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Background: The Manhattan Lupus Surveillance Program (MLSP), a population-based retrospective registry of patients with systemic lupus erythematosus (SLE), was used to investigate the prevalence of cardiovascular disease events (CVE) and compare rates among sex, age and race/ethnicity to population-based controls., Methods: Patients with prevalent SLE in 2007 aged ≥ 20 years in the MLSP were included. CVE required documentation of a myocardial infarction or cerebrovascular accident. We calculated crude risk ratios and adjusted risk ratios (ARR) controlling for sex, age group, race and ethnicity, and years since diagnosis. Data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) and the 2013-2014 NYC Health and Nutrition Examination Survey (NYC HANES) were used to calculate expected CVE prevalence by multiplying NHANES and NYC HANES estimates by strata-specific counts of patients with SLE. Crude prevalence ratios (PRs) using national and NYC estimates and age standardized prevalence ratios (ASPRs) using national estimates were calculated., Results: CVE occurred in 13.9% of 1,285 MLSP patients with SLE, and risk was increased among men (ARR:1.7, 95%CI:1.2-2.5) and older adults (age > 60 ARR:2.5, 95%CI:1.7-3.8). Compared with non-Hispanic Asian patients, CVE risk was elevated among Hispanic/Latino (ARR:3.1, 95%CI:1.4-7.0) and non-Hispanic Black (ARR:3.5, 95%CI1.6-7.9) patients as well as those identified as non-Hispanic and in another or multiple racial groups (ARR:4.2, 95%CI:1.1-15.8). Overall, CVE prevalence was higher among patients with SLE than nationally (ASPR:3.1, 95%CI:3.0-3.1) but did not differ by sex. Compared with national race and ethnicity-stratified estimates, CVE among patients with SLE was highest among Hispanics/Latinos (ASPR:4.3, 95%CI:4.2-4.4). CVE was also elevated among SLE registry patients compared with all NYC residents. Comparisons with age-stratified national estimates revealed PRs of 6.4 (95%CI:6.2-6.5) among patients aged 20-49 years and 2.2 (95%CI:2.1-2.2) among those ≥ 50 years. Male (11.3, 95%CI:10.5-12.1), Hispanic/Latino (10.9, 95%CI:10.5-11.4) and non-Hispanic Black (6.2, 95%CI:6.0-6.4) SLE patients aged 20-49 had the highest CVE prevalence ratios., Conclusions: These population-based estimates of CVE in a diverse registry of patients with SLE revealed increased rates among younger male, Hispanic/Latino and non-Hispanic Black patients. These findings reinforce the need to appropriately screen for CVD among all SLE patients but particularly among these high-risk patients., (© 2024. The Author(s).)

Interleukin-6 (IL-6) plays a crucial role in the pathogenesis of cardiovascular disease (CVD), and IL-6 receptor (IL-6R) blockade has emerged as a promising therapeutic option. However, their specific therapeutic effects in different types of CVDs remain unclear. This study aimed to assess the efficacy of IL-6R blockade in the management of various CVDs, including hypertension (HTN), coronary heart disease (CHD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF). The Mendelian randomization (MR) approach was utilized to investigate the therapeutic impact of IL-6R blockade on HTN, CHD, MI, AF, and HF based on the genome-wide association study (GWAS) summary statistics. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were used for sensitivity analysis to verify the reliability of the MR results. The Bonferroni method was used to correct for bias caused by multiple comparisons. Inverse variance weighted (IVW) results demonstrated that IL-6R blockade significantly influenced CHD (odds ratio (OR) = 0.757, 95% confidence interval (CI): 0.690 - 0.832, P = 5.804 × 10 -9 ) and MI (OR = 0.840, 95% CI: 0.744 - 0.949, P = 0.005). However, IL-6R blockade had no significant effect on HTN (OR = 1.015, 95% CI: 0.950 - 1.084, P = 0.663), AF (OR = 0.905, 95% CI: 0.800 - 1.025, P = 0.116) and HF (OR = 1.012, 95% CI: 0.921 - 1.113, P = 0.805). Genetically predicted IL-6R blockade was associated with a protective effect on CHD and MI, but not HTN, AF and HF. This study's findings offer valuable insights for tailoring IL-6R blockade treatment for different types of CVD, and serve as a reference for future research., (© 2024. The Author(s).)

Background: In this study, we explored the impact of hypothyroidism and thyroid hormone replacement therapy on the risk of developing cardiovascular diseases, including myocardial infarction, heart failure, and cardiac death, via Mendelian randomization analysis., Methods: Genetic instrumental variables related to hypothyroidism, levothyroxine treatment (refer to Participants were taking the medication levothyroxine sodium) and adverse cardiovascular events were obtained from a large publicly available genome-wide association study. Two-sample Mendelian randomization analysis was performed via inverse-variance weighting as the primary method. To ensure the reliability of our findings, we performed MR‒Egger regression, Cochran's Q statistic, and leave-one-out analysis. Additionally, multivariable Mendelian randomization was employed to regulate confounding factors, including systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), diabetes, cholesterol, low-density lipoprotein (LDL), triglycerides and metformin. A mediation analysis was conducted to assess the mediating effects on the association between exposure and outcome by treating atrial fibrillation and stroke as mediator variables of levothyroxine treatment and bradycardia as mediator variables of hypothyroidism., Results: Genetically predicted hypothyroidism and levothyroxine treatment were significantly associated with the risk of experiencing myocardial infarction [levothyroxine: odds ratio (OR) 3.75, 95% confidence interval (CI): 1.80-7.80; hypothyroidism: OR: 15.11, 95% CI: 2.93-77.88]. Levothyroxine treatment was also significantly related to the risk of experiencing heart failure (OR: 2.16, 95% CI: 1.21-3.88). However, no associations were detected between hypothyroidism and the risk of experiencing heart failure or between hypothyroidism or levothyroxine treatment and the risk of experiencing cardiac death. After adjusting for confounding factors, the results remained stable. Additionally, mediation analysis indicated that atrial fibrillation and stroke may serve as potential mediators in the relationships between levothyroxine treatment and the risk of experiencing heart failure or myocardial infarction., Conclusion: The results of our study suggest a positive association between hypothyroidism and myocardial infarction and highlight the potential effects of levothyroxine treatment, the main thyroid hormone replacement therapy approach, on increasing the risk of experiencing myocardial infarction and heart failure., (© 2024. The Author(s).)

Cathepsin B (CTSB) is a member of the cysteine protease family, primarily responsible for degrading unnecessary organelles and proteins within the acidic milieu of lysosomes to facilitate recycling. Recent research has revealed that CTSB plays a multifaceted role beyond its function as a proteolytic enzyme in lysosomes. Importantly, recent data suggest that CTSB has significant impacts on different cardiac pathological conditions, such as atherosclerosis (AS), myocardial infarction, hypertension, heart failure and cardiomyopathy. Especially in the context of AS, preclinical models and clinical sample imaging data indicate that the cathepsin activity-based probe can reliably image CTSB activity in foam cells and atherosclerotic plaques; concurrently, it allows synchronous diagnostic and therapeutic interventions. However, our knowledge of CTSB in cardiovascular disease is still in the early stage. This paper aims to provide a comprehensive review of the significance of CTSB in cardiovascular physiology and pathology, with the objective of laying a theoretical groundwork for the development of drugs targeting CTSB., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Despite major advances in cardiac research over the past three decades, cardiovascular disease (CVD) still remains the leading cause of morbidity and mortality in women and men worldwide. However, a major challenge for health care providers is that the current guidelines for cardiovascular drug therapies do not consider the impact of sex in the development of treatment plan for optimizing therapies for women. Clinical research in recent years suggests significant pharmacological and pharmacokinetic differences between females and males, which have been attributed in part to differences in body composition, plasma protein binding capacity, drug metabolism, and excretion. Herein, we provide a comprehensive review regarding sex-specific differences and drugs commonly used for CVDs in women and men. Understanding how sex-related differences influence drug efficacy and CVD outcomes is crucial for not only optimizing treatment strategies for women and men but also to encourage the implementation of specific guidelines that address sex difference as a consideration for the treatment of CVDs., Competing Interests: The authors declare no conflict of interest. All the authors have contributed to preparing and editing this manuscript and have approved its submission for publication.

Objectives: To our knowledge, there is no systematic review examining CVD risks after a SARS-CoV-2 infection over time, while also taking into account disease severity. All evidence on the risk for pulmonary embolism (PE), myocardial infarction (MI), ischaemic stroke (IS), haemorrhagic stroke (HS), and arterial thrombosis following infection was evaluated., Methods: The protocol was registered with PROSPERO. We searched Pubmed, Embase, MedRxiv and screened the titles/abstracts and full texts. We extracted the included studies, assessed their quality, and estimated pooled risks by time after infection and according to disease severity., Results: Risks were highest in the acute phase [PE: 27.1 (17.8-41.10); MI: 4.4 (1.6-12.4); stroke: 3.3 (2.1-5.2); IS: 5.6 (2.1-14.8); HS: 4.0 (0.1-326.2)] compared to the post-acute phase [PE: 2.9 (2.6-3.3); MI: 1.4 (1.1-1.9); stroke: 1.4 (1.0-2.0); IS: 1.6 (0.9-2.7)]. Highest risks were observed after infection confirmation, dropping during the first month post-infection (e.g. PE: RR(7 days) = 31; RR(1 month) = 8.1). A doubled risk was still observed until 4.5 months for PE, one month for MI and two months for IS. Risks decreased with decreasing disease severity., Conclusions: Because of increased risk of CVD outcomes, management of persons who survived a severe SARS-CoV-2 infection is required, especially during the first nine months post-infection., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Currently, the special blood pressure (BP) target for normotensive diabetic patients has not been recommended. We investigated the optimal systolic blood pressure (SBP) for lower cardiovascular disease (CVD) risk in normotensive diabetic patients., Methods: In this 12-year follow-up study using the participants of the Kailuan Study, we mainly compared which SBP, 90-119 mmHg or 120-129 mmHg, had a lower risk of occurrence of CVD (stroke and myocardial infarction) in the 3072 normotensive diabetic participants and 21,532 normotensive and non-diabetic participants, respectively. The SBP was expressed as a mean time-weighted cumulative (MTWC) SBP, calculated from the multiple measurements of SBP during the follow-up. Multivariate competing risk regression analyses were used for the analysis., Results: We found that in normotensive diabetic participants, MTWC SBP of 120-129 mmHg was associated with a lower risk of CVD (HR = 0.69 [0.50-0.95]), myocardial infarction (HR = 0.48 [0.24-0.96]), and trending towards lower risk of stroke (HR = 0.80 [0.55-1.16]), compared to MTWC SBP of 90-119 mmHg. Sensitivity analyses confirmed the relationship between low SBP and increased CVD risk. Whereas, in the normotensive and non-diabetic participants, MTWC SBP of 90-119 mmHg vs 120-129 mmHg did not exhibit any difference in the risk of CVD occurrence (HR = 0.99 [0.83-1.18])., Conclusions: The higher level of SBP in normotensive diabetic patients is especially associated with a lower risk of CVD occurrence., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Evaluate the effects of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on cardiovascular and cerebrovascular diseases., Methods: Articles of SGLT2i on cardiovascular and cerebrovascular diseases were searched. Two authors independently screened the literature, extracted the data, assessed the quality of the study and performed statistical analyses using Review Manager 5.4., Results: Random-effect model was used to merge the OR values, and the pooled effect showed that SGLT2i had significant preventive effects on cardiovascular death (OR=0.76, 95%CI 0.64 to 0.89), myocardial infarction (OR=0.90, 95%CI 0.84 to 0.96), heart failure (OR=0.69, 95%CI 0.64 to 0.74) and all-cause mortality (OR=0.65, 95%CI 0.58 to 0.73). Empagliflozin, dapagliflozin and canagliflozin all reduced the incidence of heart failure (OR=0.72, 95%CI 0.64 to 0.82; OR=0.56, 95%CI 0.39 to 0.80; OR=0.62, 95%CI 0.53 to 0.73), but only dapagliflozin displayed a favorable effect on inhibiting stroke (OR=0.78, 95%CI 0.63 to 0.98). SGLT2i could prevent stroke (OR=0.86, 95%CI 0.75 to 0.99), heart failure (OR=0.63, 95%CI 0.56 to 0.70) and all-cause mortality (OR=0.64, 95%CI 0.57 to 0.72) compared to DPP-4i. Furthermore, SGLT2i could reduce the incidence of heart failure (OR=0.72, 95%CI 0.67 to 0.77) and cardiovascular death (OR=0.72, 95%CI 0.54 to 0.95) in patients with high-risk factors., Conclusions: SGLT2i affects cardiovascular death, myocardial infarction, heart failure and all-cause mortality. Only dapagliflozin displayed a favorable effect on inhibiting stroke. SGLT2i could prevent stroke, heart failure and all-cause mortality compared to DPP-4i. In addition, SGLT2i significantly reduced the development of heart failure and cardiovascular death in patients with high-risk factors., Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024532783., 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 Wang, Li, Cui, Gu, Zhao and Wang.)

Background: Sexual minority men with HIV are at an increased risk of cardiovascular disease (CVD) and have been underrepresented in behavioral research and clinical trials., Objective: This study aims to explore perceptions of HIV-related comorbidities and assess the interest in and usability of a virtual environment for CVD prevention education in Black and Latinx sexual minority men with HIV., Methods: This is a 3-phase pilot behavioral randomized controlled trial. We report on formative phases 1 and 2 that informed virtual environment content and features using qualitative interviews, usability testing, and beta testing with a total of 25 individuals. In phase 1, a total of 15 participants completed interviews exploring HIV-related illnesses of concern that would be used to tailor the virtual environment. In phase 2, usability testing and beta testing were conducted with 10 participants to assess interest, features, and content., Results: In phase 1, we found that CVD risk factors included high blood pressure, myocardial infarction, stroke, and diabetes. Cancer (prostate, colon, and others) was a common concern, as were mental health conditions. In phase 2, all participants completed the 12-item usability checklist with favorable feedback within 30 to 60 minutes. Beta-testing interviews suggested (1) mixed perceptions of health and HIV, (2) high risk for comorbid conditions, (3) virtual environment features were promising, and (4) the need for diverse avatar representations., Conclusions: We identified several comorbid conditions of concern, and findings carry significant implications for mitigating barriers to preventive health screenings, given the shared risk factors between HIV and related comorbidities. Highly rated aspects of the virtual environment were anonymity; meeting others with HIV who identify as gay or bisexual; validating lesbian, gay, bisexual, transgender, queer, and others (LGBTQ+) images and content; and accessibility to CVD prevention education. Critical end-user feedback from beta testing suggested more options for avatar customization in skin, hair, and body representation. Our next phase will test the virtual environment as a new approach to advancing cardiovascular health equity in ethnic and racial sexual minority men with HIV., Trial Registration: ClinicalTrials.gov NCT04061915; https://clinicaltrials.gov/study/NCT05242952., International Registered Report Identifier (irrid): RR2-10.2196/38348., (©S Raquel Ramos, Harmony Reynolds, Constance Johnson, Gail Melkus, Trace Kershaw, Julian F Thayer, Allison Vorderstrasse. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.08.2024.)

Aims: As lifetime accumulation of cardiovascular risk factors is gaining importance, early identification and management of risk factors are being emphasized. The global prevalence of metabolic syndrome (MetS), a constellation of these risk factors, is increasing, particularly among young adults. In this study, we aim to investigate the association between cumulative exposure to metabolic risk and cardiovascular disease (CVD) in young adults., Methods and Results: In this nationwide population-based cohort, we analysed 3 688 787 young adults (<40 years) with 2 biennial National Health Screening examinations from 2009 to 2012. Participants were categorized into MetS-free, MetS-developed, MetS-recovered, or MetS-persistent group, based on MetS presence at each examination. The endpoint was new CVD development, including myocardial infarction (MI) and ischaemic stroke. During follow-up (median, 7.7 years), CVD occurred in 19 219 individuals (0.5%). The incidence rates of CVD were 0.58, 1.17, 1.20, and 1.83 (1000 person-years) in the MetS-free, MetS-developed, MetS-recovered, and MetS-persistent groups, respectively. The CVD risk was proportionally associated with cumulative metabolic risk exposure, with a maximum two-fold increase in the MetS-persistent group [adjusted hazard ratio (aHR) 1.94, 95% confidence interval (CI) 1.84-2.04], followed by the MetS-recovered and the MetS-developed groups with similar risks. Among the MetS components, persistent exposure to elevated blood pressure (BP) had the greatest association with CVD risk (aHR 1.69, 95% CI 1.63-1.76). This tendency was consistent in the separate analyses of the risk of MI and ischaemic stroke., Conclusion: The risk of CVD increased in an exposure-dependent manner among young adults. Efforts to optimize the cardiometabolic profile, particularly BP, even after the establishment of MetS, might help promote long-term cardiovascular prognosis., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: Evidence on weight transitions across life stages and cardiovascular diseases (CVDs) is limited. We aimed to explore weight transition patterns from birth to childhood to midlife and risk of incident CVDs., Methods: A total of 193,905 participants from the UK Biobank were included. Weight at birth, childhood, and midlife were collected at baseline (2006-2010). CVD outcomes were collected at year 2022. We constructed 27 transition patterns from birth to age 10 years to midlife. Cox proportional hazard models yielded hazard ratios (HRs) and 95% confidence intervals (CI) between weight transition patterns and CVDs. Mediation analyses were performed. Rate advancement periods (RAP) were also calculated., Results: Several weight transition patterns were clearly linked to risk of CVDs, including "Low birth weight → high weight at age 10 years → obesity at midlife" (HR 2.64, 95% CI 2.24-3.11), "Low birth weight → low weight at age 10 years → obesity at midlife" (2.27, 1.93-2.66), "High birth weight → low weight at age 10 years → obesity at midlife" (2.29, 1.96-2.67), and "High birth weight → high weight at age 10 years → obesity at midlife" (2.14, 1.89-2.42), which showed even stronger association with HF. RAPs of these patterns were 8.3-10.6 years for CVD and 10.0-13.1 for HF. 50% of the association between birth weight and CVDs was mediated by weight at midlife., Conclusions: Our findings highlight the importance of weight management throughout the life course in reducing the risk of CVDs, especially maintaining a heathy weight at midlife., Competing Interests: Declaration of competing interest All authors declare no conflict of interest for this contribution., (Copyright © 2023. Published by Elsevier Inc.)

Background: It is widely accepted that omega-3 fatty acids are beneficial in the prevention of cardiovascular disease, but many large randomized controlled trial studies and meta-analyses have come to different conclusions. The evidence for omega-3 fatty acids supplementation to prevent cardiovascular disease remains insufficient. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of several types of omega-3 fatty acids supplements., Methods: We comprehensively searched the online database and found 15 RCTs. The primary efficacy outcomes included major cardiovascular events, myocardial infarction, heart failure, atrial fibrillation, stroke, cardiovascular death, and all-cause death. The safety endpoints included gastrointestinal problems, bleeding-related disorders, and cancer. Subgroup analysis was conducted according to the main characteristics of the population, and the dose-response relationship of omega-3 fatty acids was evaluated by meta-regression. All results were calculated by the random effect model. Statistical heterogeneity was assessed using chi-square tests and quantified using I-square statistics., Results: The incidence of major cardiovascular events (RR 0.95, 95%CI 0.91 to 0.99, P = 0.026), myocardial infarction (RR 0.90, 95%CI 0.83 to 0.98; P = 0.021), and cardiovascular death (RR 0.94, 95%CI 0.88 to 0.99; P = 0.028) was reduced in the omega-3 fatty acid group compared with the control group. An increased risk of atrial fibrillation (RR 1.25, 95%CI 1.10 to 1.41; P = 0.000) was observed in patients in the omega-3 fatty acid group. No statistical differences were observed between the two groups in heart failure, stroke, and all-cause death. For safety endpoints, there were no statistically significant differences between the two groups in gastrointestinal problems, bleeding-related disorders, and cancer. Subgroup analysis showed that the cardiovascular benefit of omega-3 fatty acids was primarily attributable to the prescription of EPA ethyl ester. Omega-3 fatty acids may reduce the risk of major cardiovascular events in patients with cardiovascular disease or risk factors, and reduce the risk of myocardial infarction in patients without cardiovascular disease; however, they may increase the risk of stroke in patients with myocardial infarction. In addition, prescription omega-3 acid ethyl ester has a good safety profile, and prescription EPA ethyl ester has a high risk of bleeding., Conclusion: Moderate evidence showed that the use of omega-3 fatty acids may reduce the risk of major cardiovascular events, myocardial infarction, and cardiovascular death. Compared to other types of omega-3 fatty acids supplements, we support the use of prescription EPA ethyl ester formulations for the prevention of cardiovascular disease, but the potential risk of atrial fibrillation and bleeding cannot be ignored. It is important to note that omega-3 fatty acids should be applied with caution in patients with previous myocardial infarction, which may increase the risk of stroke. Finally, omega-3 fatty acids are relatively safe and in general do not increase gastrointestinal problems, bleeding-related disorders, or cancer, but attention needs to be paid to the risk of bleeding with prescription EPA ethyl ester formulations., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Post-traumatic stress disorder (PTSD) is increasingly recognized for its effects beyond mental health, with emerging evidence suggesting a significant association with cardiovascular diseases (CVD). This systematic review and meta-analysis aimed to synthesize available evidence on the association between PTSD and various cardiovascular outcomes., Methods: We conducted a comprehensive literature search in databases until March 15, 2024. Studies were included if they were observational in design and assessed the association between PTSD and cardiovascular outcomes. Data were extracted on study characteristics, participant demographics, PTSD assessment, cardiovascular outcomes, and effect estimates. Meta-analyses were performed using random-effects models, and heterogeneity was assessed using the I² statistic. All statistical analyses were conducted using R software version 4.3., Results: Twenty studies met the inclusion criteria, encompassing a total of over 335,000 participants. The pooled analyses demonstrated a statistically significant increased risk of any CVD (HR = 1.417, 95 % CI: 1.313-1.522), MI (HR = 1.415, 95 % CI: 1.331-1.500), and stroke (HR = 2.074, 95 % CI: 1.165-2.982) associated with PTSD. Substantial heterogeneity was observed across the studies for stroke and MACE, and evidence of publication bias was noted., Conclusion: This meta-analysis confirms a significant association between PTSD and an increased risk of several cardiovascular outcomes, indicating the importance of integrating cardiovascular risk management with psychiatric care for PTSD patients to mitigate the heightened risk of CVDs. Future research should focus on exploring the underlying mechanisms and potential interventions to manage both PTSD and its associated cardiovascular risks effectively., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

Cardiovascular diseases (CVDs) are one of the main causes of morbidity and disability worldwide. Due to modern methods of diagnosis and treatment, it is possible to protect patients with acute coronary syndromes from myocardial infarction as well from its early complications. However, the challenge remains to improve the long-term prognosis of CVDs. Analysis of body composition using the bioelectrical impedance (BIA) appears to be a good method for assessing changes in patients' organisms following various cardiac incidents, as well as those participating in rehabilitation programmes. This study aims to provide a complementary analysis of the scientific literature and a critical review of the data from the use of BIA to assess phase angle in people with a history of cardiac diseases. This critical literature review was prepared based on the Scale for the Assessment of Narrative Review Articles recommendations. Inclusion criteria included 1) original publications of a research nature, 2) papers indexed in PubMed, Scopus, Embase databases, 3) full-text articles in English, 4) recent papers published between 2013-2023, 5) papers on the use of BIA with phase angle assessment as a prognostic factor in multiple aspects of health and disease, 6) papers showing changes in body composition in the process of cardiac rehabilitation. Based on a review of PubMed, Scopus and Embase databases, 36, 31 and 114 publications were found, respectively, chosen on the basis of precisely selected keywords and included for further full-text analysis. Exploring the role of the BIA holds lots of hope as a non-invasive method that can be used as a predictive marker for changes in the state of health in various fields of medicine. In young, healthy adults, BIA parameters may be important in identifying risk factors for the development of particular diseases, in predicting the rapid development of disease symptoms and in promoting motivation to lifestyle changes. Med Pr Work Health Saf. 2024;75(3):243-254., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Cardiovascular diseases (CVDs) remain a leading global cause of morbidity and mortality. These diseases have a multifaceted nature being influenced by a multitude of biochemical, genetic, environmental, and behavioral factors. Epigenetic modifications have a crucial role in the onset and progression of CVD. Epigenetics, which regulates gene activity without altering the DNA's primary structure, can modulate cardiovascular homeostasis through DNA methylation, histone modification, and non-coding RNA regulation. The effects of environmental stimuli on CVD are mediated by epigenetic changes, which can be reversible and, hence, are susceptible to pharmacological interventions. This represents an opportunity to prevent diseases by targeting harmful epigenetic modifications. Factors such as high-fat diets or nutrient deficiencies can influence epigenetic enzymes, affecting fetal growth, metabolism, oxidative stress, inflammation, and atherosclerosis. Recent studies have shown that plant-derived bioactive compounds can modulate epigenetic regulators and inflammatory responses, contributing to the cardioprotective effects of diets. Understanding these nutriepigenetic effects and their reversibility is crucial for developing effective interventions to combat CVD. This review delves into the general mechanisms of epigenetics, its regulatory roles in CVD, and the potential of epigenetics as a CVD therapeutic strategy. It also examines the role of epigenetic natural compounds (ENCs) in CVD and their potential as intervention tools for prevention and therapy.

Background: A growing proportion of people experience incomplete recovery months after contracting coronavirus disease 2019 (COVID-19). These COVID-19 survivors develop a condition known as post-COVID syndrome (PCS), where COVID-19 symptoms persist for > 12 weeks after acute infection. Limited studies have investigated PCS risk factors that notably include pre-existing cardiovascular diseases (CVD), which should be examined considering the most recent PCS data. This review aims to identify CVD as a risk factor for PCS development in COVID-19 survivors., Methods: Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist, systematic literature searches were performed in the PubMed, Scopus, and Web of Science databases from the earliest date available to June 2023. Data from observational studies in English that described the association between CVD and PCS in adults (≥ 18 years old) were included. A minimum of two authors independently performed the screening, study selection, data extraction, data synthesis, and quality assessment (Newcastle-Ottawa Scale). The protocol of this review was registered under PROSPERO (ID: CRD42023440834)., Results: In total, 594 studies were screened after duplicates and non-original articles had been removed. Of the 11 included studies, CVD including hypertension (six studies), heart failure (three studies), and others (two studies) were significantly associated with PCS development with different factors considered. The included studies were of moderate to high methodological quality., Conclusion: Our review highlighted that COVID-19 survivors with pre-existing CVD have a significantly greater risk of developing PCS symptomology than survivors without pre-existing CVD. As heart failure, hypertension and other CVD are associated with a higher risk of developing PCS, comprehensive screening and thorough examinations are essential to minimise the impact of PCS and improve patients' disease progression., (© 2024. The Author(s).)

Background: In the CLEAR (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) Outcomes trial, treatment of statin-intolerant patients with bempedoic acid produced a 21% decrease in low-density lipoprotein cholesterol (LDL-C) relative to placebo and a 13% relative reduction in the risk of major adverse cardiovascular events., Objectives: This study sought to determine whether the relationship between LDL-C lowering and cardiovascular benefit achieved with bempedoic acid resembles that observed with statins when standardized per unit change in LDL-C., Methods: To compare the treatment effect of bempedoic acid with statins, the methodology of the Cholesterol Treatment Trialists' Collaboration (CTTC) was applied to outcomes among the 13,970 patients enrolled in the CLEAR Outcomes trial. The CTTC endpoint of "major vascular event" was a composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal stroke, or coronary revascularization. HRs for CTTC-defined endpoints were normalized to 1 mmol/L differences in LDL-C levels between bempedoic acid and placebo groups., Results: A first major vascular event occurred in 703 (10.1%) patients in the bempedoic acid group and 816 (11.7%) patients in the placebo group (HR: 0.85; 95% CI: 0.77-0.94). When normalized per 1 mmol/L reduction in LDL-C, the HR was 0.75 (95% CI: 0.63-0.90), comparable to the rate ratio of 0.78 reported for statins in the CTTC meta-analysis. Normalized risk reductions were similar for bempedoic acid and statins for the endpoints of major coronary events, nonfatal myocardial infarction, and coronary revascularization., Conclusions: Cardiovascular risk reduction with bempedoic acid is similar to that achieved with statins for a given absolute magnitude of LDL-C lowering. (Evaluation of Major Adverse Cardiovascular Events in Participants With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated with Bempedoic Acid [ETC-1002] or Placebo [CLEAR Outcomes]; NCT02993406)., Competing Interests: Funding Support and Author Disclosures This work was funded by Esperion Therapeutics, Inc. The trial was designed by the sponsor, Esperion Therapeutics, in collaboration with the Cleveland Clinic Coordinating Center for Clinical Research (C5Research) and an academic Executive Committee. At the completion of the trial, the database was transferred to C5Research. Statisticians at Esperion conducted data analyses for this paper. Dr Lincoff wrote the first draft and all subsequent drafts of the paper, which was reviewed and approved by all authors. The sponsor reviewed the paper and provided suggested revisions, but the final decision on content was reserved for the academic authors. Dr Lincoff has received research funding for this trial from Esperion; has received grants from Eli Lilly, AbbVie, CSL, AstraZeneca, and Novartis; has received personal fees from Novo Nordisk, Eli Lilly, Akebia, Alnylam, Amgen, Ardelyx, Becton-Dickson, Brainstorm Cell, Cadrenal, Endologix, Fibrogen, GlaxoSmithKline, Intarcia, Medtronic, Neovasc, Provention Bio, and ReCor; and has received travel support for attending steering committee meetings from Novo Nordisk, Esperion, and Eli Lilly. Dr Ray has received unrestricted research grants (in the last 3 years) to Imperial College London from Amgen, Sanofi, Regeneron, Daiichi-Sankyo, and Ultragenix; has received consulting fees for serving as a member of the steering committee and executive committee of clinical trials and roles as principal investigator and national lead investigator from Novartis, Daiichi-Sankyo, Kowa, Esperion, Novo Nordisk, MSD, Lilly, Silence Therapeutics, AstraZeneca, New Amsterdam Pharma, Bayer, Beren Therapeutics, Cleerly, EmendoBio, Scribe, CRISPR, Vaxxinity, Amarin, Regeneron, Ultragenix, Cargene, and Resverlogix; has served on advisory boards, providing advice on data, its interpretation, and future lines of research; has received lecture fees for Continuing Medical Education and non–Continuing Medical Education symposia at international meetings from Novartis, Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Viatris, Amarin, Biologix Pharma, Sanofi, Amgen, Esperion, Daiichi-Sankyo, and Macleod Pharma; owns stock options in New Amsterdam Pharma and PEMI31; and has served as European Atherosclerosis Society President (unpaid). Dr Sasiela was an employee of, has served as a paid consultant for, and owns stock in Esperion Therapeutics, Inc. Dr Nicholls has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Eli Lilly, Esperion, Resverlogix, Novartis, InfraReDx, and Sanofi-Regeneron; and has served as a consultant for Amgen, Akcea, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Kowa, Merck, Takeda, Pfizer, Sanofi-Regeneron, Novo Nordisk, CSL Sequiris, and Vaxxinity. Dr Li is an employee of Esperion Therapeutics, Inc. Dr Cho has served on the steering committee for the CLEAR Outcomes trial. Dr Libby has served as an unpaid consultant for Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Novo Nordisk, Novartis, Pfizer, Sanofi-Regeneron, Cartesian, Esperion, Genentech, and Moderna; has served as an unpaid scientific advisory board member for the Baim Institute, Medimmune, Dewpoint, Pfizer, DalCor Pharmaceuticals, Olatec Therapeutics, XBiotech Inc, Caristo, CSL Behring, PlaqueTech, TenSixteen Bio, Soley Therapeutics, and Elucid Bioimaging; has received laboratory funding from Pfizer and CSL Behring; holds patents pending for use of canakinumab and for treatment for brain ischemia-reperfusion injury; has served as an unpaid consultant or been involved in clinical trials for Amgen, AstraZeneca, the Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Moderna, Novo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron; has served on the scientific advisory board for Amgen, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint Therapeutics, Eulicid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, PlaqueTec, TenSixteen Bio, Soley Therapeutics, and XBiotech Inc; has received research funding to his laboratory in the last 2 years from Novartis, Novo Nordisk, and Genentech; has served on the board of directors for XBiotech Inc; has held a financial interest in Xbiotech (a company developing therapeutic human antibodies), TenSixteen Bio (a company targeting somatic mosaicism and clonal hematopoiesis of indeterminate potential to discover and develop novel therapeutics to treat age-related diseases), and Soley Therapeutics (a biotechnology company combining artificial intelligence with molecular and cellular response detection for discovering and developing new drugs, currently focusing on cancer therapeutics); and has had his interests reviewed and managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of-interest policies. Dr Goodman has received research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CYTE Ltd., Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, Idorsia, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, Valeo Pharma; and has received salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Failure Society, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, and TIMI Study Group (Brigham Health). Dr Nissen has received grant support from Esperion for the CLEAR Outcomes Trial; and the Cleveland Clinic Center for Clinical Research has received funding to perform clinical trials from AbbVie, AstraZeneca, Arrowhead, Amgen, Bristol Myers Squibb, Eli Lilly, Medtronic, MyoKardia, New Amsterdam Pharmaceuticals, Novartis, and Silence Therapeutics, in which Dr Nissen is involved in these clinical trials but receives no personal remuneration for his participation. 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.)

National guidelines define psoriasis as a risk enhancer for cardiovascular disease and recommend increased monitoring and more intense management of cardiovascular risk factors in these patients, who face an increased burden of cardiovascular disease morbidity and mortality. Screening for modifiable cardiovascular risk factors, including blood pressure, weight, cholesterol, glucose, and smoking, can be efficiently incorporated into routine dermatology clinical practice. Partnerships with primary care providers and preventive cardiologists are essential to improving management of cardiovascular risk in patients with psoriasis., Competing Interests: Disclosure J.M. Gelfand served as a consultant for Abbvie, Artax (DSMB), BMS, Boehringer Ingelheim, Celldex (DSMB), FIDE (which is sponsored by multiple pharmaceutical companies) GSK, Inmagene (DSMB), Twill, Lilly (DMC), Leo, Moonlake (DSMB), Janssen Biologics, Novartis Corp, UCB (DSMB), Neuroderm (DSMB), and Veolia North America receiving honoraria; receives research grants (to the Trustees of the University of Pennsylvania) from Amgen, United States, BMS, United States, and Pfizer Inc., United States; received payment for continuing medical education work related to psoriasis that was supported indirectly by pharmaceutical sponsors; is a co-patent holder of resiquimod for the treatment of cutaneous T-cell lymphoma; is a Deputy Editor for the Journal of Investigative Dermatology receiving honoraria from the Society for Investigative Dermatology; is the Chief Medical Editor for Healio Dermatology (receiving honoraria); and is a member of the Board of Directors for the International Psoriasis Council and the Medical Dermatology Society, receiving no honoraria. D.E. Soffer has served as consultant for Akcea, Amgen, Amryt, Ionis, Novartis, and Partnership for Health Analytics Research; was an investigator for Akcea, Amgen, Amryt, Ionis, Novartis, Regeneron, and Verve Therapeutics; and did data monitoring for Amgen., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The AUB-HAS2 Cardiovascular Risk Index is a newly derived tool for preoperative cardiovascular evaluation. It is based on six data elements: history of heart disease, symptoms of angina or dyspnea, age ≥ 75 years, hemoglobin < 12 g/dl, vascular surgery, and emergency surgery. This study compares the performance of this new index among emergency and elective surgeries., Methods and Results: The study population consisted of 1,167,414 non-cardiac surgeries registered in the American College of Surgeons National Surgical Quality Improvement Program database (153,715 were emergency and 1,013,699 were elective). Each patient was given an AUB-HAS2 score of 0, 1, 2, 3, or >3 depending on the number of data elements s/he has. The outcome measure (death, myocardial infarction, or stroke at 30 days after surgery) was higher in emergency than elective surgeries (7.0 % vs 1.4 %, p < 0.0001). The AUB-HAS2 index was able to stratify risk in both types of surgeries with a gradual increase in risk as the score increased (p < 0.0001). The discriminatory power of the AUB-HAS2 index, measured by the area under the receiver operator characteristic curves, was good and similar in the two types of surgeries (0.804 for emergency vs 0.791 for elective surgeries)., Conclusion: The AUB-HAS2 index is a versatile tool that can effectively and equally stratify risk in both emergency and elective surgeries with a good discriminatory power., Competing Interests: Declaration of competing interest None of the authors has any disclosures to declare, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The Cardiovascular safety of testosterone replacement therapy (TRT) among men with hypogonadism is not well established to date. Hence, we sought to evaluate the cardiovascular disease (CVD) outcomes among patients receiving testosterone therapy by using all recently published randomized controlled trials., Methods: We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until September 30th, 2023., Results: A total of 30 randomized trials with 11,502 patients were included in the final analysis. The mean age was ranging from 61.61 to 61.82 years. Pooled analysis of primary and secondary outcomes showed that the incidence of any CVD events (OR, 1.12 (95%CI: 0.77-1.62), P = 0.55), stroke (OR, 1.01 (95%CI: 0.68-1.51), P = 0.94), myocardial infarction (OR, 1.05 (95%CI: 0.76-1.45), P = 0.77), all-cause mortality (OR, 0.94 (95%CI: 0.76-1.17), P = 0.57), and CVD mortality (OR, 0.87 (95%CI: 0.65-1.15), P = 0.31) was comparable between TRT and placebo groups., Conclusion: Our analysis indicates that for patients with hypogonadism, testosterone replacement therapy does not increase the CVD risk and all-cause mortality., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Autoimmune blistering disorders (ABDs) might elevate cardiovascular risk, but studies are lacking., Objective: The objective of this study was to examine if ABDs elevate the risk of atherosclerotic cardiovascular disease, heart failure, arrhythmia, venous thromboembolism, and cardiovascular death., Methods: A population-based cohort of Danish patients with ABD (≥18 years of age) diagnosed during 1996-2021 (n = 3322) was compared with an age- and sex-matched comparison cohort from the general population (n = 33,195)., Results: Compared with the general population, patients with ABDs had higher 1-year risks of atherosclerotic cardiovascular disease (3.4% vs 1.6%), heart failure (1.9% vs 0.7%), arrhythmia (3.8% vs 1.3%), venous thromboembolism (1.9% vs 0.3%), and cardiovascular death (3.3% vs 0.9%). The elevated risk persisted after 10 years for all outcomes but arrhythmia. The hazard ratios associating ABDs with the outcomes during the entire follow-up were 1.24 (1.09-1.40) for atherosclerotic cardiovascular disease, 1.48 (1.24-1.77) for heart failure, 1.16 (1.02-1.32) for arrhythmia, 1.87 (1.50-2.34) for venous thromboembolism, and 2.01 (1.76-2.29) for cardiovascular death. The elevated cardiovascular risk was observed for both pemphigus and pemphigoid., Limitations: Our findings might only generalize to patients with ABDs without prevalent cardiovascular diseases., Conclusion: Patients with ABDs had an elevated cardiovascular risk compared with age- and sex-matched controls., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: To determine the reliability of hospital discharge codes for heart failure (HF), acute myocardial infarction (AMI) and stroke compared with adjudicated diagnosis, and to pilot a scalable approach to adjudicate records on a population-based sample., Methods: A population-based sample of 685 people with diabetes admitted (1274 admissions) to one of three Australian hospitals during 2018-2020 were randomly selected for this study. All medical records were reviewed and adjudicated., Results: Cardiovascular diseases were the most common primary reason for hospitalisation in people with diabetes, accounting for ~17% (215/1274) of all hospitalisations, with HF as the leading cause. ICD-10 codes substantially underestimated HF prevalence and had the lowest agreement with the adjudicated diagnosis of HF (Kappa = 0.81), compared with AMI and stroke (Kappa ≥ 0.91). While ICD-10 codes provided suboptimal sensitivity (72%) for HF, the performance was better for AMI (sensitivity 84%; specificity 100%) and stroke (sensitivity 85%; specificity 100%). A novel approach to screen possible HF cases only required adjudicating 8% (105/1274) of records, correctly identified 78/81 of HF admissions and yielded 96% sensitivity and 98% specificity., Conclusions: While ICD-10 codes appear reliable for AMI or stroke, a more complex diagnosis such as HF benefits from a two-stage process to screen for suspected HF cases that need adjudicating. The next step is to validate this novel approach on large multi-centre studies in diabetes., (© 2024 Diabetes UK.)

Background: Cardiovascular diseases (CVD) impact a substantial portion of the global population and represent a significant threat to experiencing life-threatening outcomes, such as atherosclerosis, myocardial infarction, stroke and heart failure. Despite remarkable progress in pharmacology and medical interventions, CVD persists as a major public health concern, and now ranks as the primary global cause of death and the highest consumer of global budgets. Ongoing research endeavours persist in seeking novel therapeutic avenues and interventions to deepen our understanding of CVD, enhance prevention measures, and refine treatment strategies., Methods: Nanotechnology applied to the development of new molecular probes with diagnostic and theranostic properties represents one of the greatest technological challenges in preclinical and clinical research., Results: The application of nanotechnology in cardiovascular medicine holds great promise for advancing our understanding of CVDs and revolutionizing their diagnosis and treatment strategies, ultimately improving patient care and outcomes. In addition, the capacity of drug encapsulation in nanoparticles has significantly bolstered their biological safety, bioavailability and solubility. In combination with imaging technologies, molecular imaging has emerged as a pivotal therapeutic tool, offering insight into the molecular events underlying disease and facilitating targeted treatment approaches., Conclusion: Here, we present a comprehensive overview of the recent advancements in targeted nanoparticle approaches for diagnosing CVDs, encompassing molecular imaging techniques, underscoring the significant progress in theranostic, as a novel and promising therapeutic strategy., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Aim: To assess mortality and complication trends in people with type 1 diabetes during the 11 years before the SARS-CoV2 pandemic (2009-2019)., Materials and Methods: Sequential cohorts of people in England with type 1 diabetes aged ≥20 years from the National Diabetes Audit (2006/2007 to 2016/2017) were analysed. Discretized Poisson regression models, adjusted for age, sex, ethnicity, socioeconomic deprivation and duration of diabetes, were used to calculate mortality and hospitalization rates., Results: Demographic characteristics changed little; average diabetes duration increased. All-cause mortality was unchanged. Cardiovascular and kidney disease mortality declined. Mortality from respiratory disease, diabetes and dementia increased in younger people (aged 20-74 years) as did mortality from liver disease and dementia in the elderly (aged ≥75 years). Younger Asian and Black people had lower all-cause mortality than those of White ethnicity; elderly Mixed, Asian and Black people had lower all-cause mortality. People from more deprived areas had higher all-cause mortality. The deprivation gradient for mortality was steeper at younger ages. In younger people, rates of hospitalization increased for myocardial infarction, stroke, heart failure and kidney disease but only for kidney disease in the elderly. Rates of a composite measure of cardiovascular hospitalizations increased in younger people (rate ratio [RR] 1.07, 95% confidence interval [CI] 1.03-1.11) but declined in the elderly (RR 0.91, 95% CI 0.86-0.95)., Conclusion: Between 2009 and 2019, hospitalizations for cardiovascular disease increased at younger ages (20-74 years) and hospitalizations for kidney disease increased at all ages, but mortality from cardiovascular and kidney disease declined. All-cause mortality rates were unchanged., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objectives: Cardiovascular disease is the leading cause of female death worldwide. The link between future cardiovascular events and a history of hypertensive disease in pregnancy or gestational diabetes (GDM) has been well established. Less well understood is the impact on future cardiovascular risk when gestational hypertension (GH) and GDM have occurred together. We assessed the association of GDM and GH with future cardiovascular events both alone and in combination., Study Design: All female patients discharged from French hospitals in 2013 with 5 years of subsequent and complete follow-up were identified. They were grouped depending on their history of GDM, history of GH, history of both or history of neither. After propensity score matching, patients with GDM and/or GH were matched 1:1 with patients with no GDM or GH. Hazard ratios (HR) for cardiovascular events during follow-up were adjusted by age at baseline., Results: Women with a history of GH had an increased risk of cardiovascular death (HR 5.46, 95 % confidence interval [CI] 1.93-15.49). Women with a history of GDM had no significant difference in the risk of cardiovascular events such as myocardial infarction (HR 0.88, 95 %CI 0.38-2.03) and cardiovascular death (HR 1.25, 95 %CI 0.47-3.36) during the 5 year follow up. Those with a history of both GDM and GH had a significantly increased risk of myocardial infarction (HR 23.33, 95 %CI 4.84-112.39)., Conclusion: Women with a history of both GH and GDM are at a 23-fold increased risk of myocardial infarction within the first 5 years of their postnatal lives., 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 B.V. All rights reserved.)

Objective: The aim was to investigate psychological risk profiles of cardiovascular disease (CVD). Depression and anxiety have been linked to CVD, but research has not incorporated personality and sex-specific analyses are warranted. In this study, we examine the role of sex, neuroticism, extraversion, anxiety and depression on the risk of CVD., Method: Using data from the HUNT-study and the mortality register, 32,383 (57.10% men) participants were followed for an average of 10.48 years. During this time, 142 died of myocardial infarction (MI) and 111 of stroke., Results: Cox regression showed that depression (HR = 1.07, 95% CI = [1.00, 1.14]) and neuroticism (1.23 [1.08, 1.40]) were significantly related to an increased risk of MI. One standard unit increase in depression and neuroticism was associated with 1.22 [CI 1.01, 1.47] increase and 1.43 [CI 1.14, 0.78] increase in the risk of MI respectively. For stroke, there was no significant effect of anxiety, depression or personality. However, we found a significant interaction effect between sex and extraversion where higher extraversion was associated with greater risk of stroke for women only., Conclusions: Both neuroticism and depression were related to MI. We observed an interaction between extraversion and sex with stroke, but the effect size was small. The role of extroversion as a risk factor for CVD remains inconclusive.

Background: The biological mechanisms linking environmental exposures with cardiovascular disease pathobiology are incompletely understood. We sought to identify circulating proteomic signatures of environmental exposures and examine their associations with cardiometabolic and respiratory disease in observational cohort studies., Methods: We tested the relations of >6500 circulating proteins with 29 environmental exposures across the built environment, green space, air pollution, temperature, and social vulnerability indicators in ≈3000 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults) across 4 centers using penalized and ordinary linear regression. In >3500 participants from FHS (Framingham Heart Study) and JHS (Jackson Heart Study), we evaluated the prospective relations of proteomic signatures of the envirome with cardiovascular disease and mortality using Cox models., Results: Proteomic signatures of the envirome identified novel/established cardiovascular disease-relevant pathways including DNA damage, fibrosis, inflammation, and mitochondrial function. The proteomic signatures of the envirome were broadly related to cardiometabolic disease and respiratory phenotypes (eg, body mass index, lipids, and left ventricular mass) in CARDIA, with replication in FHS/JHS. A proteomic signature of social vulnerability was associated with a composite of cardiovascular disease/mortality (1428 events; FHS: hazard ratio, 1.16 [95% CI, 1.08-1.24]; P =1.77×10 -5 ; JHS: hazard ratio, 1.25 [95% CI, 1.14-1.38]; P =6.38×10 -6 ; hazard ratio expressed as per 1 SD increase in proteomic signature), robust to adjustment for known clinical risk factors., Conclusions: Environmental exposures are related to an inflammatory-metabolic proteome, which identifies individuals with cardiometabolic disease and respiratory phenotypes and outcomes. Future work examining the dynamic impact of the environment on human cardiometabolic health is warranted., Competing Interests: Disclosures R.V. Shah is supported in part by grants from the National Institutes of Health and the American Heart Association. In the past 12 months, R.V. Shah has served for a consultant for Amgen and Cytokinetics. R.V. Shah is a co-inventor on a patent for ex-RNAs signatures of cardiac remodeling and a pending patent on proteomic signatures of fitness and lung and liver diseases. V.L. Murthy has received grant support from Siemens Healthineers, NIDDK, NIA, NHLBI and AHA. V.L. Murthy has received other research support from NIVA Medical Imaging Solutions. V.L. Murthy owns stock in Eli Lilly, Johnson & Johnson, Merck, Bristo-Myers Squibb, Pfizer and stock options in Ionetix. V.L. Murthy has received research grants and speaking honoraria from Quart Medical. M. Nayor received speaking honoraria from Cytokinetics. M. Nayor is supported by the NIH and by a Career Investment Award from the Department of Medicine, Boston University School of Medicine. B. Choi is supported by the NIH and American Heart Association. M.B. Rice is supported by the NIH and reports fees from the Conservation Law Foundation. The remaining authors report no disclosures.

Background and Aims: The contribution of ultra-processed foods (UPFs) to daily energy intake and, therefore, their health effects may vary between countries. We aimed to investigate the association between UPFs and the incidence risk of cardiovascular events (CVEs) and cardiovascular mortality in the Isfahan cohort study., Methods and Results: In 2001, 6504 participants aged ≥35 years were enrolled and followed until 2017. Dietary intake was assessed using a validated food frequency questionnaire, and the NOVA system was applied for UPF classification. Any new case of CVE, including fatal and non-fatal myocardial infarction (MI) or stroke, unstable angina (UA), and CVD death, was recorded. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated through Cox proportional hazards regression models. A total number of 819 CVE, 164 MI, 348 UA, 172 strokes, and 181 cardiovascular deaths were recorded during 61352.5 person-years of follow-up. The median (IQR) of UPF consumption was 2.47 (1.00-5.23) times/week. In the fully adjusted model, individuals in the fourth quartile of UPFs had no higher risk for incident MI and UA (HR = 1.12, 95% CI: 0.87, 1.46; P for trend = 0.364), stroke (HR = 0.93, 95% CI: 0.58, 1.46; P for trend = 0.601), cardiovascular mortality (HR = 0.95, 95% CI: 0.61, 1.47; P for trend = 0.596), and CVE (HR = 1.08, 95% CI: 0.88,1.34; P for trend = 0.515) in comparison with those in the first quartile., Conclusion: This mid-term prospective cohort study provides no evidence for a significant association between UPF and CVE risk. Longer studies are required to confirm this association., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aim: To compare the cardiovascular preventive effect associated with glucagon-like-peptide-1 receptor agonists (GLP-1 RA) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) according to the achieved target level of glycated hemoglobin (HbA1c)., Methods: We used retrospective Danish registries to include type 2 diabetes patients already in metformin treatment initiating GLP-1 RA or DPP-4i between 2007 and 2021. Patients were included 6 months after GLP-1 RA or DPP-4i initiation. The last available HbA1c measurement before inclusion was collected. The achieved HbA1c level was categorized according to a target level below or above 53 mmol/mol (7%). The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. We used a multivariable Cox proportional hazard model to estimate the effect of HbA1c levels on the outcome among GLP-1 RA users compared to DPP-4i users., Results: The study included 13 634 GLP-1 RA users (median age 56.9, interquartile range [IQR]: 48.5-65.5; 53% males) and 39 839 DPP-4i users (median age 63.4, IQR: 54.6-71.8; 61% males). The number of GLP-1 RA and DPP-4i users according to achieved HbA1c levels were as follows: HbA1c ≤ 53 mmol/mol (≤7.0%): 3026 (22%) versus 4824 (12%); HbA1c > 53 mmol/mol (>7.0%): 6577 (48%) versus 17 508 (44%); missing HbA1c: 4031 (30%) versus 17 507 (44%). During a median follow-up of 5 years (IQR: 2.6-5.0), 954 GLP-1 RA users experienced the primary outcome compared to 7093 DPP-4i users. The 5-year risk (95% confidence interval [CI]) of the outcome associated with GLP1-RA versus DPP-4i according to HbA1c categories was as follows: HbA1c ≤ 53 mmol/mol: 10.3% (8.2-12.3) versus 24.3% (22.7-25.8); HbA1c > 53 mmol/mol: 16.0% (14.3-17.6) versus 21.1% (20.3-21.9); missing HbA1c: 17.1% (15.7-18.5) versus 25.6% (24.9-26.3). The preventive effect associated with GLP-1 RA versus DPP-4i was significantly enhanced when achieving lower HbA1c levels: HbA1c ≤ 53 mmol/mol: 0.65 (0.52-0.80); HbA1c > 53 mmol/mol: 0.92 (0.83-1.03); missing HbA1c: 0.92 (0.84-1.02) (p value for interaction <.001)., Conclusion: GLP-1 RA use was associated with a lower rate of major adverse cardiovascular outcomes. The association was stronger in patients achieving the target glycemic level and weaker in patients not achieving the target glycemic level, suggestive of an interaction between achieved HbA1c level and GLP-1 RA., (© 2024 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

There are considerable sex differences regarding the risk of cardiovascular disease (CVD), including arterial hypertension, coronary artery disease (CAD) and stroke, as well as chronic renal disease. Women are largely protected from these conditions prior to menopause, and the risk increases following cessation of endogenous estrogen production or after surgical menopause. Cardiovascular diseases in women generally begin to occur at a later age than in men (on average with a delay of 10 years). Cessation of estrogen production also impacts metabolism, increasing the risk of developing obesity and diabetes. In middle-aged individuals, hypertension develops earlier and faster in women than in men, and smoking increases cardiovascular risk to a greater degree in women than it does in men. It is not only estrogen that affects female cardiovascular health and plays a protective role until menopause: other sex hormones such as progesterone and androgen hormones generate a complex balance that differentiates heart and blood vessel function in women compared to men. Estrogens improve vasodilation of epicardial coronary arteries and the coronary microvasculature by augmenting the release of vasodilating factors such as nitric oxide and prostacyclin, which are mechanisms of coronary vasodilatation that are more pronounced in women compared to men. Estrogens are also powerful inhibitors of inflammation, which in part explains their protective effects on CVD and chronic renal disease. Emerging evidence suggests that sex chromosomes also play a significant role in shaping cardiovascular risk. The cardiovascular protection conferred by endogenous estrogens may be extended by hormone therapy, especially using bioidentical hormones and starting treatment early after menopause., (Copyright © 2024. Published by Elsevier Inc.)

Antiangiogenics are associated with an increased risk of major adverse cardiac and cerebrovascular events (MACE). The identification of at-risk subjects is relevant in the case of hepatocellular carcinoma (HCC), for which anti-angiogenic TKIs and bevacizumab are used in first and subsequent lines of therapy, to select alternative drugs for patients with excessive risk. We verified the ability to predict MACE in sorafenib-treated patients of the 2022 European Society of Cardiology (ESC-2022) score for anti-angiogenics and the recently proposed CARDIOSOR score. A retrospective analysis was conducted of prospectively collected data of the ARPES and ITA.LI.CA databases. All patients received sorafenib for unresectable HCC from 2008 to 2018. Baseline information to calculate the ESC-2022 and CARDIOSOR scores and registration of evolutive events (including MACE) were available for all patients. The predictive ability of both scores was verified using competing risk regressions and tests for goodness of fit. This study included 843 patients (median follow-up 11.3 months). Thirty-four (4.0%) patients presented a MACE. The four-tier ESC-2022 classification showed a progressive risk increase for every class (cumulative risk 1.7%, 2.7%, 4.3%, and 15.0% in the low, medium, high, and high-risk tiers, respectively). The dichotomous CARDIOSOR scale identified a high-risk group with a fourfold increased risk of MACE (sHR 4.66, p = 0.010; cumulative risk 3.8% and 16.4%). ESC-2022 showed a better goodness of fit compared to the CARDIOSOR score [C-index 0.671 (0.583-0.758) vs 0.562 (0.501-0.634), p = 0.021], but this gap was eliminated using the linear version of CARDIOSOR. Both the ESC-2022 and CARDIOSOR scores discriminated patients at increased risk for MACE. The use of these scores in clinical practice should be encouraged, since therapeutic measures can mitigate the cardiovascular risk., (© 2024. The Author(s).)

Insufficient blood pressure control among patients with hypertension without elevated risk is a global concern, suggesting the need for treatment optimization. However, the potential harm of excessive blood pressure lowering among these patients is understudied. This study addressed this evidence gap by using nationally representative public health insurer database covering 30 million working-age population. Patients who were continuously using antihypertensive drugs with 10-year cardiovascular risk <10% were identified. They were categorized by on-treatment systolic and diastolic blood pressures. The primary outcome was a composite of myocardial infarction, stroke, heart failure hospitalization, and peripheral artery disease. Of 920,533 participants (mean age, 57.3 years; female, 48.3%; mean follow-up, 2.75 years), the adjusted hazard ratios for systolic blood pressure of <110, 110-119, 120-129 (reference), 130-139, 140-149, 150-159, and ≥160 mmHg were 1.05 (95% confidence interval: 0.99-1.12), 0.97 (0.93-1.02), 1 (reference), 1.05 (1.01-1.09), 1.15 (1.11-1.20), 1.30 (1.23-1.37), and 1.76 (1.66-1.86), respectively; and for diastolic blood pressure of <60, 60-69, 70-79 (reference), 80-89, 90-99, and ≥100 mmHg were 1.25 (1.14-1.38), 0.99 (0.95-1.04), 1 (reference), 1.00 (0.96-1.03), 1.13 (1.09-1.18), and 1.66 (1.58-1.76), respectively. Among low-risk patients with hypertension, diastolic blood pressure <60 mmHg was associated with increased cardiovascular events, while systolic blood pressure <110 mmHg was not. Compared to previous investigations in high-risk patients, the potential harm of excessive blood pressure lowering was less pronounced in low-risk patients with hypertension. The association between low on-treatment blood pressure and cardiovascular events has been understudied in low-risk patients with hypertension. In our study with nationally representative working-age adults from general population with hypertension without elevated risk, increased risk of cardiovascular events was observed in diastolic blood pressure of <60 mmHg, but not in systolic blood pressure of <110 mmHg. Those results contrasted with previous investigations in high-risk patients where the risk of low on-treatment blood pressure was more pronounced., (© 2024. The Author(s).)

Mast cells are tissue-resident immune cells strategically located in different compartments of the normal human heart (the myocardium, pericardium, aortic valve, and close to nerves) as well as in atherosclerotic plaques. Cardiac mast cells produce a broad spectrum of vasoactive and proinflammatory mediators, which have potential roles in inflammation, angiogenesis, lymphangiogenesis, tissue remodelling, and fibrosis. Mast cells release preformed mediators (e.g. histamine, tryptase, and chymase) and de novo synthesized mediators (e.g. cysteinyl leukotriene C4 and prostaglandin D2), as well as cytokines and chemokines, which can activate different resident immune cells (e.g. macrophages) and structural cells (e.g. fibroblasts and endothelial cells) in the human heart and aorta. The transcriptional profiles of various mast cell populations highlight their potential heterogeneity and distinct gene and proteome expression. Mast cell plasticity and heterogeneity enable these cells the potential for performing different, even opposite, functions in response to changing tissue contexts. Human cardiac mast cells display significant differences compared with mast cells isolated from other organs. These characteristics make cardiac mast cells intriguing, given their dichotomous potential roles of inducing or protecting against cardiovascular diseases. Identification of cardiac mast cell subpopulations represents a prerequisite for understanding their potential multifaceted roles in health and disease. Several new drugs specifically targeting human mast cell activation are under development or in clinical trials. Mast cells and/or their subpopulations can potentially represent novel therapeutic targets for cardiovascular disorders., Competing Interests: Conflict of interest R.P., G.M., and G.V. declare no conflict of interest in relation to this work. S.J.G. consults for Evommune, Inc. and for Jasper Therapeutics Inc., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

HIV infection and antiretroviral therapy alter mitochondrial function, which can progressively lead to mitochondrial damage and accelerated aging. The interaction between persistent HIV reservoirs and mitochondria may provide insight into the relatively high rates of cardiovascular disease and mortality in persons living with HIV. In this review, we explore the intricate relationship between HIV and mitochondrial function, highlighting the potential for novel therapeutic strategies in the context of cardiovascular diseases. We reflect on mitochondrial dynamics, mitochondrial DNA, and mitochondrial antiviral signaling protein in the context of HIV. Furthermore, we summarize how toxicities related to early antiretroviral therapy and current highly active antiretroviral therapy can contribute to mitochondrial dysregulation, chronic inflammation, and poor clinical outcomes. There is a need to understand the mechanisms and develop new targeted therapies. We further consider current and potential future therapies for HIV and their interplay with mitochondria. We reflect on the next-generation antiretroviral therapies and HIV cure due to the direct and indirect effects of HIV persistence, associated comorbidities, coinfections, and the advancement of interdisciplinary research fields. This includes exploring novel and creative approaches to target mitochondria for therapeutic intervention., Competing Interests: Disclosures None.

Cardiovascular disease (CVD) is the leading cause of death worldwide. MicroRNAs (MiRNAs) have attracted considerable attention for their roles in several cardiovascular disease states, including both the physiological and pathological processes. In this review, we will briefly describe microRNA-181 (miR-181) transcription and regulation and summarize recent findings on the roles of miR-181 family members as biomarkers or therapeutic targets in different cardiovascular-related conditions, including atherosclerosis, myocardial infarction, hypertension, and heart failure. Lessons learned from these studies may provide new theoretical foundations for CVD., (© 2024 Federation of American Societies for Experimental Biology.)

Aims: We evaluated the incidence and relative risk of major post-acute cardiovascular consequences of SARS-CoV-2 infection in a large real-world population from a primary care database in a region at moderate cardiovascular risk followed up in the period 2020-22., Methods and Results: This is a retrospective cohort analysis using data from a cooperative of general practitioners in Italy. Individuals aged >18 affected by COVID-19 starting from January 2020 have been followed up for 3 years. Anonymized data from 228 266 patients in the period 2020-22 were considered for statistical analysis and included 31 764 subjects with a diagnosis of COVID-19. An equal group of subjects recorded in the same database in the period 2017-19 was used as propensity score-matched comparison as an unquestionable COVID-19-free population. Out of the 228 266 individuals included in the COMEGEN database during 2020-22, 31 764 (13.9%) were ascertained positive with SARS-CoV-2 infection by a molecular test reported to general practitioners. The proportion of individuals with a new diagnosis of major adverse cardiovascular and cerebrovascular events was higher in the 2020-22 COVID-19 group than in the 2017-19 COMEGEN propensity score-matched comparator, with an odds ratio of 1.73 (95% confidence interval: 1.53-1.94; P < 0.001). All major adverse cardiovascular and cerebrovascular events considered showed a significantly higher risk in COVID-19 individuals. Incidence calculated for each 6-month period after the diagnosis of COVID-19 in our population was the highest in the first year (1.39% and 1.45%, respectively), although it remained significantly higher than in the COVID-19-free patients throughout the 3 years., Conclusion: The increase of cardiovascular risk associated with COVID-19 might be extended for years and not limited to the acute phase of the infection. This should promote the planning of longer follow-up for COVID-19 patients to prevent and promptly manage the potential occurrence of major adverse cardiovascular and cerebrovascular events., Competing Interests: Conflict of interest: S.B. and S.P. have received financial support from the Italian Ministry of Health; project of Ministry of University and Research (MUR-PRIN) 2022: grant 2022FJK39Z. Other authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The potential influence of tinnitus on cardiovascular disease (CVD) and all-cause mortality has yet to be explored. We aim to examine the correlations between tinnitus and the risk of cardiovascular events and all-cause mortality., Methods: We conducted a prospective cohort study utilising data from the UK Biobank. The presence of tinnitus was evaluated through a questionnaire. The primary outcome was defined as a composition of cardiovascular events, including myocardial infarction (MI), stroke, and mortality from CVD, as well as all-cause mortality. Cox proportional hazard models were employed to examine the associations between tinnitus and both the primary outcome and its individual components. Sensitivity analyses were conducted to evaluate the robustness of the primary analysis., Results: A total of 140,146 participants were included in the study. The presence of tinnitus was found to be associated with a higher incident rate of the primary outcome (HR = 1.057, 95%CI: 1.017-1.099, p  = 0.005), MI (HR = 1.139, 95%CI: 1.061-1.222, p  < 0.001) and all-cause mortality (HR = 1.053, 95%CI: 1.003-1.105, p  = 0.038) after adjusting for confounders. However, there was no significant association between tinnitus and stroke or mortality from CVD. Subgroup analysis revealed that the association between tinnitus and the primary outcome was significant in females, participants with abnormal BMI, and those without hearing difficulty, depression or anxiety. Sensitivity analyses yielded consistent results., Conclusion: The findings from this study contribute to the existing body of evidence suggesting an association between tinnitus and an increased risk of cardiovascular events and all-cause mortality.

Even with substantial progress in primary and secondary prevention, cardiovascular disease (CVD) persists as a major cause of mortality and morbidity globally. Omega-3 polyunsaturated fatty acids (Ω-3 PUFAs) have gained considerable attention for their ability to improve CV health and prognosis. Metanalyses of randomized controlled trials have demonstrated Ω-3 PUFAs' positive impact on CVD outcomes for both primary and secondary prevention endpoints. Marine Ω-3 PUFAs also improve CVD risk factors including blood pressure, lipids, and inflammation; however, many physicians do not recommend Ω-3 PUFAs, largely due to inconsistent results in randomized trials. In this comprehensive review article, we evaluate both historic and current data concerning primary and secondary prevention of CVD with use of Ω-3 PUFAs, delve into the potential causes for the varied results, and examine the most current recommendations on the usage of Ω-3 PUFAs., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: The present study aimed to evaluate the effect of statin therapy for primary prevention of cardiovascular diseases (CVDs) when initiating therapy at different baseline low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of trials on patients with T2DM with elevated LDL-C levels in every calendar month from January 2008 to December 2014. Pooled logistic regression was applied to obtain the hazard ratios for the major CVDs (stroke, myocardial infarction, heart failure), all-cause mortality and major adverse events (myopathies and liver dysfunction) of statin therapy., Results: The estimated hazard ratios (95% confidence intervals) of CVD incidence for statin initiation were 0.78 (0.72, 0.84) in patients with baseline LDL-C of 1.8-2.5 mmol/L (i.e., 70-99 mg/dL) and 0.90 (0.88, 0.92) in patients with baseline LDL-C ≥2.6 mmol/L (i.e., ≥100 mg/dL) in intention-to-treat analysis, which was 0.59 (0.51, 0.68) and 0.77 (0.74, 0.81) in per-protocol analysis, respectively. No significant increased risks were observed for the major adverse events. The absolute 10-year risk difference of overall CVD in per-protocol analysis was -7.1% (-10.7%, -3.6%) and -3.9% (-5.1%, -2.7%) in patients with baseline LDL-C 1.8-2.5 and ≥2.6 mmol/L, respectively. The effectiveness and safety were consistently observed in patients aged >75 years initiating statin at both LDL-C thresholds., Conclusions: Compared with the threshold of 2.6 mmol/L, initiating statin in patients with a lower baseline LDL-C level at 1.8-2.5 mmol/L can further reduce the risks of CVD and all-cause mortality without significantly increasing the risk of major adverse events in patients with T2DM, including patients aged >75 years., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Competing Interests: Conflicts of interest Dr Garshick reports consulting fees from AbbVie and Horizon Therapeutics. Dr Femia reports consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Author J.T. Shah, Author K.T. Shah, Dr Mazori, Dr Caplan, and Dr Hejazi have no conflicts of interest to declare.

Background: Prurigo nodularis (PN) presents with intensely itchy hard nodules. Despite being limited to the skin, PN was noted to be associated with systemic diseases including diabetes and chronic renal failure. In previous smaller retrospective studies, several cardiac and vascular diseases were found more frequently in patients with PN. However, small cohort sizes, partially discrepant outcomes, missing data, and incomplete risk assessment limit these findings., Methods: Electronic health records (EHR)s of 64,801 patients (59.44% females) with PN and an equal sized propensity-matched control group were retrieved. In these cohorts, the risks to develop cardiac and vascular diseases and mortality following the diagnosis of PN were determined. Sub-analyses included stratification for sex, ethnicity, and treatments., Findings: PN was associated with a higher risk for a broad range of acute cardiac events including heart failure and myocardial infarction. For example, the hazard ratio of myocardial infarction was 1.11 (95%-CI: 1.041-1.184, p = 0.0015) following PN diagnosis. Also, all-cause mortality was higher in patients with PN. Further, chronic vascular as well as structural heart diseases, e.g., peripheral arterial disease, chronic ischaemic heart disease and valval disorders were found more frequently following a PN diagnosis. Risks were more pronounced in white and female patients. Having established an increased risk for death and cardiovascular disease, we next addressed if dupilumab that has been recently licenced for use in this indication can modulate these risks. The risk of death but not of any cardiovascular disease was slightly reduced in patients with PN treated with dupilumab as opposed to those treated with systemic therapies other than dupilumab. The study is limited by retrospective data collection and reliance on ICD10-disease classification., Interpretation: PN is associated with higher mortality and an increased risk for the development of a wide range of cardiac and vascular diseases. Health care professionals should take this into account when managing patients with PN., Funding: This work was supported by the University of Lübeck, the Deutsche Forschungsgemeinschaft and the State of Schleswig-Holstein., Competing Interests: Declaration of interests The authors declare that this study was designed and conducted in the absence of any financial or commercial relationships that could be construed as a potential conflict of interest. HZ received travel honoraria and support for meeting attendance from TriNetX, Pfizer, UCB Pharma, Almirall and Janssen unrelated to the current work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Chronic coronary heart disease encompasses a broad spectrum of disorders that range in severity from trivial to imminently life-threatening. The primary care physician encounters coronary disease at all stages. The number of available diagnostic and therapeutic options for evaluating and treating coronary disease is vast, presenting a complex selection strategy challenge when making choices for the individual patient. The primary care physician is responsible to tailor evaluation and management strategies to each individual patient based on his/her particular disease characteristics. There are many categories of diagnostic studies and therapeutic interventions that have been shown at the population level in clinical trials to improve patient outcomes. Blindly applying the findings of all demonstrated studies and therapies to a patient with coronary disease would saddle him/her with an unsustainable burden of diagnostic tests and therapies. The core principle of the approach outlined in this article is to tailor diagnostic and therapeutic choices to the operative pathophysiology that drives a particular patient's disorder. This introductory article is intended to provide a conceptual framework for studying and applying the specialized topics discussed in the articles that follow., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To examine the association between depression, the use of antidepressants, and atherosclerotic cardiovascular disease (ASCVD)., Methods: The South Korean national claims data was used. Among a nationally representative population, 273,656 subjects who had been diagnosed with depression and prescribed antidepressants ("DEP with antidepressants") and 78,851 subjects who had been diagnosed with depression but not prescribed antidepressants ("DEP without antidepressants") were identified to be eligible. Healthy controls (HCs) were 1:1 matched with DEP with antidepressants group for age and sex. We followed up on the occurrence of ASCVD including ischemic heart diseases and ischemic stroke., Results: The risk of ASCVD was increased in the DEP with antidepressants group and decreased in the DEP without antidepressants group compared to HCs. Among those under antidepressants, tricyclic antidepressant users showed the highest risk of ASCVD compared to HCs. Among young adults, the risk of ASCVD was increased in both groups., Conclusion: The risk of ASCVD increased in depression patients taking antidepressants, while it decreased in depression patients not taking antidepressants. However, the relationship showed differences according to drug class and age group., Competing Interests: Declaration of competing interest Jungkuk Lee and Dongwoo Kang were employed by Hanmi Pharm. Co. and the remaining authors have nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Testosterone therapy (TTh) has been shown to improve libido in women with sexual dysfunction, but its utilization has been limited due to concern for cardiovascular events and past studies reporting highly variable results., Aim: To assess the association of TTh in women with major adverse cardiac events (MACEs), including heart attack, stroke, or death, using a large database., Methods: The TriNetX Diamond Network was queried from 2009 to 2022. Our study cohort included adult females with ≥3 systemic testosterone prescriptions within a year. Our control cohort excluded females with any testosterone prescriptions, polycystic ovary syndrome, or androgen excess. Both cohorts excluded females with prior heart failure, unstable angina, intersex surgery (female to male), personal history of sex reassignment, or gender identity disorders. Propensity matching between the cohorts was performed. A subanalysis by age was conducted (18-55 and >55 years)., Outcomes: We evaluated the association of TTh to the following: MACE, upper or lower emboli or deep vein thrombosis (DVT), pulmonary embolism (PE), breast neoplasm, and hirsutism within 3 years of TTh., Results: When compared with propensity-matched controls, adult females with TTh had a lower risk of MACE (risk ratio [RR], 0.64; 95% CI, 0.51-0.81), DVT (RR, 0.61; 95% CI, 0.42-0.90), PE (RR, 0.48; 95% CI, 0.28-0.82), and malignant breast neoplasm (RR, 0.48; 95% CI, 0.37-0.62). Similarly, females aged 18 to 55 years with TTh had a lower risk of MACE (RR, 0.49; 95% CI, 0.28-0.85) and DVT (RR, 0.48; 95% CI, 0.25-0.93) and a similar risk of malignant breast neoplasm (RR, 0.62; 95% CI, 0.34-1.12). Females aged ≥56 years with TTh had a similar risk of MACE (RR, 0.84; 95% CI, 0.64-1.10), DVT (RR, 0.82; 95% CI, 0.50-1.36), and PE (RR, 0.52; 95% CI, 0.26-1.05) and a significantly lower risk of malignant breast neoplasm (RR, 0.51; 95% CI, 0.38-0.68). Risk of hirsutism was consistently higher in those with TTh as compared with propensity-matched controls., Clinical Implications: Our results contribute to safety data on TTh, a therapy for sexual dysfunction in women., Strengths and Limitations: The TriNetX Diamond Network allows for significant generalizability but has insufficient information for some factors., Conclusions: We found a decreased risk of MACE among women with TTh as compared with matched controls and a similar risk of MACE in postmenopausal women while demonstrating a similar or significantly lower risk of breast cancer on age-based subanalysis., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Obesity is a worldwide health concern with serious clinical effects, including myocardial infarction (MI), stroke, cardiovascular diseases (CVDs), and all-cause mortality. The present study aimed to assess the association of obesity phenotypes and different CVDs and mortality in males and females by simultaneously considering the longitudinal and survival time data., Methods: In the Tehran Lipid and Glucose Study (TLGS), participants older than three years were selected by a multi-stage random cluster sampling method and followed for about 19 years. In the current study, individuals aged over 40 years without a medical history of CVD, stroke, MI, and coronary heart disease were included. Exclusions comprised those undergoing treatment for CVD and those with more than 30% missing information or incomplete data. Joint modeling of longitudinal binary outcome and survival time data was applied to assess the dependency and the association between the changes in obesity phenotypes and time to occurrence of CVD, MI, stroke, and CVD mortality. To account for any potential sex-related confounding effect on the association between the obesity phenotypes and CVD outcomes, sex-specific analysis was carried out. The analysis was performed using packages (JMbayes2) of R software (version 4.2.1)., Results: Overall, 6350 adults above 40 years were included. In the joint modeling of CVD outcome among males, literates and participants with a family history of diabetes were at lower risk of CVD compared to illiterates and those with no family history of diabetes in the Bayesian Cox model. Current smokers were at higher risk of CVD compared to non-smokers. In a logistic mixed effects model, odds of obesity phenotype was higher among participants with low physical activity, family history of diabetes and older age compared to males with high physical activity, no family history of diabetes and younger age. In females, based on the results of the Bayesian Cox model, participants with family history of diabetes, family history of CVD, abnormal obesity phenotype and past smokers had a higher risk of CVD compared to those with no history of diabetes, CVD and nonsmokers. In the obesity varying model, odds of obesity phenotype was higher among females with history of diabetes and older age compared to those with no history of diabetes and who were younger. There was no significant variable associated with MI among males in the Bayesian Cox model. Odds of obesity phenotype was higher in males with low physical activity compared to those with high physical activity in the obesity varying model, whereas current smokers were at lower odds of obesity phenotype than nonsmokers. In females, risk of MI was higher among those with family history of diabetes compared to those with no history of diabetes in the Bayesian Cox model. In the logistic mixed effects model, a direct and significant association was found between age and obesity phenotype. In males, participants with history of diabetes, abnormal obesity phenotype and older age were at higher risk of stroke in the Bayesian Cox model compared to males with no history of diabetes, normal obesity phenotype and younger persons. In the obesity varying model, odds of obesity phenotype was higher in males with low physical activity, family history of diabetes and older age compared to those with high physical activity, no family history of diabetes and who were younger. Smokers had a lower odds of obesity phenotype than nonsmokers. In females, past smokers and those with family history of diabetes were at higher risk of stroke compared to nonsmokers and females with no history of diabetes in the Bayesian Cox model. In the obesity varying model, females with family history of diabetes and older ages had a higher odds of obesity phenotype compared to those with no family history of diabetes and who were younger. Among males, risk of CVD mortality was lower in past smokers compared to nonsmokers in the survival model. A direct and significant association was found between age and CVD mortality. Odds of obesity phenotype was higher in males with a history of diabetes than in those with no family history of diabetes in the logistic mixed effects model., Conclusions: It seems that modifications to metabolic disorders may have an impact on the heightened incidence of CVDs. Based on this, males with obesity and any type of metabolic disorder had a higher risk of CVD, stroke and CVD mortality (excluding MI) compared to those with a normal body mass index (BMI) and no metabolic disorders. Females with obesity and any type of metabolic disorder were at higher risk of CVD(, MI and stroke compared to those with a normal BMI and no metabolic disorders suggesting that obesity and metabolic disorders are related. Due to its synergistic effect on high blood pressure, metabolic disorders raise the risk of CVD., (© 2024. The Author(s).)

Aims: Systematic Coronary Risk Evaluation Model 2 (SCORE2) was recently developed to predict atherosclerotic cardiovascular disease (ASCVD) in Europe. Whether these models could be used outside of Europe is not known. The objective of this study was to test the validity of SCORE2 in a large Canadian cohort., Methods and Results: A primary care cohort of persons with routinely collected electronic medical record data from 1 January 2010 to 31 December 2014, in Ontario, Canada, was used for validation. The SCORE2 models for younger persons (YP) were applied to 57 409 individuals aged 40-69 while the models for older persons (OPs) were applied to 9885 individuals 70-89 years of age. Five-year ASCVD predictions from both the uncalibrated and low-risk region recalibrated SCORE2 models were evaluated. The C-statistic for SCORE2-YP was 0.74 in women and 0.69 in men. The uncalibrated SCORE2-YP overestimated risk by 17% in women and underestimated by 2% in men. In contrast, the low-risk region recalibrated model demonstrated worse calibration, overestimating risk by 100% in women and 36% in men. The C-statistic for SCORE2-OP was 0.64 and 0.62 in older women and men, respectively. The uncalibrated SCORE2-OP overestimated risk by more than 100% in both sexes. The low-risk region recalibrated model demonstrated improved calibration but still overestimated risk by 60% in women and 13% in men., Conclusion: The performance of SCORE2 to predict ASCVD risk in Canada varied by age group and depended on whether regional calibration was applied. This underscores the necessity for validation assessment of SCORE2 prior to implementation in new jurisdictions., Competing Interests: Conflict of interest: K.T. receives a Research Scholar Award from the Department of Family and Community Medicine at the University of Toronto. KT holds a Chair in Family and Community Medicine Research in Primary Care at UHN and receives a research Scholar Award from the Department of Family and Community Medicine at the University of Toronto. R.K. is an Associate Editor of JAMA. He receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award K23HL153775) and the Doris Duke Charitable Foundation (under award 2022060022060). He also receives research support, through Yale, from Bristol-Myers Squibb and Novo Nordisk, unrelated to the current work. He is a co-inventor of U.S. Provisional Patent Applications 63/177 117, 63/428 569, 63/346 610, and 63/484 426. He is a co-founder of Evidence2Health, a precision health platform to improve evidence-based cardiovascular care. D.S.L. is the Ted Rogers Chair in Heart Function Outcomes, University Health Network, University of Toronto., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: We investigated the prevalence of sarcopenia and its influence on 1-year major adverse cardiac events (MACEs) in patients after successful percutaneous coronary intervention (PCI)., Methods and Results: This retrospective medical record review using purposive sampling was conducted at a tertiary care university hospital in Korea. Medical records of a total of 303 patients (≥40 years) who underwent successful PCI between January 2014 and December 2020 were analysed. We retrospectively assessed sarcopenia at initial admission. Sarcopenia was assessed by a sarcopenia index based on a ratio of serum creatinine to serum cystatin C. MACE rates were evaluated within l year after PCI. A Kaplan-Meier analysis with a log-rank test was performed to compare the time with 1-year MACE event-free survival between groups with and without sarcopenia. Cox proportional hazards regression was conducted to assess sarcopenia's influence on MACE. The prevalence of sarcopenia and 1-year MACE after PCI were 24.8 and 8.6%, respectively. We found that sarcopenia at admission (hazard ratio, 3.01; 95% confidence interval, 1.22-7.38, P = 0.017) was significantly associated with 1-year MACE among patients after PCI., Conclusion: Expanding knowledge of sarcopenia among cardiovascular nurses may aid in early recognition of patients at risk of sarcopenia. Our finding implies that the sarcopenia index based on serum creatinine and cystatin C may be available as a prognostic factor for MACE in patients undergoing PCI. Future studies should be conducted to prospectively validate the sarcopenia index with a multi-centre, large sample., Competing Interests: Conflict of interest: The authors declare no competing financial interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)