<div><h4>What about chronotropic incompetence in heart failure with mildly reduced ejection fraction? Clinical and prognostic implications from the MECKI score data-set.</h4><i>Magrì D, Gallo G, Piepoli M, Salvioni E, ... Di Lenarda A, Agostoni P</i><br /><b>Aims</b><br />Chronotropic incompetence (CI) is a strong predictor of outcome in heart failure with reduced ejection fraction (HFrEF), however no data on its clinical and prognostic impact in heart failure with mildly reduced ejection fraction (HFmrEF). Therefore, the study aims to investigate, in a large multicenter HFmrEF cohort, the prevalence of CI as well as its relationship with exercise capacity and its prognostic role over the cardiopulmonary exercise testing (CPET) parameters.<br /><b>Methods</b><br />Within the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database, we analyzed data of 864 HFmrEF out of 1164 stable outpatients who performed a maximal CPET at the cycle ergometer and who had no significant rhythm disorders or comorbidities. The primary study endpoint was cardiovascular (CV) death. All-cause death was also explored.<br /><b>Results</b><br />CI prevalence differed depending on the method (peak heart rate, pHR% versus pHR reserve, pHRR%) and the cut-off adopted (pHR% from ≤75% to ≤60% and pHRR%≤65% to ≤50%), ranging from 11% to 62%. A total of 84 (9.7%) CV deaths were collected, with 39 (4.5%) occurring within 5 year. At multivariate analysis, both pHR% [Hazard Ratio 0.97(0.95-0.99), p < 0.05] and pHRR% [Hazard Ratio 0.977(0.961-0.993), p < 0.01) were associated with the primary end-point. A pHR%≤75% and a pHRR%≤50% represented the most accurate cut-off values in predicting the outcome.<br /><b>Conclusions</b><br />The study suggests an association between blunted exercise-HR response, functional capacity, and CV death risk among patients with HFmrEF. Whether the CI presence might be adopted in daily HFmrEF management needs to be addressed in larger prospective studies.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 27 Oct 2023; epub ahead of print</small></div>

<div><h4>Triglyceride-Glucose Index, LDL and Cardiovascular Outcomes in Chronic Stable Cardiovascular Disease: Results from the ONTARGET and TRANSCEND trials.</h4><i>Haring B, Schumacher H, Mancia G, Teo KK, ... Yusuf S, Böhm M</i><br /><b>Background</b><br />The triglyceride-glucose (TyG) index has been proposed as an alternative to insulin resistance and as a predictor of cardiovascular outcomes. Little is known on its role in chronic stable cardiovascular disease and its predictive power at controlled low-density lipoprotein (LDL) levels.<br /><b>Methods</b><br />Our study population consisted of 29,960 participants in the ONTARGET and TRANSCEND trials that enrolled patients with known atherosclerotic disease. Triglycerides and glucose were measured at baseline. TyG was calculated as the logarithmized product of fasting triglycerides and glucose divided by 2. The primary endpoint of both trials was a composite of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure. The secondary endpoint was all-cause death and the components of the primary endpoint. Cox-proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) with extensive covariate adjustment for demographic, medical history and lifestyle factors.<br /><b>Results</b><br />During a mean follow-up of 4.3 years, 4,895 primary endpoints and 3,571 all-cause deaths occurred. In fully adjusted models, individuals in the highest compared to the lowest quartile of the TyG index were at higher risk for the primary endpoint (HR 1.14; 95% CI 1.05-1.25) and for myocardial infarction (HR 1.30; 95% CI 1.11-1.53). A higher TyG index did not associate with the primary endpoint in individuals with LDL levels <100 mg/dl.<br /><b>Conclusion</b><br />A higher TyG index is associated with a modestly increased cardiovascular risk in chronic stable cardiovascular disease. This association is largely attenuated when LDL levels are controlled.Clinical <br /><b>Trial registration:</b><br/>Information - https://www.clinicaltrials.gov; Identifier: NCT00153101.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 27 Oct 2023; epub ahead of print</small></div>

<div><h4>Air pollution, cardiovascular disease, and urban greening: an ecological blueprint.</h4><i>Mannucci PM</i><br /><AbstractText>A number of studies and systematic reviews indicate that exposure to greenness reduces of all-cause, non accidental mortality, particularly from cardiopulmonary and cancer causes. There is also some evidence that green space residence may be associated with improved pregnancy and birth outcomes, and with better school performances in children. Furthermore, because at least one third of the premature deaths are globally attributable to exposure to air pollution due household agents, particularly in fragile populations living in low-income countries (i.e., children, older and deprived people, pregnant women), that houseplants are an effective and economic mean for cleaning indoor air and thus reducing volatile organic compounds such as formaldehyde, benzene, toluene and others. On the whole more prospective studies are needed to further elucidate the mechanisms linking air pollution, greenness and health outcomes, although the multiple and interacting mechanisms depicted in this article are all biologically plausible.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 26 Oct 2023; 30:1608-1611</small></div>

<div><h4>Evolocumab in paediatric heterozygous familial hypercholesterolaemia: cognitive function during 80 weeks of open-label extension treatment.</h4><i>Santos RD, Ruzza A, Wang B, Maruff P, ... Gaudet D, Raal FJ</i><br /><b>Aims</b><br />PCSK9 inhibition intensively lowers low-density lipoprotein cholesterol and is well tolerated in adults and paediatric patients with familial hypercholesterolaemia (FH). HAUSER-RCT showed that 24 weeks of treatment with evolocumab in paediatric patients did not affect cognitive function. This study determined the effects of 80 additional weeks of evolocumab treatment on cognitive function in paediatric patients with heterozygous FH.<br /><b>Methods</b><br />HAUSER-OLE was an 80-week open-label extension of HAUSER-RCT, a randomized, double-blind, 24-week trial evaluating the efficacy and safety of evolocumab in paediatric patients (ages 10-17 years) with FH. During the OLE, all patients received monthly 420 mg subcutaneous evolocumab injections. Tests of psychomotor function, attention, visual learning, and executive function were administered at baseline and weeks 24 and 80 of the OLE. Changes over time were analysed descriptively and using analysis of covariance (ANCOVA). Cohen\'s d statistic was used to evaluate the magnitude of treatment effects.<br /><b>Results</b><br />ANCOVA results indicated no decrease in performance across visits during 80 weeks of evolocumab treatment for Groton Maze Learning, One Card Learning accuracy, Identification speed, or Detection speed (all P > 0.05). Performance on all tasks was similar for those who received placebo or evolocumab in the RCT (all P > 0.05). For all tests, the least square mean differences between patients who received placebo vs evolocumab in the parent study were trivial (all Cohen\'s d magnitude < 0.2).<br /><b>Conclusion</b><br />In paediatric patients with FH, 80 weeks of open-label evolocumab treatment had no negative impact on cognitive function.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 19 Oct 2023; epub ahead of print</small></div>

<div><h4>The Effect of Fibrates on Lowering Low-Density Lipoprotein Cholesterol and Cardiovascular Risk Reduction: A Systemic Review and Meta-analysis.</h4><i>Kim KA, Kim NJ, Choo EH</i><br /><b>Aims</b><br />The effect of fibrate treatment on cardiovascular risk is inconsistent. This meta-analysis aimed to assess the effect of fibrates on major adverse cardiovascular outcome (MACE) reduction.<br /><b>Methods</b><br />PubMed, Embase, and Cochrane library databases were searched up to February 2023 for randomized controlled trials comparing fibrate therapy against placebo and reporting cardiovascular outcomes and lipid profile changes. The primary outcome was the clinical outcomes of each trial that most closely corresponding to MACE, a composite of cardiovascular death, acute myocardial infarction, stroke, and coronary revascularization. A pre-specified meta-regression analysis to examine the relationship between the changes in lipid levels after fibrate treatment and the risk of MACE was also performed.<br /><b>Results</b><br />Twelve trials were selected for final analysis, with 25,781 patients and 2,741 MACEs in the fibrate group and 27,450 patients and 3,754 MACEs in the control group. Overall, fibrate therapy was associated with decreased risk of MACE (RR 0.87, 95% confidence interval [CI] 0.81-0.94) with moderate heterogeneity (I2 = 47%). In meta-regression analysis, each 1 mmol/L reduction in low-density lipoprotein cholesterol (LDL-C) after fibrate treatment reduced MACE (RR 0.71, 95% CI 0.49-0.94, p = 0.01), while triglyceride level changes did not show a significant association. (RR 0.96, 95% CI 0.53-1.40, p = 0.86) A sensitivity analysis with the composite outcome of cardiovascular death or acute myocardial infaction produced similar results.<br /><b>Conclusion</b><br />Treatment with fibrates was associated with decreased risk of MACE. The reduction in MACE risk with fibrate therapy appears to be attributable to LDL-C reduction rather than a decrease in triglyceride levels.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 19 Oct 2023; epub ahead of print</small></div>

<div><h4>Impact of hypertriglyceridaemia on cardiovascular mortality according to low-density lipoprotein cholesterol in a 15.6-million population.</h4><i>Park HB, Arsanjani R, Hong SJ, Yi JJ, Yi SW</i><br /><b>Aims</b><br />To assess the association between triglyceride (TG) levels and cardiovascular disease (CVD) mortality concerning low-density lipoprotein cholesterol (LDL-C) and age in the general population.<br /><b>Methods and results</b><br />From the Korean National Health Insurance Service database, 15,672,028 participants aged 18-99 who underwent routine health examinations were followed up for CVD mortality. Hazard ratios (HRs) for CVD mortality were calculated using Cox models after adjusting for various confounders. During a mean 8.8 years of follow-up, 105,174 individuals died of CVD. There was a clear log-linear association between TG and overall CVD mortality down to 50 mg/dL. Each two-fold increase in TG was associated with 1.10-fold (overall CVD), 1.22-fold (ischaemic heart disease [IHD]), 1.24-fold (acute myocardial infarction [AMI]), and 1.10-fold (ischaemic stroke) higher CVD mortality. Haemorrhagic stroke and heart failure were not associated with TG levels. The impact of HTG on CVD weakened but remained present in persons with LDL-C <100 mg/dL, in whom each two-fold higher TG was associated with 1.05-fold (overall CVD), 1.12-fold (IHD), 1.15-fold (AMI), and 1.05-fold (ischaemic stroke) higher CVD mortality. The younger population (18 to 44 years) had stronger associations between TG levels and mortality from overall CVD, IHD, and AMI than the older population.<br /><b>Conclusion</b><br />Hypertriglyceridaemia (HTG) independently raises CVD mortality with lingering risks in young and older individuals with low LDL-C levels, suggesting the importance of management of HTG even with controlled LDL-C.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 18 Oct 2023; epub ahead of print</small></div>

<div><h4>Determinants of exercise performance in heart failure patients with extremely reduced cardiac output and left ventricular assist device.</h4><i>Apostolo A, Vignati C, Cittar M, Baracchini N, ... Piepoli M, Agostoni P</i><br /><AbstractText>The evaluation of exercise capacity and cardiac output (QC) is fundamental in the management of patients with advanced heart failure (AdHF). QC and peak oxygen uptake (VO2) have a pivotal role in the prognostic stratification and in the definition of therapeutic interventions, including medical therapies and devices, but also specific treatments such as heart transplantation and left ventricular assist device (LVAD) implantation. Due to the intertwined relationship between exercise capacity and daily activities, exercise intolerance dramatically has impact on the quality of life of patients. It is a multifactorial process that includes alterations in central and peripheral haemodynamic regulation, anaemia and iron deficiency, pulmonary congestion, pulmonary hypertension, and peripheral O2 extraction. This paper aims to review the pathophysiological background of exercise limitations in HF patients and to examine the complex physiology of exercise in LVAD recipients, analysing the interactions between the cardiopulmonary system, the musculoskeletal system, the autonomic nervous system, and the pump. We performed a literature review to highlight the current knowledge on this topic and possible interventions that can be implemented to increase exercise capacity in AdHF patients-including administration of levosimendan, rehabilitation, and the intriguing field of LVAD speed changes. The present paper confirms the role of CPET in the follow-up of this peculiar population and the impact of exercise capacity on the quality of life of AdHF patients.</AbstractText><br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 11 Oct 2023; 30:ii63-ii69</small></div>

<div><h4>The cardiopulmonary exercise test in the prognostic evaluation of patients with heart failure and cardiomyopathies: the long history of making a one-size-fits-all suit.</h4><i>Salvioni E, Bonomi A, Magrì D, Merlo M, ... Piepoli M, Agostoni P</i><br /><AbstractText>Cardiopulmonary exercise test (CPET) has become pivotal in the functional evaluation of patients with chronic heart failure (HF), supplying a holistic evaluation both in terms of exercise impairment degree and possible underlying mechanisms. Conversely, there is growing interest in investigating possible multiparametric approaches in order to improve the overall HF risk stratification. In such a context, in 2013, a group of 13 Italian centres skilled in HF management and CPET analysis built the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score, based on the dynamic assessment of HF patients and on some other instrumental and laboratory parameters. Subsequently, the MECKI score, initially developed on a cohort of 2716 HF patients, has been extensively validated as well as challenged with the other multiparametric scores, achieving optimal results. Meanwhile, the MECKI score research group has grown over time, involving up to now a total of 27 centres with an available database accounting for nearly 8000 HF patients. This exciting joint effort from multiple HF Italian centres allowed to investigate different HF research field in order to deepen the mechanisms underlying HF, to improve the ability to identify patients at the highest risk as well as to analyse particular HF categories. Most recently, some of the participants of the MECKI score group started to join the forces in investigating a possible additive role of CPET assessment in the cardiomyopathy setting too. The present study tells the ten-year history of the MECKI score presenting the most important results achieved as well as those projects in the pipeline, this exciting journey being far to be concluded.</AbstractText><br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 11 Oct 2023; 30:ii28-ii33</small></div>

<div><h4>Dysregulation of ventilation at day and night time in heart failure.</h4><i>Contini M, Mapelli M, Carriere C, Gugliandolo P, ... Capovilla MT, Agostoni P</i><br /><AbstractText>Heart failure (HF) is characterized by an increase in ventilatory response to exercise of multifactorial aetiology and by a dysregulation in the ventilatory control during sleep with the occurrence of both central and obstructive apnoeas. In this setting, the study of the ventilatory behaviour during exercise, by cardiopulmonary exercise testing, or during sleep, by complete polysomnography or simplified nocturnal cardiorespiratory monitoring, is of paramount importance because of its prognostic value and of the possible effects of sleep-disordered breathing on the progression of the disease. Moreover, several therapeutic interventions can significantly influence ventilatory control in HF. Also, rest daytime monitoring of cardiac, metabolic, and respiratory activities through specific wearable devices could provide useful information for HF management. The aim of the review is to summarize the main studies conducted at Centro Cardiologico Monzino on these topics.</AbstractText><br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 11 Oct 2023; 30:ii16-ii21</small></div>

<div><h4>Fluid balance in heart failure.</h4><i>Cosentino N, Marenzi G, Muratori M, Magrì D, Cattadori G, Agostoni P</i><br /><AbstractText>Fluid retention is a major determinant of symptoms in patients with heart failure (HF), and it is closely associated with prognosis. Hence, congestion represents a critical therapeutic target in this clinical setting. The first therapeutic strategy in HF patients with fluid overload is optimization of diuretic intervention to maximize water and sodium excretion. When diuretic therapy fails to relieve congestion, renal replacement therapy represents the only alternative option for fluid removal, as well as a way to restore diuretic responsiveness. On this background, the pathophysiology of fluid balance in HF is complex, with heart, kidney, and lung being deeply involved in volume regulation and management. Therefore, the interplay between these organs should be appreciated and considered when fluid overload in HF patients is targeted.</AbstractText><br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 11 Oct 2023; 30:ii9-ii15</small></div>

<div><h4>Exercise in hypoxia: a model from laboratory to on-field studies.</h4><i>Vignati C, Contini M, Salvioni E, Lombardi C, ... Parati G, Agostoni P</i><br /><AbstractText>Clinical outcome and quality of life of patients with chronic heart failure (HF) have greatly improved over the last two decades. These results and the availability of modern lifts allow many cardiac patients to spend leisure time at altitude. Heart failure per se does not impede a safe stay at altitude, but exercise at both simulated and real altitudes is associated with a reduction in performance, which is inversely proportional to HF severity. For example, in normal subjects, the reduction in functional capacity is ∼2% every 1000 m altitude increase, whereas it is 4 and 10% in HF patients with normal or slightly diminished exercise capacity and in HF patients with markedly diminished exercise capacity, respectively. Also, the on-field experience with HF patients at altitude confirms safety and shows overall similar data to that reported at simulated altitude. Even \'optimal\' HF treatment in patients spending time at altitude or at hypoxic conditions is likely different from optimal treatment at sea level, particularly with regard to the selectivity of β-blockers. Furthermore, high altitude, both simulated and on-field, represents a stimulating model of hypoxia in HF patients and healthy subjects. Our data suggest that spending time at altitude (<3500 m) can be safe even for HF patients, provided that subjects are free from comorbidities that may directly interfere with the adaptation to altitude and are stable. However, HF patients experience a reduction of exercise capacity directly proportional to HF severity and altitude. Finally, HF patients should be tested for functional capacity and must undergo a specific \'hypoxic-tailored treatment\' to avoid pharmacological interference with altitude adaptation mechanisms, particularly with regard to the selectivity of β-blockers.</AbstractText><br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 11 Oct 2023; 30:ii40-ii46</small></div>

<div><h4>Beyond VO2: the complex cardiopulmonary exercise test.</h4><i>Mattavelli I, Vignati C, Farina S, Apostolo A, ... Zaffalon D, Agostoni P</i><br /><AbstractText>Cardiopulmonary exercise test (CPET) is a valuable diagnostic tool with a specific application in heart failure (HF) thanks to the strong prognostic value of its parameters. The most important value provided by CPET is the peak oxygen uptake (peak VO2), the maximum rate of oxygen consumption attainable during physical exertion. According to the Fick principle, VO2 equals cardiac output (Qc) times the arteriovenous content difference [C(a-v)O2], where Ca is the arterial oxygen and Cv is the mixed venous oxygen content, respectively; therefore, VO2 can be reduced both by impaired O2 delivery (reduced Qc) or extraction (reduced arteriovenous O2 content). However, standard CPET is not capable of discriminating between these different impairments, leading to the need for \'complex\' CPET technologies. Among non-invasive methods for Qc measurement during CPET, inert gas rebreathing and thoracic impedance cardiography are the most used techniques, both validated in healthy subjects and patients with HF, at rest and during exercise. On the other hand, the non-invasive assessment of peripheral muscle perfusion is possible with the application of near-infrared spectroscopy, capable of measuring tissue oxygenation. Measuring Qc allows, by having haemoglobin values available, to discriminate how much any VO2 deficit depends on the muscle, anaemia or heart.</AbstractText><br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 11 Oct 2023; 30:ii34-ii39</small></div>

<div><h4>The alveolar-capillary unit in the physiopathological conditions of heart failure: identification of a potential marker.</h4><i>Banfi C, Gugliandolo P, Paolillo S, Mallia A, Gianazza E, Agostoni P</i><br /><AbstractText>In this review, we describe the structure and function of the alveolar-capillary membrane and the identification of a novel potential marker of its integrity in the context of heart failure (HF). The alveolar-capillary membrane is indeed a crucial structure for the maintenance of the lung parenchyma gas exchange capacity, and the occurrence of pathological conditions determining lung fluids accumulation, such as HF, might significantly impair lung diffusion capacity altering the alveolar-capillary membrane protective functions. In the years, we found that the presence of immature forms of the surfactant protein-type B (proSP-B) in the circulation reflects alterations in the alveolar-capillary membrane integrity. We discussed our main achievements showing that proSP-B, due to its chemical properties, specifically binds to high-density lipoprotein, impairing their antioxidant activity, and likely contributing to the progression of the disease. Further, we found that immature proSP-B, not the mature protein, is related to lung abnormalities, more precisely than the lung function parameters. Thus, to the list of the potential proposed markers of HF, we add proSP-B, which represents a precise marker of alveolar-capillary membrane dysfunction in HF, correlates with prognosis, and represents a precocious marker of drug therapy.</AbstractText><br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 11 Oct 2023; 30:ii2-ii8</small></div>

<div><h4>Physiology of exercise and heart failure treatments: cardiopulmonary exercise testing as a tool for choosing the optimal therapeutic strategy.</h4><i>Campodonico J, Contini M, Alimento M, Mapelli M, ... Bonomi A, Agostoni P</i><br /><AbstractText>In the last decades, the pharmacological treatment of heart failure (HF) become more complex due to the availability of new highly effective drugs. Although the cardiovascular effects of HF therapies have been extensively described, less known are their effects on cardiopulmonary function considered as a whole, both at rest and in response to exercise. This is a \'holistic\' approach to disease treatment that can be accurately evaluated by a cardiopulmonary exercise test. The aim of this paper is to assess the main differences in the effects of different drugs [angiotensin-converting enzyme (ACE)-inhibitors, Angiotensin II receptor blockers, β-blockers, Angiotensin receptor-neprilysin inhibitors, renal sodium-glucose co-transporter 2 inhibitors, iron supplementation] on cardiopulmonary function in patients with HF, both at rest and during exercise, and to understand how these differences can be taken into account when choosing the most appropriate treatment protocol for each individual patient leading to a precision medicine approach.</AbstractText><br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 11 Oct 2023; 30:ii54-ii62</small></div>

<div><h4>Activities of daily living in heart failure patients and healthy subjects: when the cardiopulmonary assessment goes beyond traditional exercise test protocols.</h4><i>Mapelli M, Salvioni E, Mattavelli I, Gugliandolo P, ... Piepoli M, Agostoni P</i><br /><AbstractText>Heart failure (HF) patients traditionally report dyspnoea as their main symptom. Although the cardiopulmonary exercise test (CPET) and 6 min walking test are the standardized tools in assessing functional capacity, neither cycle ergometers nor treadmill maximal efforts do fully represent the actual HF patients\' everyday activities [activities of daily living (ADLs)] (i.e. climbing the stairs). New-generation portable metabolimeters allow the clinician to measure task-related oxygen intake (VO2) in different scenarios and exercise protocols. In the last years, we have made considerable progress in understanding the ventilatory and metabolic behaviours of HF patients and healthy subjects during tasks aimed to reproduce ADLs. In this paper, we describe the most recent findings in the field, with special attention to the relationship between the metabolic variables obtained during ADLs and CPET parameters (i.e. peak VO2), demonstrating, for example, how exercises traditionally thought to be undemanding, such as a walk, instead represent supramaximal efforts, particularly for subjects with advanced HF and/or artificial heart (left ventricular assist devices) wearers.</AbstractText><br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 11 Oct 2023; 30:ii47-ii53</small></div>

<div><h4>Exercise oscillatory ventilation: the past, present, and future.</h4><i>Cunha G, Apostolo A, De Martino F, Salvioni E, Matavelli I, Agostoni P</i><br /><AbstractText>Exercise oscillatory ventilation (EOV) is a fascinating event that can be appreciated in the cardiopulmonary exercise test and is characterized by a cyclic fluctuation of minute ventilation, tidal volume, oxygen uptake, carbon dioxide production, and end-tidal pressure for oxygen and carbon dioxide. Its mechanisms stem from a dysregulation of the normal control feedback of ventilation involving one or more of its components, namely, chemoreflex delay, chemoreflex gain, plant delay, and plant gain. In this review, we intend to breakdown therapeutic targets according to pathophysiology and revise the prognostic value of exercise oscillatory ventilation in the setting of heart failure and other diagnoses.</AbstractText><br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 11 Oct 2023; 30:ii22-ii27</small></div>

<div><h4>Effects of Detraining on Left Ventricular Mass in Endurance-Trained Individuals: A Systematic Review and Meta-Analysis.</h4><i>Massarotto RJ, Campbell AJ, Kreiter E, Claydon VE, Cote AT</i><br /><AbstractText>Detraining refers to a loss of training adaptations resulting from reductions in training stimulus due to illness, injury, or active recovery breaks in a training cycle and is associated with a reduction in left ventricular mass (LVM). The purpose of this study was to conduct a systematic review and meta-analysis to determine the influence of detraining on LVM in endurance-trained, healthy individuals. Using electronic databases (e.g., EMBASE & MEDLINE), a literature search was performed looking for prospective detraining studies in humans. Inclusion criteria were: adults, endurance-trained individuals with no known chronic disease, detraining intervention >1 week, and pre- and post-detraining LVM reported. A pooled statistic for random effects was used to assess changes in LVM with detraining. Fifteen investigations (19 analyses) with a total of 196 participants (ages 18 to 55 years, 15% female) met inclusion criteria, with detraining ranging between 1.4 and 15 weeks. The meta-analysis revealed a significant reduction in LVM with detraining (standardized mean difference = -0.586; 95%CI = -0.817, -0.355, p<0.001). Independently, length of detraining was not correlated with the change in LVM. However, a meta-regression model revealed length of the detraining, when training status was accounted for, was associated with the reduction of LVM (Q=15.20, df=3, p=0.0017). Highly trained/elite athletes had greater reductions in LVM compared with recreational and newly trained individuals (p<0.01). Limitations included limited number of female participants and inconsistent reporting of intervention details. In summary, LVM is reduced following detraining of one week or more. Further research may provide a greater understanding of the effects of sex, age and type of detraining, on changes in LVM in endurance-trained individuals.</AbstractText><br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 11 Oct 2023; epub ahead of print</small></div>

<div><h4>Nationwide time trends in patients hospitalized for acute coronary syndrome: a worrying generational and social effect among women.</h4><i>Grave C, Gabet A, Cinaud A, Tuppin P, Blacher J, Olié V</i><br /><b>Aims</b><br />To estimate the time trends in the annual incidence of patients hospitalized for acute coronary syndrome (ACS) in France from 2009 to 2021 and to analyse the current sex and social differences in ACS, management, and prognosis.<br /><b>Methods and results</b><br />All patients hospitalized for ACS in France were selected from the comprehensive National Health Insurance database. Age-standardized rates were computed overall and according to age group (over or under 65 years), sex, proxy of socioeconomic status, and ACS subtype [ST-segment elevation (STSE) and non-ST-segment elevation]. Patient characteristics and outcomes were described for patients hospitalized in 2019. Differences in management (coronarography, revascularization), and prognosis were analysed by sex, adjusting for cofonders. In 2019, 143,670 patients were hospitalized for ACS, including 53,227 STSE-ACS (mean age = 68.8 years; 32% women). Higher standardized incidence rates among the most socially deprived people were observed. Women were less likely to receive coronarography and revascularization but had a higher excess in-hospital mortality. In 2019, the age-standardized rate for hospitalized ACS patients reached 210 per 100 000 person-year. Between 2009 and 2019, these rates decreased by 11.4% (men: -11.2%; women: -14.0%). Differences in trends of age-standardized incidence rate have been observed according to sex, age, and social status. Middle aged women (45-64 years) showing more unfavourable trends than in other age classes or in men. In addition, among women the temporal trends were more unfavourable as social deprivation increased.<br /><b>Conclusion</b><br />Despite encouraging overall trends in patients hospitalized for ACS rates, the increasing trends observed among middle-aged women, especially socially deprived women, is worrying. Targeted cardiovascular prevention and close surveillance of this population should be encouraged.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 05 Oct 2023; epub ahead of print</small></div>

<div><h4>Deep learned representations of the resting 12-lead electrocardiogram to predict V̇O2 at peak exercise.</h4><i>Khurshid S, Churchill TW, Diamant N, Di Achille P, ... Lubitz SA, Guseh JS</i><br /><b>Aim</b><br />To leverage deep learning on the resting 12-lead ECG to estimate peak oxygen consumption (V̇O2  PEAK) without cardiopulmonary exercise testing (CPET).<br /><b>Methods</b><br />V̇O2  PEAK estimation models were developed in 1,891 individuals undergoing CPET at Massachusetts General Hospital (age 45±19 years, 38% female) and validated in a separate test set (MGH Test, n=448) and external sample (BWH Test, n=1,076). Three penalized linear models were compared: a) age, sex, and body mass index (\"Basic\"), b) Basic plus standard ECG measurements (\"Basic + ECG Parameters\"), and c) Basic plus 320 deep learning-derived ECG variables instead of ECG measurements (\"Deep ECG-V̇O2\"). Associations between estimated V̇O2  PEAK and incident disease were assessed using proportional hazards models within 84,718 primary care patients without CPET.<br /><b>Results</b><br />Inference ECGs preceded CPET by 7 days (median, interquartile range 27-0 days). Among models, Deep ECG-V̇O2 was most accurate in MGH Test (r=0.845, 95%CI 0.817-0.870; mean absolute error [MAE] 5.84, 95%CI 5.39-6.29) and BWH Test (r=0.552, 95%CI 0.509-0.592, MAE 6.49, 95%CI 6.21-6.67). Deep ECG-V̇O2 also outperformed the Wasserman, Jones, and FRIEND reference equations (p<0.01 for comparisons of correlation). Performance was higher in BWH Test when individuals with heart failure were excluded (r=0.628, 95%CI 0.567-0.682; MAE 5.97, 95%CI 5.57-6.37). Deep ECG-V̇O2 estimated V̇O2  PEAK <14 mL/kg/min was associated with increased risks of incident atrial fibrillation (hazard ratio 1.36 [95%CI 1.21-1.54]), myocardial infarction (1.21 [1.02-1.45]), heart failure (1.67 [1.49-1.88]), and death (1.84 [1.68-2.03]).<br /><b>Conclusions</b><br />Deep learning-enabled analysis of the resting 12-lead ECG can estimate exercise capacity (V̇O2  PEAK) at scale to enable efficient cardiovascular risk stratification.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 05 Oct 2023; epub ahead of print</small></div>

<div><h4>Clinical outcomes with the use of sodium-glucose cotransporter-2 inhibitors in patients with atrial fibrillation and type 2 diabetes mellitus: a multicenter, real-world cohort study.</h4><i>Jang J, Park S, Kim S, Kim SH, ... Ihm SH, Choi Y</i><br /><b>Aim</b><br />Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to improve cardiovascular outcomes and reduce the incidence of atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM). We investigated the clinical outcomes with and without the use of SGLT2is in patients with T2DM and concomitant AF.<br /><b>Methods</b><br />We derived patient data from a clinical data warehouse constructed from the electronic medical records of 7 medical centers. Data for 11,012 patients diagnosed with both AF and T2DM were analyzed. New SGLT2i users were classified into the SGLT2i group and those who were not prescribed SGLT2is were classified into the control group. We performed a 1:2 propensity score (PS)-matching analysis. The primary endpoint was a composite of all-cause death or hospitalization due to heart failure (HF) events in three years.<br /><b>Results</b><br />The PS-matched population consisted of 1,115 patients in the SGLT2i group and 2,050 patients in the control group. Incidence of the primary endpoint was significantly lower in the SGLT2i group (8.4% vs. 14.6%, hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.55-0.87). SGLT2i use was associated with significantly lower all-cause mortality (HR 0.43, 95% CI 0.29-0.67) and HF hospitalization (HR 0.77, 95% CI 0.59-0.99). Adverse renal events, defined as more than 50% increase in serum creatinine level or an initiation of dialysis, occurred less often in the SGLT2i group (HR 0.50, 95% CI 0.38-0.66, p<0.001).<br /><b>Conclusion</b><br />Use of SGLT2is in patients with T2DM and concomitant AF was associated with reduced mortality or HF hospitalization events.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 05 Oct 2023; epub ahead of print</small></div>

<div><h4>Blood DNA methylation signature of diet quality, and association with cardiometabolic traits.</h4><i>Domínguez-Barragán J, Fernández-Sanlés A, Hernáez Á, Llauradó-Pont J, ... Elosua R, Lassale C</i><br /><b>Background</b><br />Diet quality might influence cardiometabolic health through epigenetic changes, but this has been little investigated in adults. Our aim was to identify Cytosine-phosphate-Guanine (CpG) dinucleotides associated with diet quality by conducting an epigenome-wide association study (EWAS) based on blood DNA methylation (DNAm), and to assess how diet-related CpGs associate with inherited susceptibility to cardiometabolic traits: body mass index (BMI), systolic blood pressure (SBP), triglycerides, type 2 diabetes (T2D) and coronary heart disease (CHD).<br /><b>Methods</b><br />Meta-EWAS including 5,274 participants in four cohorts from Spain, the US and the UK. We derived three dietary scores (exposures) to measure adherence to a Mediterranean diet (MMDS), to a healthy plant-based diet (HPDI) and to the Dietary Approaches to Stop Hypertension (DASH). Blood DNAm (outcome) was assessed with the Infinium arrays Human Methylation 450 K BeadChip and MethylationEPIC BeadChip. For each diet score, we performed linear EWAS adjusted for age, sex, blood cells, smoking and technical variables, and BMI in a second set of models. We also conducted Mendelian randomization analyses to assess the potential causal relationship between diet-related CpGs and cardiometabolic traits.<br /><b>Results</b><br />We found 18 differentially methylated CpGs associated with dietary scores (p-value < 1.08 × 10-7; Bonferroni correction), of which 12 were previously associated with cardiometabolic traits. Enrichment analysis revealed overrepresentation of diet-associated genes in pathways involved in inflammation and cardiovascular disease. Mendelian randomization analyses suggested that genetically determined methylation levels corresponding to lower diet quality at cg02079413 (SNORA54), cg02107842 (MAST4), and cg23761815 (SLC29A3) were causally associated with higher BMI, and at cg05399785 (WDR8) with greater SBP; and methylation levels associated with higher diet quality at cg00711496 (PRMT1) with lower BMI, T2D risk and CHD risk, and at cg0557921 (AHRR) with lower CHD risk.<br /><b>Conclusions</b><br />Diet quality in adults was related to differential methylation in blood at 18 CpGs, some of which related to cardiometabolic health.Availability: The R code for the analysis is available in the following Github repository: https://github.com/jorgedb98/B64_DIAMETR.git.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 04 Oct 2023; epub ahead of print</small></div>

<div><h4>Validation of Systematic Coronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons in the EPIC Norfolk prospective population cohort.</h4><i>van Trier TJ, Snaterse M, Boekholdt SM, Scholte Op Reimer WJM, ... Peters RJG, Jørstad HT</i><br /><b>Background</b><br />The European Systematic Coronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons (OP) models are recommended to identify individuals at high 10-year risk for cardiovascular disease (CVD). Independent validation and assessment of clinical utility is needed.<br /><b>Aim</b><br />To assess discrimination, calibration and clinical utility of low-risk SCORE2 and SCORE2-OP.<br /><b>Methods</b><br />Validation in individuals aged 40-69 years (SCORE2) and 70-79 years (SCORE2-OP) without baseline CVD or diabetes from the European Prospective Investigation of Cancer (EPIC)-Norfolk prospective population study. We compared 10-year CVD risk estimates with observed outcomes (cardiovascular mortality, non-fatal myocardial infarction and stroke).<br /><b>Results</b><br />For SCORE2, 19,560 individuals (57% women) had 10-year CVD risk estimates of 3.7% (95% confidence interval (CI) 3.6-3.7) versus observed 3.8% (95% CI 3.6-4.1) (observed (O)/expected (E) ratio 1.0 (95% CI 1.0-1.1). The area under the curve (AUC) was 0.75 (95% CI 0.74-0.77), with underestimation of risk in men (O/E 1.4 (95% CI 1.3-1.6)) and overestimation in women (O/E 0.7 (95% CI 0.6-0.8). Decision curve analysis (DCA) showed clinical benefit. SCORE2-OP in 3,113 individuals (58% women) predicted 10-year CVD events in 10.2% (95% CI 10.1-10.3) versus observed 15.3% (95% CI 14.0-16.5) (O/E ratio 1.6 (95% CI 1.5-1.7)). The AUC was 0.63 (95% CI 0.60-0.65) with underestimation of risk across sex and risk ranges. DCA showed limited clinical benefit.<br /><b>Conclusion</b><br />In a UK population cohort, the SCORE2 low-risk model showed fair discrimination and calibration, with clinical benefit for preventive treatment initiation decisions. In contrast, in individuals aged 70-79 years, SCORE2-OP demonstrated poor discrimination, underestimated risk in both sexes, and limited clinical utility.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 04 Oct 2023; epub ahead of print</small></div>

<div><h4>Soluble urokinase Plasminogen Activator Receptor (suPAR) mediates the effect of a lower education level on adverse outcomes in patients with coronary artery disease.</h4><i>Füller D, Liu C, Ko YA, Alkhoder AA, ... Sperling LS, Quyyumi AA</i><br /><b>Aims</b><br />To investigate whether the adverse impact of lower educational attainment on mortality risk in patients with coronary artery disease (CAD) is mediated by activation of inflammatory and immune pathways, estimated as elevated suPAR levels.<br /><b>Methods</b><br />In 3,164 patients undergoing coronary angiography, we investigated multivariable associations between suPAR and educational attainment and assessed the relationship between a lower educational level (defined as high school degree or less as highest educational qualification) and outcomes using Cox proportional hazard and Fine and Gray\'s sub-distribution competing risk models. Potential mediating effect through suPAR and hs-CRP was assessed using mediation analysis.<br /><b>Results</b><br />1,814 patients (57.3%) had achieved a higher (≥college), and 1,350 patients (42.7%) a lower (≤high school) education level. SuPAR levels were 9.0% [95% CI 6.3-11.8, p ≤0.0001] higher in patients with lower compared to higher educational qualifications after covariate adjustment. Lower educational attainment was associated with a higher risk of cardiovascular death after adjustment for demographic, clinical, and behavioral covariates, including CAD severity and heart failure history, medication use, and hs-CRP levels (HR 1.26 [95% CI 1.02-1.55, p=0.03]). However, after adjustment for suPAR levels, the effect of a lower educational level on cardiovascular death became insignificant. Values were similar for all-cause death. SuPAR levels mediated 49% and hs-CRP levels 17% of the cardiovascular death risk attributable to lower educational attainment.<br /><b>Conclusion</b><br />Circulating suPAR levels importantly mediate the effects of lower educational attainment on mortality, indicating the importance of systemic inflammation and immune dysregulation as biologic mediators of adverse social determinants of health.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 03 Oct 2023; epub ahead of print</small></div>

<div><h4>Long-term lifestyle change and risk of mortality and type 2 diabetes in patients with cardiovascular disease.</h4><i>Bonekamp NE, Visseren FLJ, Cramer MJ, Dorresteijn JAN, ... Geleijnse JM, Koopal C</i><br /><b>Aims</b><br />To quantify the relationship between self-reported long-term lifestyle changes (smoking, waist circumference, physical activity, and alcohol consumption) and clinical outcomes in patients with established cardiovascular disease (CVD).<br /><b>Methods</b><br />Data was used from 2,011 participants (78% male, age 57 ± 9 years) from the UCC-SMART cohort who returned for a reassessment visit (SMART2) after approximately 10 years. Self-reported lifestyle change was classified as persistently healthy, improved, worsened or persistently unhealthy. Cox proportional hazard models were used to quantify the relationship between lifestyle change and risk of (cardiovascular) mortality and incident type 2 diabetes (T2D).<br /><b>Results</b><br />Fifty-seven percent of participants was persistently healthy, 17% improved their lifestyle, 8% worsened, and 17% was persistently unhealthy. During a median follow-up time of 6.1 [IQR 3.6-9.6] years after the SMART2 visit, 285 deaths occurred and 99 new T2D diagnoses were made. Compared to a persistently unhealthy lifestyle, individuals who maintained a healthy lifestyle had a lower risk of all-cause mortality (HR 0.48, 95%CI 0.36-0.63), cardiovascular mortality (HR 0.57, 95%CI 0.38-0.87), and incident T2D(HR 0.46, 95%CI 0.28-0.73). Similarly, those who improved their lifestyle had a lower risk of all-cause mortality (HR 0.52, 95%CI 0.37-0.74), cardiovascular mortality (HR 0.46, 95%CI 0.26-0.81), and incident T2D (HR 0.50, 95%CI 0.27-0.92).<br /><b>Conclusion</b><br />These findings suggest that maintaining or adopting a healthy lifestyle can significantly lower mortality and incident T2D risk in CVD patients. This study emphasizes the importance of ongoing lifestyle optimization in CVD patients, highlighting the potential for positive change regardless of previous lifestyle habits.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 29 Sep 2023; epub ahead of print</small></div>

<div><h4>Development and validation of cardiovascular risk prediction equations in 76,000 people with known cardiovascular disease.</h4><i>Holt A, Batinica B, Liang J, Kerr A, ... Jackson R, Poppe KK</i><br /><b>Background</b><br />Multiple health administrative databases can be individually linked in Aotearoa New Zealand, using encrypted identifiers. These databases were used to develop cardiovascular risk prediction equations for patients with known cardiovascular disease (CVD).<br /><b>Methods</b><br />Administrative health databases were linked to identify all people aged 18-84 years with known CVD, living in Auckland and Northland, Aotearoa New Zealand on 1 January 2014. The cohort was followed until study outcome, death, or 5 years. The study outcome was death or hospitalisation due to ischaemic heart disease, stroke, heart failure, or peripheral vascular disease. Sex-specific 5-year cardiovascular disease risk prediction equations were developed using multivariable Fine and Gray models.<br /><b>Results</b><br />43,862 men (median age: 67 years [interquartile range: 59-75]) and 32,724 women (median age: 70 years [interquartile range: 60-77) had 14,252 and 9,551 cardiovascular events, respectively. Equations were well calibrated with good discrimination. Increasing age and deprivation, recent cardiovascular hospitalisation, Māori ethnicity, smoking history, heart failure, diabetes, chronic renal disease, atrial fibrillation, use of blood-pressure lowering and anti-thrombotic drugs, haemoglobin A1c, total cholesterol/HDL cholesterol, and creatinine were statistically significant independent predictors of the study outcome. 14% of men and 23% of women had predicted 5-year cardiovascular risk <15%, while 28% and 24%, had ≥40% risk.<br /><b>Conclusion</b><br />Robust cardiovascular risk prediction equations were developed from linked routine health databases, a currently underutilised resource worldwide. The marked heterogeneity demonstrated in predicted risk suggests that preventive therapy in people with known CVD would be better informed by risk stratification beyond a one-size-fits-all high-risk categorisation.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 28 Sep 2023; epub ahead of print</small></div>

<div><h4>Concomitant exposure to air pollution, green space and noise, and risk of myocardial infarction. A Cohort study from Denmark.</h4><i>Harbo Poulsen A, Sørensen M, Hvidtfeldt UA, Ketzel M, ... Münzel T, Raaschou-Nielsen O</i><br /><b>Background:</b><br/>and aims</b><br />The three correlated environmental exposures: air pollution, road traffic noise, and green space have all been associated with the risk of myocardial infarction (MI). The present study aimed to analyse their independent and cumulative association with MI.<br /><b>Methods</b><br />In a cohort of all Danes aged 50 or older in the period 2005 to 2017, five-year time-weighted average exposure to fine particles (PM2.5), ultrafine particles, elemental carbon, nitrogen dioxide (NO2), and road traffic noise at the most and least exposed façades of residence was estimated. Green space around residences was estimated from land use maps. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% interval (CI), and cumulative risk indices (CRI) were calculated. All expressed per inter quartile range. Models were adjusted for both individual and neighbourhood-level sociodemographic covariates.<br /><b>Results</b><br />The cohort included 1,964,702 persons. During follow-up, 71,285 developed MI. In single-exposure models, all exposures were associated with an increased risk of MI. In multipollutant analyses, an independent association with risk of MI was observed for PM2.5 (HR: 1.026, 95% CI: 1.002-1.050), noise at most exposed façade (HR: 1.024, 95% CI: 1.012-1.035) and lack of green space within 150 m of residence (HR: 1.018, 95% CI: 1.010-1.027). All three factors contributed significantly to the CRI (1.089, 95% CI: 1.076-1.101).<br /><b>Conclusions</b><br />In a nationwide cohort study, air pollution, noise and lack of green space were all independently associated with an increased risk of MI. The air pollutant PM2.5 was closest associated with MI risk.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 21 Sep 2023; epub ahead of print</small></div>

<div><h4>A systematic review and cluster analysis approach of 103 studies of high-intensity interval training on cardiorespiratory fitness.</h4><i>Cadenas-Sanchez C, Fernández-Rodríguez R, Martínez-Vizcaíno V, de Los Reyes González N, ... Galán-Mercant A, Jiménez-Pavón D</i><br /><b>Aims</b><br />To systematically review the systematic reviews and meta-analyses examining the effect of high-intensity interval training (HIIT) protocols on improving cardiorespiratory fitness (CRF) and to characterize the main patterns of HIIT modalities using clustering statistical procedures to examine their potential differences on improving CRF. Finally, we aimed to develop a comprehensive guideline for reporting HIIT protocols.<br /><b>Methods</b><br />A systematic review was conducted on PubMed and Web of Science from their inception to 31 October 2022 for systematic reviews and meta-analysis aimed at assessing the effect of HIIT on CRF in the entire study population. The AMSTAR 2 tool was used to evaluate the risk of bias of each review. Additionally, a principal component analysis testing the data adequacy for the factor solution through the Kaiser-Meyer-Olkin procedures test was conducted. Once the number of factors was identified, in order to identify data patterns according to the main characteristics of the HIIT protocols, a two-step cluster analysis was conducted.<br /><b>Results</b><br />Nineteen systematic reviews and/or meta-analyses comprising 103 studies were included. Clustering of systematic reviews and meta-analyses identified three HIIT modalities (\"HIIT-normal mixed\", \"HIIT-long running\" and \"HIIT-short cycling\") underlying the interventions across the included studies. Similar effectiveness in increasing CRF among the three HIIT modalities was observed. Subgroup analyses showed no significant differences in CRF by sex, weight status, study design, and baseline physical activity level (p > 0.05), but differences were observed by age group, and exercise intensity indicator used in the HIIT programs (p < 0.05).<br /><b>Conclusion</b><br />All three HIIT modalities produced significant improvements of CRF, although some modalities showed greater changes for some specific age groups or intensity indicators.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 21 Sep 2023; epub ahead of print</small></div>

<div><h4>Cumulative social disadvantage and cardiovascular disease burden and mortality.</h4><i>Hahad O, Gilan DA, Chalabi J, Al-Kindi S, ... Wild PS, Münzel T</i><br /><b>Aims</b><br />To investigate the association between cumulative social disadvantage and cardiovascular burden and mortality in a large cohort of the general population.<br /><b>Methods and results</b><br />Cross-sectional (n = 15 010, aged 35 to 74 years, baseline investigation period 2007 to 2012) and longitudinal data (5- and 10-year follow-ups from 2012 to 2022) from the Gutenberg Health Study were used to investigate the association between individual socioeconomic status (SES, measured via a validated questionnaire) and cardiovascular disease (CVD, composite of atrial fibrillation, coronary artery disease, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and/or venous thromboembolism) risk and mortality. Subjects with prevalent CVD had a lower SES sum score, as well as lower education, occupation, and household net-income scores (all P < 0.0001). Logistic regression analysis showed that a low SES (vs. high, defined by validated cut-offs) was associated with 19% higher odds of prevalent CVD [odds ratio (OR) 1.19, 95% CI 1.01; 1.40] in the fully adjusted model. At 5-year follow-up, low SES was associated with both increased cardiovascular [hazard ratio (HR) 5.36, 2.24; 12.82] and all-cause mortality (HR 2.23, 1.51; 3.31). At 10-year follow-up, low SES was associated with a 68% higher risk of incident CVD (OR 1.68, 1.12; 2.47) as well as 86% higher all-cause mortality (HR 1.86, 1.55; 2.24). In general, the education and occupation scores were stronger related to risk of CVD and death than the household net-income score. Low SES was estimated to account for 451.45 disability-adjusted life years per 1000 people (years lived with disability 373.41/1000 and years of life lost 78.03/1000) and an incidence rate of 11 CVD cases and 3.47 CVD deaths per 1000 people per year. The population attributable fraction for CVD incidence after 5 years was 4% due to low SES.<br /><b>Conclusion</b><br />Despite universal healthcare access, cumulative social disadvantage remains associated with higher risk of CVD and mortality. Dimensions of education and occupation, but not household net income, are associated with outcomes of interest.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 18 Sep 2023; epub ahead of print</small></div>

<div><h4>Cumulative Remnant Cholesterol Predicts Cardiovascular Outcomes in Elderly Patients with Atherosclerotic Cardiovascular Disease.</h4><i>Xiao Z, Lin Z, Xu L, Xu W, ... Feng W, Chen Y</i><br /><b>Aims</b><br />Remnant cholesterol (RC) reportedly mediates residual cardiovascular risk in atherosclerotic cardiovascular diseases (ASCVD). However, few studies have characterized long-term cumulative RC exposure among elderly people. The study aimed to evaluate the association between cumulative exposure to RC and incident major adverse cardiovascular events (MACE) by analyzing a cohort of elderly patients with ASCVD.<br /><b>Methods</b><br />This retrospective multicenter cohort study enrolled ASCVD participants aged ≥75 years with baseline visits occurring from 2006 to 2012 followed by four in-person visits. Cumulative RC was estimated as the area under the curve using measurements from the first to fourth visits by using 9-year data. The time-weighted average (TWA) RC was expressed as cumulative exposure to RC averaged by years. All outcomes were follow-up from visit fourth to year 2021. Outcomes included a composite of MACE (stroke, unstable angina pectoris, myocardial infarction, and cardiac death).<br /><b>Results</b><br />We included 4,680 participants (73.1% male, mean age 79.3 ± 2.5 years). The median follow-up duration was 6.1 years (interquartile range: 3.4-6.6 years). In the multivariable model adjusted for traditional cardiovascular risk factors, low-density lipoprotein cholesterol level, and most recent RC level, the hazard ratios for MACE that compared the high and low tertiles of the RC variables were 1.30 (95% confidence interval [CI], 1.16-1.44) for cumulative RC and 1.36 (95% CI, 1.23-1.52) for TWA RC. Consistent significant associations were observed among most propensity score analyses.<br /><b>Conclusions</b><br />Long-term cumulative RC was independently associated with incident MACE in elderly participants with ASCVD, suggesting that achieving and maintaining optimal RC levels later in life may still improve cardiovascular outcomes.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 14 Sep 2023; epub ahead of print</small></div>

<div><h4>Five-year Changes in Weight and Risk of Atrial Fibrillation in the Danish Diet, Cancer, and Health Cohort.</h4><i>Frederiksen TC, Krogh Christiansen M, Benjamin EJ, Overvad K, ... Dahm CC, Kjærulf Jensen H</i><br /><b>Background</b><br />Obesity is a major risk factor for atrial fibrillation (AF). Compared to stable weight, gaining weight was associated with a higher risk of incident AF in observational studies. The results, however, are conflicting regarding weight loss and risk of AF. This study aimed to assess the association between five-year weight changes and risk of incident AF.<br /><b>Methods</b><br />The study was based on participants from the Danish Diet, Cancer and Health cohort. Body mass index (BMI) was assessed at a baseline examination and at a second examination five years later. Diagnoses of AF and comorbidities were retrieved from the Danish National Patient Registry.<br /><b>Results</b><br />In total, 43,758 participants without prior AF were included. The median age was 61 years and 54% were female. During a median follow-up of 15.7 years, 5,312 individuals had incident AF (incidence rate 8.6/1,000 person-years). Compared to stable weight, weight gain between 2.5 to 5 BMI units (kg/m2) was associated with a higher risk of AF (HR 1.24, 95% CI 1.09-1.41). Weight gain of 5 or more BMI units (kg/m2) was associated with a HR of 1.95 (95% CI 1.48-2.56) of incident AF. However, there was no statistically significant association between weight loss and risk of AF.<br /><b>Conclusions</b><br />Five-year weight gain was associated with greater risk of AF compared with stable weight in the Danish Diet, Cancer and Health cohort. There was no statistically significant association between weight loss and risk of AF.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 14 Sep 2023; epub ahead of print</small></div>

<div><h4>Denture use and Risk for Cardiometabolic Disease: Observational and Mendelian Randomization analyses.</h4><i>Liu Y, Qin H, Li T, Feng C, ... Tonetti M, Zong G</i><br /><b>Aims</b><br />Denture use may potentially increase the risk of cardiometabolic diseases (CMDs), but the casual relevance and strength of the associations are currently unknown.<br /><b>Methods</b><br />495 938 participants from the UK Biobank were included in the observational analyses. Linkage disequilibrium score (LDSC) regression and Mendelian randomization analyses were employed to estimate genetic correlation and the associations between the genetic liability for denture use with coronary artery disease, myocardial infarction, heart failure (HF), any stroke (AS), ischemic stroke, hemorrhagic stroke, type 2 diabetes (T2D), and related clinical risk factors.<br /><b>Results</b><br />In observational analysis, denture use was associated with 14-25% higher risks of various CMDs. LDSC analysis found that denture use showed a positive genetic correlation with CMDs (rg 0.21-0.38). Genetic liability for denture use was associated with an elevated risk of HF [odds ratio:1.49 (1.20-1.83)] and T2D [1.11 (1.01-1.24)]. By integrating genetic summary data of denture use with the sum of Decayed, Missing, and Filled tooth Surfaces (DMFS), a clinical measure of dental caries obtained from an independent source, genetically-determined denture use/DMFS was also associated with an elevated risk of AS [1.21 (1.04-1.40)]. Furthermore, genetically-predicted denture use/DMFS was significantly associated with established cardiometabolic risk factors, including high-density lipoprotein cholesterol, triglycerides, waist circumference, waist-to-hip ratio, and height.<br /><b>Conclusion</b><br />Our study supported potential causal associations between the genetic liability for denture use and risks for HF, AS, and T2D, and related clinical risk factors. These findings may inform prevention and intervention strategies targeting dental diseases and cardiometabolic diseases.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 11 Sep 2023; epub ahead of print</small></div>

<div><h4>Changes in alcohol consumption habits and risk of atrial fibrillation: a nationwide population-based study.</h4><i>Leea JW, Roh SY, Yoon WS, Kim J, ... Kan HT, Lee DI</i><br /><b>Aims</b><br />Heavy alcohol consumption is an established risk factor for atrial fibrillation (AF). However, the association between habitual changes in heavy habitual drinkers and incident AF remains unclear. The aim of this study was to evaluate whether absolute abstinence or reduced drinking decreases incident AF in heavy habitual drinkers.<br /><b>Methods and results</b><br />Atrial fibrillation-free participants with heavy alcohol consumption registered in the Korean National Health Insurance Service database between 2005 and 2008 were enrolled. Habitual changes in alcohol consumption between 2009 and 2012 were classified as sustained heavy drinking, reduced drinking, and absolute abstinence. The primary outcome measure was new-onset AF during the follow-up. To minimize the effect of confounding variables on outcome events, inverse probability of treatment weighting (IPTW) analysis was performed. Overall, 19 425 participants were evaluated. The absolute abstinence group showed a 63% lower incidence of AF (IPTW hazard ratio: 0.379, 95% confidence interval: 0.169-0.853) than did the sustained heavy drinking group. Subgroup analysis identified that abstinence significantly reduced incident AF in participants with normal body mass index and without hypertension, diabetes, dyslipidaemia, heart failure, stroke, chronic kidney disease, or coronary artery disease (all P-value <0.05). There was no statistical difference in incident AF in participants with reduced drinking compared with sustained heavy alcohol group.<br /><b>Conclusion</b><br />Absolute abstinence could reduce the incidence of AF in heavy alcohol drinkers. Comprehensive clinical measures and public health policies are warranted to motivate alcohol abstinence in heavy drinkers.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 06 Sep 2023; epub ahead of print</small></div>

<div><h4>Cost-effectiveness and diagnostic accuracy of focused cardiac ultrasound in the pre-participation screening of athletes: the SPORT-FoCUS Study.</h4><i>Halasz G, Capelli B, Nardecchia A, Cattaneo M, ... Piepoli M, Via G</i><br /><b>Background</b><br />The role of Pre-participation screening (PPS) modalities in preventing sudden cardiac death (SCD) in athletes is debated due to a high false positive rate. Focused Cardiac Ultrasound (FoCUS) has shown higher sensitivity and specificity, but its cost-effectiveness remains uncertain. This study aimed to determine the diagnostic performance and cost-effectiveness of FoCUS use in PPS.<br /><b>Methods</b><br />2111 athletes (77.4% male, mean age 24.9±15,2years) underwent standardized family and medical history collection (MH), physical examination (PEX), resting ECG, FoCUS (10min/5views-protocol), comprehensive Echocardiography and exercise stress test(EST). We prospectively evaluated three PPS incremental models: Model-A = standardized MH and physical examination; Model-B = Model-A plus resting and stress-ECG; Model-C = Model-B plus FoCUS (10min/5views-protocol). We determined their incremental diagnostic accuracy and cost-effectiveness ratio.<br /><b>Results</b><br />30 athletes were diagnosed with a cardiac condition associated with SCD: 3 were identified by Model-A, 14 by Model-B, 13 athletes by Model-C. The introduction of FoCUS markedly increased the Sensitivity of PPS, compared with model-A and model-B (Sensitivity 94% vs. 19% vs. 58%, Specificity 93% vs. 93% vs. 92%). The total screening cost (TSC) were: Model-A 35.64Eur, Model-B 87.68Eur and Model-C 120.89Eur. Considering the sole conditions at risk of SCD, the Incremental Cost Effectiveness Ratio was 135.62Eur for model-B and 114.31 for model-C.<br /><b>Conclusions</b><br />The implementation of FoCUS into the PPS allows to identify a significantly greater number of athletes at risk of SCD and markedly lowers the false negative rate. Furthermore, the incorporation of FoCUS into the screening process has shown to be cost-effective.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 05 Sep 2023; epub ahead of print</small></div>

<div><h4>Leg-focused high-weight resistance training improves ventricular stroke volume, exercise capacity and strength in young patients with a Fontan circulation.</h4><i>Scheffers LE, Helbing WA, Pereira T, Utens EMWJ, ... van den Berg LE, Rotterdam Exercise Team </i><br /><b>Introduction</b><br />Effective therapy to improve exercise capacity in Fontan patients is lacking. Leg-focused high-weight resistance training might augment the peripheral muscle pump and thereby improve exercise capacity.<br /><b>Methods</b><br />This randomized semi-cross-over controlled trial investigated effects of a 12-week leg-focused high-weight resistance training plus high-protein diet, on (sub)maximal exercise capacity, cardiac function (assessed with cardiovascular magnetic resonance), muscle strength and quality of life in pediatric Fontan patients.<br /><b>Results</b><br />Twenty-eight pediatric Fontan patients were included, 27 patients, (median age 12.9 [10.5-15.7]), successfully completed the program. Peak oxygen uptake (PeakVO2) at baseline was reduced (33.3 ml/kg/min [27.1-37.4],73% [62-79] of predicted). After training PeakVO2/kg and Peak workload improved significantly with +6.2 ml/kg/min [95%CI: 3.4-9.0](+18%) p<0.001 and +22 Watts [95%CI: 12-32](+18%) p<0.001 respectively, compared to the control period. Indexed single ventricle stroke volume increased significantly (43 ml/beat/m2 [40-49] versus 46 [41-53], p=0.014), as did inferior vena cava flow (21 ml/beat/m2 [18-24] versus 23 [20-28], p=0.015), while superior vena cava flow remained unchanged. Strength of all measured leg muscles increased significantly compared to the control period. Self-reported quality of life improved on the physical functioning and change in health domains of the child health questionnaire, parent-reported quality of life improved on the bodily pain, general health perception, and change in health domains compared to the control period.<br /><b>Conclusion</b><br />In a relatively large group of 27 older Fontan children, 12-weeks of leg-focused high-weight resistance training improved exercise capacity, stroke volume, (sub)maximal exercise capacity, muscle strength, and domains of quality of life.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 05 Sep 2023; epub ahead of print</small></div>

<div><h4>Worldwide trends in mortality for hypertensive heart disease from 1990 to 2019 with projection to 2034: data from the Global Burden of Disease 2019 study.</h4><i>Lu WL, Yuan JH, Liu ZY, Su ZH, ... Li SJ, Zhang H</i><br /><b>Aims</b><br />This study aims to analyse the worldwide trends in hypertensive heart disease (HHD) mortality and associations with age, period, and birth cohort and predict the future burden of HHD deaths.<br /><b>Methods and results</b><br />Mortality estimates were obtained from Global Burden of Disease 2019 study. We used age-period-cohort (APC) model to examine the age, period, and cohort effects on HHD mortality between 1990 and 2019. Bayesian APC model was utilized to predict HHD deaths to 2034. The global HHD deaths were 1.16 million in 2019 and were projected to increase to 1.57 million in 2034, with the largest increment in low- and middle-income countries (LMICs). Between 1990 and 2019, middle/high-middle socio-demographic index (SDI) countries had the largest mortality reductions (annual percentage change = -2.06%), whereas low SDI countries saw a lagging performance (annual percentage change = -1.09%). There was a prominent transition in the age distribution of deaths towards old-age population in middle/high-middle SDI countries, while the proportion of premature deaths (aged under 60 years) remained at 24% in low SDI countries in 2019. Amongst LMICs, Brazil, China, and Ethiopia showed typically improving trends both over time and in recent birth cohorts, whereas 63 countries including Indonesia, the Philippines, and Pakistan had unfavourable or worsening risks for recent periods and birth cohorts.<br /><b>Conclusion</b><br />The HHD death burden in 2019 is vast and is expected to increase rapidly in the next decade, particularly for LMICs. Limited progress in HHD management together with high premature mortality would exact huge human and medical costs in low SDI countries. The examples from Brazil, China, and Ethiopia suggest that efficient health systems with action on improving hypertension care can reduce HHD mortality effectively in LMICs.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 04 Sep 2023; epub ahead of print</small></div>

<div><h4>Oxidative stress-related genetic variation and antioxidant vitamin intake in intact and ruptured abdominal aortic aneurysm: a Swedish population-based retrospective cohort study.</h4><i>Vats S, Sundquist K, Sundquist J, Zhang N, ... Gottsäter A, Memon AA</i><br /><b>Aims</b><br />The aim of this study is to investigate how genetic variations in genes related to oxidative stress, intake of antioxidant vitamins, and any potential interactions between these factors affect the incidence of intact abdominal aortic aneurysm (AAA) and its rupture (rAAA), accounting for sex differences where possible.<br /><b>Methods and results</b><br />The present retrospective cohort study (n = 25 252) uses baseline single-nucleotide polymorphisms (SNPs) and total antioxidant vitamin intake data from the large population-based, Malmö Diet and Cancer Study. Cumulative incidence of intact AAA was 1.6% and of rAAA 0.3% after a median follow-up of 24.3 years. A variant in NOX3 (rs3749930) was associated with higher rAAA risk in males [adjusted hazard ratio (aHR): 2.49; 95% confidence interval (CI): 1.36-4.35] and the overall population (aHR: 1.88; 95% CI: 1.05-3.37). Higher intakes of antioxidant vitamins, riboflavin, and folate were associated with 20% and 19% reduced intact AAA incidence, respectively. Interestingly, the inverse associations between riboflavin and vitamin D intake with intact AAA incidence were stronger in the individuals carrying the NOX3 variant as compared with the wild-type recessive genotype, i.e. by 60% and 66%, respectively (P for interaction < 0.05). Higher riboflavin intake was associated with a 33% male-specific intact AAA risk reduction, while higher intake of vitamin B12 intake was associated with 55% female-specific intact AAA risk increase; both these associations were significantly modified by sex (P for interaction < 0.05).<br /><b>Conclusions</b><br />Our findings highlight the role of oxidative stress genetic variations and antioxidant vitamin intake in AAA. Although a low AAA/rAAA sample size limited some analyses, especially in females, our findings highlight the need for future randomized controlled trials and mechanistic studies, to explore the potential benefits of antioxidant vitamins while accounting for genetic and sex differences.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 04 Sep 2023; epub ahead of print</small></div>

<div><h4>Association of Tobacco Smoke Exposure with Metabolic Profile from Childhood to Early Adulthood. The Special Turku Coronary Risk Factor Intervention Project (STRIP).</h4><i>Lehtovirta M, Pahkala K, Rovio SP, Magnussen CG, ... Ala-Korpela M, Raitakari OT</i><br /><b>Aims</b><br />To investigate the associations between passive tobacco smoke exposure and daily smoking with a comprehensive metabolic profile, measured repeatedly from childhood to adulthood.<br /><b>Methods</b><br />Study cohort was derived from the Special Turku Coronary Risk Factor Intervention Project(STRIP). Smoking status was obtained by questionnaire, while serum cotinine concentrations were measured using gas chromatography. Metabolic measures were quantified by nuclear magnetic resonance metabolomics at 9(n = 539), 11(n = 536), 13(n = 525), 15(n = 488), 17(n = 455), and 19(n = 409) years. Association of passive tobacco smoke exposure with metabolic profile compared participants who reported less-than-weekly smoking and had serum cotinine concentration <1 ng/mL(no exposure) to those whose cotinine concentration was ≥10 ng/mL(passive tobacco smoke exposure). Associations of daily smoking with metabolic profile in adolescence were analysed by comparing participants reporting daily smoking to those reporting no tobacco use and having serum cotinine concentrations <1 ng/mL.<br /><b>Results</b><br />Passive tobacco smoke exposure was directly associated with the serum ratio of monounsaturated fatty acids to total fatty acids (β=0.34SD, [0.17-0.51], p < 0.0001) and inversely associated with the serum ratios of polyunsaturated fatty acids. Exposure to passive tobacco smoke was directly associated with VLDL particle size (β=0.28SD, [0.12-0.45], p = 0.001), and inversely associated with HDL particle size (β=-0.21SD, [-0.34-(-0.07)], p = 0.003). Daily smokers exhibited a similar metabolic profile to those exposed to passive tobacco smoke. These results persisted after adjusting for body mass index, STRIP study group allocation, dietary target score, pubertal status, and parental socio-economic status.<br /><b>Conclusions</b><br />Both passive and active tobacco smoke exposure during childhood and adolescence are detrimentally associated with circulating metabolic measures indicative of increased cardiometabolic risk.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 01 Sep 2023; epub ahead of print</small></div>

<div><h4>Refining prediction of stroke in sinus node dysfunction patients without atrial fibrillation using a P-combined score: a multi-centre study.</h4><i>Dong H, Zhang Y, Sun D, Wang G, ... Xia Y, Yang X</i><br /><b>Aims</b><br />Isolated sinus node dysfunction (ISND) is a sinus node dysfunction without atrial fibrillation. A high risk of ischaemic stroke (IS) has been reported in ISND populations. However, current guidelines do not recommend anticoagulation in ISND management. P-wave indicates ISND-related atrial remodelling. P-wave indices and the CHA2DS2-VASc score may contribute to risk stratification for ISND-related IS.<br /><b>Methods and results</b><br />In this multi-centre longitudinal cohort, ISND patients were divided into development (n = 1185) and external validation (n = 988) cohorts. Ischaemic stroke prediction capacity of the P-combined score was assessed with regard to discrimination, calibration, and clinical effectiveness. The cut-off value of the score was confirmed by using a restricted cubic spline curve. One hundred and twenty-four (10.46%) ISND patients developed IS [1.63%/year; 95% confidence interval (CI): 1.49-1.78%/year] after a median 3.02-year follow-up in the development cohort. The P-wave terminal force in electrocardiogram-lead V1 (PTFV1) was the only significantly abnormal P-wave index (adjusted hazard ratio: 2.56; 95% CI: 1.72-3.80). Therefore, we incorporated the PTFV1 with the CHA2DS2-VASc score to generate a P-combined score. For a 5-year IS risk, the P-combined score improved Harrell\'s C-statistic (95% CI) from 0.678 (0.618-0.738) to 0.716 (0.657-0.774) and 0.747 (0.677-0.816) to 0.808 (0.747-0.868) in the development and validation cohorts, respectively, along with calibration and decision curve analyses. The cut-off value of the score was 3 in the development cohort and well-discriminated in the validation cohort.<br /><b>Conclusion</b><br />Chinese ISND patients have a higher IS risk than the general population. Compared with the CHA2DS2-VASc score, the PTFV1-combined CHA2DS2-VASc score shows a better risk-stratification capacity for ISND-related IS.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 31 Aug 2023; epub ahead of print</small></div>

<div><h4>Effects of weight loss in heart failure patients with overweight and obesity: a systematic review and meta-analysis.</h4><i>Chi M, Nie Y, Su Y, Wang N, ... Ma T, Hou Y</i><br /><b>Aims</b><br />To perform a systematic review and meta-analysis to evaluate the impact of weight loss (WL) on the prognosis of overweight and obese patients with heart failure (HF).<br /><b>Methods and results</b><br />We reviewed the literature up to February 1, 2023 from PubMed, Web of Science, Embase, Cochrane Library and Chinese databases for cohort studies and randomized controlled trials (RCTs). Data from eligible studies were extracted, and statistical analyses were performed using Review Manager 5.3. A total of 19 studies (involving 449,882 patients) were included in the systematic review and meta-analyses. The results showed that WL did not reduce the mortality and rehospitalization rates in overweight and obese HF patients, but could improve the quality of life (p = 0.002), cardiac function (p = 0.0001) and exercise capacity (p = 0.03). The subgroup analysis showed that WL from bariatric surgery (BS) reduced the risk of death (p < 0.00001), WL from medication or exercise was not significantly associated with risk of death (p = 0.18), and WL was associated with a higher mortality in the subgroup with unspecified WL modality or unintentional WL (p < 0.00001). In addition, it did not reduce the risk of short-term rehospitalization (p = 0.11), but reduce the rehospitalization rates over the long term (p = 0.03).<br /><b>Conclusion</b><br />WL improves the long-term rehospitalization (> 3 months), quality of life, cardiac function, and exercise capacity in overweight and obese HF patients. Although overall WL is not proved effective, subgroup analysis shows that BS can reduce mortality.<br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 31 Aug 2023; epub ahead of print</small></div>

<div><h4>Down the Rabbit Hole: Reviewing the Evidence for Primary Prevention of Cardiovascular Disease in People with Obesity.</h4><i>Stumpf MAM, Cercato C, de Melo ME, Santos RD, Mancini MC</i><br /><AbstractText>Obesity is a prevalent chronic disorder and a well-known risk factor for cardiovascular disease. However, the evidence of treating obesity for primary prevention of major cardiovascular events is still scarce and controversial. In this review, we provided a comprehensive description of the current evidence in treating obesity regarding cardiovascular protection. Bariatric surgery appears to be the most robust method to reduce events in people without established cardiovascular disease. High compliance to lifestyle interventions can further reduce cardiovascular risk. Concerning pharmacological therapies, a post-hoc analysis from SUSTAIN-6 and a meta-analysis from STEP trials suggest that semaglutide, a GLP-1 receptor agonist, could reduce cardiovascular events in people without established cardiovascular disease. The first study addressed specifically a high-risk population with diabetes and, the second, low or intermediary-risk individuals without diabetes. Tirzepatide, a novel dual GIP/GLP-1 agonist, although not yet tested in specific cardiovascular outcomes trials, could be an alternative since it induces loss in weight similar to the achieved by bariatric surgery. Therefore, extrapolated data in distinct baseline cardiovascular risk populations suggest that these two drugs could be used in primary prevention with the aim of preventing cardiovascular events, but the grade of this evidence is still low. Specifically designed studies are needed to address this specific topic.</AbstractText><br /><br />© 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.<br /><br /><small>Eur J Prev Cardiol: 30 Aug 2023; epub ahead of print</small></div>