Metabolic Syndrome among Patients Taking Atypical Antipsychotics: A Comparative Cross-Sectional Study at Erada and Mental Health Complex in Taif, Saudi Arabia.

Introduction: Second-Generation Antipsychotics (SGAs) are widely used for treating psychiatric disorders due to their favorable side effect profile compared to First-Generation Antipsychotics (FGAs). However, SGAs are associated with significant metabolic side effects. This study aims to explore the sociodemographic and health differences between individuals using SGAs and those not using them. Methods: A comparative cross-sectional study was conducted with 148 participants, including 102 SGA users and 46 non-users. Data were collected from patients and medical records, encompassing sociodemographic factors and health variables including diabetes mellitus, hypertension, cardiovascular disease, hyperlipidemia, waist circumference, fasting blood glucose, cholesterol, triglycerides, HDL, LDL, and BMI. Statistical analyses included chi-square and Fisher's exact tests to compare the two groups. Results: SGA users had higher rates of overweight and obesity compared to non-users (p = 0.000), with 30.4% overweight and 29.4% obese among SGA users versus 21.7% overweight and 4.3% obese among non-users. A higher prevalence of cardiovascular disease was observed in SGA users (11.8% vs. 2.2%, p = 0.076). Although not statistically significant, trends indicated higher rates of diabetes mellitus and hyperlipidemia in non-users (30.4% vs. 18.6%, p = 0.110 and 7% vs. 0%, p = 0.083, respectively). Conclusion: This study highlights significant differences in BMI and cardiovascular disease prevalence between SGA users and non-users, reinforcing the need for comprehensive metabolic monitoring in patients treated with SGAs. The findings underscore the importance of considering sociodemographic factors in managing the health risks associated with SGA use. Further research with larger sample sizes and longitudinal designs is warranted to better understand these associations and develop targeted interventions.

Association between methylphenidate use and long-term cardiovascular risk in paediatric patients with attention deficit and hyperactivity disorder.

BACKGROUND: There have been concerns about the potential cardiovascular (CV) adverse effects associated with methylphenidate (MTH) use. However, only limited evidence exists on the long-term safety of MTH. OBJECTIVE: To evaluate whether MTH use is associated with long-term CV risk. METHODS: This was a retrospective cohort study using 2003-2017 data from the Health and Welfare Database in Taiwan. Patients newly diagnosed with attention deficit and hyperactivity disorder (ADHD) and between 3 and 18 years of age were included. Two treatment statuses were assessed: initial treatment ≥7 days and ≥180 days. Patients treated with MTH were compared with those receiving non-medication therapy. One-to-one propensity score matching was used to balance between-group differences. Study outcomes included major CV events, chronic CV disease, cardiogenic shock and all-cause mortality. Cox proportional hazard models were used to estimate HRs between the two groups. RESULTS: We began with 307 459 patients with ADHD. After exclusion, 224 732 patients were included in the final cohort. The results showed that compared with non-ADHD medication users, patients who were treated with MTH for more than 7 days had a similar risk of major CV events (HR 0.85, 95% CI 0.72 to 0.99; p=0.040). Identical trends were found in groups who were treated for more than 180 days (HR 0.83, 95% CI 0.69 to 1.00; p=0.050). The results of the sensitivity analyses were consistent with the main analyses across all groups and individual outcomes. CONCLUSION: Short-term MTH use did not increase CV risk among patients with ADHD. More evidence on long-term MTH use and risk of cardiogenic shock and death is warranted.

Association between daily circulatory emergency ambulance dispatches and short-term PM2.5 exposure in a heavily polluted area.

Emergency ambulance dispatches (EAD) have been proven to be associated with ambient particulate matter with diameter < 2.5 µm (PM2.5) concentration, but the associations of circulatory EAD remained inconclusive, especially in heavily polluted areas. In this time series conducted in Shenyang City, Northeastern China, we explored the associations between circulatory EAD and ambient PM2.5 and its constituents. Data including 113,508 circulatory EAD records, five types of PM2.5 constituents, and meteorological information spanning from 2014 to 2019 were retrieved. Using generalized additive models (GAMs), we explored the association between circulatory EAD and calculated excess risks induced by a 10 µg/m3 increase (ERR10) in PM2.5 mass and its constituents. ERR by percentage change (ERRpc) to compare among the different constituents were also calculated. Positive associations between circulatory EAD and PM2.5 mass, sulfates, organic matters, and black carbon, were found particularly at lag0 and lag0-5, with the ERR10 of 3.8% (3.2%-4.4%), 6.5% (2.2%-10.8%), 4.2% (1.7%-6.6%), and 30.2% (17.2%-43.4%) at lag0-5, respectively. Similar associations were observed for cardiovascular EAD, while cerebrovascular EAD suggested a positive association with O3 rather than PM2.5 or its constituents. Notably, PM2.5 mass exhibited the largest ERRpc for circulatory and cardiovascular EAD, followed by sulfates and black carbon. Moreover, the risks were enhanced for circulatory and cardiovascular EAD in males compared to females and during warmer seasons compared to colder seasons. Our findings contribute new evidence on PM2.5 exposure and circulatory EAD in relatively polluted areas.

Adverse Effects of Gliptins in Type 2 Diabetics in Morocco.

INTRODUCTION: Gliptins are a relatively recent class of oral antidiabetic agents used in the treatment of type 2 diabetes. The aim of this study is to identify the adverse effects of gliptins in patients with type 2 diabetes, compare the tolerability of these drugs with data from the literature, and determine patients' behavior in the face of these adverse effects with a view to optimizing their management. METHODS: Our study is cross-sectional, descriptive, and analytical, involving 100 patients aged over 20 years, followed at the Endocrinology Department of the Military Hospital Mohammed V. RESULTS: The average age of the patients was 63 years, with a sex ratio F/H of 1.13. The median age of diabetes in the patients was 13 years, with an average blood glucose level of 1.64 and an average hemoglobin A1c of 8.26. The comorbidities were 30% cardiovascular disease, 25% hypertension, and 14% dyslipidemia, and 30% of patients had no comorbidities. Forth-six percent of patients reported adverse events and 54% did not report any adverse event. Twenty-eight percent of the adverse events were gastrointestinal, 18% skin disorders, 14% urinary tract infections, 12% hypoglycemia, 12% nervous system disorders, 8% airway infections, and 8% general disorders. CONCLUSION: This study shows that gliptins remain a safe option as the side effects seem fairly well tolerated by patients. Adverse events may impact patient compliance and pose a problem of adherence to treatment. Thus, it would be advantageous to develop therapeutic education for diabetic patients to detect and manage adverse effects.

Résumé Introduction:Les gliptines sont une classe relativement récente d'antidiabétiques oraux utilisés dans le traitement du diabète de type 2. Le but de cette étude est d'identifier les effets indésirables des gliptines chez les patients diabétiques de type 2, de comparer la tolérance de ces médicaments avec les données de la littérature et de déterminer le comportement des patients face à ces effets indésirables afin d'optimiser leur prise en charge.Méthodes:Notre étude est transversale, descriptive et analytique, portant sur 100 patients âgés de plus de 20 ans, suivis au service d'endocrinologie de l'hôpital militaire Mohammed V.Résultats:L'âge moyen des patients était de 63 ans, avec un sex-ratio F/H de 1,13. L'âge médian d'apparition du diabète chez les patients était de 13 ans, avec une glycémie moyenne de 1,64 et une hémoglobine A1c moyenne de 8,26%. Les comorbidités étaient les suivantes: 30 % de maladies cardiovasculaires, 25 % d'hypertension et 14 % de dyslipidémie; 30 % des patients n'avaient aucune comorbidité. Quarante-six pour cent des patients ont signalé des effets indésirables et 54 % n'ont signalé aucun effet indésirable. Vingt-huit pour cent des effets indésirables étaient d'ordre gastro-intestinal, 18 % des troubles cutanés, 14 % des infections urinaires, 12 % des hypoglycémies, 12 % des troubles du système nerveux, 8 % des infections des voies respiratoires et 8 % des troubles généraux.Conclusion:Cette étude montre que les gliptines restent une option sûre car les effets secondaires semblent assez bien tolérés par les patients. Les effets indésirables peuvent avoir un impact sur la compliance des patients et poser un problème d'adhésion au traitement. Ainsi, il serait avantageux de développer l'éducation thérapeutique des patients diabétiques pour détecter et gérer les effets indésirables.

Cardiovascular and pulmonary complications of recreational drugs: A pictorial review.

Recreational drug abuse constitutes a serious health problem worldwide. Consumption of cocaine, amphetamine-type stimulants, opioids and cannabis can lead to multiple acute and chronic cardiopulmonary complications, resulting in high morbidity and mortality. These complications may be first detected at imaging, since clinical presentation is usually non-specific. Cardiovascular complications include myocardial infarction, endocarditis, aortic dissection, infectious pseudoaneurysm, retained needle fragments, cardiomyopathy and pulmonary arterial hypertension. Pulmonary complications encompass pulmonary oedema, crack lung, pneumonia, septic emboli, barotrauma, airway disease, emphysema and excipient lung disease. Knowledge of the cardiopulmonary imaging manifestations of illicit drug use in conjunction with clinical history and a high grade of suspicion enable an accurate diagnosis and appropriate management plan. In this article we aim to provide a pictorial review of the most frequent cardiopulmonary manifestations of recreational drugs, emphasizing the underlying pathophysiologic mechanisms and the various imaging appearances.

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors in Kidney Disease.

BACKGROUND: Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors are an oral treatment for anemia of chronic kidney disease (CKD). In this systematic review and meta-analysis, we assessed long-term safety of HIF prolyl hydroxylase inhibitors. METHODS: We searched MEDLINE, Embase, and Cochrane databases for randomized trials comparing HIF prolyl hydroxylase inhibitors with an erythropoiesis-stimulating agent (ESA) or placebo with greater than or equal to 48 weeks of follow-up. The primary outcome was major adverse cardiovascular event (MACE), defined as a composite of all-cause death, myocardial infarction, or stroke. Treatment effects were pooled using random-effects models. RESULTS: Twenty-five trials involving 26,478 participants were included. Of these, 13 trials enrolled 13,230 participants with dialysis-dependent CKD, and 12 trials enrolled 13,248 participants with nondialysis-dependent CKD. There was no evidence that HIF prolyl hydroxylase inhibitors and ESA had different effects on MACE in people with dialysis-dependent CKD (risk ratio, 0.99; 95% confidence interval [CI], 0.92 to 1.08) or people with nondialysis-dependent CKD (risk ratio, 1.08; 95% CI, 0.95 to 1.22). Similarly, there was no evidence that HIF prolyl hydroxylase inhibitors and placebo had different effects on MACE (risk ratio, 1.10; 95% CI, 0.96 to 1.27) in people with nondialysis-dependent CKD. The lack of difference between HIF prolyl hydroxylase inhibitors and ESA or placebo was observed for individual components of MACE and cardiovascular death. Safety of HIF prolyl hydroxylase inhibitors for other outcomes was comparable with ESA in dialysis-dependent CKD. In nondialysis-dependent CKD, dialysis access thrombosis, venous thromboembolism, infections, and hyperkalemia occurred more frequently with HIF prolyl hydroxylase inhibitors in placebo-controlled trials but not in ESA-controlled trials. CONCLUSIONS: There was no evidence of a difference in the long-term cardiovascular safety profile of HIF prolyl hydroxylase inhibitors and ESA in adults with dialysis-dependent CKD and adults with nondialysis-dependent CKD. (PROSPERO registration number, CRD42021278011.).

Association between phthalates exposure and myocardial damage in the general population: A cross-sectional study.

BACKGROUND: Cardiovascular consequences of phthalates exposure have been given increasing attention, but the association of phthalates with subclinical cardiovascular disease (CVD) was unknown. Accordingly, this study aimed to investigate the association between phthalates exposure and high-sensitivity cardiac troponin I (hs-cTnI), a marker of myocardial injury, which was detectable in the subclinical stage of CVD. METHODS: Participants aged 6 years or older with available urinary phthalates metabolites and serum hs-cTnI concentrations were included in the National Health and Nutrition Examination Survey 2003-2004 cycle. Multivariable linear regression and weighted quantiles sum (WQS) regression were used to assess the association of hs-cTnI with individual phthalates and their co-exposure. Di-2-ethylhexylphthalate (ΣDEHP), high-molecular-weight phthalate (ΣHMWP), and low-molecular-weight phthalate (ΣLMWP) were defined as the molecular sum of phthalates metabolites in urine. RESULTS: 2241 participants were finally included. The percent change of serum hs-cTnI concentrations related to per 1-standard deviation increase of logarithmic urinary phthalates concentrations was 3.4% (0.1-6.7, P = 0.04) for ΣDEHP, 3.6% (0.3-6.9, P = 0.03) for ΣHMWP, and 3.5% (0.2-6.8, P = 0.04) for ΣLMWP. Co-exposure to phthalates metabolites expressed as the WQS index also demonstrated a positive association with hs-cTnI. A similar association pattern was found in the population with no prior CVD. CONCLUSIONS: This study indicated the potential of phthalates to myocardial injury which may occur even before clinically apparent CVD was identified, emphasizing the significance of reducing phthalates in the prevention of CVD.

Metformin's dual impact on Gut microbiota and cardiovascular health: A comprehensive analysis.

Cardiovascular diseases (CVD) cause significant global morbidity, mortality and public health burden annually. CVD alters richness, diversity, and composition of Gut microbiota along with RAS and histopathological differences. Present study explores Metformin role in mitigating doxorubicin induced cardiovascular toxicity/remodeling. Animals were divided into 4 groups with n=6: Group I (N. Control) free access to diet and water; Group II (MET. Control) on oral Metformin (250 mg/kg) daily; Group III (DOX. Control) alternate day intraperitoneal Doxorubicin (3 mg/kg) totaling 18 mg/kg; Group IV (DOX. MET. Control) received both daily oral Metformin (250 mg/kg) and alternate day Doxorubicin (3 mg/kg). Gut microbial analysis was made from stool before animals were sacrificed for biochemical and histopathological analysis. Significant alterations were observed in ɑ and ß-diversity with new genus from Firmicutes, specifically Clostridia_UCG-014, Eubacterium ruminantium, and Tunicibacter, were prevalent in both the DOX. Control and DOX.MET groups. Proteobacteria, represented by Succinivibrio, were absent in all groups. Additionally, Parabacteroides from the Bacteroidia phylum was absent in all groups except the N. control. In the DOX.MET Control group, levels of Angiotensin II ( 7.75± 0.49 nmol/min, p<0.01) and Renin (2.60±0.26 ng/ml/hr) were significantly reduced. Conversely, levels of CK-MB, Fibrinogen, Troponin, CRP ( p < 0.0001), and TNFɑ (p < 0.05) were elevated. Histopathological examination revealed substantial cardiac changes, including Fibrinogen and fat deposition and eosinophilic infiltration, as well as liver damage characterized by binucleated cells and damaged hepatocytes, along with altered renal tissues in the DOX.MET.Control group. The findings suggest that MET. significantly modifies gut microbiota, particularly impacting the Firmicutes and Proteobacteria phyla. The reduction in Angiotensin II levels, alongside increased inflammatory markers and myocardial damage, highlights the complex interactions and potential adverse effects associated with MET therapy on cardiovascular health.

Remdesivir-Related Cardiac Adverse Effects in COVID-19 Patients: A Case-Control Study.

BACKGROUND: There have been reports of serious side effects of Remdesivir, including cardiovascular complications. The present study aimed to determine the adverse cardiovascular effects of Remdesivir and the factors affecting them in COVID-19 patients. METHODS: The patients were classified into two groups: those receiving Remdesivir without cardiac complications and those receiving Remdesivir with cardiovascular complications. After reviewing the patient's medical records, the relationship of some factors with the incidence of adverse cardiovascular effects was measured. RESULTS: Chi-square test showed that the distribution of complications in men was significantly higher than in women (P=0.001). The independent t-test revealed that the mean age in the group with complications was significantly higher than the group without complications (P=0.013). Fisher's exact test demonstrated a significant relationship between smoking and cardiovascular complications (P=0.05). According to the Mann-Whitney test, a significant difference was found in the mean changes of Bilirubin (P=0.02) and ALKP (P=0.01) before and after treatment in the groups with and without heart complications. CONCLUSION: Our findings indicated that most of the COVID-19 patients suffered from sinus bradycardia, and the distribution of complications was more pronounced in men than in women. The mean age in the group with complications was higher than the group without complications. Smoking was found to be associated with the occurrence of cardiovascular complications and the mean changes of Bilirubin and ALKP before and after treatment were significantly different in the groups with and without cardiovascular complications.

Cardiovascular toxicities by calcineurin inhibitors: Cellular mechanisms behind clinical manifestations.

Calcineurin inhibitors (CNI), including cyclosporine A (CsA) and tacrolimus (TAC), are cornerstones of immunosuppressive therapy in solid organ transplant recipients. While extensively recognized for their capacity to induce nephrotoxicity, hypertension, and dyslipidemia, emerging reports suggest potential direct cardiovascular toxicities associated with CNI. Evidence from both in vitro and in vivo studies has demonstrated direct cardiotoxic impact of CNI, manifesting itself as induction of cardiomyocyte apoptosis, enhanced oxidative stress, inflammatory cell infiltration, and cardiac fibrosis. CNI enhances cellular apoptosis through CaSR via activation of the p38 MAPK pathway and deactivation of the ERK pathway, and enhancement of miR-377 axis. Although CNI could attenuate cardiac hypertrophy in certain animal models, CNI concurrently impaired systolic function, enhanced cardiac fibrosis, and increased the risk of heart failure. Evidence from in vivo studies demonstrated that CNI prolong the duration of action potentials through a decrease in potassium current. CNI also exerted direct effects on endothelial cell injury, inducing apoptosis and enhancing oxidative stress. CNI may induce vascular inflammation through TLR4 via MyD88 and TRIF pathways. In addition, CNI affects vascular function by impairing endothelial-dependent vasodilation and promoting vasoconstriction. Clinical studies in transplant patients also revealed an increased incidence of cardiac remodeling. However, the evidence is constrained by the limited number of participants and potential confounding factors. Several studies indicate differing cardiovascular toxicity profiles between CsA and TAC, and these could be potentially due to their different interactions with calcineurin subunits and calcineurin-independent effects. Further studies are needed to clarify these mechanisms to improve cardiovascular outcomes for transplant patients with CNI.

Unveiling the link: Neonicotinoids and elevated cardiometabolic risks in Chinese rural residents-from a prospective cohort study combing mendelian randomization study.

PURPOSE: This study aimed to evaluate the relationships of separate and mixed exposure of neonicotinoids on cardiometabolic risk at baseline and follow-up and its change over 3 years, and further explore whether inflammatory markers levels and platelet traits (PLT) mediate these relationships. METHODS: In this prospective cohort study from the Henan Rural Cohort Study, 2315 participants were involved at baseline, and 1841 participants completed cardiometabolic risk predictors determinations during the 3-year follow-up. Each neonicotinoid pesticide was normalized to imidacloprid (IMIeq) using the relative potency factor approach. Quantile-based g-computation (Qgcomp) regression was used to evaluate the effect of the mixtures of neonicotinoids mediation analysis was employed to explore whether inflammatory markers levels and platelet traits mediated these relationships. A two-sample mendelian randomization (MR) study was further used to causal association. RESULTS: Qgcomp regression revealed a statistically positive relationship between neonicotinoids mixture exposure and cardiometabolic risk score at baseline and follow-up over 3 years. Both neutrophils/monocytes and PLT were mediators in the relationship between IMIeq and cardiometabolic risk score at baseline and follow-up over 3 years. The causal risk effect of pesticide exposure were 2.50 (0.05, 4.95) and 5.24 (1.28, 9.19) for cardiometabolic risk indicators including insulin resistance and triglyceride, respectively. Nevertheless, there was no correlation discovered between pesticide exposure and other markers of cardiometabolic risk. CONCLUSION: Neonicotinoid insecticides exposure was connected to an increased cardiometabolic risk, especially in individuals with T2DM. Furthermore, inflammatory markers and PLT seem to be two vital mediators of these associations. Additionally, genetic evidence on pesticide exposure and cardiometabolic risk still needs to be validated by multiregional and multiethnic GWAS studies.

Prevalence of cardiovascular drug-related adverse drug reactions consultations in UK primary care: A cross-sectional study.

BACKGROUND: Adverse drug reactions (ADRs) represent a significant barrier to achieve optimal treatment outcomes. Cardiovascular drugs, including antihypertensive drugs, lipid-lowering drugs, and antithrombotic drugs, are among the most prescribed medications in the primary care setting. OBJECTIVES: To estimate the prevalence of cardiovascular drug-related ADRs consultations in United Kingdom (UK) primary care and identify risk factors of these ADRs. METHODS: This was a cross-sectional study of cardiovascular drug users between 2000-2019 using UK IQVIA Medical Research Data. ADRs consultations were identified using database screening method employing standardised designated codes. The overall and annual age-standardised prevalence was estimated using direct standardisation method using 2019 mid-year UK population. Risk factors of ADRs consultations were estimated using logistic regression model stratified by therapeutic areas. RESULTS: The standardised prevalence of consultations related to cardiovascular drugs ADRs was 10.60 (95% CI. 10.46, 10.75) per 1000 patients. Patients aged 70-79 years had the highest occurrence of ADRs consultations. The most frequently drug classes implicated in the ADRs consultations were statins (n = 9,993 events, 27.09%), beta-blockers (n = 8,538 events, 23.15%), ACEIs/ARBs (n = 8,345 events, 22.62%), and aspirin (n = 6,482 events, 17.57%). Risk factors of ADRs consultations were previous history of cardiovascular diseases, e.g., myocardial infarction and stroke; advanced age, comorbidities; diabetes and dyslipidaemia; and polypharmacy. CONCLUSIONS: The burden of cardiovascular drug-related ADRs consultations in primary care was considerable. Statins, beta-blockers, ACEIs/ARBs, and aspirin were the most frequently implicated drug classes. Closer clinical monitoring should be performed for patients affected by the ADRs to mitigate the risk of suboptimal treatment outcomes.

Cardiovascular Toxicity in Cancer Therapy: Protecting the Heart while Combating Cancer.

PURPOSE OF REVIEW: This review explores the cardiovascular toxicity associated with cancer therapies, emphasizing the significance of the growing field of cardio-oncology. It aims to elucidate the mechanisms of cardiotoxicity due to radiotherapy, chemotherapy, and targeted therapies, and to discuss the advancements in human induced pluripotent stem cell technology (hiPSC) for predictive disease modeling. RECENT FINDINGS: Recent studies have identified several chemotherapeutic agents, including anthracyclines and kinase inhibitors, that significantly increase cardiovascular risks. Advances in hiPSC technology have enabled the differentiation of these cells into cardiovascular lineages, facilitating more accurate modeling of drug-induced cardiotoxicity. Moreover, integrating hiPSCs into clinical trials holds promise for personalized cardiotoxicity assessments, potentially enhancing patient-specific therapeutic strategies. Cardio-oncology bridges oncology and cardiology to mitigate the cardiovascular side-effects of cancer treatments. Despite advancements in predictive models using hiPSCs, challenges persist in accurately replicating adult heart tissue and ensuring reproducibility. Ongoing research is essential for developing personalized therapies that balance effective cancer treatment with minimal cardiovascular harm.

Differential Expression of Circulating miRNAs and Carfilzomib-Related Cardiovascular Adverse Events in Patients with Multiple Myeloma.

This study investigates the association between circulating microRNA (miRNA) expression and cardiovascular adverse events (CVAE) in multiple myeloma (MM) patients treated with a carfilzomib (CFZ)-based regimen. A cohort of 60 MM patients from the Prospective Observation of Cardiac Safety with Proteasome Inhibitor (PROTECT) study was analyzed. Among these, 31 patients (51.6%) developed CVAE post-CFZ treatment. The Taqman OpenArray Human microRNA panels were used for miRNA profiling. We identified 13 differentially expressed miRNAs at baseline, with higher expressions of miR-125a-5p, miR-15a-5p, miR-18a-3p, and miR-152-3p and lower expression of miR-140-3p in patients who later developed CVAE compared to those free of CVAE, adjusting for age, gender, race, and higher B-type natriuretic peptide levels. We also identified three miRNAs, including miR-150-5p, that were differentially expressed in patients with and without CVAE post-treatment. Additionally, five miRNAs responded differently to CFZ treatment in CVAE vs. non-CVAE patients, including significantly elevated post-treatment expression of miR-140-3p and lower expressions of miR-598, miR-152, miR-21, and miR-323a in CVAE patients. Pathway enrichment analysis highlighted the involvement of these miRNAs in cardiovascular diseases and vascular processes. These findings suggest that specific miRNAs could serve as predictive biomarkers for CVAE and provide insights into the underlying mechanisms of CFZ-CVAE. Further investigation is warranted before these findings can be applied in clinical settings.

Cardiovascular adverse events associated with immune checkpoint inhibitors: a meta-analysis.

Objective: To evaluate the cardiovascular safety of anticancer drug immune checkpoint inhibitors (ICIs) used in patients with malignant tumors. Methods: Four clinical research databases that have been completed since their establishment were searched, and the odds ratios and 95% confidence intervals of each indicator were statistically calculated. Results: 62 randomized controlled trial and controlled trials were included. In single drug treatment ICIs group, the overall risk of cardio cerebral Vascular disease at all levels was higher than that in the placebo/chemotherapy group. Especially in all grades of Myocarditis and above grade 3 compared with normal controls, except for pericardial lesions, other indicators have no obvious side effects. Conclusion: Single drug use of an anti-tumor ICIs may increase cardiovascular side effects risk in cancer patients, so we need to strengthen monitoring, identification and management, and timely intervention to manage ICI induced adverse events.

Cardiovascular risk associated with changes in anticholinergic load on four different scales: a registry-based cohort study of geriatric outpatients.

BACKGROUND: Recent studies have shown that anticholinergic medications are associated with cardiovascular disease. Little is known about how discontinuation of anticholinergic medication affects this association. We investigated how baseline anticholinergic load and change in anticholinergic load associates with major adverse cardiovascular events (MACE) on four different scales. METHODS: We included all geriatric outpatients aged 65 and older in Denmark between January 2011 and December 2018. Data were sourced from Danish national registries. Anticholinergic drug exposure was assessed at first contact to the outpatient clinic (baseline) and changes were assessed at 180 days after outpatient contact. Anticholinergic scales were the CRIDECO Anticholinergic Load Scale, Anticholinergic Drugs Scale, Anticholinergic Cognitive Burden and a scale by the Danish Institute of Rational Pharmacotherapy. Multivariate analyses were conducted to investigate the 1- and 5-year risk of MACE by baseline anticholinergic load and changes in anticholinergic load after 180 days. RESULTS: We included a total of 64 378 patients in the analysis of baseline anticholinergic load and 54 010 patients remained after 180 days for inclusion in the analysis of change in anticholinergic load. At baseline the mean age was 81.7 year (SD 7.5) and 68% were women. Higher level of anticholinergic load on any scale associated with greater risk of MACE in a dose response pattern. There were no association between reduction in anticholinergic load and risk of MACE. CONCLUSION: While anticholinergic load at baseline was associated with MACE, reducing anticholinergic load did not lower the risk of MACE indicating the association may not be causal.

Early Methylglyoxal Exposure Leads to Worsened Cardiovascular Function in Young Rats.

BACKGROUND: Though maternal diabetes effects are well described in the literature, the effects of maternal diabetes in postnatal phases are often overlooked. Diabetic individuals have higher levels of circulating glycotoxins, and there is a positive correlation between maternal-derived glycotoxins and circulating glycotoxins in their progeny. Previous studies evaluated the metabolic effects of high glycotoxin exposure during lactation in adult animals. However, here we focus on the cardiovascular system of juvenile rats. METHODS: For this, we used two experimental models: 1. High Methylglyoxal (MG) environment: pregnant Wistar rats were injected with PBS (VEH group) or Methylglyoxal (MG group; 60 mg/kg/day; orally, postnatal day (PND) 3 to PND14). 2. GLO-1 inhibition: pregnant Wistar rats were injected with dimethyl sulfoxide (VEH group) or a GLO-1 inhibitor (BBGC group; 5 mg/kg/day; subcutaneously, PND1-PND5). The offspring were evaluated at PND45. RESULTS: MG offspring presented cardiac dysfunction and subtly worsened vasomotor responses in the presence of perivascular adipose tissue, without morphological alterations. In addition, an endogenous increase in maternal glycotoxins impacts offspring vasomotricity due to impaired redox status. CONCLUSIONS: Our data suggest that early glycotoxin exposure led to cardiac and vascular impairments, which may increase the risk for developing cardiovascular diseases later in life.