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Background: Patients with overweight and obesity are at increased risk of death from multiple causes, including cardiovascular (CV) death, with few therapies proven to reduce the risk., Objectives: This study sought to assess the effect of semaglutide 2.4 mg on all-cause death, CV death, and non-CV death, including subcategories of death and death from coronavirus disease-2019 (COVID-19)., Methods: The SELECT (Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity) trial randomized 17,604 participants ≥45 years of age with a body mass index ≥27 kg/m 2 with established CV disease but without diabetes to once-weekly subcutaneous semaglutide 2.4 mg or placebo; the mean trial duration was 3.3 years. Adjudicated causes of all deaths, COVID-19 cases, and associated deaths were captured prospectively., Results: Of 833 deaths, 485 (58%) were CV deaths, and 348 (42%) were non-CV deaths. Participants assigned to semaglutide vs placebo had lower rates of all-cause death (HR: 0.81; 95% CI: 0.71-0.93), CV death (HR: 0.85; 95% CI: 0.71-1.01), and non-CV death (HR: 0.77; 95% CI: 0.62-0.95). The most common causes of CV death with semaglutide vs placebo were sudden cardiac death (98 vs 109; HR: 0.89; 95% CI: 0.68-1.17) and undetermined death (77 vs 90; HR: 0.85; 95% CI: 0.63-1.15). Infection was the most common cause of non-CV death and occurred at a lower rate in the semaglutide vs the placebo group (62 vs 87; HR: 0.71; 95% CI: 0.51-0.98). Semaglutide did not reduce incident COVID-19; however, among participants who developed COVID-19, fewer participants treated with semaglutide had COVID-19-related serious adverse events (232 vs 277; P = 0.04) or died of COVID-19 (43 vs 65; HR: 0.66; 95% CI: 0.44-0.96). High rates of infectious deaths occurred during the COVID-19 pandemic, with less infectious death in the semaglutide arm, and resulted in fewer participants in the placebo group being at risk for CV death., Conclusions: Compared to placebo, patients treated with semaglutide 2.4 mg had lower rates of all-cause death, driven similarly by CV and non-CV death. The lower rate of non-CV death with semaglutide was predominantly because of fewer infectious deaths. These findings highlight the effect of semaglutide on mortality across a broad population of patients with CV disease and obesity. (Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity [SELECT]; NCT03574597)., Competing Interests: Funding Support and Author Disclosures Dr Scirica has received institutional research grants to Brigham and Women’s Hospital from Better Therapeutics, Merck, Novo Nordisk, and Pfizer; has received consulting fees from Allergan, Amgen, Boehringer Ingelheim, Better Therapeutics, Elsevier Practice Update Cardiology, Esperion, Hanmi, Lexicon, and Novo Nordisk; and holds equity in Health [at] Scale and Doximity. Dr Lincoff has received research grants from AbbVie Inc, AstraZeneca, CSL Behring, Eli Lilly and Company, Esperion Therapeutics, Inc, and Novartis paid to his institution; and has served as a consultant for Akebia Therapeutics Inc, Alnylam Pharmaceuticals Inc, Ardelyx, Eli Lilly and Company, FibroGen, GlaxoSmithKline, Intarcia, Medtronic Vascular Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk, Provention Bio, Entity, and ReCor Medical. Dr Lingvay has received research grants from Boehringer Ingelheim, Merck, Mylan Pharmaceuticals Inc, Novo Nordisk, Pfizer, and Sanofi US Services Inc; has served as a consultant for AstraZeneca, Bayer Healthcare Pharmaceuticals Inc, Biomea, Boehringer Ingelheim, Carmot, Eli Lilly and Company, Intarcia, Intercept Pharmaceuticals, Inc, Janssen Global Services, LLC, Johnson & Johnson Medical Devices & Diagnostics Group-Latin America, LLC, MannKind Corporation, Merck, Novo Nordisk, Pfizer Inc, Sanofi US Services Inc, Shionogi Inc, Structure Therapeutics, Target Pharma, Valeritas, Inc, and Zealand Pharma; and has received travel expenses from Boehringer Ingelheim, Eli Lilly and Company, Johnson & Johnson Medical Devices & Diagnostics Group-Latin America, LLC, Novo Nordisk, Sanofi US Services Inc, and Zealand Pharma A/S. Dr Buscemi has received advisory/consulting honoraria from Novo Nordisk, Eli Lilly, Pfizer, Boehringer Ingelheim, and Dompè. Dr Colhoun has served on advisory panels for Novo Nordisk and Bayer; has received research funding from Sanofi, Roche, and IQVIA; has received grants from Chief Scientist Office, Diabetes UK, European Commission, Juvenile Diabetes Research Foundation, and Medical Research Council; has served on the Speakers Bureau for Novo Nordisk; and holds equity in Roche Pharmaceuticals and Bayer. Dr Craciun has received advisory/consulting fees and/or other support from Novo Nordisk, Eli Lilly, Sanofi, Boehringer Ingelheim, Servier, Berlin Chemie, and Viatris. Dr Hardt-Lindberg is an employee of and stakeholder in Novo Nordisk. Dr Jeppesen is an employee of and stakeholder in Novo Nordisk. Dr Matos is an employee of and stakeholder in Novo Nordisk. Dr Node has received honoraria from AstraZeneca, Bayer Yakuhin, Boehringer Ingelheim Japan, Daiichi-Sankyo, Eli Lilly Japan, Mitsubishi Tanabe Pharma, Merck Sharp & Dohme, Novartis Pharma, and Otsuka; has received research grants from Astellas, Bayer Yakuhin, Boehringer Ingelheim Japan, Fujiyakuhin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, and Novartis Pharma; and has received scholarships from Abbott, Boehringer Ingelheim Japan, Daiichi-Sankyo, Mitsubishi Tanabe Pharma, and Teijin Pharma. Dr Toplak has received institutional research grants from Amgen, Daiichi-Sankyo, Novo Nordisk, and Novartis; and has received consulting/speaker honoraria from Amgen, Daiichi-Sankyo, Novartis, and Novo Nordisk. Dr van Beek has been contracted via the University of Groningen (no personal payment) to undertake consultancy for Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr Weeke is an employee of and stakeholder in Novo Nordisk. Dr Wiviott has received research grants from Amgen, AstraZeneca, Janssen, Merck, and Pfizer; has received consulting fees from Icon, Novo Nordisk, and Verian; has received speaking honoraria from Harvard Medical School; is a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc, Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Roche, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, The Medicines Company, and Zora Biosciences; and his spouse, Dr Caroline Fox, is a former employee of Merck, Flagship Labs, and current employee of Vertex. Dr Deanfield has received consulting honoraria from Amgen, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, and Bayer; and has received research grants from British Heart Foundation, MRC(UK), National Institute for Health and Care Research, PHE, Merck Sharp & Dohme, Pfizer, Aegerion, Colgate, and Roche. Dr Ryan has received consulting honoraria from Altimmune, Amgen, Biohaven, Boehringer Ingelheim, Calibrate, Carmot Therapeutics, CinRx, Eli Lilly, Epitomee, Gila Therapeutics, Ifa Celtic, Novo Nordisk, Pfizer, Rhythm, Scientific Intake, Wondr Health, and Zealand; and has received stock options from Calibrate, Epitomee, Scientific Intake, and Xeno Bioscience. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cardiovascular disease (CVD) is the leading cause of excessive and premature mortality in patients with bipolar disorder (BD). Despite immune cells participating considerably in the pathogenesis of CVD, limited data are available regarding leukocyte phenotypes in patients with BD and CVD. This study aimed to evaluate associations between circulating leukocyte subset and CVD among patients with BD., Methods: A total of 109 patients with BD-I and cardiologist-confirmed CVD diagnosis (i.e., case) were matched with 109 BD-I patients without CVD (i.e., control) according to the age (± 2 years), sex, and date of most recent psychiatric admission because of acute mood episode (± 2 years). Leukocyte subset data were retrieved from complete blood count tests performed on the next morning after the most recent acute psychiatric admission., Results: During the most recent acute psychiatric hospitalization, circulating monocyte counts in the case group were significantly higher than those in the age- and sex-matched controls (p = 0.020). In addition, monocyte-lymphocyte ratios (MLRs) in the case group were significantly higher than those in the control group (p = 0.032). Multiple logistic regression showed that together with serum levels of uric acid and manic symptoms, circulating monocyte counts (95% CI, OR: 1.01-1.05) and MLRs (95% CI, OR: 1.01-1.09) were significantly associated with CVD in patients with BD, respectively., Conclusions: Monocyte activation in an acute manic episode may play a critical role in the pathogenesis of CVD among patients with BD. Future research is required to investigate markers of monocyte activation and indices of cardiovascular structure and function across the different mood states of BD., (© 2024. The Author(s).)

Aims: The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals., Methods and Results: The updated LIFE-CVD (i.e. LIFE-CVD2) models were derived using individual participant data from 44 cohorts in 13 countries (687 135 individuals without established CVD, 30 939 CVD events in median 10.7 years of follow-up). LIFE-CVD2 uses sex-specific functions to estimate the lifetime risk of fatal and non-fatal CVD events with adjustment for the competing risk of non-CVD death and is systematically recalibrated to four distinct European risk regions. The updated models showed good discrimination in external validation among 1 657 707 individuals (61 311 CVD events) from eight additional European cohorts in seven countries, with a pooled C-index of 0.795 (95% confidence interval 0.767-0.822). Predicted and observed CVD event risks were well calibrated in population-wide electronic health records data in the UK (Clinical Practice Research Datalink) and the Netherlands (Extramural LUMC Academic Network). When using LIFE-CVD2 to estimate potential gain in CVD-free life expectancy from preventive therapy, projections varied by risk region reflecting important regional differences in absolute lifetime risk. For example, a 50-year-old smoking woman with a systolic blood pressure (SBP) of 140 mmHg was estimated to gain 0.9 years in the low-risk region vs. 1.6 years in the very high-risk region from lifelong 10 mmHg SBP reduction. The benefit of smoking cessation for this individual ranged from 3.6 years in the low-risk region to 4.8 years in the very high-risk region., Conclusion: By taking into account geographical differences in CVD incidence using contemporary representative data sources, the recalibrated LIFE-CVD2 model provides a more accurate tool for the prediction of lifetime risk and CVD-free life expectancy for individuals without previous CVD, facilitating shared decision-making for cardiovascular prevention as recommended by 2021 European guidelines., Competing Interests: Conflict of interest: Due to the very long author list, these will be provided per author using ICMJE forms at the revision stage, if applicable., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Identifying patients with established cardiovascular disease (CVD) who are at high risk of type 2 diabetes (T2D) may allow for early interventions, reducing the development of T2D and associated morbidity. The aim of this study was to develop and externally validate the CVD2DM model to estimate the 10-year and lifetime risks of T2D in patients with established CVD., Methods and Results: Sex-specific, competing risk-adjusted Cox proportional hazard models were derived in 19 281 participants with established CVD and without diabetes at baseline from the UK Biobank. The core model's pre-specified predictors were age, current smoking, family history of diabetes mellitus, body mass index, systolic blood pressure, fasting plasma glucose, and HDL cholesterol. The extended model also included HbA1c. The model was externally validated in 3481 patients from the UCC-SMART study. During a median follow-up of 12.2 years (interquartile interval 11.3-13.1), 1628 participants with established CVD were diagnosed with T2D in the UK Biobank. External validation c-statistics were 0.79 [95% confidence interval (CI) 0.76-0.82] for the core model and 0.81 (95% CI 0.78-0.84) for the extended model. Calibration plots showed agreement between predicted and observed 10-year risk of T2D., Conclusion: The 10-year and lifetime risks of T2D can be estimated with the CVD2DM model in patients with established CVD, using readily available clinical predictors. The model would benefit from further validation across diverse ethnic groups to enhance its applicability. Informing patients about their T2D risk could motivate them further to adhere to a healthy lifestyle., Competing Interests: Conflict of interest: M.W. has received consultancy fees from Amgen and Freeline. The other authors have nothing to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Predicting major adverse cardiovascular events (MACE) is crucial due to its high readmission rate and severe sequelae. Current risk scoring model of MACE are based on a few features of a patient status at a single time point. We developed a self-attention-based model to predict MACE within 3 years from time series data utilizing numerous features in electronic medical records (EMRs). In addition, we demonstrated transfer learning for hospitals with insufficient data through code mapping and feature selection by the calculated importance using Xgboost. We established operational definitions and categories for diagnoses, medications, and laboratory tests to streamline scattered codes, enhancing clinical interpretability across hospitals. This resulted in reduced feature size and improved data quality for transfer learning. The pre-trained model demonstrated an increase in AUROC after transfer learning, from 0.564 to 0.821. Furthermore, to validate the effectiveness of the predicted scores, we analyzed the data using traditional survival analysis, which confirmed an elevated hazard ratio for a group with high scores., (© 2024. The Author(s).)

Objective: Recent studies have reported that gout is associated with a risk of cardiovascular disease (CVD) later in life. However, the predictive value of genetic predisposition to gout combined with lifestyle habits for CVD risk remains unclear. This study aimed to examine the association between genetic predisposition to gout and lifestyle habits and the risk of developing CVD in two diverse prospective cohorts from different ancestries., Methods: A total of 224 689 participants of European descent from the UK Biobank and 50 364 participants of East Asian descent from the Korean Genome and Epidemiology Study were included. The genetic risk for gout was assessed using a polygenic risk score (PRS) derived from a meta-genome-wide association study (n=444 533). The incident CVD risk was evaluated according to genetic risk, lifestyle and metabolic syndrome (MetS)., Results: Individuals at high genetic risk for gout had a higher risk of incident CVD than those with low genetic risk across ancestry. Notably, a reduction in CVD risk by up to 62% (HR 0.38; 95% CI 0.31 to 0.46; p <0.001) was observed in individuals at both low and high genetic risk for gout when they maintained ideal MetS and favourable lifestyle habits., Conclusions: Our findings indicate that a higher genetic risk of gout is significantly associated with an increased risk of CVD. Moreover, adherence to a favourable lifestyle can significantly reduce CVD risk, particularly in individuals with high genetic risk. These results underscore the potential of PRS-based risk assessment to improve clinical outcomes through tailored preventative strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite the implementation of preventive measures to counteract the obesity epidemics, the prevalence of childhood obesity is still alarming all over the world. Childhood obesity is the most common risk factor for both cardiovascular and metabolic diseases. In fact, an earlier onset of obesity can cause a greater risk of adiposity tracking across the lifespan and consequently a longer exposure to cardiometabolic risk factors. Accumulating evidence provided by prospective and intervention studies demonstrated the link between pediatric obesity and selected subclinical signs of cardiovascular damage (atherosclerosis and left ventricular hypertrophy), or fatal and not fatal cardiovascular events as early as 40 years of age.The numerous guidelines and scientific documents published in the last years demonstrate the relevance of assessing cardiometabolic risk factors in children and adolescents with OB.This Position paper, released by experts of the "Childhood Obesity study group" within the Italian Society for Pediatric Endocrinology and Diabetology, aims to review the assessment of cardiometabolic risk factors and comorbidities in children and adolescents with OW/OB on the light of the most recent scientific evidence.The main recommendations are: (a) early detection of comorbidities, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, polycystic ovary syndrome, inactivity, obstructive sleep apnea and decline in kidney function; (b) weight loss treatment, which is associated with a reduction of all cardiometabolic risk factors; (c) specific treatment of comorbidities, through lifestyle modifications or pharmacological treatment added to lifestyle for suitable individuals; d). monitoring comorbidities for mitigating future morbidity and mortality., (© 2024. The Author(s).)

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention., (© The European Society of Cardiology 2024. All rights reserved. For permissions, please email: journals.permissions@oup.com.This article has been co-published with permission in the European Heart Journal and the European Journal of Preventive Cardiology. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.)

Background: Patients with radiographic axial spondyloarthritis (r-axSpA) are at increased risk of incident cardiovascular events. Tumor necrosis factor inhibitors (TNFi) have shown a protective effect against incident cardiovacular events. However, the incidence of recurrent cardiovascular events in patients with r-axSpA with a history of cardiovascular events, and the effect of TNFi on recurrent cardiovascular events remain unclear. We aimed to assess the incidence rate of recurrent cardiovascular events in patients with r-axSpA with a history of cardiovascular events and evaluate the effect of TNFi on the risk of recurrent cardiovascular events., Methods: This nationwide cohort study used data from the Korean National Claims Database. Data of patients with r-axSpA who had a history of cardiovascular events after being diagnosed with r-axSpA were extracted from the database. The outcome of interest was the recurrence of cardiovascular events (myocardial infarction or stroke). Patients were followed from the index date (date of the first cardiovascular event) to the date of cardiovascular event recurrence, the last date with claims data, or December 31, 2021, whichever occured first. The incidence rate of recurrent cardiovascular events was calculated. An inverse probability weighted Cox model was used to assess the effect of TNFi exposure on the risk of recurrent cardiovascular events., Results: This study included 413 patients (TNFi non-exposure, n = 338; TNFi exposure, n = 75). The incidence rate of recurrent cardiovascular events was 32 (95% confidence interval [CI] 22-42) per 1,000 person-years (TNFi non-exposure, 36 [95% CI 24-48] per 1,000 person-years; TNFi exposure, 19 [95% CI 2-35] per 1,000 person-years). In the inverse probability weighted Cox model, TNFi exposure was significantly associated with a lower risk of recurrent cardiovascular events (hazard ratio 0.33, 95% CI 0.12-0.94)., Conclusions: The incidence rate of recurrent cardiovascular events in patients with r-axSpA is substantial. TNFi exposure was associated with a lower risk of recurrent cardiovascular events., (© 2024. The Author(s).)

Importance: A previous cohort study in the US found that women with higher cardiovascular risk were more likely to have a history of migraine but less likely to have active migraine. Extrapolating these results to men and European individuals is crucial to understanding the complex association between migraine activity status and vascular health in other populations., Objective: To evaluate the association pattern between a cardiovascular risk score, the most recent European version of the Systematic Coronary Risk Evaluation 2 (SCORE2) risk estimation system, and migraine activity status in Dutch men and women., Design, Setting, and Participants: The prospective population-based Lifelines cohort consists of community-dwelling adults residing in the northern part of the Netherlands. Individuals with a terminal illness, incapacitated individuals, including those with a severe mental illness, or who were unable to visit their general practitioner or complete the questionnaires were excluded from participation within Lifelines. Participants whose data on the cardiovascular risk scores and migraine status were complete were included in the analysis. Data on baseline characteristics were collected between November 1, 2006, to December 31, 2014. Cross-sectional and follow-up analyses were conducted within the prospective cohort. Questionnaires were sent approximately every 1.5 to 2.5 years, and the last self-reported migraine assessment took place between October 1, 2019, and January 31, 2021. Data were analyzed from March 1, 2022, to August 16, 2024., Exposures: The SCORE2 is a sex-specific European cardiovascular risk score that includes age, cholesterol levels, smoking status, diabetes, and systolic blood pressure., Main Outcomes and Measures: The primary outcome was the association pattern between cardiovascular risk scores and migraine activity status. SCORE2 risk scores were measured once at baseline; groups of the SCORE2 (<1.0%, 1.0% to <2.5%, 2.5% to <5.0%, 5.0% to <7.5%, 7.5% to <10.0%, and ≥10.0%) were created based on the sum of points of individual risk factors. Migraine activity status was assessed using self-reported questionnaires and classified as (1) prevalent (ie, migraine at baseline), (2) incident (ie, no migraine at baseline but migraine in ≥1 follow-up), and (3) none. To evaluate the influence of age, we conducted stratified analyses of the SCORE2 by age categories (<40, 40-49, and ≥50 years)., Results: The total study population consisted of 140 915 individuals at baseline with a mean (SD) age of 44.4 (12.7) years, of whom 58.5% were women. In total, 25 915 individuals (18.4% of the total population) had prevalent migraine and 2224 (1.9% of the 115 000 without prevalent migraine) had incident migraine. The odds of having prevalent and incident migraine, compared with individuals with a SCORE2 category of less than 1.0%, varied and decreased with increasing SCORE2 categories, with odds ratios (ORs) for prevalent migraine ranging from 0.93 (95% CI, 0.90-0.96) for a SCORE2 category of 1.0% to less than 2.5% to 0.43 (95% CI, 0.39-0.48) for a SCORE2 category of at least 10.0% and, for incident migraine, from 0.63 (95% CI, 0.57-0.69) for a SCORE2 category of 1.0% to less than 2.5% to 0.17 (95% CI, 0.10-0.27) for a SCORE2 category of at least 10.0%. A similar pattern was observed in both sexes but more profound in women. In women, ORs for prevalent migraine ranged from 1.21 (95% CI, 1.16-1.25) to 0.70 (95% CI, 0.58-0.83) (vs 1.19 [95% CI, 1.09-1.29] to 0.84 [95% CI, 0.72-0.99] in men) and, for incident migraine, 0.72 (95% CI, 0.64-0.80) to 0.20 (95% CI, 0.07-0.43) (vs 1.18 [95% CI, 0.92-1.52] to 0.44 [95% CI, 0.22-0.78] in men). Models with incident migraine as the outcome showed lower ORs across the ascending cardiovascular risk score categories. Age stratification suggested that the association between cardiovascular risk scores and migraine activity status were unlikely to be strongly influenced by age., Conclusions and Relevance: In this cohort study of community-dwelling Dutch adults, the odds of having prevalent or incident migraine decreased with increasing cardiovascular risk score categories. These results support the hypothesis that a relatively healthy cardiovascular system increases the probability of having active or developing migraine in the future, especially among women. Sex differences might play a pathophysiological role in the association between migraine activity and vascular health.

Objective: Sex differences in lipid metabolism associated with prevalent small dense (S-) low-density lipoprotein (LDL) cholesterol particles are not elucidated. An LDL to apolipoprotein B (ApoB) ratio < 1.2 can estimate how prevalent S-LDL particles are and, thus, reflect cardiovascular risk. The aim of this study was to evaluate the sex distribution of LDL/ApoB ratio among patients with type 2 diabetes (DM) and to assess, in both sexes, the correlations between key lipid parameters and LDL/ApoB < 1.2., Subjects and Methods: The study included 190 Caucasian participants (mean age 51.8 ± 6.4 years) with DM (DM group) or without DM (control group) divided into subgroups according to sex. The participants were examined for levels of several lipid parameters, selected lipid-related oxidative stress markers, and estimated S-LDL prevalence., Results: An LDL/ApoB < 1.2 (p < 0.05) was observed in 67% of male and female patients with DM. Although triglyceride levels did not differ between men and women, women had higher levels of total cholesterol (p < 0.05) and LDL cholesterol (p < 0.01) than men. Among women with LDL/ApoB < 1.2, strong correlations were observed between values of lipid hydroperoxides (LOOH) and atherogenic index of plasma (p < 0.005) and between levels of triglycerides and LOOH (p < 0.005) and ApoB (p < 0.0001)., Conclusions: The findings indicate that women with LDL/ApoB < 1.2 tend to have a higher cardiovascular risk than men. Additionally, LDL/ApoB < 1.2 can be a surrogate marker for estimating the S-LDL prevalence in individuals with potentially increased cardiovascular risk., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

Adverse cardiovascular (CV) events have declined in Western countries due at least in part to aggressive risk factor control, including dyslipidemia management. The American and European (Western) dyslipidemia treatment guidelines have contributed significantly to the reduction in atherosclerotic cardiovascular disease (ASCVD) incidence in the respective populations. However, their direct extrapolation to Indian patients does not seem appropriate for the reasons described below. In the US, mean low-density lipoprotein cholesterol (LDL-C) levels have markedly declined over the last 2 decades, correlating with a proportional reduction in CV events. Conversely, poor risk factor control and dyslipidemia management have led to increased CV and coronary artery disease (CAD) mortality rates in India. The population-attributable risk of dyslipidemia is about 50% for myocardial infarction, signifying its major role in CV events. In addition, the pattern of dyslipidemia in Indians differs considerably from that in Western populations, requiring unique strategies for lipid management in Indians and modified treatment targets. The Lipid Association of India (LAI) recognized the need for tailored LDL-C targets for Indians and recommended lower targets compared to Western guidelines. For individuals with established ASCVD or diabetes with additional risk factors, an LDL-C target of <50 mg/dL was recommended, with an optional target of ≤30 mg/dL for individuals at extremely high risk. There are several reasons that necessitate these lower targets. In Indian subjects, CAD develops 10 years earlier than in Western populations and is more malignant. Additionally, Indians experience higher CAD mortality despite having lower basal LDL-C levels, requiring greater LDL-C reduction to achieve a comparable CV event reduction. The Indian Council for Medical Research-India Diabetes study described a high prevalence of dyslipidemia among Indians, characterized by relatively lower LDL-C levels, higher triglyceride levels, and lower high-density lipoprotein cholesterol (HDL-C) levels compared to Western populations. About 30% of Indians have hypertriglyceridemia, aggravating ASCVD risk and complicating dyslipidemia management. The levels of atherogenic triglyceride-rich lipoproteins, including remnant lipoproteins, are increased in hypertriglyceridemia and are predictive of CV events. Hypertriglyceridemia is also associated with higher levels of small, dense LDL particles, which are more atherogenic, and higher levels of apolipoprotein B (Apo B), reflecting a higher burden of circulating atherogenic lipoprotein particles. A high prevalence of low HDL-C, which is often dysfunctional, and elevated lipoprotein(a) [Lp(a)] levels further contribute to the heightened atherogenicity and premature CAD in Indians. Considering the unique characteristics of atherogenic dyslipidemia in Indians, lower LDL-C, non-HDL-C, and Apo B goals compared to Western guidelines are required for effective control of ASCVD risk in Indians. South Asian ancestry is identified as a risk enhancer in the American lipid management guidelines, highlighting the elevated ASCVD risk of Indian and other South Asian individuals, suggesting a need for more aggressive LDL-C lowering in such individuals. Hence, the LDL-C goals recommended by the Western guidelines may be excessively high for Indians and could result in significant residual ASCVD risk attributable to inadequate LDL-C lowering. Further, the results of Mendelian randomization studies have shown that lowering LDL-C by 5-10 mg/dL reduces CV risk by 8-18%. The lower LDL-C targets proposed by LAI can yield these incremental benefits. In conclusion, Western LDL-C targets may not be suitable for Indian subjects, given the earlier presentation of ASCVD at lower LDL-C levels. They may result in greater CV events that could otherwise be prevented with lower LDL-C targets. The atherogenic dyslipidemia in Indian individuals necessitates more aggressive LDL-C and non-HDL-C lowering, as recommended by the LAI, in order to stem the epidemic of ASCVD in India., (© Journal of the Association of Physicians of India 2024.)

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality for both men and women among all ethnicities worldwide. Although significant improvements in the management of CVD occurred in the 20th century, non-invasive, universal, early diagnostic biomarkers and newer therapeutic drugs are needed for clinical treatment by physicians. MicroRNAs (miRNAs) are a class of endogenous, non-coding, single-stranded, small RNA molecules that are critically controlled by all human biological processes. Moreover, dysregulated miRNA expression is directly involved in various CVDs, including stable coronary artery disease and acute coronary syndrome. Several miRNAs that are enriched in the plasma of CVD patients have potential as clinical biomarkers, and overexpression or inhibition of specific miRNAs has novel therapeutic significance in the management of CVD. Aging is a multifactorial physiological process that gradually deteriorates tissue and organ function and is considered a non-modifiable major risk factor for CVDs. Recently, several studies established that various miRNAs essentially regulate aging and aging-related disease processes. This narrative review briefly discusses the recently updated molecular involvement of miRNAs in CVDs, their possible diagnostic, prognostic, and therapeutic value, and their relationship to the aging process., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Cardiovascular disease (CVD) stands as one of the leading causes of death in the United States, with its prevalence steadily on the rise. Traditional therapeutic approaches, such as pharmacological treatment, cardiovascular intervention, and surgery, have inherent limitations. In response to these challenges, cardiac gene therapy has emerged as a promising alternative for treating CVD patients. However, several obstacles persist, including the low efficiency of gene transduction, immune reactions to vectors or transduced cells, and the occurrence of off-target effects. While preclinical research has demonstrated significant success in various CVD model in both small and large animals, the translation of these findings to clinical applications has, for the most part, yielded disappointing results, except for some early, albeit small, trials. This review aims to provide a comprehensive summary of recent preclinical and clinical studies on gene therapy for various CVDs. Additionally, we discuss the existing limitations and challenges that hinder the widespread clinical application of cardiac gene therapy., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Renal denervation (RDN) is a neuromodulation therapy performed in patients with hypertension using an intraarterial catheter. Recent randomized sham-controlled trials have shown that RDN has significant antihypertensive effects that last for more than 3 years. Based on this evidence, the US Food and Drug Administration has approved two devices, the ultrasound-based ReCor Paradise TM RDN system and the radiofrequency-based Medtronic Symplicity Spyral TM RDN system, as adjunctive therapy for patients with refractory and uncontrolled hypertension. On the other hand, there have been no randomized sham-controlled prospective outcome trials on RDN, and the effects of RDN on cardiovascular events such as myocardial infarction, heart failure, and stroke have not been elucidated. This mini-review summarizes the latest findings focusing on the effects of RDN on organ protection and physiological function and symptoms in both preclinical and clinical studies. Furthermore, the feasibility of using blood pressure as surrogate marker for cardiovascular outcomes is discussed in the context of relevant clinical studies on RDN. A comprehensive understanding of the beneficial effects of RDN on the incidence and severity of cardiovascular diseases with their underlying mechanisms will enhance physicians' ability to incorporate RDN into clinical strategies to prevent cardiovascular events including myocardial infarction, heart failure, and stroke. This mini-review focuses on the effects of RDN on organ protection and physiological function and symptoms in preclinical and clinical studies. RDN is expected to reduce the onset and progression of cardiovascular diseases including myocardial infarction, heart failure, and stroke in clinical practice. LV left ventricular, LVEF left ventricular ejection fraction, VO2max maximal oxygen uptake, VT ventricular tachycardia, VF ventricular fibrillation, 6MWD 6-min walk distance, NT-proBNP N-terminal pro-B-type natriuretic peptide, NYHA New York Heart Association, BBB blood-brain barrier, BP blood pressure., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Objective: We aimed to investigate the correlation between long-term blood pressure variability (BPV) and the risk of cardiovascular diseases (CVDs) among population with different blood pressure statuses (normotension, well-controlled hypertension, and uncontrolled hypertension)., Methods: In this ambispective cohort study, CVD-free residents aged over 50 years were consecutively enrolled from two community health service centers (CHCs) in Tianjin, China from April 2017 to May 2017. Information on blood pressure was retrospectively extracted from electronic medical records of CHCs between January 2010 and May 2017, and the occurrence of new-onset CVDs was prospectively observed during follow-up until September 2019. Long-term variation of SBP and DBP was assessed using four indicators: SD, coefficient of variation (CV), average successive variability (ASV), and average real variability (ARV). Cox proportional hazards regression model was developed to identify the potential impact of BPV on the incidence of CVDs. The receiver operating characteristic curve (ROC) was utilized to evaluate the predictive value of BPV indicators for the occurrence of CVDs., Results: Of 1275 participants included, 412 (32.3%) experienced new CVD events during the median 7.7 years of follow-up, with an incidence density of 499/10 000 person-year in the whole cohort. Cox regression analysis revealed that almost all SBP and DBP variability indicators (except for SBP-SD) were significantly related to the risk of CVDs, especially among individuals with well-controlled hypertension. A trend toward an increased risk of CVDs across BPV quartiles was also observed. Moderate predictive abilities of BPV were observed, with the area under ROC curves ranging between 0.649 and 0.736. For SBP variability, SD had the lowest predictive ability, whereas for DBP variability, ARV had the lowest predictive ability. No significant association of CVDs with SBP-SD was found in all analyses, no matter as a continuous or categorical variable., Conclusion: Elevated long-term BPV is associated with an increased risk of CVDs, especially among individuals with well-controlled hypertension. CV and ASV had higher predictive values than SD and ARV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabolite concentrations. In the EPIC-Potsdam cohort, a difference in the MLS, reflecting better dietary fat quality, was associated with a significant reduction in the incidence of cardiovascular disease (-32%; 95% confidence interval (95% CI): -21% to -42%) and type 2 diabetes (-26%; 95% CI: -15% to -35%). We built a closely correlated simplified score, reduced MLS (rMLS), and observed that beneficial rMLS changes, suggesting improved dietary fat quality over 10 years, were associated with lower diabetes risk (odds ratio per standard deviation of 0.76; 95% CI: 0.59 to 0.98) in the Nurses' Health Study. Furthermore, in the PREDIMED trial, an olive oil-rich Mediterranean diet intervention primarily reduced diabetes incidence among participants with unfavorable preintervention rMLS levels, suggestive of disturbed lipid metabolism before intervention. Our findings indicate that the effects of dietary fat quality on the lipidome can contribute to a more precise understanding and possible prediction of the health outcomes of specific dietary fat modifications., (© 2024. The Author(s).)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally designed to manage blood sugar levels in individuals with type 2 diabetes (T2D), have emerged as a crucial class of drugs for managing cardio-renal diseases. These drugs work by targeting the SGLT2 protein in the kidneys, promoting the excretion of glucose and influencing metabolic pathways beyond glucose control. The relationship between cardio-renal diseases and SGLT2 inhibitors has been explored through landmark trials and real-world evidence (RWE) studies, demonstrating significant reductions in cardio-renal complications. This review discusses the importance of RWE studies alongside randomized controlled trials in understanding the real-world effectiveness and safety of SGLT2 inhibitors. It outlines the advantages and disadvantages of RWE compared to RCTs, highlighting their complementary roles in providing comprehensive insights into treatment outcomes. By examining a range of RWE studies, the review underscores the cardio-renal benefits of SGLT2 inhibitors across various patient populations. Safety assessments indicate that SGLT2 inhibitors are generally well tolerated, with severe adverse events being rare. Common issues, such as genital mycotic infections and urinary tract infections, are acknowledged, alongside less frequent but significant adverse events including diabetic ketoacidosis, lower-limb amputations, and bone fractures. In summary, SGLT2 inhibitors show promising cardio-renal protective effects in real-world scenarios across diverse populations in T2D, indicating their potential as early intervention measures. Continued research is essential for gaining a thorough understanding of their long-term effects and safety profiles., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Cardiovascular diseases (CVDs) continue to pose a significant burden on global health, prominently contributing to morbidity and mortality rates worldwide. Recent years have witnessed an increasing recognition of the intricate involvement of neutrophil extracellular traps (NETs) in the pathology of diverse cardiovascular conditions. This review provides a comprehensive analysis of the multifaceted functions of NETs in cardiovascular diseases, shedding light on the impact on atherosclerosis, myocardial infarction, heart failure, myocarditis, atrial fibrillation, aortic stenosis, and the potential therapeutic avenues targeting NETs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The study aimed to determine the most crucial parameters associated with CVD and employ a novel data ensemble refinement procedure to uncover the optimal pattern of these parameters that can result in a high prediction accuracy., Methods and Results: Data were collected from 369 patients in total, 281 patients with CVD or at risk of developing it, compared to 88 otherwise healthy individuals. Within the group of 281 CVD or at-risk patients, 53 were diagnosed with coronary artery disease (CAD), 16 with end-stage renal disease, 47 newly diagnosed with diabetes mellitus 2 and 92 with chronic inflammatory disorders (21 rheumatoid arthritis, 41 psoriasis, 30 angiitis). The data were analyzed using an artificial intelligence-based algorithm with the primary objective of identifying the optimal pattern of parameters that define CVD. The study highlights the effectiveness of a six-parameter combination in discerning the likelihood of cardiovascular disease using DERGA and Extra Trees algorithms. These parameters, ranked in order of importance, include Platelet-derived Microvesicles (PMV), hypertension, age, smoking, dyslipidemia, and Body Mass Index (BMI). Endothelial and erythrocyte MVs, along with diabetes were the least important predictors. In addition, the highest prediction accuracy achieved is 98.64%. Notably, using PMVs alone yields a 91.32% accuracy, while the optimal model employing all ten parameters, yields a prediction accuracy of 0.9783 (97.83%)., Conclusions: Our research showcases the efficacy of DERGA, an innovative data ensemble refinement greedy algorithm. DERGA accelerates the assessment of an individual's risk of developing CVD, allowing for early diagnosis, significantly reduces the number of required lab tests and optimizes resource utilization. Additionally, it assists in identifying the optimal parameters critical for assessing CVD susceptibility, thereby enhancing our understanding of the underlying mechanisms., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose of Review: Analyze current evidence on racial/ethnic disparities in cardiovascular outcomes among cancer survivors, identifying factors and proposing measures to address health inequities., Recent Findings: Existing literature indicates that the Black population experiences worse cardiovascular outcomes following the diagnosis of both initial primary cancer and second primary cancer, with a notably higher prevalence of cardio-toxic events, particularly among breast cancer survivors. Contributing socioeconomic factors to these disparities include unfavorable social determinants of health, inadequate insurance coverage, and structural racism within the healthcare system. Additionally, proinflammatory epigenetic modification is hypothesized to be a contributing genetic variation factor. Addressing these disparities requires a multiperspective approach, encompassing efforts to address racial disparities and social determinants of health within the healthcare system, refine healthcare policies and access, and integrate historically stigmatized racial groups into clinical research. Racial and ethnic disparities persist in cardiovascular outcomes among cancer survivors, driven by multifactorial causes, predominantly associated with social determinants of health. Addressing these healthcare inequities is imperative, and timely efforts must be implemented to narrow the existing gap effectively., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is present in lean people. However, the magnitude of the prognostic hepatic and cardiovascular risk in these patients compared to non-lean counterparts remains unclear. We aimed to investigate this topic, and to explore whether these risks change based on factors related to NAFLD severity., Methods: PubMed and Embase databases were searched for cohort studies (published through April 2024) that evaluated liver and cardiovascular (CV) outcomes in lean and non-lean individuals with NAFLD and reported unadjusted or adjusted data. We pooled risk ratios (RRs) or hazard ratios (HRs) using a random-effects modeling and performed subgroup and meta-regressions analyses., Results: We identified 22 studies with over 1 million NAFLD patients (13.0% were lean). Lean NAFLD showed a similar risk of liver-related events in unadjusted analysis (RR 1.08, 95% CI 0.79-1.49, I 2  = 31%), but a higher risk in adjusted analysis (HR 1.66, 95% CI 1.17-2.36, I 2  = 83%) compared to non-lean NAFLD. Lean NAFLD had a higher risk of liver-related mortality (RR 2.22, 95% CI 1.57-3.15, I 2  = 0%; HR 2.26, 95% CI 1.14-4.51, I 2  = 0%). For CV outcomes, lean NAFLD had a lower risk of any cardiovascular disease in unadjusted analysis (RR = 0.82, 95% CI 0.70-0.95, I 2  = 88%), but similar risk in adjusted analysis (HR 0.89, 95% CI 0.77-1.02, I 2  = 78%), and similar risk of cardiovascular mortality (RR 1.09, 95% CI 0.71-1.66, I 2  = 85%; HR 1.26, 95% CI 0.89-1.78, I 2  = 46%) compared to non-lean NAFLD., Conclusions: Lean NAFLD patients have worse liver outcomes, but similar CV outcomes compared to non-lean NAFLD patients, highlighting the importance of monitoring both groups closely., (© 2024. Asian Pacific Association for the Study of the Liver.)

Aims: Clinical guidelines support the use of fixed-dose combinations (FDC) for prevention of cardiovascular disease. Implementation of FDC into clinical care remains challenging, and current population-based data are scarce., Methods and Results: Claims data on dispensed drugs in an outpatient care setting of approximately 87% of the German population were analysed regarding the use of FDC according to time, age of the insured persons, and active ingredients. The overarching trend for all FDC revealed a decrease from 77.3 defined daily doses per 1000 statutory health-insured (SHI) persons per day (DID) in the second half-year of 2018 (2018HY02) to 60.8 DID in the first half-year of 2023 (2023HY01) (Spearman ρ = -0.988; P  < 0.001). The total DID for all antihypertensives (AHT) increased from 590.6 in 2018HY02 to 624.8 in 2023HY01 (ρ = 0.855; P  = 0.002), but the DID for fixed-dose AHT (AHT-FDC) declined from 74.1 in 2018HY02 to 55.0 in 2023HY01 (ρ = -0.988; P  < 0.001). Conversely, the use of all lipid-lowering agents (LLA) and LLA-FDC continuously increased: The total DID of all LLA rose from 92.5 in 2018HY02 to 134.4 in 2023HY01 (ρ = 1.000; P  = 0.000), and for LLA-FDC from 3.1 in 2018HY02 to 5.5 DID in 2023HY01 (ρ = 0.915; P  < 0.001). AHT-FDC and LLA-FDC were less frequently dispensed to patients at least 80 years than to patients less than 80 years. Dispensing of multiple purpose FDC increased from 2018HY02 to 2023HY01 from 0.11 DID to 0.26 DID (ρ = 1.000; P  = 0.000) but remained negligible., Conclusion: Use of AHT-FDC in Germany is declining. In contrast, FDC containing LLA are increasingly prescribed. Dispensing of multiple purpose FDC is very low. Strategies are needed to facilitate the use of FDC as recommended by current guidelines., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Evidence suggests that COVID-19 predisposes to cardiovascular diseases (CVDs). While monocytes/macrophages play a central role in the immunopathogenesis of atherosclerosis, less is known about their immunopathogenic mechanisms that lead to CVDs during COVID-19. Natural killer (NK) cells, which play an intermediary role during pathologies like atherosclerosis, are dysregulated during COVID-19. Here, we sought to investigate altered immune cells and their associations with CVD risk during severe COVID-19., Methods: We measured plasma biomarkers of CVDs and determined phenotypes of circulating immune subsets using spectral flow cytometry. We compared these between patients with severe COVID-19 (severe, n=31), those who recovered from severe COVID-19 (recovered, n=29), and SARS-CoV-2-uninfected controls (controls, n=17). In vivo observations were supported using in vitro assays to highlight possible mechanistic links between dysregulated immune subsets and biomarkers during and after COVID-19. We performed multidimensional analyses of published single-cell transcriptome data of monocytes and NK cells during severe COVID-19 to substantiate in vivo findings., Results: During severe COVID-19, we observed alterations in cardiometabolic biomarkers including oxidized-low-density lipoprotein, which showed decreased levels in severe and recovered groups. Severe patients exhibited dysregulated monocyte subsets, including increased frequencies of proinflammatory intermediate monocytes (also observed in the recovered) and decreased nonclassical monocytes. All identified NK-cell subsets in the severe COVID-19 group displayed increased expression of activation and tissue-resident markers, such as CD69 (cluster of differentiation 69). We observed significant correlations between altered immune subsets and plasma oxidized-low-density lipoprotein levels. In vitro assays revealed increased uptake of oxidized-low-density lipoprotein into monocyte-derived macrophages in the presence of NK cells activated by plasma of patients with severe COVID-19. Transcriptome analyses confirmed enriched proinflammatory responses and lipid dysregulation associated with epigenetic modifications in monocytes and NK cells during severe COVID-19., Conclusions: Our study provides new insights into the involvement of monocytes and NK cells in the increased CVD risk observed during and after COVID-19., Competing Interests: None.

Introduction: Patients with chronic obstructive pulmonary disease (COPD) frequently have cardiovascular comorbidities, increasing the risk of hospitalised COPD exacerbations (H-ECOPDs) or death. This pragmatic study examined the effects of adding an inhaled corticosteroid (ICS) to long-acting bronchodilator(s) (LABDs) in patients with COPD and cardiac comorbidities who had a recent H-ECOPD., Methods: Patients >60 years of age with COPD and ≥1 cardiac comorbidity, within 6 months after discharge following an H-ECOPD, were randomised to receive LABD(s) with or without ICS, and were followed for 1 year. The primary outcome was the time to first rehospitalisation and/or all-cause death., Results: The planned number of patients was not recruited (803/1032), limiting the strength of the conclusions. In the intention-to-treat population, 89/403 patients (22.1 %) were rehospitalised or died in the LABD group (probability 0.257 [95 % confidence interval 0.206, 0.318]), vs 85/400 (21.3 %) in the LABD+ICS group (0.249 [0.198, 0.310]), with no difference between groups in time-to-event (hazard ratio 1.116 [0.827, 1.504]; p = 0.473). All-cause and cardiovascular mortality were lower in patients receiving LABD(s)+ICS, with relative reductions of 19.7 % and 27.4 %, respectively (9.8 % vs 12.2 % and 4.5 % vs 6.2 %), although the groups were not formally statistically compared for these endpoints. Fewer patients had adverse events in the LABD+ICS group (43.0 % vs 50.4 %; p = 0.013), with 4.9 % vs 5.4 % reporting pneumonia adverse events., Conclusions: Results suggest addition of ICS to LABDs did not reduce the time-to-combined rehospitalisation/death, although it decreased all-cause and cardiovascular mortality. ICS use was not associated with an increased risk of adverse events, particularly pneumonia., Competing Interests: Declaration of competing interest In addition to the medical writing support disclosed below, the authors have the following conflicts of interest. Alberto Papi reports grants to his institution from Chiesi, AstraZeneca, GlaxoSmithKline and Sanofi, consulting fees from Chiesi, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals, Moderna, and Roche, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chiesi, AstraZeneca, GlaxoSmithKline, Menarini, Zambon, Mundipharma, Sanofi, Edmond Pharma, Iqvia, Avillion, Sanofi, and Regeneron, and participation on advisory boards for Chiesi, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals, and Moderna. All are outside the scope of the current manuscript. Giacomo Forini has no other conflicts to disclose. Mauro Maniscalco declares grants or contracts (with payments to Istituti Clinici Scientifici Maugeri IRCCS) from GlaxoSmithKline and AstraZeneca, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GlaxoSmithKline, AstraZeneca, and Chiesi. All are outside the scope of the current manuscript. Elena Bargagli has no other conflicts to disclose. Claudia Crimi received honoraria for lectures from Fisher & Paykel, ResMed, AstraZeneca, Sanofi, GlaxoSmithKline, and Vitalaire. All are outside the scope of the current manuscript. Pierachille Santus declares research grants from AstraZeneca, Edmondpharma, GlaxoSmithKline, and Novartis (payments were made to the Department of Biomedical and Clinical Sciences of University of Milan), consulting fees from GlaxoSmithKline, Sanofi, Edmondpharma, Dompè, Valeas, and Neopharmed, and honoraria for lectures from AstraZeneca, Sanofi, GlaxoSmithKline, Berlin Chemie, Edmondpharma, and Zambon Brasil. All are outside the scope of the current manuscript. Antonio Molino has no other conflicts to disclose. Valeria Bandiera is an employee of Alira Health SrI, which received funding from the Università degli Studi di Ferrara to provide biometrics services to the study. Federico Baraldi received a short-term research fellowship from the European Respiratory Society, outside the scope of the current manuscript Silvestro Ennio D'Anna has no other conflicts to disclose. Mauro Carone received honoraria as speaker from GlaxoSmithKline and AstraZeneca, and honoraria for participation in speaker bureaus from Boehringer Ingelheim, support for attending meetings and travel from the Associazione Italiana Pneumologi Ospedalieri – Italian Thoracic Society (AIPO-ITS/ETS), and an unpaid role as the National President of the AIPO-ITS/ETS. All are outside the scope of the current manuscript. Maurizio Marvisi has no other conflicts to disclose. Corrado Pelaia received honoraria for lectures from AstraZeneca, GlaxoSmithKline, and Sanofi, all outside the scope of the current manuscript. Giulia Scioscia has no other conflicts to disclose. Vincenzo Patella has no other conflicts to disclose. Maria Aliani has no other conflicts to disclose. Leonardo M Fabbri received consulting fees from Alfasigma, AstraZeneca, Chiesi, GlaxoSmithKline, ICON, Menarini, Novartis, and Verona Pharma, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chiesi, GlaxoSmithKline, Glenmark, Lusofama, and Novartis, support for attending meetings and/or travel from the Italian Society of Allergy, Asthma and Clinical Immunology and the Menarini Foundation, and participated in a data safety monitoring board or advisory board for Novartis, Chiesi, and ICON. All are outside the scope of the current manuscript., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Momordica charantia (bitter melon), a traditional medicinal plant, has been demonstrated to have potential in managing diabetes, gastrointestinal problems, and infections. Among its bioactive compounds, momordicine I, a cucurbitane-type triterpenoid, has attracted attention due to its substantial biological activities. Preclinical studies have indicated that momordicine I possesses antihypertensive, anti-inflammatory, antihypertrophic, antifibrotic, and antioxidative properties, indicating its potential as a therapeutic agent for cardiovascular diseases. Its mechanisms of action include modulating insulin signaling, inhibiting inflammatory pathways, and inducing apoptosis in cancer cells. The proposed mechanistic pathways through which momordicine I exerts its cardiovascular benefits are via the modulation of nitric oxide, angiotensin-converting enzymes, phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt), oxidative stress, apoptosis and inflammatory pathways. Furthermore, the anti-inflammatory effects of momordicine I are pivotal. Momordicine I might reduce inflammation through the following mechanisms: inhibiting pro-inflammatory cytokines, reducing adhesion molecules expression, suppressing NF-κB activation, modulating the Nrf2 pathway and suppressing c-Met/STAT3 pathway. However, its therapeutic use requires the careful consideration of potential side effects, contraindications, and drug interactions. Future research should focus on elucidating the precise mechanisms of momordicine I, validating its efficacy and safety through clinical trials, and exploring its pharmacokinetics. If proven effective, momordicine I could considerably affect clinical cardiology by acting as a novel adjunct or alternative therapy for cardiovascular diseases. To date, no review article has been published on the role of bitter-melon bioactive metabolites in cardiovascular prevention and therapy. The present work constitutes a comprehensive, up-to-date review of the literature, which highlights the promising therapeutic potential of momordicine I on the cardiovascular system and discusses future research recommendations.

Background: Cardiovascular diseases (CVDs) are a leading cause of disability-adjusted life years in Indonesia. Although obesity is a known risk factor for CVDs, the relative contributions of overall versus abdominal obesity are less clear. We aimed to estimate the 10-year CVD risks of the Indonesian population and investigate the separate and joint associations of overall and abdominal obesity with these risks., Methods: Using nationally representative data from the Indonesian Health Survey (n = 33,786), the 10-year CVD risk was estimated using the Framingham Score. The score was calculated as %-risk, with >20% indicating high risk. Overall obesity was measured by BMI, while abdominal obesity was measured by waist circumference. We performed sex-stratified multivariable linear regressions to examine the associations of standardized units of BMI and waist circumference with the 10-year CVD risk, mutually adjusted for waist circumference and BMI., Results: Mean (SD) 10-year CVD risks were 14.3(8.9)% in men and 8.0(9.3)% in women, with 37.3% of men and 14.1% of women having high (>20%) risks. After mutual adjustment, one SD in BMI and waist circumference were associated with 0.75(0.50-1.01) and 0.95(0.72-1.18) increase in the %-risk of CVD in men, whereas in women, the β(95% CIs) were 0.43(0.25-0.61) and 1.06(0.87-1.26)., Conclusion: Abdominal fat accumulation showed stronger associations with 10-year CVD risks than overall adiposity, particularly in women. Although men had higher overall CVD risks, women experienced more detrimental cardiovascular effects of obesity. Raising awareness of abdominal/visceral obesity and its more damaging cardiovascular effects in women is crucial in preventing CVD-related morbidity and mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sigit et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite inflammation being implicated in cardiovascular disease (CVD) in people with human immunodeficiency virus (PWH), considerable heterogeneity within populations of PWH exists. Stratifying CVD risk based on inflammatory phenotype could play an important role. Using principal component analyses and unsupervised hierarchical clustering, we examined 38 biomarkers to identify inflammatory phenotypes in 2 independent cohorts of PWH. We identified 3 distinct inflammatory clusters present in both cohorts that were associated with altered risk of both subclinical CVD (cohort 1) and prevalent clinical CVD (cohort 2) after adjusting for CVD risk factors. These data support precision medicine approaches to enhance CVD risk assessment in PWH., Competing Interests: Potential conflicts of interest. P. W. G. M. and/or his institution has received grants, honoraria, and/or speaker’s fees from Gilead Sciences, ViiV Healthcare, BMS, MSD, and Janssen-Cilag. A. L. has acted as consultant to Abbott, Merck Group, and Gilead Sciences. A. G.-C. has received honorarium, educational/travel support, or unrestricted research grants from Gilead Sciences, MSD, ViiV Healthcare, and Janssen-Cilag. C.S. has received honoraria for preparation and delivery of educational materials from Gilead Sciences and ViiV Healthcare. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Parkinson's disease (PD) reports high rates of morbidity and mortality, but the risk of adverse cardiovascular outcomes in patients with PD has not been fully elucidated. This bi-center retrospective cohort study using the electronic health records (EHR) database of two tertiary hospitals screened a total of 327,292 subjects who visited the outpatient clinic, and 1194 patients with PD were propensity score-matched with a control population. The primary outcome was the occurrence of major adverse cardiovascular events (MACE). Key secondary outcomes included all-cause death, cardiovascular (CV) death, stroke, myocardial infarction (MI), heart failure hospitalization and 30-day CV death. After PS matching, MACE occurrence was not significantly different between PD and non-PD groups (18.2% vs. 17.5%, log-rank p = 0.98). Key secondary outcomes were also similar between the two groups. In patients with PD, MACE rate, and also CV risk score, were higher in patients with more severe PD (according to Hoehn and Yahr scale and unified Parkinson's disease rating scale), and after multivariable analysis, PD severity was not an independent predictor of MACE. Patients with PD are at an increased risk of adverse cardiovascular outcomes, but the contribution from other common CV risk factors cannot be ignored. The management of prevalent CV risk factors is therefore important in mitigating adverse outcomes among patients with PD., (© 2024. The Author(s).)

Competing Interests: Conflict of interest: N.S.: none. M.S.: none. C.N.B.M.: serves as Board of Director for iRhythm, and fees were paid through CSMC from Abbott Diagnostics and SHL Telemedicine. C.L.S.: none.

Background: Incarceration is a social determinant of cardiovascular health but is rarely addressed in clinical settings or public health prevention efforts. People who have been incarcerated are more likely to develop cardiovascular disease (CVD) at younger ages and have worse cardiovascular outcomes compared with the general population, even after controlling for traditional risk factors. This study aims to identify incarceration-specific factors that are associated with uncontrolled CVD risk factors to identify potential targets for prevention., Methods and Results: Using data from JUSTICE (Justice-Involved Individuals Cardiovascular Disease Epidemiology), a prospective cohort study of individuals released from incarceration with CVD risk factors, we examine the unique association between incarceration-specific factors and CVD risk factor control. Participants (N=471), with a mean age of 45.0±10.8 (SD) years, were disproportionately from racially minoritized groups (79%), and poor (91%). Over half (54%) had at least 1 uncontrolled CVD risk factor at baseline. People released from jail, compared with prison, had lower Life's Essential 8 scores for blood pressure and smoking. Release from jail, as compared with prison, was associated with an increased odds of having an uncontrolled CVD risk factor, even after adjusting for age, race and ethnicity, gender, perceived stress, and life adversity score (adjusted odds ratio 1.62 [95% CI, 1.02-2.57])., Discussion: Release from jail is associated with poor CVD risk factor control and requires tailored intervention, which is informative as states design and implement the Centers of Medicare & Medicaid Services Reentry 1115 waiver, which allows Medicaid to cover services before release from correctional facilities.

Introduction & Objectives: To evaluate whether cardiovascular risk factors and their management differ in primary prevention between adult males and females with type 1 diabetes (T1D) in two European countries in 2020-2022 and sex inequalities in achievement of standards of care in diabetes., Methods: We used 2020-2022 data of patients without a cardiovascular history in the Prospective Diabetes Follow-up registry (DPV) centres, in Germany, and the Société Francophone du Diabète- Cohorte Diabète de Type 1 cohort (SFDT1), in France., Results: We included 2,657 participants from the DPV registry and 1,172 from the SFDT1 study. Body mass indexes were similar in females and males with similar proportions of HbA1c < 7% (DPV: 36.6 vs 33.0%, p = 0.06, respectively; SFDT1: 23.4 vs 25.7%, p = 0.41). Females were less overweight compared to men in DPV (55.4 vs 61.0%, p < 0.01) but not in SFDT1 (48.0 vs 44.9%, p = 0.33) and were less prone to smoke (DPV: 19.7 vs 25.8%, p < 0.01; SFDT1: 21.0 vs 26.0%, p = 0.07). Systolic blood pressure was lower in females than males with a higher rate of antihypertensive therapy in case of hypertension in females in DPV (70.5 vs 63.7%, p = 0.02) but not in SFDT1 (73.3 vs 68.6%, p = 0.64). In the case of microalbuminuria, ACEi-ARB were less often prescribed in women than men in DPV (21.4 vs 37.6%, p < 0.01) but not SFDT1 (73.3 vs 67.5.0%, p = 0.43). In females compared to males, HDL-cholesterol levels were higher; triglycerides were lower in both countries. In those with LDL-cholesterol > 3.4 mmol/L (DPV: 19.9 (females) vs 23.9% (males), p = 0.01; SFDT1 17.0 vs 19.2%, p = 0.43), statin therapy was less often prescribed in females than males in DPV (7.9 vs 17.0%, p < 0.01), SFDT1 (18.2 vs 21.0%, p = 0.42)., Conclusion: In both studies, females in primary prevention have a better cardiovascular risk profile than males. We observed a high rate of therapeutic inertia, which might be higher in females for statin treatment and nephroprotection with ACEi-ARB, especially in Germany. Diabetologists should be aware of sex-specific differences in the management of cardiorenal risk factors to develop more personalized prevention strategies., (© 2024. The Author(s).)

Context: Long-term glucocorticoid levels in scalp hair (HairGCs), including cortisol and the inactive form cortisone, represent the cumulative systemic exposure to glucocorticoids over months. HairGCs have repeatedly shown associations with cardiometabolic and immune parameters, but longitudinal data are lacking., Design: We investigated 6341 hair samples of participants from the Lifelines cohort study for cortisol and cortisone levels and associated these to incident cardiovascular diseases (CVD) during 5 to 7 years of follow-up. We computed the odds ratio (OR) of HairGC levels for incident CVD via logistic regression, adjusting for classical cardiovascular risk factors, and performed a sensitivity analysis in subcohorts of participants < 60 years and ≥ 60 years of age. We also associated HairGC levels to immune parameters (total leukocytes and subtypes)., Results: Hair cortisone levels (available in n = 4701) were independently associated with incident CVD (P < .001), particularly in younger individuals (multivariate-adjusted OR 4.21, 95% CI 1.91-9.07 per point increase in 10-log cortisone concentration [pg/mg], P < .001). All immune parameters except eosinophils were associated with hair cortisone (all multivariate-adjusted P < .05)., Conclusion: In this large, prospective cohort study, we found that long-term cortisone levels, measured in scalp hair, represent a relevant and significant predictor for future CVD in younger individuals. These results highlight glucocorticoid action as possible treatment target for CVD prevention, where hair glucocorticoid measurements could help identify individuals that may benefit from such treatments., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: The impact of cardiovascular diseases on cognition raises important research questions. The study aimed to investigate the relationship between demographic data, cardiovascular diseases, kidney disease and depressive symptoms on cognition., Methods: A cross-sectional study of patients with cardiovascular diseases was performed. The Montreal Cognitive Assessment (MoCA) was applied for cognitive evaluation. Based on MoCA three groups were defined: preserved cognition, mild, and advanced cognitive dysfunction (CD). Data were analyzed using Cronbach alpha (Cα) and McDonald's ω (Mω) for internal consistency. The Chi-square test, Cramer's V test, and correlation analyses were also applied., Results: Of 628 patients, 55.2% had mild CD, and the mean age was 67.95 (SD 9.53) years. Cα and Mω were 0.7, indicating good internal consistency. We found a moderate positive correlation between depression and the severity of CD ( r  = 0.25, p  = 0.0001). A weak association between CD and female gender ( p  = 0.016), atrial fibrillation ( p  = 0.03), stroke ( p  = 0.009), and a moderate association for age group ( p  < 0.0001), education level ( p  < 0.0001), smoking ( p  < 0.0001), and renal dysfunction ( p  < 0.0001) was found. Age ≥ 70 years, eGFR 30-59 mL/min/1.73m 2 significantly increased the likelihood for mild and advanced CD, while smoking and > 9 classes decreased it. Female gender, history of atrial fibrillation, and stroke significantly increased the likelihood of advanced CD., Conclusion: Mild CD was the most common in patients with cardiovascular diseases. Older age, lower education, being a non-smoker, and renal dysfunction were risk factors for both mild and advanced CD. Female gender, previous diagnosis of atrial fibrillation, and stroke are risk factors for advanced CD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pal, Iantovics, Preg, Nemes-Nagy, Nyulas, Baba and German-Sallo.)

Aldosterone is a mineralocorticoid hormone involved in controlling electrolyte balance, blood pressure, and cellular signaling. It plays a pivotal role in cardiovascular and metabolic physiology. Excess aldosterone activates mineralocorticoid receptors, leading to subsequent inflammatory responses, increased oxidative stress, and tissue remodeling. Various mechanisms have been reported to link aldosterone with cardiovascular and metabolic diseases. However, mitochondria, responsible for energy generation through oxidative phosphorylation, have received less attention regarding their potential role in aldosterone-related pathogenesis. Excess aldosterone leads to mitochondrial dysfunction, and this may play a role in the development of cardiovascular and metabolic diseases. Aldosterone has the potential to affect mitochondrial structure, function, and dynamic processes, such as mitochondrial fusion and fission. In addition, aldosterone has been associated with the suppression of mitochondrial DNA, mitochondria-specific proteins, and ATP production in the myocardium through mineralocorticoid receptor, nicotinamide adenine dinucleotide phosphate oxidase, and reactive oxygen species pathways. In this review, we explore the mechanisms underlying aldosterone-induced cardiovascular and metabolic mitochondrial dysfunction, including mineralocorticoid receptor activation and subsequent inflammatory responses, as well as increased oxidative stress. Furthermore, we review potential therapeutic targets aimed at restoring mitochondrial function in the context of aldosterone-associated pathologies. Understanding these mechanisms is vital, as it offers insights into novel therapeutic strategies to mitigate the impact of aldosterone-induced mitochondrial dysfunction, thereby potentially improving the outcomes of individuals affected by cardiovascular and metabolic disorders.

Background: Cardiovascular autonomic neuropathy (CAN) is known to affect patients with diabetes mellitus (DM) and cause adverse renal outcomes. We aimed to analyze the association between CAN and diabetic kidney disease (DKD)., Method: We enrolled 254 DM patients (mean age, 56.7 ± 15.2 years; male: female ratio, 1.17:1) with 19 (7.5%) type 1 DM patients and 235 (92.5%) type 2 DM patients. All patients had undergone cardiovascular autonomic function tests between January 2019 and December 2021 in a tertiary hospital in Korea. Cardiovascular autonomic neuropathy was categorized as normal, early, or definite after measuring three heart rate variability parameters. Diabetic kidney disease refers to a persistently elevated urinary albumin-creatinine ratio (uACR ≥30 mg/g) or reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m 2 ). Logistic and Cox regression analyses were performed., Results: Patients with elevated uACR (n=107) and reduced eGFR (n=32) had a higher rate of definite CAN. After adjusting for covariates, definite CAN was associated with elevated uACR (OR=2.4, 95% CI 1.07-5.36) but not with reduced eGFR (OR=3.43, 95% CI 0.62-18.90). A total of 94 patients repeated uACR measurements within 2 years (mean follow-up, 586.3 ± 116.8 days). Both definite and early CAN were independent risk factors for elevated uACR (HR=8.61 and 8.35, respectively; both p <0.05). In addition, high-density lipoprotein cholesterol, ACE inhibitors/angiotensin receptor blockers and glucagon-like peptide-1 receptor agonists were independent protective factors for elevated uACR (HR=0.96, 0.25, and 0.07, respectively; all p <0.05)., Conclusion: Cardiovascular autonomic neuropathy is a potential indicator of DKD. Comprehensive management of DKD in the early stages of CAN may prevent microalbuminuria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cho, Lim, Kwon, Chung, Moon, Yoon and Won.)

Background and Aims: The purpose of this meta-analysis was to investigate the effect of vitamin D supplementation on hemoglobin A1C (HbA1C), fasting blood sugar (FBS), low-density lipoprotein (LDL), high-density lipoprotein (HDL), systolic blood pressure (SBP), and the total vitamin D level in patients with Type 2 diabetes (T2DM). Methods: A systematic search was conducted in databases such as PubMed (Medline), Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov using relevant keywords from January 1990 to January 2024. After screening and extracting data, a qualitative evaluation of articles was performed using the Cochrane risk-of-bias tool for randomized trials (RoB 2). Results: The findings revealed that vitamin D supplementation significantly decreased the mean HbA1C (SMD: -0.15; 95% CI: -0.29, -0.20; I square : 79.76%; p value < 0.001) and mean FBS (SMD: -0.28; 95% CI: -0.40, -0.15; I square : 70.13%; p value < 0.001), lowered SBP (SMD: -0.06; 95% CI: -0.16, -0.05; I square : 39.63%; p value = 0.23), and reduced LDL (SMD: -0.11; 95% CI: -0.28, -0.05; I square : 73.66%; p value < 0.001) in patients with T2DM. Subgroup analyses showed that weight gain, BMI, and duration of the disease could reduce the effect of vitamin D supplementation on diabetes control in affected patients. I The results also indicated that taking vitamin D supplements in the amount of 50,000 IU had a significant effect on reducing the indicators related to diabetes control. Based on the combined evidence, the findings of this meta-analysis suggest that vitamin D supplementation can significantly improve glycemic control and reduce the risk of complications associated with T2DM, especially cardiovascular diseases (CVDs).square : 79.33%; p value < 0.001) and vitamin D levels (SMD: 1.78; 95% CI: 1.53, 2.04; I square : 91.92%; p value < 0.001) in patients with T2DM. Subgroup analyses showed that weight gain, BMI, and duration of the disease could reduce the effect of vitamin D supplementation on diabetes control in affected patients. Conclusion: The results also indicated that taking vitamin D supplements in the amount of 50,000 IU had a significant effect on reducing the indicators related to diabetes control. Based on the combined evidence, the findings of this meta-analysis suggest that vitamin D supplementation can significantly improve glycemic control and reduce the risk of complications associated with T2DM, especially cardiovascular diseases (CVDs)., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Maryam Afraie et al.)

Introduction: Various strategies aim to better assess risks and refine prevention for patients with type 2 diabetes mellitus (T2DM), who vary in cardiovascular disease (CVD) risk. However, the prognostic value of personality and its association with lifestyle factors remain elusive., Research Design and Methods: We identified 8794 patients with T2DM from the UK Biobank database between 2006 and 2010 and followed them up until the end of 2021. We assessed personality traits using the Big Five proxies derived from UK Biobank data: sociability, warmth, diligence, curiosity, and nervousness. Healthy lifestyle behaviors were determined from information about obesity, smoking status, and physical activity. The primary outcome was a composite of incident CVD, including myocardial infarction (MI), ischemic stroke (IS), atrial fibrillation (AF), and heart failure (HF)., Results: During a median follow-up of 13.6 years, a total of 2110 patients experienced CVDs. Among personality traits, diligence was significantly associated with a reduced risk of primary and secondary outcomes. The adjusted HRs with 95% CIs were: composite CVD, 0.93 (0.89-0.97); MI 0.90 (0.82-1.00); IS 0.83 (0.74-0.94); AF 0.92 (0.85-0.98); HF 0.84 (0.76-0.91). Healthy lifestyle behaviors significantly reduced the risk of composite CVDs in groups with high and low diligence. The findings of a structural equation model showed that diligence directly affected the risk of the primary outcome or indirectly by modifying lifestyle behaviors., Conclusion: This study revealed which personality traits can influence CVD risk during T2DM and how patients might benefit from adopting healthy lifestyle behaviors in relation to personality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Knowledge of the risk of developing cardiovascular diseases (CVD) in the population is an important risk management strategy for the prevention of this disease. This is especially true for India, which has resource-restrained settings with an increased risk in a younger population for the development of the disease. An important modifiable risk factor for CVD is hypertension, with its influence on the development of CVD., Methods: The data from the first wave of the Longitudinal Ageing Study in India (LASI) was used to calculate the 10-year CVD Risk Score among older adults ≥45 years using a WHO (2019) non-laboratory- based chart for South Asia. Univariate analysis was done using Pearson's chi-square test, and multivariable analysis using ordinal logistic regression. Categories of CVD risk score were considered as dependent variable. Socio-demographic variables, regular exercise, history of diabetes and hyperlipidaemia were considered as the independent variables. Relationship between CVD Risk score and hypertensives and self-reported hypertensives were presented using restricted cubic splines., Result: Two-thirds (68.8%) of the population had a 10-year CVD risk of <10, and 2.8% had a risk of ≥20%. The self-reported hypertensives were distributed linearly in restricted cubic splines, with a more scattered distribution in higher scores, while actual hypertensives showed a sigmoid pattern. Urban residents (OR-0.88), being unmarried (OR-0.86), being in the richer (OR-0.94) and richest (OR-0.86) monthly per capita expenditure (MPCE) quintile and exercising regularly (OR-0.68) decreased the odds of being in a higher CVD risk score. Less than primary schooling (1.21) and diabetics (1.69) had higher odds for a higher CVD risk score., Conclusion: In this population, two-thirds had <10% risk for the development of CVD. The study shows a higher risk among rural, poor, and those with a lower education and lower CVD risk for those undertaking physical activity. The sigmoid pattern in actual hypertensives highlights the need for early detection. Even those with undiagnosed hypertension but with a higher BP had a similar risk for disease development, thus highlighting the need for an early detection of hypertension., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mamgai, Halder, Behera, Goel, Pal, Amudhamozhi, Sharma and Kiran.)

Background: Artificial intelligence (AI) is increasingly used for prevention, diagnosis, monitoring, and treatment of cardiovascular diseases. Despite the potential for AI to improve care, ethical concerns and mistrust in AI-enabled healthcare exist among the public and medical community. Given the rapid and transformative recent growth of AI in cardiovascular care, to inform practice guidelines and regulatory policies that facilitate ethical and trustworthy use of AI in medicine, we conducted a literature review to identify key ethical and trust barriers and facilitators from patients' and healthcare providers' perspectives when using AI in cardiovascular care., Methods: In this rapid literature review, we searched six bibliographic databases to identify publications discussing transparency, trust, or ethical concerns (outcomes of interest) associated with AI-based medical devices (interventions of interest) in the context of cardiovascular care from patients', caregivers', or healthcare providers' perspectives. The search was completed on May 24, 2022 and was not limited by date or study design., Results: After reviewing 7,925 papers from six databases and 3,603 papers identified through citation chasing, 145 articles were included. Key ethical concerns included privacy, security, or confidentiality issues (n = 59, 40.7%); risk of healthcare inequity or disparity (n = 36, 24.8%); risk of patient harm (n = 24, 16.6%); accountability and responsibility concerns (n = 19, 13.1%); problematic informed consent and potential loss of patient autonomy (n = 17, 11.7%); and issues related to data ownership (n = 11, 7.6%). Major trust barriers included data privacy and security concerns, potential risk of patient harm, perceived lack of transparency about AI-enabled medical devices, concerns about AI replacing human aspects of care, concerns about prioritizing profits over patients' interests, and lack of robust evidence related to the accuracy and limitations of AI-based medical devices. Ethical and trust facilitators included ensuring data privacy and data validation, conducting clinical trials in diverse cohorts, providing appropriate training and resources to patients and healthcare providers and improving their engagement in different phases of AI implementation, and establishing further regulatory oversights., Conclusion: This review revealed key ethical concerns and barriers and facilitators of trust in AI-enabled medical devices from patients' and healthcare providers' perspectives. Successful integration of AI into cardiovascular care necessitates implementation of mitigation strategies. These strategies should focus on enhanced regulatory oversight on the use of patient data and promoting transparency around the use of AI in patient care., (© 2024. The Author(s).)

Importance: Positive airway pressure (PAP) is the first-line treatment for obstructive sleep apnea (OSA), but evidence on its beneficial effect on major adverse cardiovascular events (MACE) and mortality prevention is limited., Objective: To determine whether PAP initiation and utilization are associated with lower mortality and incidence of MACE among older adults with OSA living in the central US., Design, Setting, and Participants: This retrospective clinical cohort study included Medicare beneficiaries with 2 or more distinct OSA claims identified from multistate, statewide, multiyear (2011-2020) Medicare fee-for-service claims data. Individuals were followed up until death or censoring on December 31, 2020. Analyses were performed between December 2021 and December 2023., Exposures: Evidence of PAP initiation and utilization based on PAP claims after OSA diagnosis., Main Outcomes and Measures: All-cause mortality and MACE, defined as a composite of myocardial infarction, heart failure, stroke, or coronary revascularization. Doubly robust Cox proportional hazards models with inverse probability of treatment weights were used to estimate treatment effect sizes controlling for sociodemographic and clinical factors., Results: Among 888 835 beneficiaries with OSA included in the analyses (median [IQR] age, 73 [69-78] years; 390 598 women [43.9%]; 8115 Asian [0.9%], 47 122 Black [5.3%], and 760 324 White [85.5%] participants; median [IQR] follow-up, 3.1 [1.5-5.1] years), those with evidence of PAP initiation (290 015 [32.6%]) had significantly lower all-cause mortality (hazard ratio [HR], 0.53; 95% CI, 0.52-0.54) and MACE incidence risk (HR, 0.90; 95% CI, 0.89-0.91). Higher quartiles (Q) of annual PAP claims were progressively associated with lower mortality (Q2 HR, 0.84; 95% CI, 0.81-0.87; Q3 HR, 0.76; 95% CI, 0.74-0.79; Q4 HR, 0.74; 95% CI, 0.72-0.77) and MACE incidence risk (Q2 HR, 0.92; 95% CI, 0.89-0.95; Q3 HR, 0.89; 95% CI, 0.86-0.91; Q4 HR, 0.87; 95% CI, 0.85-0.90)., Conclusions and Relevance: In this cohort study of Medicare beneficiaries with OSA, PAP utilization was associated with lower all-cause mortality and MACE incidence. Results might inform trials assessing the importance of OSA therapy toward minimizing cardiovascular risk and mortality in older adults.

Background: There is a growing burden of non-obese people with diabetes mellitus (DM). However, their cardiovascular risk (CV), especially in the presence of cardiovascular-kidney-metabolic (CKM) comorbidities is poorly characterised. The aim of this study was to analyse the risk of major CV adverse events in people with DM according to the presence of obesity and comorbidities (hypertension, chronic kidney disease, and dyslipidaemia)., Methods: We analysed persons who were enrolled in the prospective Silesia Diabetes Heart Project (NCT05626413). Individuals were divided into 6 categories according to the presence of different clinical risk factors (obesity and CKM comorbidities): (i) Group 1: non-obese with 0 CKM comorbidities; (ii) Group 2: non-obese with 1-2 CKM comorbidities; (iii) Group 3: non-obese with 3 CKM comorbidities (non-obese "extremely unhealthy"); (iv) Group 4: obese with 0 CKM comorbidities; (v) Group 5: obese with 1-2 CKM comorbidities; and (vi) Group 6: obese with 3 CKM comorbidities (obese "extremely unhealthy"). The primary outcome was a composite of CV death, myocardial infarction (MI), new onset of heart failure (HF), and ischemic stroke., Results: 2105 people with DM were included [median age 60 (IQR 45-70), 48.8% females]. Both Group 1 and Group 6 were associated with a higher risk of events of the primary composite outcome (aHR 4.50, 95% CI 1.20-16.88; and aHR 3.78, 95% CI 1.06-13.47, respectively). On interaction analysis, in "extremely unhealthy" persons the impact of CKM comorbidities in determining the risk of adverse events was consistent in obese and non-obese ones (P int =0.824), but more pronounced in individuals aged < 65 years compared to older adults (P int = 0.028)., Conclusion: Both non-obese and obese people with DM and 3 associated CKM comorbidities represent an "extremely unhealthy" phenotype which are at the highest risk of CV adverse events. These results highlight the importance of risk stratification of people with DM for risk factor management utilising an interdisciplinary approach., (© 2024. The Author(s).)

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have demonstrated associations with lowering cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, the impact of SGLT-2is on individuals at dialysis commencement remains unclear. The aim of this real-world study is to study the association between SGLT-2is and outcomes in patients with T2DM at dialysis commencement., Methods: This is a retrospective cohort study of electronic health records (EHRs) of patients with T2DM from TriNetX Research Network database between January 1, 2012, and January 1, 2024. New-users using intention to treatment design was employed and propensity score matching was utilized to select the cohort. Clinical outcomes included major adverse cardiac events (MACE) and all-cause mortality. Safety outcomes using ICD-10 codes, ketoacidosis, urinary tract infection (UTI) or genital infection, dehydration, bone fracture, below-knee amputation, hypoglycemia, and achieving dialysis-free status at 90 days and 90-day readmission., Results: Of 49,762 patients with T2DM who initiated dialysis for evaluation, a mere 1.57% of patients utilized SGLT-2is within 3 months after dialysis. 771 SGLT-2i users (age 63.3 ± 12.3 years, male 65.1%) were matched with 771 non-users (age 63.1 ± 12.9 years, male 65.8%). After a median follow-up of 2.0 (IQR 0.3-3.9) years, SGLT-2i users were associated with a lower risk of MACE (adjusted Hazard Ratio [aHR] = 0.52, p value < 0.001), all-cause mortality (aHR = 0.49, p < 0.001). SGLT-2i users were more likely to become dialysis-free 90 days after the index date (aHR = 0.49, p < 0.001). No significant differences were observed in the incidence of ketoacidosis, UTI or genital infection, hypoglycemia, dehydration, bone fractures, below-knee amputations, or 90-day readmissions., Conclusions: Our findings indicated a lower incidence of all-cause mortality and MACE after long-term follow-up, along with a higher likelihood of achieving dialysis-free status at 90 days in SGLT-2i users. Importantly, they underscored the potential cardiovascular protection and safety of SGLT-2is use in T2DM patients at the onset of dialysis., (© 2024. The Author(s).)