, Regeneron, Sanofi, Merck, AstraZeneca, Novo Nordisk and New Amsterdam, and participation on a Data Safety Monitoring Board or Advisory Board for Novartis, Amgen, Regeneron, Sanofi, Merck, AstraZeneca, Novo Nordisk and New Amsterdam. B.E. reports institutional unrestricted research support to institution from Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, consulting fees from Novo Nordisk, Sanofi, Eli Lilly, Boehringer Ingelheim, Mundipharma, AMGEN, AstraZeneca and MSD, and payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novo Nordisk, Sanofi, Eli Lilly, Boehringer Ingelheim, Mundipharma, AstraZeneca and MSD. C.P. reports grants or contracts from MRC DTP PhD Studentship. C.SN. reports support for present manuscript from German Federal Ministry of Health through providing funding to conduct national health surveys BGS98 and DEGS1, and grants or contracts from Federal Ministry of Health (Germany). D.M. reports consulting fees from Ferrer, Merch, Sharp & Dohme, Novo Nordisk and Sanofi, and receiving payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Almirall, Amgen, Esteve, Ferrer, Jansen, Lilly, Merch, Sharp & Dohme, Novo Nordisk and Sanofi. D.V. reports receiving grants or contracts from Bayer, Sanofi, Aventis, Novo Nordisk and Boehringer Ingelheim, participation on a Data Safety Monitoring Board or Advisory Board for FENO, leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for European Diabetes Epidemiology Group as a Chair of the Steering Committee, and reports owning stock or stock options at Novo Nordisk. E.D.A. reports support from British Heart Foundation and NIHR Senior Investigator Award, and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Our Future Health, EURAC. F.B. received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer, and support for attending meetings and/or travel from Bayer and Novo Nordisk. J.D. reports support from British Heart Foundation Professorship and NIHR Senior Investigator Award, grants, personal fees and non-financial support from Merck Sharp & Dohme, Novartis, Pfizer, and AstraZeneca outside the submitted work, royalties or licences from Wellcome Trust Sanger Institute, leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Cambridge University Hospital NHS Foundation Trust, UK Biobank, MRC International Advisory Group, MRC High Throughput Science ‘Omics Panel, Scientific Advisory Committee for Sanofi, Wellcome Sanger Institute, Novartis, and Nightingale Health. J.FN. reports consulting fees from Novo Nordisk and Boehringuer Ingelheim and unpaid leadership or fiduciary role in other board, society, committee or advocacy group from Fundación redGDPS. L.Po. reports receiving payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Sanofi, Lilly, Boehringer Ingelheim, AstraZeneca and Novo Nordisk, and participation on a Data Safety Monitoring Board or Advisory Board for Novo Nordisk. M.H. reports consulting fees from Medical Park Cardiac Rehab Group and Abbott, payment or honoraria for lectures, presentations, speakers bureaus, manuscript from BMS, Amgen, Daichii-Sankyo, and Medi, leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from European Association of Preventive Cardiology. N.H. reports support for present manuscript from NHS England. N.S. reports grants paid to institution from AstraZeneca, Boehringer Ingelheim, Novartis and Roche Diagnostics, consulting fees from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Merck, Shatp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics and Sanofi, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen and Novo Nordisk. O.T. reports receiving grants or contracts paid to institution and to himself from British Heart Foundation Centre of Research Excellence PhD Stipend RHAG/372. P.R. reports grants or contracts from AstraZeneca, Novo Nordisk and Bayer AG, consulting fees from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Sanofi, Aventis and Gilead. P.V. reports consulting fees from Hygeia Hospitals Group and European Society of Cardiology. T.P. reports grants or contracts from Sanofi, and payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Sanofi and Salveo. R.G. reports payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events made to him from Annals of Epidemiology due to being an Associate Editor. S.Ka. reports support for present manuscript from British Heart Foundation, UK Medical Research Council and National Institute for Health and Care Research. S.Ki. reports receiving grants or contract from VASCage (Research Centre on Vascular Ageing and Stroke, project number 868624) of the Austrian Research Promotion Agency FFG (COMET program–Competence Centers for Excellent Technologies) funded by the Federal Ministry for Climate Protection, Environment, Energy, Transport, Innovation and Technology; the Federal Ministry for Labour and Economy; and the federal states Tyrol (via Standortagentur), Salzburg, and Vienna (via Vienna Business Agency). W.H. reports support for present manuscript from Medical Research Council UK and Kidney Research UK, grants or contracts from Boehringer Ingelheim and Eli Lilly, and participation on a Data Safety Monitoring Board or Advisory Board for Bayer. Z.X. reports grants or contracts from China Scholarship Council., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The 'polypill' stands for fixed-dosed combination pills with generic drugs that act on multiple cardiovascular risk factors. Data from randomized controlled trials show consistent beneficial effects of treatment with a polypill on both cardiovascular risk factors and relevant marjor cardiovascular endpoints. However, polypills are not readily available worldwide and only a limited number of polypills is marketed in Europe. Physicians have to embrace polypills in regular care to let the patient benefit from the advantages of the polypill. Licensing more polypills is an essential step to implement these pills in clinical care. Regulatory agencies need to reduce the dossier content requirements for registrations of new fixed-dosed combination pills so generic pharmaceutical companies can expand the number of marketed polypills.

The purpose of this study is to understand the conflicting results from previous studies on the association between carbohydrate intake and cardiovascular disease (CVD) by conducting a systematic review and meta-analysis to summarize the most recent scientific evidence. A systematic review used three electronic databases to gather literature on the association between carbohydrate intake and CVD. Considering the discrepancies, either fixed or random effect models were chosen to determine the effect size, and sensitivity analysis results, as well as publication bias, were also presented. The meta-analysis found that individuals with the highest carbohydrate intake had a 1.15-fold increased risk of CVD compared to those with the lowest intake (hazard ratio, HR: 1.15, 95% confidence interval, CI: 1.07-1.23). Further subgroup analysis revealed that this association was only present in Asia, with a 1.52-fold increased risk (HR: 1.52, 95% CI: 1.17-1.97), while no associations were seen in the Americas, Europe, and Oceania. The relationship between carbohydrate intake and CVD was non-linear, with a marked escalation beyond 60% of total energy from carbohydrates. Our findings suggest that a high-carbohydrate diet may raise the risk of CVD, particularly in Asian populations. This association may be due to the higher carbohydrate consumption and genetic variations found in Asia.

Background: Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies., Methods: The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014-2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined., Findings: Among 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions., Interpretation: Results from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors., Competing Interests: Declaration of Competing Interest Avraham Karasik has received research grants and consulting fees from Boehringer Ingelheim; research grants from Astra Zeneca; research grants, consulting fees, and speaker fees from Novo Nordisk. Daisuke Yabe has received consulting/lecture fees from Eli Lilly Japan K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Company Limited, and grants from Arkray Inc., Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim, Ono Pharmaceutical Co. Ltd., Taisho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, and Terumo Corporation. Dae Jung Kim has received grants support from Boehringer Ingelheim, AstraZeneca, Sanofi-Aventis Korea, Jeil Pharmaceutical, and Chong Kun Dang, speaker fees from Boehringer-Ingelheim, Novo Nordisk, Boryung, Hanmi, Novartis, Donga ST, Celltrion, AstraZeneca, and Dong Wha Pharmaceuticals. Wayne HH Sheu has been an advisor and/or speaker for AstraZeneca, Bayer HealthCare, Boehringer Ingelheim Pharmaceuticals, Daiichi-Sankyo, Eli Lilly and Company, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals, Novo Nordisk, Pfizer, Sanofi-Aventis, Takeda Pharmaceutical Company. Kamlesh Khunti has acted as a consultant, speaker or received consultation/lecture grants for investigator-initiated studies for Astra Zeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer. Francesco Zaccardi has received speaker fees from Boehringer Ingelheim and Napp Pharmaceuticals. Thomas Nyström has received unrestricted grants from AstraZeneca and NovoNordisk and has been a national advisor of Abbot, Amgen, Novo Nordisk, Sanofi-Aventis, Eli Lilly, MSD, and Boehringer Ingelheim. Leo Niskanen has received speaker and consulting fees from Boehringer Ingelheim, MSD, AstraZeneca, and Sanofi, research grant to the institution, consulting fees, and speaker fees from Novo Nordisk. Majken Linnemann Jensen, Fabian Hoti, Riho Klement are employees of IQVIA and contracted by Boehringer Ingelheim to conduct the analyses. Soulmaz Fazeli Farsani, Anouk Déruaz-Luyet are employees of Boehringer Ingelheim International GmbH. Moe H Kyaw was employee of Boehringer Ingelheim. Lisette Koeneman is employee of Eli Lilly & Company and owns stock of Eli Lilly & Company. Dorte Vistisen has received research grants from Bayer A/S, Sanofi, Novo Nordisk A/S, and Boehringer Ingelheim. She holds shares in Novo Nordisk A/S. Sigrun Halvorsen has received speaker fees from Sanofi, Novartis, Boehringer Ingelheim, Bayer, Pfizer, and Bristol-Myers Squibb. Gisle Langslet has received consulting/lecture fees from Amgen, Sanofi, and Boehringer Ingelheim. Elisabetta Patorno has received a research grant from Boehringer Ingelheim. Julio Núñez reports personal fees from AstraZeneca, Novartis, Boehringer-Ingelheim, Eli Lilly, Rovi, Novo Nordisk, and Vifor Pharma (outside the submitted work). Stefanie Lanzinger, Reinhard W Holl, Elise Chia-Hui Tan, Cheli Melzer-Cohen, Kyong Hwa, Bendix Carstensen: None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Type 2 diabetes and its complications represent a huge burden to public health. With this prospective, observational cohort study, we aimed to estimate and to compare the incidence rate (IR) of renal and cardiovascular outcomes and all-cause mortality in patients with type 2 diabetes in different European countries., Methods: The renal endpoint was a composite of a sustained decline in estimated GFR of at least 40%, a sustained increase in albuminuria of at least 30% including a transition in albuminuria class, progression to kidney failure with replacement therapy, or death from renal causes. The cardiovascular endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke., Results: 3,131 participants from four European countries (Austria, Hungary, The Netherlands, and Scotland) with a median follow-up time of 4.4 years were included. IRs were adjusted for several risk factors including sex, age, estimated GFR, albuminuria, HbA1c, blood pressure, and duration of type 2 diabetes. Across countries, the adjusted IR for the renal endpoint was significantly higher in Hungary and Austria, and the adjusted IR for the cardiovascular endpoint was significantly higher in Scotland and Austria. All-cause mortality was significantly higher in Scotland compared to all other countries., Conclusion: Our findings show how the longitudinal outcome of patients with type 2 diabetes varies significantly across European countries even after accounting for the distribution of underlying risk factors., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Purpose: The Research on Obesity and Diabetes among African Migrants (RODAM) prospective (RODAM-Pros) cohort study was established to identify key changes in environmental exposures and epigenetic modifications driving the high burden of cardiovascular disease (CVD) risk among sub-Saharan African migrants., Participants: All the participants in the RODAM cross-sectional study that completed the baseline assessment (n=5114) were eligible for the follow-up of which 2165 participants (n=638 from rural-Ghana, n=608 from urban-Ghana, and n=919 Ghanaian migrants in Amsterdam, the Netherlands) were included in the RODAM-Pros cohort study. Additionally, we included a subsample of European-Dutch (n=2098) to enable a comparison to be made between Ghanaian migrants living in the Netherlands and the European-Dutch host population., Findings to Date: Follow-up data have been collected on demographics, socioeconomic status, medical history, psychosocial environment, lifestyle factors, nutrition, anthropometrics, blood pressure, fasting blood, urine and stool samples. Biochemical analyses included glucose metabolism, lipid profile, electrolytes and renal function, liver metabolism and inflammation. In a subsample, we assessed DNA methylation patterns using Infinium 850K DNA Methylation BeadChip. Baseline results indicated that migrants have higher prevalence of CVD risk factors than non-migrants. Epigenome-wide association studies suggest important differences in DNA methylation between migrants and non-migrants. The follow-up study will shed further light on key-specific environmental exposures and epigenetic modifications contributing to the high burden of CVD risk among sub-Saharan African migrants., Future Plans: Follow-up is planned at 5-year intervals, baseline completed in 2015 and first follow-up completed in 2021., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Non-alcoholic fatty liver disease (NAFLD) is a well-established risk factor for cardiovascular disease, with ethnic and regional differences noted. With the recent surge of research within this field, we re-examine the evidence associating NAFLD with subclinical atherosclerosis, and investigate potential regional differences., Methods: This is a systematic review and meta-analysis. PubMed and EMBASE were systematically searched for publications from January 1967 to July 2020 using standardised criteria. Original, observational studies investigating the association between NAFLD and either carotid intima-media thickness (CIMT) and/or coronary artery calcification (CAC) were included. Key outcomes included differences in mean CIMT, the presence of increased CIMT, the presence of CAC and the development/progression of CAC. Pooled ORs and pooled standard differences in means were calculated using random-effects models. Between-study heterogeneity was quantified using the Q statistic and I². Subgroup analyses stratified by region of study (Asian vs Western) were also conducted., Results: 64 studies involving a total of 172 385 participants (67 404 with NAFLD) were included. 44 studies assessed the effect of NAFLD on CIMT, with the presence of NAFLD associated with increased CIMT (OR 2.00, 95% CI 1.56 to 2.56). 22 studies assessed the effects of NAFLD on CAC score, with the presence of NAFLD associated with the presence of any coronary calcification (OR 1.21, 95% CI 1.12 to 1.32), and the development/progression of CAC (OR 1.26, 95% CI 1.04 to 1.52). When stratified by region, these associations remained consistent across both Asian and Western populations (p>0.05). The majority (n=39) of studies were classified as 'high quality', with the remaining 25 of 'moderate quality'., Conclusions: There is a significant positive association between various measures of subclinical atherosclerosis and NAFLD, seen across both Western and Asian populations. These results re-emphasise the importance of early risk evaluation and prophylactic intervention measures to preclude progression to clinical cardiovascular disease in patients with NAFLD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cardiovascular diseases are the most common causes of hospitalization, death and disability in Europe. Despite our knowledge of nonmodifiable and modifiable cardiovascular classical risk factors, the morbidity and mortality in this group of diseases remains high, leading to high social and economic costs. Therefore, it is necessary to explore new factors, such as the gut microbiome, that may play a role in many crucial pathological processes related to cardiovascular diseases. Diet is a potentially modifiable cardiovascular risk factor. Fats, proteins, carbohydrates, vitamins and minerals are nutrients that are essential to the proper function of the human body. The style and composition of the human diet has changed over time, evolving from a hunter-gatherer diet to an industrialized and Westernized modern diet that includes processed products. The relationship between the gut microbiome, diet and cardiovascular diseases is complex and still not fully understood. In this review, we discuss, in the context of diet, why particular microbes occur in individuals and how they can influence the host's cardiovascular system in health and disease. We investigate the role of particular microorganisms and changes in the Firmicutes/Bacteroidetes ratio.

Purpose: This study was aimed to analyze the mediation role of cardiorespiratory fitness (CRF) on the association between fatness and cardiometabolic risk scores (CMRs) in European adolescents., Methods: A cross-sectional study was conducted in adolescents (n = 525; 46% boys; 14.1 ± 1.1 years old, mean ± SD) from 10 European cities involved in the Healthy Lifestyle in Europe by Nutrition in Adolescence study. CRF was measured by means of the shuttle run test, while fatness measures included body mass index (BMI), waist to height ratio, and fat mass index estimated from skinfold thicknesses. A clustered CMRs was computed by summing the standardized values of homeostasis model assessment, systolic blood pressure, triglycerides, total cholesterol/high-density lipoprotein cholesterol ratio, and leptin., Results: Linear regression models indicated that CRF acted as an important and partial mediator in the association between fatness and CMRs in 12-17-year-old adolescents (for BMI: coefficients of the indirect role β = 0.058 (95% confidence interval (95%CI): 0.023-0.101), Sobel test z = 3.11 (10.0% mediation); for waist to height ratio: β = 4.279 (95%CI: 2.242-7.059), z =3.86 (11.5% mediation); and for fat mass index: β = 0.060 (95%CI: 0.020-0.106), z = 2.85 (9.4% mediation); all p < 0.01)., Conclusion: In adolescents, the association between fatness and CMRs could be partially decreased with improvements to fitness levels; therefore, CRF contribution both in the clinical field and public health could be important to consider and promote in adolescents independently of their fatness levels., (Copyright © 2019. Production and hosting by Elsevier B.V.)

Introduction : The European Society of Cardiology and European Atherosclerosis Society (ESC/EAS) have recently published three major revisions of their guidelines for the management of chronic heart disease, blood lipids, and diabetes. Areas covered : We have scrutinized these guidelines in detail and found that the authors have ignored many studies that are in conflict with their conclusions and recommendations. Expert commentary : The authors of the guidelines have ignored that LDL-cholesterol (LDL-C) of patients with acute myocardial infarction is lower than normal; that high cholesterol is not a risk factor for diabetics; that the degree of coronary artery calcification is not associated with LDL-C; and that 27 follow-up studies have shown that people with high total cholesterol or LDL-C live just as long or longer than people with low cholesterol. They have also ignored the lack of exposure-response in the statin trials; that several of these trials have been unable to lower CVD or total mortality; that no statin trial has succeeded with lowering mortality in women, elderly people, or diabetics; and that cholesterol-lowering with statins has been associated with many serious side effects.

Objectives: Endothelial dysfunction contributes to the onset and progression of cardiovascular diseases. However, direct associations of vasoactive mediators with cardiovascular risk are poorly understood., Methods: We have determined associations of circulating levels of stable metabolites of nitric oxide, nitrate and nitrite (NOx), endothelin-1, and the endothelin-1/NOx ratio with blood pressure in 177 asymptomatic subjects without signs of coronary atherosclerosis; associations with blood pressure and with presence of coronary lesions were also evaluated in 457 patients suspected to have coronary heart disease with or without coronary lesions confirmed by coronary angiography. All participants were on a low nitrate diet 24 h prior to blood sampling., Results: In men, NOx levels were inversely correlated with blood pressure similar to women with low (0-4%) European Systematic Coronary Risk Estimation (SCORE). However, the correlation was not significant in women with high SCORE (5-8%). High systolic blood pressure over 140 mm Hg was negatively associated with NOx levels in asymptomatic men (p=0.05) but not in women. This association is disrupted in male and female patients with coronary atherosclerosis. In male patients, NOx (p=0.05), endothelin (p=0.01), and the endothelin/NOx ratio (p=0.04) were associated with presence of coronary lesions., Conclusions: Thus, elevated cardiovascular risk according to SCORE over 4% in asymptomatic women, but not in men, is associated with a shift in markers of endothelial dysfunction. Presence of coronary lesions in patients is associated with significant changes in circulating levels of markers of endothelial dysfunction in men but not in women., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: To examine the association of lipoprotein lipase (LPL) polymorphisms with cardiovascular disease (CVD) risk factors in European adolescents, along with the influence of physical activity on these associations., Methods: A total of 13 LPL polymorphisms were genotyped in 1.057 European adolescents (12-18 years old) from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. Serum lipids, glucose, insulin, and leptin (LEP) levels were measured and a CVD risk score was computed. We also measured body weight and height, waist and hip circumferences, and triceps and subscapular skinfold thickness. Physical activity was objectively measured by accelerometry for 7 days., Results: The rs1534649, rs258, rs320, and rs328 polymorphisms were associated with several CVD risk factors (ie, body mass index, triglycerides [TG], LEP, and cholesterol/high-density lipoprotein [HDL], low-density lipoprotein [LDL]/HDL, TG/HDL ratios). TG and TG/HDL were associated with haplotype blocks 3 (rs282, rs285 polymorphisms) and 4 (rs3126, rs320, rs328, rs10099160 polymorphisms), being the latter also associated with the CVD risk score. Physical activity modulated the association of adiposity with rs1534649 and rs258 polymorphisms., Conclusions: Polymorphisms rs1534649, rs258, rs320 and rs328, and two haplotypes of LPL were significantly associated with CVD risk factors in European adolescents. Higher levels of moderate to vigorous physical activity may attenuate the effects of rs1534649 and rs258 polymorphisms on adiposity., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The 2018 American Heart Association/American College of Cardiology/Multisociety (AHA/ACC) guidelines and the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on lipid management were published less than a year apart. Both guidelines focus on reducing cardiovascular risk, but they follow different approaches in terms of methods of risk estimation, definitions of at-risk groups, and treatment goals to achieve this common underlying objective. Both recommend achieving risk-based percentage reductions of low-density lipoprotein cholesterol (LDL-C) levels with statin therapy. The ESC/EAS guidelines additionally recommend target LDL-C levels and are more liberal in supporting the use of both statin and nonstatin therapies across broader patient groups. The AHA/ACC guidelines may be considered more conservative, reserving the addition of nonstatins to maximally tolerated statins for only select patient groups based on specific LDL-C thresholds. One of the main reasons for these differences is incorporation of cost value considerations by the AHA/ACC guidelines, whereas the ESC/EAS guidelines consider an ideal setting with unlimited resources while making recommendations. In this review, we discuss similarities and differences between the 2 lipid guidelines to help clinicians become more cognizant of these recommendations and provide the best individualized patient care., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Aims: Abuse of crystal methamphetamine (MA) poses a growing problem for health services worldwide. This review summarizes the current literature on the effects of MA on the cardiovascular system., Methods and Results: This article is a presentation of a case report and review of the current literature. In Europe, especially the eastern countries and the eastern states of Germany are affected. MA increases the concentration of catecholamines in the synaptic gap leading to euphoria, alertness, and hunger suppression as well as psychiatric and gastrointestinal complications. MA consumption is associated with hypertension, acute and chronic myocardial toxicity, stroke, coronary artery disease, and sudden cardiac death. Although many aspects of the underlying pathophysiology remain unknown, catecholamine-mediated pathologies appear to play an important role. The duration of MA consumption is the most important determinant for the prognosis., Conclusions: Awareness is needed as cardiac complications are important causes of morbidity and mortality in patients with MA consumption. Drug abstinence is the mainstay of therapy, cardiac and other complications should be treated according to the respective guidelines. Incompliance to therapy and frequent relapses are the main challenges for successful treatment. Further research is required to improve the understanding of this rapidly increasing cardiomyopathy., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Chronotropic insufficiency (CI) is defined as the inability of the heart to increase its rate commensurate with increased demand. Exercise CI is an established predictor of major adverse cardiovascular events in patients with cardiovascular diseases., Aim: The aim of this study was to evaluate how exercise CI phenotypes different levels of cardiovascular risk and how it may better perform in defining cardiovascular risk when analysed in the context of cardiopulmonary exercise test (CPET)-derived measures and standard echocardiography in a healthy population with variable cardiovascular risk profile., Methods: Apparently healthy individuals ( N  = 702, 53.8% females) with at least one major cardiovascular risk factor (MCVRF; hypertension, diabetes, tabagism, dyslipidaemia, body mass index > 25), enrolled in the Euro-EX prevention trial, underwent CPET. CI was defined as the inability to reach 80% of the chronotropic index, that is, the ratio of peak heart rate - rest heart rate/peak heart rate - age predicted maximal heart rate (AMPHR: 220 - age), they were divided into four groups according to the heart rate reserve (<80%>) and respiratory gas exchange ratio (RER; < 1.05>) as a marker of achieved maximal performance. Subjects with a RER < 1.05 ( n  = 103) were excluded and the final population ( n  = 599) was divided into CI group ( n  = 472) and no-CI group ( n  = 177)., Results: Compared with no-CI, CI subjects were more frequently females with a history of hypertension in a high rate. CI subjects also exhibited a significantly lower peak oxygen uptake (VO 2 ) and circulatory power and an echocardiographic pattern indicative of higher left atrial volume index and left ventricular mass index. An inverse stepwise relationship between heart rate reserve and number of MCVRFs was observed (one MCVRF: 0.71 ± 0.23; two MCVRFs: 0.68 ± 0.24, three MCVRFs: 0.64 ± 0.20; four MCVRFs: 0.64 ± 0.23; five MCVRFs: 0.57 ± 18; p  < 0.01). In multivariate analysis the only variable found predicting CI was peak VO 2 ( p  < 0.05; odds ratio 0.91; confidence interval 0.85-0.97)., Conclusions: In a population of apparently healthy subjects, exercise CI is common and phenotypes the progressive level of cardiovascular risk by a tight relationship with MCVRFs. CI patients exhibit some peculiar abnormal exercise gas exchange patterns (lower peak VO 2 and exercise oscillatory ventilation) and echo-derived measures (higher left atrium size and left ventricle mass) that may well anticipate evolution toward heart failure.

Background: The association between anthropometric variables and cardiovascular disease (CVD) risk among Africans is unclear. We examined the discriminative ability of anthropometric variables and estimate cutoffs for predicting CVD risk among Africans., Methods: The Research on Obesity and Diabetes among African Migrants (RODAM) study was a multisite cross-sectional study of Africans in Ghana and Europe. We calculated AHA/ACC Pooled Cohort Equations (PCE) scores for 3661 participants to ascertain CVD risk, and compared a body shape index (ABSI), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), Relative Fat Mass (RFM), and Waist to Height Ratio (WHtR). Logistic regression and receiver operating curve analyses were performed to derive cutoffs for identifying high predicted CVD risk (PCE score ≥7.5%)., Results: Among men, WC (adjusted Odds Ratio (aOR): 2.25, 95% CI; 1:50-3:37) was strongly associated with CVD risk. Among women, WC (aOR: 1.69, 95% CI: 1:33-2:14) also displayed the strongest association with CVD risk in the BMI-adjusted model but WHR displayed the strongest fit. All variables were superior discriminators of high CVD risk in men (c-statistic range: 0.887-0.891) than women (c-statistic range: 0.677-0.707). The optimal WC cutoff for identifying participants at high CVD risk was 89 cm among men and identified the most cases (64%). Among women, the recommended WC cutoff of 94 cm or WHR cutoff of 0.90 identified the most cases (92%)., Conclusions: Anthropometric variables were stronger discriminators of high CVD risk in African men than women. Greater WC was associated with high CVD risk in men while WHR and WC were associated with high CVD risk in women., (Copyright © 2020 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease., Material and Methods: There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations., Results and Conclusions: The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices., Competing Interests: This workshop was funded through an unrestricted grant from DENTAID SA to the European Federation of Periodontology to organize the EFP/EHF Workshop. All individual experts participating in the workshop have declared no conflict of interest with the results of the consensus workshop or the publication., (Copyright: © 2020 The Author(s).)

Objectives: Outdoor air pollution is a serious environmental problem worldwide. Current systematic reviews (SRs) and meta-analyses (MAs) mostly focused on some specific health outcomes or some specific air pollution., Design: This evidence gap map (EGM) is to identify existing gaps from SRs and MAs and report them in broad topic areas., Data Sources: PubMed, Cochrane, Scopus and Web of Science were searched from their inception until June 2018. Citations and reference lists were traced., Eligibility Criteria: SRs and MAs that investigated the impact of outdoor air pollution on human health outcomes were collected. This study excluded original articles and qualitative review articles., Data Extraction and Synthesis: Characteristics of the included SRs and MAs were extracted and summarised. Extracted data included authors, publication year, location of the corresponding author(s), publication journal discipline, study design, study duration, sample size, study region, target population, types of air pollution and health outcomes., Results: Asia and North America published 93% of SRs and MAs included in this EGM. 31% of the SRs and MAs (27/86) included primary studies conducted in 5-10 countries. Their publication trends have increased during the last 10 years. A total of 2864 primary studies was included. The median number of included primary studies was 20 (range, 7-167). Cohort studies, case cross-over studies and time-series studies were the top three most used study designs. The mostly researched population was the group of all ages (46/86, 53%). Cardiovascular diseases, respiratory diseases and health service records were mostly reported. A lack of definite diagnostic criteria, unclear reporting of air pollution exposure and time period of primary studies were the main research gaps., Conclusions: This EGM provided a visual overview of health outcomes affected by outdoor air pollution exposure. Future research should focus on chronic diseases, cancer and mental disorders., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Summary: Several decades of research provides compelling evidence that exposure to air pollution causes various diseases. Time series studies in Europe and the USA examined the short term effects on mortality and found about 1% increase for cardiovascular mortality per 10 μg/m3 increase in daily PM2.5 concentration. A comprehensive analysis of 12 European cohort studies addressing the long term effects found a 13% increased risk of coronary events per 5 μg/m3 increase in estimated annual mean PM2.5. Noise exposure triggers an increase in sympathetic responses (fight-flight reactions) and increased release of corticoids (defeat reactions). In 2018 the World Health Organization has published new Environmental Noise Guidelines reporting an 8% increase in risk of incident ischemic heart disease per 10 dB(A) increase in road traffic noise exposure. Transportation noise and air pollution impact health through different pathways, though they also share many biologic pathways. In a recent cohort study, we did not find indications for synergistic or antagonistic effects from combined exposure to noise and air pollution. A study estimating the Environmental Burden of Disease in Europe concluded that ambient air pollution and transportation noise are the two most relevant environmental stressors for the population living in Europe., Competing Interests: The authors of this article have no conflict of interests to disclose., (Copyright© by Aracne Editrice, Roma, Italy.)

Dysglycaemia (i.e. type 2 diabetes mellitus or impaired glucose tolerance) is not only common in patients with cardiovascular disease but increases the risk for future cardiovascular complications. Hyperglycaemia, the hallmark of diabetes, has since long been considered to be the link between diabetes and cardiovascular disease. Diabetes is, however, a complex, multifactorial disorder to which, for example, insulin resistance, endothelial dysfunction and factors such as increased thrombogenicity, hypertension and dyslipidaemia contribute. Thus, treatment needs to be multifactorial and to take cardiovascular aspects into account. Life-style adjustments are, together with blood pressure, lipid and glucose control, important parts of such management. Recent trial data reveal a beneficial effect on cardiovascular prognosis and mortality of blood glucose lowering agents belonging to the classes: sodium-glucose-transporter 2 inhibitors and glucagon-like peptide 1 agonists. The precise mechanisms by which certain sodium-glucose-transporter 2 inhibitors and glucagon-like peptide receptor agonists lead to these beneficial effects are only partly understood. An important impact of the benefits of sodium-glucose-transporter 2 inhibitors is a reduction in heart failure while glucagon-like peptide receptor agonists may retard the development of atherosclerotic vascular disease or stabilising plaques. Although there has been a considerable improvement in the prognosis for people with atherosclerotic diseases over the last decades there is still a gap between those with dysglycaemia, who are at higher risk, than those without dysglycaemia. This residual risk is reasonably related to two major factors: a demand for improved management and a need for new and improved therapeutic opportunities of type 2 diabetes, both routes to an improved prognosis that are at hands. This review is a comprehensive description of the possibilities to improve the prognosis for patients with dysglycaemia by a multifactorial management according to the most recent European guidelines issued in 2019 by the European Society of Cardiology in collaboration with the European Association for the Study of Diabetes.

At present, both tropospheric ozone (O 3 ) and particulate matters (PM) are among the most threatening air pollutants for human health in cities. The air pollution effects over public health include increased risk of hospital admissions and mortality for respiratory and cardiovascular diseases even when air pollutant concentrations are below European and international standards. The aim of this study was to (i) estimate the burden of mortality and morbidity for cardiovascular and respiratory diseases attributed to PM 2.5 , PM 10 and O 3 in nine selected cities in France, Iran and Italy in 2015 and 2016 and to (ii) compare estimated burdens at current O 3 and PM levels with pre-industrial levels. The selected Mediterranean cities are among the most affected by the air pollution in Europe, in particular by rising O 3 while the selected Iranian cities rank as the most polluted by PM in the world. The software AirQ+ was used to estimate the short-term health effects, in terms of mortality and morbidity by using in situ air quality data, city-specific relative risk values and baseline incidence. Compared to pre-industrial levels, long-term exposures to ambient PM 2.5 , PM 10 and O 3 have substantially contributed to mortality and hospital admissions in selected cities: about 8200 deaths for non-accidental causes, 2400 deaths for cardiovascular diseases, 540 deaths for respiratory diseases, 220 deaths for chronic obstructive pulmonary diseases as well as 18,800 hospital admissions for cardiovascular diseases and 3400 for respiratory diseases were reported in 2015. The study supports the need of city-specific epidemiological data and urgent strategies to mitigate the health burden of air pollution.

Background: The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiorespiratory comorbidity on postoperative complications for patients treated for esophageal or gastroesophageal junction cancer., Patients and Methods: A European multicenter cohort study from five high-volume esophageal cancer centers including patients treated between 2010 and 2017 was conducted. The effect of cardiorespiratory comorbidity and respiratory function upon postoperative outcomes was assessed., Results: In total 1590 patients from five centers were included; 274 (17.2%) had respiratory comorbidity, and 468 (29.4%) had cardiac comorbidity. Respiratory comorbidity was associated with increased risk of overall postoperative complications, anastomotic leak, pulmonary complications, pneumonia, increased Clavien-Dindo score, and critical care and hospital length of stay. After neoadjuvant chemoradiotherapy, respiratory comorbidity was associated with increased risk of anastomotic leak [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.11-3.04], pneumonia (OR 1.65, 95% CI 1.10-2.47), and any pulmonary complication (OR 1.52, 95% CI 1.04-2.22), an effect which was not observed following neoadjuvant chemotherapy or surgery alone. Cardiac comorbidity was associated with increased risk of cardiovascular and pulmonary complications, respiratory failure, and Clavien-Dindo score ≥ IIIa. Among all patients, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio > 70% was associated with reduced risk of overall postoperative complications, cardiovascular complications, atrial fibrillation, pulmonary complications, and pneumonia., Conclusions: The results of this study suggest that cardiorespiratory comorbidity and impaired pulmonary function are associated with increased risk of postoperative complications after esophagectomy performed in high-volume European centers. Given the observed interaction with neoadjuvant approach, these data indicate a potentially modifiable index of perioperative risk.

Background: Psychosocial stress could be an underlying factor for emerging risk of cardiovascular diseases (CVD) in Africans. We assessed the association between psychosocial stress and estimated CVD risk among non-migrant Ghanaians and migrant Ghanaians living in Europe., Methods: Data from the Research on Obesity and Diabetes among African Migrants (RODAM) study, involving 2315 migrant and 1549 non-migrants aged 40-70 years were used for this study. Psychosocial stress included self-reported stress at work and home, recent negative life events and perceived discrimination. CVD risk was estimated using the pooled cohort equations with estimates ≥7.5% over 10 years defining high CVD risk. Adjusted Odds Ratios (AOR) and 95% confidence intervals (95% CI) were calculated by logistic regression with adjustments for socioeconomic status., Results: Prevalence for migrant and non-migrants were; 72.5% and 84.9% for psychosocial stress and 35.9% and 27.4% for high estimated CVD risk. Stress at work and home was not associated with a high estimated CVD risk in either group. Recent negative life events were associated with a high estimated CVD risk in non-migrants only (AOR 1.29, 95%CI 1.02-1.68, p = 0.048). Higher levels of perceived discrimination were associated with a high estimated CVD risk in migrants only (AOR 2.74, 95%CI 1.95-3.86, p < 0.001)., Conclusions: Among migrant populations, higher levels of perceived discrimination were associated with a high estimated CVD risk, and this was also true for recent negative life events among non-migrant populations. Further research is needed to identify context specific mechanisms that underlie associations between psychological characteristics and CVD risk., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Ambient air pollution is a major health risk, leading to respiratory and cardiovascular mortality. A recent Global Exposure Mortality Model, based on an unmatched number of cohort studies in many countries, provides new hazard ratio functions, calling for re-evaluation of the disease burden. Accordingly, we estimated excess cardiovascular mortality attributed to air pollution in Europe., Methods and Results: The new hazard ratio functions have been combined with ambient air pollution exposure data to estimate the impacts in Europe and the 28 countries of the European Union (EU-28). The annual excess mortality rate from ambient air pollution in Europe is 790 000 [95% confidence interval (95% CI) 645 000-934 000], and 659 000 (95% CI 537 000-775 000) in the EU-28. Between 40% and 80% are due to cardiovascular events, which dominate health outcomes. The upper limit includes events attributed to other non-communicable diseases, which are currently not specified. These estimates exceed recent analyses, such as the Global Burden of Disease for 2015, by more than a factor of two. We estimate that air pollution reduces the mean life expectancy in Europe by about 2.2 years with an annual, attributable per capita mortality rate in Europe of 133/100 000 per year., Conclusion: We provide new data based on novel hazard ratio functions suggesting that the health impacts attributable to ambient air pollution in Europe are substantially higher than previously assumed, though subject to considerable uncertainty. Our results imply that replacing fossil fuels by clean, renewable energy sources could substantially reduce the loss of life expectancy from air pollution., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Sub-Saharan African populations are disproportionately affected by cardiovascular disease (CVD). Although diet is an important lifestyle factor associated with CVD, evidence on the relation between dietary patterns (DPs) and CVD risk among sub-Saharan African populations is limited., Objective: We assessed the associations of DPs with estimated 10-y atherosclerotic cardiovascular disease (ASCVD) risk in Ghanaian adults in Ghana and Europe., Methods: Three DPs ('mixed'; 'rice, pasta, meat, and fish'; and 'roots, tubers, and plantain') were derived by principal component analysis (PCA) based on intake frequencies obtained by a self-administered Food Propensity Questionnaire in the multi-center, cross-sectional RODAM (Research on Obesity and Diabetes among African Migrants) study. The 10-y ASCVD risk was estimated using the Pooled Cohort Equations (PCE) for 2976 subjects, aged 40-70 y; a risk score ≥7.5% was defined as 'elevated' ASCVD risk. The associations of DPs with 10-y ASCVD risk were determined using Poisson regression with robust variance., Results: Stronger adherence to a 'mixed' DP was associated with a lower predicted 10-y ASCVD in urban and rural Ghana and a higher 10-y ASCVD in Europe. The observed associations were attenuated after adjustment for possible confounders with the exception of urban Ghana (prevalence ratio [PR] for Quintile 5 compared with 1: 0.70; 95% CI: 0.53, 0.93, P-trend = 0.013). The 'rice, pasta, meat, and fish' DP was inversely associated with 10-y ASCVD across all study sites, with the adjusted effect being significant only in urban Ghana. A 'roots, tubers, and plantain' DP was directly associated with increased 10-y ASCVD risk., Conclusions: Adherence to 'mixed' and 'rice, pasta, meat, and fish' DPs appears to reduce predicted 10-y ASCVD risk in adults in urban Ghana. Further investigations are needed to understand the underlying contextual-level mechanisms that influence dietary habits and to support context-specific dietary recommendations for CVD prevention among sub-Saharan African populations., (Copyright © American Society for Nutrition 2019.)

Background: Ertugliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), approved in the United States and European Union to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). The VERTIS cardiovascular (CV) outcomes trial (NCT01986881) has a primary objective to demonstrate non-inferiority of ertugliflozin versus placebo on major adverse CV events: time to the first event of CV death, nonfatal myocardial infarction, or nonfatal stroke. Secondary objectives are to demonstrate superiority of ertugliflozin versus placebo on time to: 1) the composite outcome of CV death or hospitalization for heart failure (HF); 2) CV death; and 3) the composite outcome of renal death, dialysis/transplant, or doubling of serum creatinine from baseline., Methods: Patients ≥40 years old with T2DM (HbA1c 7.0-10.5%) and established atherosclerotic cardiovascular disease (ASCVD) of the coronary, cerebral, and/or peripheral arterial systems, were randomized 1:1:1 to once daily double-blind placebo, ertugliflozin 5 mg or 15 mg added to existing therapy., Results: 8246 patients were randomized and 8238 received at least 1 dose of investigational product. Mean age was 64.4 years, 11.0% were ≥75 years old, and mean diabetes duration was 12.9 years with screening HbA1c of 8.3%. At entry, coronary artery disease, cerebrovascular disease, and peripheral arterial disease were present in 76.3%, 23.1%, and 18.8% of patients, respectively. HF was present in 23.1%, and Stage 3 kidney disease in 21.6% of patients., Conclusion: The results from the VERTIS-CV trial will define the CV and renal safety and efficacy of ertugliflozin in patients with T2DM and ASCVD., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: To compare the prevalence of cardiovascular diseases and risk factors in Holocaust survivors with that of Jewish immigrants from Europe and America., Design: Population-based, cross-sectional study., Setting: Clalit, a large Israeli healthcare provider., Participants: Holocaust survivors (n=83,971) and a comparison group of Jewish individuals born in North or South America or European countries not under Nazi occupation or who immigrated to Israel before 1939 (n=16,058) (mean age 84±7, 61% female) MEASUREMENTS: Univariate and multivariable logistic regression analyses of cardiovascular diseases and risk factors. Matching the comparison group to Holocaust Survivors on propensity scores for exposure., Results: The prevalence of ischemic heart disease (38.7% vs 31.3%), congestive heart failure (10.9% vs 9.1%), past stroke (15.7% vs 13.4%), and peripheral vascular disease (9.5% vs 7.9%) was higher in Holocaust survivors (p<.001 for all comparisons). Similar results were found for cardiovascular risk factors (diabetes mellitus (14.4% vs 13.6%), hypertension (89.3% vs 86.4%), dyslipidemia (75.9% vs 74.0%) (p<.001 for all comparisons). In multivariable analysis, matched on propensity scores and controlled for confounders, odds ratios for men and women were higher for diabetes (1.23, 1.55), dyslipidemia (1.53, 1.51), hypertension (1.56 , 1.94), stroke (1.18, 1.17), and ischemic heart disease (1.18, 1,40), but not congestive heart failure (0.95, 1.02). A Positive association was noted for peripheral vascular disease in males (1.20) but not females (0.96)., Conclusion: Prevalence of cardiovascular diseases and risk factors was higher in Holocaust survivors. These associations were stronger in women in most cases., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Cardiovascular disease in patients with multiple myeloma may derive from factors unrelated to the disease (age, diabetes, dyslipidemia, obesity, prior cardiovascular diseases), related to the disease (cardiac AL-amyloidosis, hyperviscosity, high-output failure, arteriovenous shunting, anemia, renal dysfunction) and/or related to anti-myeloma treatment (anthracyclines, corticosteroids, alkylating agents, immunomodulatory drugs, proteasome inhibitors). Good knowledge of cardiovascular events, effective dose reductions, prevention and management of early and late cardiovascular side effects of chemotherapeutic agents are essential in current clinical practice. Myeloma experts are obliged to carefully balance the efficacy and toxicity of drugs for each individual patient. This review summarizes current data and novel insights into cardiovascular adverse events of today's anti-myeloma treatment, focusing on carfilzomib, as a starting point for developing consensus recommendations on preventing and managing cardiovascular side effects in patients with multiple myeloma., (Copyright© 2018 Ferrata Storti Foundation.)

Background/aims: Climate influences the regulation of blood pressure (BP). Our objective was to precisely estimate BP seasonality in hemodialysis (HD) patients from five European cities with marked climate differences., Methods: Stable prevalent HD patients from 5 European facilities (Santa Cruz de Tenerife (Spain), Seville (Spain), Montpellier (France), Ottignies (Belgium), Umea (Sweden)) present over the years 1995-1999 were included in this historical longitudinal observational study. Individual monthly averages of pre-dialysis BP level were computed from all facility BP measurements (> 90 000 observations). The association between BP level and location, seasons and meteorological measurements was analyzed by mixed models., Results: 261 patients were included and followed-up for a median duration of 2 years (6903 monthly observations). Pre-dialysis SBP and DBP were minimal in summer (July) and maximal in winter (November and December), and mean changes were respectively 4.2 [3.0; 5.4] and 2.0 [1.3; 2.7] mmHg. Seasonality was confirmed in 4 locations (Pseason≤0.001 for SBP and DBP), but not in Umea (both Pseason> 0.05). Seasonal changes in DBP were larger in southern locations (Pinteraction=0.02). BP level was associated with climate parameters: in a positive manner with humidity or rainfall, and inversely with sunshine duration or temperature. The effects of temperature and rainfall on DBP varied with latitude (Pinteraction< 0.02) and were greater in southern locations., Conclusion: BP varies with seasons and climate in different European areas and seasonality can be more important in southern locations. These changes in BP deserve attention as they may be responsible for a significant increase in cardiovascular risk which may be preventable., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background: For migrant populations from sub-Saharan Africa, adverse cardiovascular disease (CVD) risk factors have been observed to be higher than found in their home country-based counterparts or among the host populations in high-income countries. Differences in absolute overall CVD risk, however, remain largely unexplained. We, therefore, predicted the differences in 10-year CVD risk among sub-Saharan African migrants (Ghanaians) living in 3 European cities and Ghana., Methods and Results: For 3864 subjects aged 40 to 70 years from the multicenter RODAM study (Research on Obesity and Diabetes Among African Migrants) conducted among Ghanaian adults residing in rural and urban Ghana and 3 European cities (Amsterdam, Berlin, and London), 10-year risk of CVD was estimated using the Pooled Cohort Equations with estimates ≥7.5% defining high CVD risk. Logistic regressions were used to determine the association of migration on CVD risk. The proportion with CVD risk ≥7.5% among Ghanaian men was 34.7% in rural Ghana, 45.4% in urban Ghana, 53.9% in Amsterdam, 61.0% in Berlin, and 52.2% in London. Compared with rural Ghana, CVD risk was significantly increased for Ghanaian men living in Berlin (adjusted odds ratio, 2.80; 95% confidence interval, 1.76-4.45) and Amsterdam (1.88; 1.25-2.84). Increased risk observed for men was largely not seen for women. CVD risk increased with longer stay in Europe., Conclusions: Knowledge about predictors of increased CVD risk among sub-Saharan African migrants in Europe and nonmigrants in urban centers will inform and support targeted health care and interventions to these populations., (© 2017 American Heart Association, Inc.)

Background: The picture of primary prevention obtained from real-life practice makes possible scheduling measures for prevention improvement., Aim: To analyze features of drug and non-drug therapy aimed at decreasing cardiovascular risk in Russian patients with a high risk (HR) of CVD compared with the study general population., Materials and Methods: 14 European countries, including the Russian Federation, participated in this cross-sectional study. The study included patients aged 18-80 without clinical signs of atherosclerosis who have received antihypertensive and/or lipid-lowering therapy and/or therapy for diabetes mellitus (DM) within >6 to.

Relevance: Evaluation of the effectiveness of risk management in persons with high cardiovascular risk is an important element in reducing the death rate of the population from cardiovascular diseases (CVD)., Aim: Analysis of the prevalence and level of risk factors control in patients with high CV risk CVD from the Russian centers of the primary care unit of the EUROASPIRE IV study in comparison with the general population of the study., Materials and Methods: In this cross-sectional study, 14 European countries, including the Russian Federation, participated. Patients aged 18 to 79 years were included in the study, without clinical manifestations of atherosclerosis, who were prescribed antihypertensive therapy and/or lipid lowering therapy and/or treatment for diabetes between the ages of ≥6 months and.

In recent history, some dietary recommendations have treated dairy fat as an unnecessary source of calories and saturated fat in the human diet. These assumptions, however, have recently been brought into question by current research on regular fat dairy products and human health. In an effort to disseminate, explore and discuss the state of the science on the relationship between regular fat dairy products and health, symposia were programmed by dairy industry organizations in Europe and North America at The Eurofed Lipids Congress (2014) in France, The Dairy Nutrition Annual Symposium (2014) in Canada, The American Society for Nutrition Annual Meeting held in conjunction with Experimental Biology (2015) in the United States, and The Federation of European Nutrition Societies (2015) in Germany. This synopsis of these symposia describes the complexity of dairy fat and the effects regular-fat dairy foods have on human health. The emerging scientific evidence indicates that the consumption of regular fat dairy foods is not associated with an increased risk of cardiovascular disease and inversely associated with weight gain and the risk of obesity. Dairy foods, including regular-fat milk, cheese and yogurt, can be important components of an overall healthy dietary pattern. Systematic examination of the effects of dietary patterns that include regular-fat milk, cheese and yogurt on human health is warranted.

Objective: The aim of the study was to assess the associations of individual and combined physical fitness components with single and clustering of cardio-metabolic risk factors in children., Subjects/methods: This 2-year longitudinal study included a total of 1635 European children aged 6-11 years. The test battery included cardio-respiratory fitness (20-m shuttle run test), upper-limb strength (handgrip test), lower-limb strength (standing long jump test), balance (flamingo test), flexibility (back-saver sit-and-reach) and speed (40-m sprint test). Metabolic risk was assessed through z-score standardization using four components: waist circumference, blood pressure (systolic and diastolic), blood lipids (triglycerides and high-density lipoprotein) and insulin resistance (homeostasis model assessment). Mixed model regression analyses were adjusted for sex, age, parental education, sugar and fat intake, and body mass index., Results: Physical fitness was inversely associated with clustered metabolic risk (P<0.001). All coefficients showed a higher clustered metabolic risk with lower physical fitness, except for upper-limb strength (β=0.057; P=0.002) where the opposite association was found. Cardio-respiratory fitness (β=-0.124; P<0.001) and lower-limb strength (β=-0.076; P=0.002) were the most important longitudinal determinants. The effects of cardio-respiratory fitness were even independent of the amount of vigorous-to-moderate activity (β=-0.059; P=0.029). Among all the metabolic risk components, blood pressure seemed not well predicted by physical fitness, while waist circumference, blood lipids and insulin resistance all seemed significantly predicted by physical fitness., Conclusion: Poor physical fitness in children is associated with the development of cardio-metabolic risk factors. Based on our results, this risk might be modified by improving mainly cardio-respiratory fitness and lower-limb muscular strength.

Objectives: In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes., Method: We performed a prospective observational study using the latest 2013 data extract from the EULAR scleroderma trials and research (EUSTAR) cohort. We looked at (i) sex influence on disease characteristics at baseline and (ii) then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival., Results: 9182 patients with SSc were available (1321 men) for the baseline analyses. In multivariate analysis, male sex was independently associated with a higher risk of diffuse cutaneous subtype (OR: 1.68, (1.45 to 1.94); p<0.001), a higher frequency of digital ulcers (OR: 1.28 (1.11 to 1.47); p<0.001) and pulmonary hypertension (OR: 3.01 (1.47 to 6.20); p<0.003). In the longitudinal analysis (n=4499), after a mean follow-up of 4.9 (±2.7) years, male sex was predictive of new onset of pulmonary hypertension (HR: 2.66 (1.32 to 5.36); p=0.006) and heart failure (HR: 2.22 (1.06 to 4.63); p=0.035). 908 deaths were recorded, male sex predicted deaths of all origins (HR: 1.48 (1.19 to 1.84); p<0.001), but did not significantly account for SSc-related deaths., Conclusions: Although more common in women, SSc appears as strikingly more severe in men. Our results obtained through the largest worldwide database demonstrate a higher risk of severe cardiovascular involvement in men. These results raise the point of including sex in the management and the decision-making process., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Patients with diabetes mellitus and cardiovascular disease may not achieve adequate low-density lipoprotein cholesterol (LDL-C) lowering on statin monotherapy, attributed partly to atherogenic dyslipidemia. More intensive LDL-C-lowering therapy can be considered for these patients. A previous randomized, controlled study demonstrated greater LDL-C lowering in diabetic patients with symptomatic cardiovascular disease who switched from simvastatin 20 mg (S20) or atorvastatin 10 mg (A10) to combination ezetimibe/simvastatin 10/20 mg (ES10/20) therapy, compared with statin dose-doubling (to S40 or A20) or switching to rosuvastatin 10 mg (R10). The effect of these regimens on novel biomarkers of atherogenic dyslipidemia (low- and high-density lipoprotein particle number and lipoprotein-associated phospholipase A2 [Lp-PLA2]) was assessed., Methods and Results: Treatment effects on low- and high-density lipoprotein particle number (by NMR) and Lp-PLA2 (by ELISA) were evaluated using plasma samples available from 358 subjects in the study. Switching to ES10/20 reduced low-density lipoprotein-particle number numerically more than did statin dose-doubling and was comparable with R10 (-133.3, -94.4, and -56.3 nmol/L, respectively; P>0.05). Increases in high-density lipoprotein particle number were significantly greater with switches to ES10/20 versus statin dose-doubling (1.5 and -0.5 μmol/L; P<0.05) and comparable with R10 (0.7 μmol/L; P>0.05). Percentages of patients attaining low-density lipoprotein particle number levels <990 nmol/L were 62.4% for ES10/20, 54.1% for statin dose-doubling, and 57.0% for R10. Switching to ES10/20 reduced Lp-PLA2 activity significantly more than did statin dose-doubling (-28.0 versus -3.8 nmol/min per mL, P<0.05) and was comparable with R10 (-28.0 versus -18.6 nmol/min per mL; P>0.05); effects on Lp-PLA2 concentration were modest., Conclusions: In diabetic patients with dyslipidemia, switching from statins to combination ES10/20 therapy generally improved lipoprotein subclass profile and Lp-PLA2 activity more than did statin dose-doubling and was comparable with R10, consistent with its lipid effects., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00862251., (© 2015 The Authors. [Ngoc‐Anh Le and Peter W. F. Wilson] and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. All rights reserved. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: High center procedural volume has been shown to reduce postoperative mortality (POM); however, the cause of POM has been poorly studied previously. The aim of this study was to define the pattern of POM and major morbidity in relation to center procedural volume., Methods: Data from 2,944 consecutive adult patients undergoing esophagectomy for esophageal cancer in 30 centers between 2000 and 2010 were retrospectively collected. Data between patients who suffered 30-day POM were compared with those who did not. Factors associated with POM were identified using binary logistic regression, with propensity matching to compare low- (LV) and high-volume (HV) centers., Results: The 30-day and in-hospital POM rates were 5.0 and 7.3 %, respectively. Pulmonary complications were the most common, affecting 38.1 % of patients, followed by surgical site infection (15.5 %), cardiovascular complications (11.2 %), and anastomotic leak (10.2 %). Factors that were independently associated with 30-day POM included American Society of Anesthesiologists grade IV, LV center, anastomotic leak, pulmonary, cardiovascular and neurological complications, and R2 resection margin status. Surgical complications preceded POM in approximately 30 % of patients compared to medically-related causes in 68 %. Propensity-matched analysis demonstrated LV centers were significantly associated with increased 30-day POM, and POM secondary to anastomotic leak, and pulmonary- and cardiac-related causes., Conclusions: The results of this large, multicenter study provide further evidence to support the centralization of esophagectomy to HV centers, with a lower rate of morbidity and better infrastructure to deal with complications following major surgery preventing further mortality.

Objectives: To assess the safety and efficacy of pitavastatin in children and adolescents with hyperlipidemia., Study Design: A total of 106 children and adolescents with hyperlipidemia, ages 6 to 17 years, were enrolled in a 12-week randomized, double-blind, placebo-controlled study and randomly assigned to pitavastatin 1 mg, 2 mg, 4 mg, or placebo. During a 52-week extension period, subjects were up-titrated from 1 mg pitavastatin to a maximum dose of 4 mg in an effort to achieve an optimum low-density lipoprotein cholesterol (LDL-C) treatment target of <110 mg/dL (2.8 mmol/L). Adverse events rates, including abnormal clinical laboratory variables, vital signs, and physical examination were assessed., Results: Compared with placebo, pitavastatin 1, 2, and 4 mg significantly reduced LDL-C from baseline by 23.5%, 30.1%, and 39.3%, respectively, and in the open-label study 20.5% of the subjects reached the LDL-C goal <110 mg/dL (2.8 mmol/L). No safety issues were evident., Conclusions: Pitavastatin at doses up to 4 mg is well tolerated and efficacious in children and adolescents aged 6-17 years., Trial Registration: Registered with EudraCT 2011-004964-32 and EudraCT 2011-004983-32., (Copyright © 2015 Elsevier Inc. All rights reserved.)