Cardiovascular Events In Patients Research Articles

534 - Incidence of venous thromboembolic events and atherosclerotic cardiovascular disease risk factors in adolescents and adults with atopic dermatitis in Denmark: a population-based cohort study

Abstract Background Atopic dermatitis (AD) is associated with substantial impairment in quality of life, including sleep disturbances, anxiety, and depression, which may increase the risk of cardiovascular disease (CVD). However, the association between CVD and AD is not well established. Objectives To evaluate incidence rates (IRs) of venous thromboembolism (VTE), deep vein thrombosis (DVT), and pulmonary embolism (PE) in patients with and without AD in a population-based cohort study in Denmark, and to assess IRs of malignancies, major adverse cardiovascular events (MACE), VTE, and the distribution of Atherosclerotic Cardiovascular Disease (ASCVD) risk factors in patients with AD and rheumatoid arthritis (RA) in a nested cohort analysis. Methods Data from all individuals aged ≥12 years (≥18 years in the nested cohort analysis) between January 1, 2000, and December 31, 2018, were extracted from the Danish National Patient Registry. Patients with ≥1 AD diagnosis during the study period were matched on sex and age with 10 individuals from the general population. The nested cohort analysis included patients diagnosed with RA as an additional comparison population. In the overall cohort, IRs of VTE, DVT, and PE were assessed; the nested cohort analysis evaluated the distribution of ASCVD risk factors and incidence of malignancies, MACE, and VTE in patients with and without ASCVD risk factors (age ≥65 years, and history of smoking, coronary artery disease, stroke, DVT, PE, and malignancy). The follow-up period was from the first diagnosis during the study period until the occurrence of death or an endpoint, the first instance of migration, or December 31, 2018. IRs are shown per 100 patient-years (PY) of exposure with 95% confidence intervals. Results The population-based cohort comprised 190,751 patients, including 17,341 patients with AD and 173,410 age- and sex-matched controls. The IR/100 PY of VTE was similar between the AD cohort (0.14 [95% CI, 0.12-0.16]) and the general population (0.11 [0.11-0.12]). The IR/100 PY for VTE was higher in patients with AD aged ≥65 years (0.71 [0.56-0.90]) than the age-matched general population (0.50 [0.46-0.54]) and lower in the younger AD cohorts (12 to <18 years, 0.02 [0.00-0.08]; 18 to <65 years, 0.12 [0.09-0.13]). The IRs/100 PY of DVT and PE were comparable between the AD cohort (DVT, 0.08 [0.06-0.09]; PE, 0.06 [0.05-0.08]) and the general population (DVT, 0.06 [0.06-0.07]; PE, 0.05 [0.05-0.05]).. The nested cohort analysis comprised 195,807 patients, including 13,432 with AD, 48,055 with RA, and 134,320 age- and sex-matched controls. Distribution of risk factors for malignancies (excluding nonmelanoma skin cancer [NMSC]), MACE, and VTE was comparable in the AD cohort and general population, but higher in patients with RA. The IR/100 PY for malignancies (excluding NMSC) was higher in patients with AD with a history of malignancy (11.41 [9.83-13.25]) than those without (0.44 [0.40-0.48]), and in those aged ≥65 years (3.09 [2.75-3.48]) versus <65 years (0.36 [0.33-0.40]). Similarly, the IR/100 PY for MACE was higher in patients with AD aged ≥65 years (2.30 [2.01-2.63]) versus <65 years (0.15 [0.13-0.17]), and patients with a history of ASCVD (5.02 [4.37-5.76]) versus without (0.15 [0.13-0.18]). Patients with AD with a history of VTE (including DVT/PE) and inherited thrombophilia had a greater risk of VTE than patients without these risk factors. Conclusions In these 2 large cohort studies of adults and adolescents with AD, IRs of VTE, DVT, and PE were comparable with the general Danish population. The risk of VTE, malignancy, and MACE was higher in patients with AD with a history of risk factors for ASCVD. This underscores the need for appropriate monitoring and reporting of cardiovascular events in patients with AD, and active management of risk factors with early and effective therapeutic intervention.

Pre-procedural Stratification by the Endothelial Function in Patients with Heart Failure Undergoing Atrial Fibrillation Ablation

BackgroundEndothelial dysfunction (ED), a well-established risk marker of cardiovascular events, is associated with heart failure (HF) and atrial fibrillation (AF). Its relationship with cardiovascular events in patients with HF undergoing AF ablation remains unclear. We aimed to elucidate the association between ED and the outcomes after AF ablation in patients with HF. MethodsThis prospective cohort study included patients with HF who underwent an endothelial function assessment using the peripheral vascular reactive hyperemia index (RHI) before first-time AF ablation. We defined AF recurrence according to the following types: the conventional form (AF≥30 seconds) and persistent form (requiring cardioversion). An RHI<2.1 indicated ED. Those with and without ED were compared in terms of the 3-year incidence of AF recurrence and cardiovascular events after AF ablation. ResultsAmong 421 patients with HF (69 ± 9 years and 38% females), 343 (81.5%) had ED. Although the incidence of the conventional form of AF recurrence was similar between the groups, that of the persistent form was significantly higher in the ED group (25.7% vs. 15.3%, log-rank P = 0.028). The ED group also had a significantly higher rate of cardiovascular events (14.8% vs. 3.6%, log-rank P = 0.028). Pre-procedural ED was identified as an independent predictor of a persistent form of AF recurrence (adjusted hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.06–5.06, P = 0.035) and that of cardiovascular events (adjusted HR 4.26, 95% CI 1.03–17.7, P = 0.028), respectively. ConclusionsThe endothelial function assessment enabled the risk stratification of clinically problematic outcomes after AF ablation in patients with HF.

Abstract 9: Efficacy of Colchicine for Prevention of Stroke and Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease: A Meta-Analysis of 15 Randomized Controlled Trials

Background: Clinical evidence supports the role of Inflammation in atherosclerosis and associated complications. Colchicine as a potential anti-inflammatory treatment among such patients has attracted much attention in recent years. However, its efficacy on cerebrovascular and cardiovascular events is still controversial. Objective: We sought to evaluate the efficacy of Colchicine for coronary artery disease patients. Methods: We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until August 30th, 2023. Odds ratios (OR) were pooled using a random-effect model, and a p-value of &lt;0.05 was considered statistically significant. Results: A total of 15 randomized controlled trials were included (6863 in Colchicine and 6756 in the control group) in the analysis. Pooled analysis of primary and secondary endpoints showed that Colchicine significantly reduced the risk of incidence of stroke by 50% (OR, 0.50 (95%CI: 0.31-0.81), P&gt;0.001), myocardial infarction by 40% (OR, 0.60 (95%CI: 0.44-0.84), P&gt;0.001), new acute coronary syndrome by 53% (OR, 0.47(95%CI: 0.47-0.85), P&gt;0.001), and major adverse cardiovascular events 45% (OR, 0.55(95%CI: 0.39-0.78), P&gt;0.001) compared with control. However, the risk of all-cause mortality (OR, 1.06(95%CI: 0.83-1.35), P=0.55) was comparable between both groups of patients. Conclusion: Colchicine was associated with an overall reduction in the risk of incidence of stroke, MI, MACE, ACS in patients with coronary heart disease. However, no such effect was observed with mortality.

The Fibrosis-5 Index Predicts Major Adverse Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

This study aimed to evaluate the fibrosis-5 (FIB-5) index as a marker of liver fibrosis for major adverse cardiovascular events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). A total of 406 STEMI patients were enrolled in the study. Over an average follow-up of 27months, 143 of the patients developed MACE. The patients were subgrouped into tertiles based on the FIB-5 index and Kaplan-Meier survival (MACE-free) curves were plotted, showing statistically significant differences (log-rank test, P < .001). In the adjusted Cox regression model, the hazard ratio (HR) of MACE was 1.95 (95% CI 1.21-3.13; P = .006) in tertile 3 and 0.98 (95% CI 0.97-1.00; P = .013) for per unit increase in the FIB-5 index. The area under the curve (AUC) of the FIB-5 index predicting the occurrence of MACE in STEMI patients after PCI was 0.645 (95% CI 0.590-0.701; P < .001). Low FIB-5 may be a useful predictor of MACE in STEMI patients undergoing PCI.

Association between high plasma levels of legumain and cardiovascular events in patients undergoing coronary angiography.

Degradation of vascular extracellular matrix is important in atherosclerosis. Cysteine protease legumain is upregulated in atherosclerotic plaques. We recently reported that plasma legumain levels are high in patients with complex coronary lesions. This study investigated the association between legumain levels and cardiovascular events in 372 patients undergoing coronary angiography. Patients with acute coronary syndrome were excluded. Of the 372 patients, 225 had coronary artery disease (CAD). During a mean follow-up of 7.0 ± 4.3 years, cardiovascular events occured in 62 patients. Compared with 310 patients without events, 62 with events tended to have higher prevalence of complex lesions (15% vs. 10%). Notably, patients with events had higher legumain levels (median 5.51 vs. 4.90 ng/mL, P < 0.01) than those without events. A Kaplan-Meier analysis showed lower event-free survival in patients with legumain > 5.0 ng/mL than in those with ≤ 5.0 ng/mL (P < 0.01). In multivariate Cox regression analysis, legumain level was an independent predictor of cardiovascular events. The hazard ratio for legumain > 5.0 ng/mL for cardiovascular events was 2.18 (95%CI = 1.27-3.77, P < 0.01). Only among 225 patients with CAD, patients with events had higher legumain levels (5.49 vs. 4.73 ng/mL) than without events (P < 0.02). Legumain level was also a predictor of cardiovascular events in patients with CAD. Thus, high plasma legumain levels were associated with an increased risk of cardiovascular events in patients undergoing coronary angiography and those with stable CAD.

Increased Cardiovascular Risk in Young Patients with CKD and the Role of Lipid-Lowering Therapy.

Chronic kidney disease (CKD) is associated with a significantly increased risk of cardiovascular disease (CVD). This review summarizes known risk factors, pathophysiological mechanisms, and current therapeutic possibilities, focusing on lipid-lowering therapy in CKD. Novel data on lipid-lowering therapy in CKD mainly stem from clinical trials and clinical studies. In addition to traditional CVD risk factors, patients with CKD often present with non-traditional risk factors that include, e.g., anemia, proteinuria, or calcium-phosphate imbalance. Dyslipidemia remains an important contributing CVD risk factor in CKD, although the mechanisms involved differ from the general population. While statins are the most commonly used lipid-lowering therapy in CKD patients, some statins may require dose reduction. Importantly, statins showed diminished beneficial effect on cardiovascular events in patients with severe CKD and hypercholesterolemia despite high CVD risk and effective reduction of LDL cholesterol. Ezetimibe enables the reduction of the dose of statins and their putative toxicity and, in combination with statins, reduces CVD endpoints in CKD patients. The use of novel drugs such as PCSK9 inhibitors is safe in CKD, but their potential to reduce cardiovascular events in CKD needs to be elucidated in future studies.

Cost Effectiveness of Endovascular Ultrasound Renal Denervation in Patients with Resistant Hypertension.

Resistant hypertension (rHTN) is defined as blood pressure (BP) of ≥ 140/90mmHg despite treatment with at least three antihypertensive medications, including a diuretic. Endovascular ultrasound renal denervation (uRDN) aims to control BP alongside conventional BP treatment with antihypertensive medication. This analysis assesses the cost effectiveness of the addition of the Paradise uRDN System compared with standard of care alone in patients with rHTN from the perspective of the United Kingdom (UK) health care system. Using RADIANCE-HTN TRIO trial data, we developed a state-transition model. Baseline risk was calculated using Framingham and Prospective Cardiovascular Münster (PROCAM) risk equations to estimate the long-term cardiovascular risks in patients treated with the Paradise uRDN System, based on the observed systolic BP (SBP) reduction following uRDN. Relative risks sourced from a meta-analysis of randomised controlled trials were then used to project cardiovascular events in patients with baseline SBP ('control' patients); utility and mortality inputs and costs were derived from UK data. Costs and outcomes were discounted at 3.5% per annum. Modelled outcomes were validated against trial meta-analyses and the QRISK3 algorithm and real-world evidence of RDN effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty surrounding the model inputs and sensitivity of the model results to changes in parameter inputs. Results were reported as incremental cost-effectiveness ratios (ICERs). A mean reduction in office SBP of 8.5mmHg with uRDN resulted in an average improvement in both absolute life-years (LYs) and quality-adjusted life-years (QALYs) gained compared with standard of care alone (0.73 LYs and 0.67 QALYs). The overall base-case ICER with uRDN was estimated at £5600 (€6500) per QALY gained (95% confidence interval £5463-£5739 [€6341-€6661]); modelling demonstrated > 99% probability that the ICER is below the £20,000-£30,000 (€23,214-€34,821) per QALYs gained willingness-to-pay threshold in the UK. Results were consistent across sensitivity analyses and validation checks. Endovascular ultrasound RDN with the Paradise system offers patients with rHTN, clinicians, and healthcare systems a cost-effective treatment option alongside antihypertensive medication.

Elevated Glucose on Admission Was an Independent Risk Factor for 30-Day Major Adverse Cardiovascular Events in Patients with STEMI but Not NSTEMI

Elevated Glucose on Admission Was an Independent Risk Factor for 30-Day Major Adverse Cardiovascular Events in Patients with STEMI but Not NSTEMI

P616 Prescribing practices of tofacitinib and preferences amongst high-risk patients in the UK

Abstract Background Tofacitinib was licensed for use in patients with ulcerative colitis in August 2018. Because it is administered orally, has a rapid onset of action and is relatively inexpensive, it was quickly adopted in real-world practice. Safety warnings linking high-dose tofacitinib use to venous thromboembolic events (VTE) and death followed. Further warnings were issued linking its use to an increased risk of malignancy and adverse cardiovascular events in patients: over 65 years, with a history of diabetes, current or past smokers, and those with a history of coronary vascular disease. The most recent Medicines and Healthcare products Regulatory Agency (MHRA) statement advised against the use of all commercially available JAKi in this high-risk cohort unless a suitable alternative is unavailable (MHRA 2023). We sought to define the number of patients who had, or were, being treated with tofacitinib who were in this high-risk group and the proportion who opted to switch therapy once we had outlined their risk-status and the MHRA advice to them. Methods We conducted a retrospective observational cohort study of 131 patients with UC and IBD-U (61% male [80/131]; median age 43 years [range 16-85]; 46% [60/131] patients had previously had at least one biologic agent) treated with tofacitinib from October 2018 to December 2022 in our centre with at least 3 months follow-up. Patients were categorised as high-risk according to the MHRA statement if they had at least one of the criteria above. Results Overall, about one-third, 31.3% [41/131] patients that we had treated with tofacitinib were classified in the MHRA high-risk group. Rates of treatment discontinuation were similar in the high-risk versus no risk group. In the high-risk group ten patients (24.4% [10/41]) had discontinued treatment due to lack of response (4) or an adverse event (6). The most common adverse events were herpes zoster infections (14.6%), malignancy (3.3%) and infections requiring hospitalisation (3.3%). Two patients died while on treatment (one due to complications following cervical spinal surgery and the other due to ischaemic heart disease). There were no incidences of VTE. We clinically reviewed 29 high risk patients who were being treated with tofacitinib after a median of 2.4 years (range 0.6-4.56) of treatment. 25/29 high-risk patients decided on continuing their treatment in spite of the health care warnings and alternative therapies being available. Conclusion About one-third of our tofacitinib-treated patients were classified as at high-risk. The majority of high-risk patients opted to continue therapy even though alternative therapies were available.

Comment on: The risk of major adverse cardiovascular events in patients with systemic sclerosis: a nationwide, population-based cohort study.

Comment on: The risk of major adverse cardiovascular events in patients with systemic sclerosis: a nationwide, population-based cohort study.

The functional role of cellular senescence during vascular calcification in chronic kidney disease.

Vascular calcification (VC) has emerged as a key predictor of cardiovascular events in patients with chronic kidney disease (CKD). In recent years, an expanding body of research has put forth the concept of accelerated vascular aging among CKD patients, highlighting the significance of vascular cells senescence in the process of VC. Within the milieu of uremia, senescent vascular endothelial cells (VECs) release extracellular microvesicles (MV) that promote vascular smooth muscle cells (VSMCs) senescence, thereby triggering the subsequent osteogenic phenotypic switch and ultimately contributing to the VC process. In addition, senescent vascular progenitor or stem cells with diminished ability to differentiate into VECs and VSMCS, compromise the repair of vascular integrity, on the other hand, release a cascade of molecules associated with senescence, collectively known as the senescence-associated secretory phenotype (SASP), perpetuating the senescence phenomenon. Furthermore, SASP triggers the recruitment of monocytes and macrophages, as well as adjacent VECs and VSMCs into a pro-adhesive and pro-inflammatory senescent state. This pro-inflammatory microenvironment niche not only impacts the functionality of immune cells but also influences the differentiation of myeloid immune cells, thereby amplifying the reduced ability to effectively clear senescent cells of senescent macrophages, promoted calcification of VSMCs. The objective of this paper is to provide a comprehensive review of the contribution of vascular cell senescence to the emergence and advancement of VC. Gaining a comprehensive understanding of the involvement of cellular senescence within the vessel wall is pivotal, especially when it comes to its intersection with VC. This knowledge is essential for advancing groundbreaking anti-aging therapies, aiming to effectively mitigate cardiovascular diseases.

Risk of adverse reactions associated with inhaled corticosteroids for chronic obstructive pulmonary disease: A meta-analysis.

In the majority of current therapeutic regimens for chronic obstructive pulmonary disease (COPD), bronchodilators are coupled with inhaled corticosteroids (ICS) to lower the inflammatory response and improve symptoms. This study aims to evaluate the safety of ICS in the treatment of COPD. Randomized controlled trials related to ICS for COPD that were eligible up to 1 June 2023 were searched in PubMed, EMBASE, and Cochrane. We searched and screened eligible studies for the occurrence of total adverse events, cardiovascular events, upper respiratory tract infections (URTI), pneumonia, oral Candida infections, and musculoskeletal disorders, and finally analyzed them by Review Manager 5.4.1. The results showed that ICS increased the incidence of adverse reactions in COPD patients (RR = 1.06, 95% CI: 1.03-1.10, P = .0004); ICS treatment did not increase the risk of cardiovascular events in COPD patients (RR = 0.95, 95% CI: 0.88-1.02, P = .14); ICS increased the incidence of URTI in COPD patients (RR = 1.29, 95% CI: 1.02-1.62, P = .03); ICS increased the incidence of pneumonia in patients with COPD (RR = 2.09, 95% CI: 1.63-2.69, P < .00001); ICS treatment significantly increased the incidence of oral Candida in patients with COPD (RR = 2.96, 95% CI: 1.99-4.41, P < .00001); ICS increased the incidence of musculoskeletal disorders in patients with COPD (RR = 2.87, 95% CI: 1.51-5.45, P = .001). ICS does not increase the risk of cardiovascular events in patients with COPD, but it does increase the risk of URTI, pneumonia, oral Candida infections, and musculoskeletal disorders in patients with COPD.

Comment on: The risk of major adverse cardiovascular events in patients with systemic sclerosis: a nationwide, population-based cohort study. Reply.

Comment on: The risk of major adverse cardiovascular events in patients with systemic sclerosis: a nationwide, population-based cohort study. Reply.

Impact of Bempedoic Acid on Total Cardiovascular Events

The ATP citrate lyase (ACL) inhibitor, bempedoic acid, reduces low-density lipoprotein cholesterol (LDL-C) level and major adverse cardiovascular events (MACE) by 13% in patients at high cardiovascular risk with intolerance of statin and high-intensity statin medications. The effects of bempedoic acid on total cardiovascular events remain unknown. To determine the impact of bempedoic acid on the total incidence of MACE. Included in this prespecified analysis of the Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes trial were patients with, or at high risk for, cardiovascular disease, with hypercholesterolemia and inability to take guideline-recommended statins. Study data were analyzed from December 2016 to November 2022. Patients were randomly assigned to treatment with bempedoic acid or placebo daily. The primary end point was the time to first event for a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization (MACE-4). The key secondary end point was time to first event for cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (MACE-3). This prespecified analysis compared the total number of cardiovascular events in the treatment groups. A total of 13 970 patients (mean [SD] age, 65 [9] years; 7230 male [51.8%]) were included in the study. A total of 9764 participants (69.9%) had prior atherosclerotic cardiovascular disease and a baseline LDL-C level of 139 mg/dL; treatment with bempedoic acid resulted in a 21% reduction in LDL-C level and a 22% reduction in high-sensitivity C-reactive protein (hsCRP) level at 6 months. Median (IQR) follow-up was 3.4 (3.1-3.9) years. A total of 1746 positively adjudicated first MACE-4 events and 915 additional MACE events in 612 patients were recorded, with coronary revascularization representing 32.8% (573 of 1746) of first events and 69.4% (635 of 915) of additional events. For the total incidence of cardiovascular events, treatment with bempedoic acid was associated with a reduction in risk of MACE-4 (hazard ratio [HR], 0.80; 95% CI, 0.72-0.89; P <.001), MACE-3 (HR, 0.83; 95% CI, 0.73-0.93; P = .002), myocardial infarction (HR, 0.69; 95% CI, 0.58-0.83; P < .001), and coronary revascularization (HR, 0.78; 95% CI, 0.68-0.89; P <.001), although no statistically significant difference was observed for stroke (HR, 0.80; 95% CI, 0.63-1.03). A lower HR for protection with bempedoic acid was observed with increasing number of MACE events experienced by patients. Lowering LDL-C level with bempedoic acid reduced the total number of cardiovascular events in patients with high cardiovascular risk, statin therapy intolerance, and elevated LDL-C levels.

Intermediate monocytes are associated with the first major adverse cardiovascular event in patients with stable coronary artery disease

BackgroundTraditional risk stratification modestly predicts adverse cardiovascular events in patients with coronary artery disease (CAD). Our aim was to investigate the association between monocyte subsets numbers and function, and the first major adverse cardiovascular event (MACE) in patients with symptomatic stable CAD and angiographically documented coronary atherosclerosis. MethodsPatients with stable CAD were screened for inclusion. Using flow cytometry, we identified classical, intermediate, and non-classical monocyte subsets and we assessed cytokine production capacity after ex-vivo stimulation of peripheral blood mononuclear cells. Clinical follow-up was performed after four years. The endpoint was the composite of cardiovascular death, acute myocardial infarction, and ischemic stroke. ResultsA cohort of 229 patients was recruited. The percentage of intermediate monocytes was positively associated with adverse cardiovascular events at follow-up (HR 1.09; 95%CI 1.02–1.16; p = 0.006), while the percentage of classical monocytes was identified as a protective factor for adverse outcomes (HR 0.96; 95%CI 0.94–0.99; p = 0.02). The percentage of intermediate monocytes remained independently associated with outcomes after adjusting for age, systolic blood pressure, and left ventricular ejection fraction (HR 1.07; 95% CI 1.01–1.14; p = 0.04). Several correlations were identified between monocyte subsets and stimulated cytokine production, but cytokine production capacity was not associated with adverse outcomes. ConclusionsIn patients with stable CAD, intermediate monocytes were associated with MACE at follow-up. The association was not due to an increased cytokine production capacity. Novel biomarkers could improve risk stratification in patients with stable CAD and could represent new pharmacological targets against atherosclerosis progression.

Machine learning-based prediction of composite risk of cardiovascular events in patients with stable angina pectoris combined with coronary heart disease: development and validation of a clinical prediction model for Chinese patients.

Objective: To develop a risk score model for the occurrence of composite cardiovascular events (CVE) in patients with stable angina pectoris (SA) combined with coronary heart disease (CHD) by comparing the modeling effects of various machine learning (ML) algorithms. Methods: In this prospective study, 690 patients with SA combined with CHD attending the Department of Integrative Cardiology, China-Japan Friendship Hospital, from October 2020 to October 2021 were included. The data set was randomly divided into a training group and a testing group in a 7:3 ratio in the per-protocol set (PPS). Model variables were screened using the least absolute shrinkage selection operator (LASSO) regression, univariate analysis, and multifactor logistic regression. Then, nine ML algorithms are integrated to build the model and compare the model effects. Individualized risk assessment was performed using the SHapley Additive exPlanation (SHAP) and nomograms, respectively. The model discrimination was evaluated by receiver operating characteristic curve (ROC), the calibration ability of the model was evaluated by calibration plot, and the clinical applicability of the model was evaluated by decision curve analysis (DCA). This study was approved by the Clinical Research Ethics Committee of China-Japan Friendship Hospital (2020-114-K73). Results: 690 patients were eligible to finish the complete follow-up in the PPS. After LASSO screening and multifactorial logistic regression analysis, physical activity level, taking antiplatelets, Traditional Chinese medicine treatment, Gensini score, Seattle Angina Questionnaire (SAQ)-exercise capacity score, and SAQ-anginal stability score were found to be predictors of the occurrence of CVE. The above predictors are modeled, and a comprehensive comparison of the modeling effectiveness of multiple ML algorithms is performed. The results show that the Light Gradient Boosting Machine (LightGBM) model is the best model, with an area under the curve (AUC) of 0.95 (95% CI = 0.91-1.00) for the test set, Accuracy: 0.90, Sensitivity: 0.87, and Specificity: 0.96. Interpretation of the model using SHAP highlighted the Gensini score as the most important predictor. Based on the multifactorial logistic regression modeling, a nomogram, and online calculators have been developed for clinical applications. Conclusion: We developed the LightGBM optimization model and the multifactor logistic regression model, respectively. The model is interpreted using SHAP and nomogram. This provides an option for early prediction of CVE in patients with SA combined with CHD.

Mineralocorticoid receptor antagonists and atrial fibrillation: a meta-analysis of clinical trials.

Mineralocorticoid receptor antagonists (MRAs) improve cardiovascular outcomes in a variety of settings. This study aimed to assess whether cardioprotective effects of MRAs are modified by heart failure (HF) and atrial fibrillation (AF) status and to study their impact on AF events. MEDLINE, Embase, and Cochrane Central databases were searched to 24 March 2023 for randomized controlled trials evaluating the efficacy of MRAs as compared with placebo or usual care in reducing cardiovascular outcomes and AF events in patients with or at risk for cardiovascular diseases. Random-effects models and interaction analyses were used to test for effect modification. Meta-analysis of seven trials (20 741 participants, mean age: 65.6 years, 32% women) showed that the efficacy of MRAs, as compared with placebo, in reducing a composite of cardiovascular death or HF hospitalization remains consistent across patients with HF [risk ratio = 0.81; 95% confidence interval (CI): 0.67-0.98] and without HF (risk ratio = 0.84; 95% CI: 0.75-0.93; interaction P = .77). Among patients with HF, MRAs reduced cardiovascular death or HF hospitalization in patients with AF (hazard ratio = 0.95; 95% CI: 0.54-1.66) to a similar extent as in those without AF (hazard ratio = 0.82; 95% CI: 0.63-1.07; interaction P = .65). Pooled data from 20 trials (21 791 participants, mean age: 65.2 years, 31.3% women) showed that MRAs reduce AF events (risk ratio = 0.76; 95% CI: 0.67-0.87) in both patients with and without prior AF. Mineralocorticoid receptor antagonists are similarly effective in preventing cardiovascular events in patients with and without HF and most likely retain their efficacy regardless of AF status. Mineralocorticoid receptor antagonists may also be moderately effective in preventing incident or recurrent AF events.

High plasma levels of endosialin and cardiovascular events in patients undergoing coronary angiography.

Endosialin, also known as tumor endothelial marker-1, is a transmembrane glycoprotein that plays a role in inflammation and tumor progression. Endosialin is upregulated in atherosclerotic lesions. To elucidate the association between blood endosialin levels and cardiovascular events, we measured plasma endosialin levels in 389 patients undergoing coronary angiography who were followed up for a mean follow-up of 6.4 ± 4.2 years for cardiovascular events (cardiovascular death, myocardial infarction, unstable angina, heart failure, stroke, or need for coronary revascularization). Of the 389 patients, 223 had coronary artery disease (CAD). No significant difference was found in plasma endosialin levels between patients with and without CAD (median 0.92 vs. 0.92 ng/mL). During the follow-up, cardiovascular events occurred in 62 patients. Compared with patients without events, those with events had higher endosialin levels (1.12 vs. 0.89 ng/mL), and more often had endosialin level of > 1.1 ng/mL (53% vs. 31%) (P < 0.01). A Kaplan-Meier analysis showed lower event-free survival in patients with endosialin > 1.1 ng/mL than those with ≤ 1.1 ng/mL (P < 0.01). In a multivariate Cox regression analysis, endosialin > 1.1 ng/mL was an independent predictor of cardiovascular events (hazard ratio = 2.00; 95%CI = 1.21-3.32; P < 0.01). Thus, high plasma endosialin levels were associated with an increased risk of cardiovascular events in patients undergoing coronary angiography.

Prognostic value of right ventricular trabecular complexity in patients with arrhythmogenic cardiomyopathy.

The present study aimed to investigate the incremental prognostic value of the right ventricular fractal dimension (FD), a novel marker of myocardial trabecular complexity by cardiac magnetic resonance (CMR) in patients with arrhythmogenic cardiomyopathy (ACM). Consecutive patients with ACM undergoing CMR were followed up for major cardiac events, including sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter defibrillator intervention. Prognosis prediction was compared by Cox regression analysis. We established a multivariable model supplemented with RV FD and evaluated its discrimination by Harrell's C-statistic. We compared the category-free, continuous net reclassification improvement (cNRI) and integrated discrimination index (IDI) before and after the addition of FD. A total of 105 patients were prospectively included from three centers and followed up for a median of 60 (48, 66) months; experienced 36 major cardiac events were recorded. Trabecular FD displayed a strong unadjusted association with major cardiac events (p < 0.05). In the multivariable Cox regression analysis, RV maximal apical FD maintained an independent association with major cardiac events (hazard ratio, 1.31 (1.11-1.55), p < 0.002). The Hosmer-Lemeshow goodness of fit test displayed good fit (X2 = 0.68, p = 0.99). Diagnostic performance was significantly improved after the addition of RV maximal apical FD to the multivariable baseline model, and the continuous net reclassification improvement increased 21% (p = 0.001), and the integrated discrimination index improved 16% (p = 0.045). In patients with ACM, CMR-assessed myocardial trabecular complexity was independently correlated with adverse cardiovascular events and provided incremental prognostic value. The application of FD values for assessing RV myocardial trabeculae may become an accessible and promising parameter in monitoring and early diagnosis of risk factors for adverse cardiovascular events in patients with ACM. • Ventricular trabecular morphology, a novel quantitative marker by CMR, has been explored for the first time to determine the severity of ACM. • Patients with higher maximal apical fractal dimension of RV displayed significantly higher cumulative incidence of major cardiac events. • RV maximal apical FD was independently associated with major cardiac events and provided incremental prognostic value in patients with ACM.

A fully automated stress regional strain score as a prognostic marker of cardiovascular events in patients with normal CMR.

A fully automated stress regional strain score as a prognostic marker of cardiovascular events in patients with normal CMR.