Major Cardiovascular Events Research Articles

The effect of empagliflozin on circulating endothelial progenitor cells in patients with diabetes and stable coronary artery disease.

Diabetes mellitus (DM) is associated with premature atherosclerotic disease, coronary artery disease (CAD) and chronic heart failure (HF), leading to increased morbidity and mortality. Sodium-Glucose Co-transporter 2 Inhibitors (SGLT2i) exhibit cardioprotective benefits beyond glucose lowering, reducing the risk of major cardiovascular events (MACE) and HF hospitalizations in patients with DM and CAD. Endothelial progenitor cells (EPCs) are bone marrow-derived cells involved in vascular repair, mobilized in response to vascular injury. The number and function of circulating EPCs (cEPCs) are negatively affected by cardiovascular risk factors, including DM. This study aimed to examine the response of cEPCs to SGLT2i treatment in DM patients with stable CAD. A prospective single-center study included patients with DM and stable CAD who were started on an SGLT2i (empagliflozin). Peripheral blood samples were collected at baseline, 1 month, and 3 months to evaluate cEPC levels and function by flow cytometry, immunohistochemistry and MTT assays. Eighteen patients were included in the study (median age 73, (IQR 69, 77) years, 67% male). After 1 month of treatment with empagliflozin, there was no significant change in cEPCs level or function. However, following 3 months of treatment, a significant increase was observed both in cell levels (CD34(+)/VEGFR-2(+): from 0.49% (IQR 0.32, 0.64) to 1.58% (IQR 0.93, 1.82), p = 0.0006; CD133(+)/VEGFR-2(+): from 0.38% (IQR 0.27, 0.6) to 0.82% (IQR 0.7, 1.95), p = 0.0001) and in cell function (from 0.25 CFUs (IQR 0, 0.5) at baseline, to 2 CFUs (IQR 1, 2) at 3 months, p = 0.0012). Empagliflozin treatment in patients with DM and stable CAD increases cEPC levels and function, implying a cardioprotective mechanism. These findings highlight the potential of SGLT2i in treating cardiovascular diseases, warranting further research to explore these effects and their long-term implications.

Blood pressure lowering efficacy of antihypertensive drugs and their combinations: a systematic review and meta-analysis of 500 randomised, double-blind placebo-controlled trials

Abstract Background Each 1 mmHg reduction in systolic blood pressure (SBP) reduces the risk of major cardiovascular disease events by about 2%. However, there are currently no tools to provide randomised trial-derived estimates of blood pressure (BP)-lowering efficacy of different antihypertensive regimens despite the vast number of possible drug-dose permutations. There has also been no attempt to classify efficacy of treatment regimens into low, moderate, and high intensity. Purpose We aimed to quantify the BP-lowering efficacy of the five major classes of antihypertensive drugs and their combinations. Methods We conducted a systematic review and meta-analysis of randomised double-blind placebo-controlled trials. CENTRAL, MEDLINE and Epistimonikos were searched from inception until December 2022 to identify trials, that compared angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, calcium channel blockers, and diuretics versus placebo, for 4-26 weeks. Primary outcomes were reduction in SBP and diastolic blood pressure (DBP). Doses were classified into standard dose based on the World Health Organisation Defined Daily Dose. BP-lowering efficacy was estimated for each drug and dose using fixed-effects meta-analyses and meta-regressions, standardised to baseline SBP 154 mmHg. Treatment regimens were categorised into low, moderate, and high intensity according to estimated SBP-lowering efficacy of <10, 10-19 and ≥20 mmHg, respectively. Results A total of 500 trials (106,358 participants, 44% female) were included, which included 66 single antihypertensive drugs (monotherapy) and 89 two drug (dual) combinations. The mean baseline BP was 154/100 mmHg and mean follow-up was 8.6 weeks. Monotherapy at one standard dose reduced SBP by 8.5 (95% CI, 8.2-8.9) mmHg, with an additional 1.2 (1.0-1.5) mmHg reduction for each 10 mmHg higher pre-treatment SBP, and an additional 1.5 (1.2-1.8) mmHg reduction with each doubling in dose. There was significant heterogeneity between monotherapies, and 72% were classified as low intensity efficacy. Dual combinations at one standard doses of both the drugs reduced SBP by 15.2 (13.4-17.1) mmHg, and an additional 2.6 (1.4-3.8) mmHg reduction with doubling the doses of both the drugs. There was considerable heterogeneity between dual combinations and 59% were classified as moderate, and 11% as high intensity efficacy. The BP lowering efficacy of adding additional drug classes was confirmed to be additive after accounting for pre-treatment SBP. Triple combinations were classified as high intensity efficacy based on meta-regression analyses. Conclusions There is significant variability in the efficacy of different BP-lowering regimens. The present analyses, available in an online tool, can estimate the BP lowering efficacy for any combination of drug(s) and dose(s), and can classify treatment regimens into low, moderate or high intensity.

Satisfactory self-rated health is associated with better clinical outcomes in patients with ST-segment elevation myocardial infarction

Abstract Background It is well known that health status is a risk factor for cardiovascular diseases, but its specific impact on the prognosis of patients with acute myocardial infarction remains unclear. Purpose This study was aimed to investigate the impact of varying health self-evaluation on the long-term outcomes of patients diagnosed with ST-elevation myocardial infarction (STEMI). Methods Data for this study were obtained from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospital from 2010 to 2023. Patients were divided into satisfied group and dissatisfied group based on their responses to a self-assessment health questionnaire. Baseline data of the two groups were compared, and the relationship between health status and major cardiovascular and cerebrovascular adverse events (MACCE) was analyzed using multivariate cox regression. MACCE, defined as the composite endpoint of cardiac death, recurrent myocardial infarction, stroke and revascularization, was the primary endpoint, with each component considered a secondary endpoint. Results Among STEMI patients, 25214 patients reported satisfaction with their health, while 375 patients expressed dissatisfaction. The satisfied group exhibited a younger age, fewer females, a higher rate of primary percutaneous coronary intervention (PPCI) and PCI during hospitalization, a better Killips classification and a lower prevalence of concomitant disease such as diabetes, hypertension, chronic kidney disease, and cerebrovascular disease. After a median follow-up of 1626 days, the satisfied group demonstrated significantly lower proportions of total death, cardiac death, recurrent myocardial infarction and stroke compared to dissatisfied group. Multivariate COX regression showed that satisfactory health self-rating was associated with a decreased risk of MACCE (HR 0.813, 95%CI 0.704-0.939, P=0.005), stroke (HR 0.670, 95%CI 0.511-0.878, P=0.003), and recurrent myocardial infarction (HR 0.732, 95%CI 0.548-0.979, P=0.035). Conclusions Satisfactory self-rated health is associated with better clinical outcomes in STEMI patients.

Prognostic prediction of cardiovascular adverse events in patients after percutaneous coronary intervention using machine learning

Abstract Introduction While prevention of major cardiovascular adverse events (MACE) is important in the management of patients after percutaneous coronary intervention (PCI), risk stratification of MACE remains a significant challenge with increasingly diverse and complex patient backgrounds. In response to that, this retrospective observational study aimed to explore whether machine learning (ML) methods can predict future MACE after PCI using a variety of features extracted from electronic medical records (EMRs). Methods In 3,016 patients with coronary artery disease who performed PCI, 3 machine learning (ML) algorithms (gentle boost, random forest, and neural network) and statistical model were retrospectively applied to predict the occurrence of MACE within two years after PCI (564 patients, 18.7%). MACE was defined as composite endpoint of cardiac death, myocardial infarction (MI), any revascularization, and congestive heart failure (CHF). Basic patient information (e.g., age, sex, coronary risk factors) and laboratory test results were used for the analysis. Feature importance was calculated to identify key factors for MACE. Hold-out method with an 8:2 split between training and test was used to calculate sensitivity, specificity, positive predictive value, negative predictive value, and F-value for each model. Results As shown in Figure 1, ML models showed excellent diagnostic accuracies in the prediction of MACE after PCI, demonstrating higher F-values compared with statistical model (logistic regression analysis). Similar results were seen in the subgroup analyses for estimating cardiac death, MI, revascularization, or CHF. Although the weighting of feature importance for MACE recurrence varied among ML models, infarct size (peak CK levels), increased inflammatory status, and traditional coronary risk factors were identified as important features for predicting MACE within two years after PCI (Figure 2). Conclusions It is suggested that ML using EMRs is promising for inferring future MACE within two years after PCI. Further studies are warranted to address whether ML-based risk stratification could lead to improved clinical decision-making after PCI.

Predicting atrial fibrillation within 7 years follow-up using machine learning models

Abstract Background The prevalence of atrial fibrillation (AF), the most common type of cardiac arrhythmia, has increased globally. AF is also the leading cardiac factor for several cardiovascular and cerebrovascular events. Early prediction and treatment of AF prevents major cardiovascular and cerebrovascular events. Purpose Our objective is to predict AF risk within 7-years follow-up using only twelve basic factors and applying machine learning (ML) models. Methods Data from the German epidemiological trial on ankle brachial index (getABI) were utilized in this work. GetABI includes 6,457 patients with mean age of 72.53 years. 3,985 individuals were assessed for AF of which 393 patients suffered from AF at 7-years follow-up. The feature selection was initially done manually, ending up in 45 features. The 10 best features were extracted from this dataset according to the SHAP (SHapley Additive exPlanations) values. The final features were body mass index, sensitive CRP, cholesterol, LDL-cholesterol, troponin I, NT-pro-BNP, glomerular filtration rate, ratio of triglycerides and HDL-cholesterol, gamma-GT, heart rate, including age and sex as major factors. The handling of missing values was achieved by SimpleImputer, estimating the mean values. XGBoost and Random Forest predicted AF. Logistic Regression was also used as a baseline model. The data were split into training and test set and ML models were applied for 100 iterative runs, extracting results with mean values. Results XGBoost was the most accurate model, predicting the AF with 71.19 % mean accuracy, 66.37 % mean sensitivity and 75.61 % mean specificity. Figure 1 depicts the performance of all models. Additionally, Receiver Operating Characteristic Curve (ROC) and Area Under Curve (AUC) for each model are presented in Figure 2. XGBoost also outperformed all the others models, achieving the highest mean AUC value, equal to 70.99 %. Contrariwise, logistic regression had the lowest overall performance. Conclusion ML models, specifically XGBoost, achieved accurate AF prediction in 3,985 individuals utilizing only twelve clinical-routine data.Evaluation results of each used model.ROC curve and AUC value of each model.

Levosimendan improves the early prognosis of patients with Non ST-segment elevation myocardial infarction and Killip class > II

Abstract Background Levosimendan is an inotropic agent known for its calcium-sensitizing myofilament effect and ATP-dependent potassium channel opening mechanism, which enhances myocardial contractility without increasing oxygen consumption. Despite its potential benefits, the impact of levosimendan on the prognosis of patients with myocardial infarction remains uncertain and requires further investigation through larger-scale studies. Purpose This study aimed to investigate the effect of levosimendan on the short-term prognosis of patients with Non-ST-segment elevation myocardial infarction (NSTEMI) and Killip> II. Methods The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals in the City from 2010 to 2023. A total of 12472 patients with NSTEMI and Killip > II were included. Patients were divided into the levosimendan group and the non-leosimendan group based on whether levosimendan was used during hospitalization. Propensity score matching (PSM) was employed to balance covariates between the two groups. Multivariate Cox regression was used to evaluate the relationship between levosimendan and clinical outcomes. Covariates adjusted in PSM included age, sex, Killip class, early PCI, previous PCI, previous medical conditions (diabetes, hypertension, ischemic stroke, and chronic kidney disease), and medications during hospitalization (aspirin, clopidogrel, indobufen, ticagrelor, statins, cedilanid, recombinant human brain natriuretic peptide [rhBNP], milrinone, dopamine, dobutamine, and angiotensin converting enzyme inhibitor/angiotensin receptor blockers [ACEI/ARB]). The primary endpoint was major cardiovascular and cerebrovascular adverse events (MACCE), defined as the composite endpoint of cardiac death, myocardial infarction, and ischemic stroke within 3 months. Results The levosimendan group comprised 782 patients, while the non-leosimendan group included 11690 patients. After PSM, the covariates were balanced, resulting in 756 well-matched pairs. In PSM patients, the levosimendan group exhibited a significantly lower incidence of MACCE (aHR, 0.573; 95%CI, 0.466–0.704; p < 0.001) and cardiac death (aHR, 0.500; 95%CI, 0.399-0.626; p < 0.001). However, there was no significant difference in the incidence of myocardial infarction and ischemic stroke. Conclusions Levosimendan was associated with a lower incidence of MACCE within 3 months in patients with NSTEMI and Killip> II, mainly driven by lower incidence of cardiac death. However, these findings are based on observational data and require confirmation through adequately powered, randomized, controlled trials.

Elective endovascular reperfusion therapies in intermediate-high risk pulmonary embolism after PERT assesment

Abstract Background The ideal management of patients with intermediate-high risk (IHR) pulmonary embolism (PE) is still unknown. A multidisciplinary approach by Pulmonary Embolism Response Teams (PERT) in combination with the advent of endovascular therapies sounds promising. Purpose Evaluate in-hospital events of elective endovascular reperfussion therapies in selected IHR PE patients after PERT assesment in a single center initial experience. Methods Analysis of consecutive patients with PE admitted from Jan/2017 to Jan/2024. The in-hospital evolution of an elective invasive strategy defined by an institutional PERT (since April/2021) in IHR PE patients was compared against the current standard of care (isolated anticoagulation and reperfusion only after hemodynamic collapse). Patients with limitations of therapeutic efforts due to comorbidities were excluded. Results 361 patients with PE were treated with 76 (21.1%) stratified as IHR. After excluding 14 patients due to limitations of therapeutic efforts (78±9.4 years; 64.3% active cancer), 62 were included for analysis. An elective endovascular treatment was performed in 20 (31.3%) patients; these were younger and with fewer comorbidities. However, they had more tachypnea, greater central distribution of thrombotic burden and signs of right ventricle overload assessed by flattening of the interventricular septum. Baseline characteristics, clinical presentation and management are described in table 1. Within the invasive group, endovascular reperfusion was performed with local thrombolysis (70%), aspiration thrombectomy (15%) or their combination (15%). During hemodynamic evaluation, hidden shock was detected in 42.9% (6/14), with improvements in cardiac index observed after reperfusion therapy (n=8; 2.1 vs. 2.5). Improvement was also observed in pulmonary artery systolic pressure (n=14, 56.9 vs. 37.1mmHg; p<0.001) and right ventricular function (n=15, TAPSE 16 vs. 22mm; p<0.001). Compared with the current standard of care, an elective invasive approach was associated with a shorter hospital stay (6.5 vs. 9 days; p=0.02), less hemodynamic collapse (0% vs. 19.1%; p=0.04), need for mechanical ventilation (0% vs. 19.1%; p=0.04) and in-hospital mortality (0% vs. 21.4%; p=0.04) without differences in the incidence of major bleeding (Fig 1). After multivariate logistic regression analysis, the mortality benefit persisted in favor of an invasive strategy (p=0.014). Conclusions An "elective" invasive strategy in selected patients with IHR PE after PERT assessment was safe and resulted in less major in-hospital cardiovascular events in a single-center initial experience. Although these results should be taken with caution given the limitations of this study (single-center, small observational sample), they are in line with recent reports and are the focus of ongoing large randomized clinical trials.Table 1

Galectin-3 and cancer mortality in patients with suspected or known coronary artery disease: the ANOX study

Abstract Background Galectin-3 is a multifunctional carbohydrate-binding lectin that is involved in inflammation, tissue remodeling, and fibrosis. High circulating levels of galectin-3 are associated with all-cause mortality, cardiovascular (CV) mortality, and/or major adverse CV events in patients with CV diseases such as heart failure and coronary artery disease (CAD). However, the associations of galectin-3 with non-CV mortality and cancer mortality in patients with suspected or known CAD are unknown. Methods Serum galectin-3 levels were measured in 2,418 patients with suspected or known CAD undergoing elective coronary angiography. The outcomes were all-cause death, CV death, non-CV death, cancer death, and other non-CV death. Patients were followed up over a 6-year period. Results During the follow-up, 536 (22.2%) deaths occurred, including 166 (6.9%) CV deaths, 326 (13.5%) non-CV deaths, 128 (5.3%) cancer deaths, 198 (8.2%) other non-CV deaths, and 44 (1.8%) undetermined deaths. After adjustment for potential clinical confounders (i.e., age, sex, body mass index, hypertension, dyslipidemia, diabetes, current smoker, estimated glomerular filtration rate, the Gensini score, previous myocardial infarction, previous stroke, previous heart failure hospitalization, atrial fibrillation, valvular heart disease, malignancies, anemia, antihypertensive drug use, statin use, and aspirin use) and established CV biomarkers (i.e., N-terminal pro-brain natriuretic peptide, high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein), galectin-3 levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.22; 95% confidence interval [CI], 1.13–1.31), CV death (HR, 1.16; 95% CI, 1.02–1.33), non-CV death (HR, 1.27; 95% CI, 1.15–1.40), cancer death (HR, 1.31; 95% CI, 1.07–1.61), and other non-CV death (HR, 1.30; 95% CI, 1.15–1.46). The addition of galectin-3 levels to the model with potential clinical confounders and established CV biomarkers significantly improved the prediction of all-cause death (P<0.001 for continuous net reclassification improvement [NRI], P<0.001 for integrated discrimination improvement [IDI]) and cancer death (P=0.001 for NRI, P=0.005 for IDI), but not that of CV death (P=0.601 for NRI, P= 0.708 for IDI), non-CV death (P=0.060 for NRI, P=0159 for IDI), or other non-CV death (P=0.266 for NRI, P=0.699 for IDI). Conclusions The galectin-3 level independently predicted all-cause mortality and cancer mortality in patients with suspected or known CAD.

Impact of diabetes on vascular endothelial growth factor D and cardiovascular mortality in patients with suspected or known coronary artery disease: the ANOX study

Abstract Background Vascular endothelial growth factor D (VEGF-D) is a secreted glycoprotein that can induce lymphangiogenesis and angiogenesis. We recently demonstrated that serum levels of VEGF-D are independently associated with all-cause mortality in patients with suspected or known coronary artery disease (CAD). However, the impact of diabetes mellitus (DM) on the association between VEGF-D and cardiovascular (CV) mortality in those patients is unclear. Methods Serum VEGF-D levels were measured in 2418 patients with suspected or known CAD undergoing elective coronary angiography. The primary outcome was CV death. The secondary outcomes were all-cause death, major adverse CV events (MACE) defined as a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke, and heart failure (HF) hospitalization. Patients were divided into 2 groups according to the presence (DM, n=1087) or absence (non-DM, n=1331) of DM, and followed up over a 6-year period. Results During the follow-up, 166 (81 DM and 85 non-DM) patients died from CV disease, 536 (284 DM and 252 non-DM) patients died from any cause, 297 (156 DM and 141 non-DM) patients developed MACE, and 268 (131 DM and 137 non-DM) patients developed HF hospitalization. After adjustment for potential clinical confounders and established CV biomarkers (i.e., N-terminal pro-brain natriuretic peptide, high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein), VEGF-D levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.20; 95% confidence interval [CI], 1.08–1.33) and HF hospitalization (HR, 1.23; 95% CI, 1.08–1.40), but not with CV death (HR, 1.18; 95% CI, 0.98–1.43) or MACE (HR, 1.11; 95% CI, 0.96–1.28), in DM patients, while VEGF-D levels were significantly associated with CV death (HR, 1.24; 95% CI, 1.08–1.43) and MACE (HR, 1.16; 95% CI, 1.03–1.32), but not with all-cause death (HR, 1.10; 95% CI, 0.99–1.22) or HF hospitalization (HR, 1.13; 95% CI, 0.99–1.28), in non-DM patients. The addition of VEGF-D levels to the model with potential clinical confounders and established CV biomarkers did not improve the prediction of CV death (P=0.92 for continuous net reclassification improvement [NRI], P= 0.32 for integrated discrimination improvement [IDI]), all-cause death (P=0.098 for NRI, P=0.12 for IDI), MACE (P=0.80 for NRI, P=0.53 for IDI) or HF hospitalization (P=0.96 for NRI, P=0.39 for IDI) in DM patients, whereas the addition of VEGF-D levels significantly improved the prediction of CV death (P=0.002 for NRI, P=0.03 for IDI) and all-cause death (P<0.001 for NRI, P=0.02 for IDI), but not that of MACE (P=0.11 for NRI, P= 0.09 for IDI) or HF hospitalization (P=0.89 for NRI, P=0.83 for IDI), in non-DM patients. Conclusions In patients with suspected or known CAD, the VEGF-D level independently predicted CV mortality in non-DM, but not in DM patients. The association between VEGF-D and CV mortality was attenuated in the presence of DM.

Interactive effects of outdoor fine particulate matter and metabolic, behavioural, and psychosocial risk factors on cardiovascular disease: analysis of the PURE-China cohort study

Abstract Background Long-term PM2.5 exposure has been associated with an elevated risk of cardiovascular disease (CVD) and its associated risk factors.[1–4] There is a paucity of studies investigating the interactive effects of PM2.5 exposure and a comprehensive list of risk factors including metabolic, behavioural, and psychosocial risk factors on CVD risk.[5] Purpose This study aims to examine the interactive effects of PM2.5 exposure and metabolic, behavioural, and psychosocial risk factors on incident CVD. Methods The Prospective Urban Rural Epidemiology (PURE)-China cohort study is a population-based cohort study recruiting participants aged 35–70 years from 115 communities in 12 provinces of China between 2005 and 2009, and followed up until August 31, 2021.[6] Participants’ metabolic, behavioural, and psychosocial risk factor information was recorded. PM2.5 concentrations were extracted from a 1x1 km2 global model.[7,8] For this analysis, we included participants aged 35–70 years at baseline without a history of CVD, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (CVD deaths, myocardial infarction, stroke, and heart failure). Additive interaction was measured by relative excess risk due to interaction (RERI), the proportion of disease attributable to interaction (AP), and the synergy index (SI).[9,10] To comply with the additive interaction method, we classified concentrations of PM2.5 into low and high levels by the median of 3-year average PM2.5 concentration (45.7 μg/m3, IQR: 33.7-74). Cox proportional hazard models were used to assess the associations of metabolic, behavioural, and psychosocial risk factors on incident CVD by PM2.5 concentrations. Results The PURE-China study recruited 47 931 participants, of which 39 329 are eligible for this analysis. During the median follow-up period of 11.9 years (IQR: 9.6-12.6), 1462 and 2155 major CVD events had occurred in the low and high PM2.5 group respectively. There was a synergistic interaction between PM2.5 and the systolic blood pressure (SBP) for CVD: RERI: 0.363, 95% CI: 0.196-0.531; AP: 0.098, 95% CI: 0.081-0.115; SI: 1.155, 95% CI: 1.132-1.177; high LDL cholesterol: RERI: 0.219, 0.003-0.436; AP: 0.135, 0.008-0.263; SI: 1.549, 0.947-2.533. A significant synergistic interaction was also identified between PM2.5 and household air pollution (RERI: 0.457, 0.292-0.622; AP: 0.277, 0.184-0.37; SI: 3.362, 1.409-8.019). Interactions between PM2.5 and low grip strength on CVD were significantly synergistic, but antagonistic between PM2.5 and low physical activity (RERI: -0.248, -0.485--0.012; AP: -0.174, -0.349-0.001; SI: 0.633, 0.412-0.971). Conclusion Addictive interaction was between PM2.5 and SBP, high LDL cholesterol, household air pollution, low grip strength and low physical activity on incident CVD, indicating the benefit of coordinated control strategies for metabolic, physical, and environmental risk factors for the prevention of CVD.

Assessment of a Therapeutic Education Program for Coronary Patients: Quasi-Experimental Study

Abstract Introduction Therapeutic education is a patient-centered, approach aimed at addressing the patient’s needs and resources. It is intended not only to help the patient understand their illness and treatment but also to empower them to become autonomous. So far, in Tunisia, we lack structures for therapeutic education specifically tailored for coronary patients. In this context, we implemented a Therapeutic Education Program (TEP) for coronary patients visiting the cardiology department at Sahloul University Hospital with the aim of assessing the impact of this program in the short, medium (3 months), and long term (12 months). Methods We conducted a quasi-experimental study on TEP for patients with coronary artery disease over one year at Sahloul University Hospital. Patients were divided into two groups, intervention, and control. Outcome measures included major cardiovascular events, improvement in knowledge, and biological indicators, with statistical analysis performed using SPSS in accordance with ethical considerations. Results The study included 129 patients, of whom 38 underwent a therapeutic education program. TEP demonstrated a significant improvement in knowledge about coronary artery disease, with program satisfaction rated ≥8 on a scale of 0 to 10.Our program also showed improvement in biological parameters, particularly lipid profiles, within the educated group before and after 3 months, such as LDL cholesterol levels (2.53 vs 1.88, P < 0.001), and compared to the control group (1.88 vs 2.9, P = 0.001).Moreover, it led to a significant reduction in long-term cardiovascular events compared to the control group (21.1% vs 59.3%, p < 0.001). Conclusions this study underscores the crucial importance of therapeutic education in enhancing the care and quality of life of coronary patients, highlighting its central role in a proactive, personalized approach to medical management. Key messages • The significance of therapeutic education in empowering patients to understand their condition and become self-reliant. • Need for Structured Programs specifically for coronary patients in Tunisia.

Ankle brachial index,a non invasive tool predicts cardiovascular events after acute myocardial infarction:a 3 year follow -up study

Abstract Background / Introduction The ankle-brachial index (ABI) is a non-invasive tool that was initially used for the diagnosis of lower-extremity peripheral artery disease (PAD). It has been proven that ABI is a marker of atherosclerosis in other vascular sites and can therefore be used to predict cardiovascular events regardless the presence or not of PAD symptoms. Purpose This study aims to examine the prognostic value of ABI in the setting of acute myocardial infarction (MI), as up till now there is not enough relevant evidence. Method We followed up 441 patients [79% male;mean age 62 years;67% hypertnesive; 30% with diabetes mellitus (DM); 52% current smokers] who were hospitalized because of MI for a period of three years. All patients underwent baseline estimation of clinical and laboratory parameters during theri hospitalization.The ABI was measured according to established methodology using a certified automated device and abnormal ABI defined as a value ≤ 0.9. The primary endpoint was a composite of all-cause and cardiovascular death, as well as major cardiovascular events including decompensated heart failure, new acute coronary syndrome, cerebrovascular event, malignant arrhythmia, PAD event and new onset renal dysfunction. All events were assessed both in-hospital and within 3 years of follow-up. Results Our study population had a mean ABI of 1.1 (IQR: 1.00 to 1.18). With the use of reduced multivariate regression models ABI was proven to be a prognostic indicator for the in-hospital composite endpoint. Patients with an abnormal ABI had a threefold risk of in-hospital events [HR 2.93, 95% CI: 1.48-5.81, p=0.002]. After conducting multivariate analysis ABI maintained its predictive power of all-cause mortality [HR 2.88, 95% CI: 1.53 – 5.42, p=0.001], regardless of hypertension DM, LDL levels and smoking status of the study population in 3 years follow-up. Conclusion An impaired ABI is associated with greater risk of in-hospital events in patients with acute MI. Moreover, ABI emerges as an independent predictor of long-term all-cause mortality in those patients.The findings of this study suggest that subclinical and clinical PAD are associated with poor outcomes among patients with acute MI; thus, routine ABI tests enhance risk stratification and might carry important prognostic significance in these patients regardless of PAD symptoms.

Semaglutide for the secondary prevention of cardiovascular disease in people with overweight or obesity, but without diabetes: a cost-effectiveness analysis

Abstract Background The recently published trial, SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) [1], was the first study to demonstrate that the glucagon-like peptide 1 receptor agonist, semaglutide, was superior to placebo in reducing the risk of major cardiovascular events in people with existing cardiovascular disease (CVD) and a body mass index of ≥27kg/m² but without diabetes. Despite the promising clinical benefits, the high cost of the medication has raised concerns about its financial viability and accessibility within healthcare systems. Purpose To explore whether use of semaglutide in addition to standard care (background use of lipid lowering, anti-hypertensive and/or anti-platelet therapies) for the secondary prevention of CVD in people with overweight or obesity is cost effective from the Australian healthcare perspective. Methods A Markov model was developed based on the SELECT trial, to evaluate the clinical outcomes and costs of a hypothetical population treated with semaglutide versus placebo over 20 years. With each annual cycle, subjects were at risk of having non-fatal CVD events (MI or stroke) or dying. Treatment efficacy, transition probabilities, and utilities were derived from the SELECT trial and published literature. Costs were obtained from Australian sources. The cost of semaglutide at a dosage of 2.4 mg/week (in line with SELECT) was estimated to be ~A$80 per week or A$4175 per year. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. All outcomes and costs were discounted by 5% per year. Costs are reported in 2023 Australian dollars (A$). Results Over a 20 year time horizon, treatment of 1000 hypothetical subjects with overweight or obesity and existing CVD with semaglutide compared to placebo prevented 126 non-fatal CVD events and 81 deaths, and yielded an additional 0.46 discounted life years and 0.48 discounted QALYs per person. The difference in total discounted costs was A$43,955 per person. This equated to ICERs of A$99,853 per YoLS and A$96,055 per QALY gained. Conclusions Assuming a willingness-to-pay-threshold of A$50,000 per QALY gained, semaglutide would not be considered cost-effective for the secondary prevention of CVD in people with overweight or obesity in Australia at current prices. A price reduction of 52% to less than A$2000 per year would be required for it to be considered a cost-effective treatment strategy in this setting. Given the modest event rates reported in SELECT, cost-effectiveness is likely to improve if use of semaglutide is targeted to higher risk groups. Moreover, SELECT primarily focused on cardiovascular benefits, however data supporting the impact of semaglutide on a number of other weight-related complications are anticipated and will inform a more holistic understanding of its cost effectiveness.

In-hospital initiation of Vericiguat and short-term cardiovascular function improvement in heart failure patients with worsened renal function

Abstract Background and Aims Vericiguat, a novel soluble guanylate cyclase (sGC) stimulator, is approved for treating heart failure (HF) with reduced ejection fraction (HFrEF). This study aims to assess the short-term improvement in cardio-function resulting from in-hospital initiation of Vericiguat among patients with chronic kidney dysfunction (CKD), utilizing real-world data from a single-center experience in western China. Method Data were obtained from the Biobank of our hospital, spanning from January 2023 to December 2023. A total of 213 HF patients with Vericiguat initiation were screened for eligibility. Echocardiography was employed to evaluate cardio-function after 1- and 3-month short-term follow-up in each patient. Statistical analyses were conducted using one-way ANOVA (followed by Geisser-Greenhouse correction and Tukey’s multiple comparison) to assess significance between different timepoints. Results Among the 213 patients randomized in this study, baseline characteristics were compared based on estimated glomerular filtration rate (eGFR) ≤ 30 (worsened renal function group, WRF, n = 20) and >30 mL/min/1.73 m2 (n = 193). No significant differences were observed in age, gender, and other biochemical parameters expect hemoglobin and creatine between the two groups (Table 1). Analysis of cardiac function after 1- and 3-month follow-up revealed a promising increase in left ventricular ejection fraction (EF) (37.2% vs. 43.9%, Mean diff -6.7, 95% CI -12.78 to -0.62, p = 0.03), fractional shortening (FS) (20.9% vs. 25.3%, Mean diff -4.42, 95% CI -8.57 to -0.27, p = 0.04), and a significant decrease in left ventricular end-diastolic dimension (LVEDD) (65.0mm vs. 60.6mm, Mean diff 4.35, 95% CI 0.33 to 8.38, p = 0.03) after 3-month follow-up compared to Vericiguat initiation in WRF patients. However, no significant changes were observed between the beginning and 1-month follow-up in echocardiographic measurements (Figure 1). Conclusion In this real-world single-center study, Vericiguat demonstrated effectiveness in short-term improvement of cardiac function among HF patients with worsened renal function. The long-term efficacy in reducing major cardiovascular events in this subgroup, based on real-world experience, warrants further exploration.

The evolution of endothelial dysfunction according to the length of the implanted stent on the background of nebivolol therapy

Abstract Introduction The development of atherosclerosis is the driving cause for arterial interventions using coronary stents. Long-stent implantation can increase the vascular injury thereby contributing to the progression of endothelial dysfunction (ED) by the degradation and reduction bioavailability of the nitric oxide (NO) - thus increasing the risk of major cardiovascular events. Purpose Evaluation the evolution of endothelial dysfunction biomarker depending on the length of the stent implanted on the background of nebivolol therapy. Methods The study included 100 patients with stable angina pectoris II–III functional class (age 59.72±0.59 years) undergoing PCI with stent implantation who started the treatment with nebivolol 5mg per day tangent to the conventional treatment and were exposed to PCI with stent implantation, depending on the stent’s length they were divided in three groups: I group - 14 patients with implanted stent’s length ≤15 mm, II group - 57 subjects with implanted stent’s length =15-30 mm and the III group -29 cases where the implanted stent’s length was ≥30 mm. In all the groups was appreciated in blood the endothelial dysfunction’s marker - NO. This marker was assessed preprocedural, postprocedural (after 24 hours) and at intervals of one month, 3,6,12 months after coronary angioplasty, the NO level being compared between these groups and the reference pattern consisting of 20 healthy people. Results The circulating level of nitric oxide determined in I group -61,28±6,92 μM/L and in the II group -56.6±3.03 μM/L and the III group52.39±3.35 was compromised at the preprocedural stage versus the reference pattern - 78.67±2.72 μM/L. During the post- PCI period (first 24 hours), the biomarker level’s was reduced in I group -52.35±1.66 μM/ L, II group -53.74±2.77 μM/L and III group - 52.98±2.91 μM/L. After one month after the intervention on the backroung of the treatment with nebivolol, was recorded a gaing of the NO value in I group - 64.97±5.35 μM/L, II group -63.15±3.99 μM /L and the III group-59.38±4.46 μM/L. The NO serum concentration during the period 3 and 6 months continued to increase in all groups vs the reference pattern. At the 12-month period, the NO level remained high in all the studied groups versus the baseline: I group 99.2±1.1 μM / L (p>0.05), II group-97.96±2.2 μM/L (p<0.001) and the III group -97.65±1.9 μM/L (p<0.001). Conclusion The stent’s length = 15-30 mm and ≥30 mm reveals the presence of an expanded atherosclerotic process, the substrate of which is constituted by the endothelial dysfunction, this being confirmed by the low preprocedural level of NO. The stent implantation procedure induced the accentuation of endothelial dysfunction, and the 12-month nebivolol treatment favored the increase of NO serum concentraon in all groups by 24.9% vs the reference pattern and by 73.3% vs baseline.

Predictors of Right vEntricular Failure aftER LVAD implantation: PREFER LVAD study

Abstract Introduction The use of left ventricular assist devices (LVAD) is increasing both as bridge-to-transplantation or destination therapy, considering the lack of heart donors for transplantation in advanced heart failure (AHF) population. Right ventricular post-implantation failure, major bleedings and infective events remain the principal adverse events in LVAD carriers, thus an accurate selection of candidates is needed. Purpose To identify between clinical, laboratory, standard and advanced (Speckle Tracking, STE) echocardiography, and right heart catheterization (RHC) indices, the best predictors of outcome after LVAD implantation. Materials and Methods We screened in our third-level center 30 patients with AHF, followed up from May 2013 to February 2022, for the assessment of LVAD implantation suitability. They all underwent a complete cardiological history collection, electrocardiography, standard and STE left ventricular (LV) and left atrial (LA) size and function assessment. Regarding the right ventricle, SIENA score parameters, including RV sphericity index, RV free wall longitudinal strain (LS), right ventricular fractional area change (RVFAC), and 3D ejection fraction were used for exclude RV disfunction. RHC was performed on the same day of echocardiography. Follow-up was conducted at 1, 3, 6, 9 and 12 months repeating all the assessments, for the occurrence of RV failure, all-causes mortality, hemorrhagic events and re-hospitalization for heart failure. With a univariate and multivariate statistical analysis, we went to test among all the parameters the possible predictors of outcome. Results The final population consists of 29 patients (93% male, mean age of 63±11 years), in NYHA class III or IV and a severe reduction of left ventricular (LV) ejection fraction (EF), in whom arterial hypertension and smoking, present or previous, were present in 58% and 65% of cases, respectively. The population was divided into two groups according to the occurrence of at least one cardiovascular event. 11 major events were recorded: including 4 hemorrhagic events, 3 all-causes mortality and 4 hospital admission for HF. No RV failure occurred in the first 12 months of follow-up. No differences were identified between the two groups in terms of echocardiographic indices and RV function, including RVFAC or RV-FWLS. At univariate analysis (see Table 1), the only parameter able to predict major CV events was central venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) ratio, obtained by RHC, an index of balance between right and left heart filling pressure. Conclusions A careful application of SIENA score indices before LVAD implantation can significantly reduce the incidence of post-operative RV failure, as in our small population. Our results also confirmed the paramount role of RHC in the diagnostic work up of AHF.

Comparison of risk factors and mortality in veterans with HIV and those without HIV suffering first major acute cardiovascular events.

Previous studies have demonstrated that people with HIV have an increased atherosclerotic plaque vulnerability, making them more susceptible to severe cardiovascular complications. This study aimed to examine the clinical characteristics of people with HIV in comparison to people without HIV admitted to Veterans Health Administration (VHA) with their first major acute cardiovascular events (MACE) and compare their total mortality. We used national VHA data to extract data of those admitted to VHA hospitals with MACE defined as acute myocardial infarction (AMI), acute cerebrovascular accident (CVA) or cardiac arrest during the fiscal years 2003-2021. The hazard ratio (HR) of mortality for people with HIV versus people without HIV was estimated using Cox proportional hazard regression analysis. Out of 280 311 veterans, 2510 people with HIV and 277 801 people without HIV had their first MACE during the study period. People with HIV were younger, more likely to be African American, had a lower prevalence of diabetes mellitus and hypertension, similar total cholesterol levels and a lower mean 10-year cardiovascular risk score (25.4 in people with HIV vs. 28.7 in people without HIV). Among MACE components, people with HIV had a higher proportion of CVA (27% vs. 21.3%, p < 0.001) and cardiac arrest (13.0% vs. 8.4%, p < 0.001) but a lower incidence of AMI (62.4% vs. 72.5%, p < 0.001) than people without HIV. Additionally, people with HIV had a higher risk of total mortality (adjusted HR: 2.05, 95% confidence interval: 1.90-2.22) compared with people without HIV. People with HIV experience MACE at younger ages despite lower cardiovascular risks and similar baseline cholesterol and blood pressure levels. People with HIV had higher mortality and a higher risk of having ventricular fibrillation arrest and stroke as their first MACE.

The Impact of Blood Pressure Rhythm and Perioperative Blood Pressure Variability on Short-Term Prognosis in Patients with Type A Aortic Dissection.

Aims/Background Previous studies have indicated a strong correlation between disturbances in blood pressure (BP) circadian rhythm and major cardiovascular adverse events. Similarly, blood pressure variability (BPV) has been closely linked to cerebral small vessel disease and leukoaraiosis. This study aims to investigate the relationship between BP rhythm and BPV with the short-term prognosis of patients with Type A aortic dissection, offering insights for targeted perioperative nursing interventions and improving patient outcomes. Methods This retrospective study included patients undergoing surgical treatment for Type A aortic dissection at Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) from June 2022 to March 2024. The study followed patients from the completion of surgery to 30 days postoperatively, with all-cause mortality within 30 days as the endpoint representing poor short-term prognosis. Clinical data were compared along with: types of BP rhythm; BPV parameters including the mean 24-hour systolic BP (24hSBP), 24-hour diastolic BP (24hDBP), and pulse pressure; and the coefficient of variability (CV) for 24hSBP, 24hDBP, and pulse pressure. Multivariate logistic regression analysis was utilized to identify risk factors for poor short-term outcomes in these patients, and receiver operating characteristic (ROC) curves were plotted to assess the predictive value of BP rhythm types and BPV indicators. Results The study ultimately included 115 participants, with 31 deaths occurring within 30 days post-surgery, resulting in a postoperative mortality rate of 26.96%. The multivariate logistic regression analysis revealed that white blood cell count, neutrophil count, non-dipping BP rhythm, pulse pressure, and the CV for 24hSBP, 24hDBP, and pulse pressure, were significant risk factors for poor short-term prognosis (p < 0.05). The ROC curve analysis demonstrated that non-dipping BP rhythm, pulse pressure, 24hSBP-CV, 24hDBP-CV, and pulse pressure-CV had areas under the curve (AUC) of 0.685, 0.749, 0.751, 0.773, and 0.763, respectively. The combination of these indicators yielded the highest AUC at 0.918. Conclusion A combination of BP rhythm and BPV indicators provides significant predictive value for poor short-term outcomes in patients with Type A aortic dissection. Clinicians and nursing staff can use these features to formulate targeted preventive measures.

Systematic Review: Comparative Efficacy and Safety of Losartan vs. Candesartan for the Treatment of Hypertension

Hypertension is one of the most significant modifiable risk factors for cardiovascular disease (CVD) and remains a leading cause of morbidity and mortality globally. Effective management of hypertension is essential for preventing comp lications such as stroke, myocardial infarction, and heart failure. Angiotensin II receptor blockers (ARBs) like losartan and candesartan are well-established therapeutic options for blood pressure (BP) control and are widely prescribed due to their favorable side-effect profiles and organ-protective properties. Despite being members of the same drug class, these ARBs differ in their pharmacokinetics, receptor binding affinity, and clinical efficacy. This systematic review aims to provide a detailed comparison of the efficacy and safety of losartan versus candesartan in managing hypertension. We conducted a comprehensive search of the PubMed, Embase, and Cochrane databases, retrieving studies published from 2000 to 2024 that compared the two ARBs directly in hypertensive populations. A total of 25 randomized controlled trials (RCTs) and observational studies, comprising more than 12,000 participants, were included in the analysis. The primary outcomes evaluated were the reduction in systolic and diastolic blood pressure, cardiovascular event prevention, and adverse event profiles. The results suggest that both losartan and candesartan effectively lower BP, but candesartan consistently demonstrated greater reductions in both systolic and diastolic BP compared to losartan. Candesartan also appeared to have superior cardiovascular outcomes, with a lower incidence of major cardiovascular events such as stroke, myocardial infarction, and heart failure hospitalizations. The safety profiles of both drugs were comparable, though losartan was associated with a slightly higher incidence of cough and discontinuation due to adverse events. Overall, candesartan may offer a slight clinical advantage over losartan, particularly in patients requiring more potent or sustained BP control. However, both drugs remain valuable options in the management of hypertension. Further long-term studies are recommended to confirm these findings and to investigate the potential benefits of each drug in specific patient subgroups.

Drug-gene interactions in older patients with coronary artery disease

BackgroundOlder patients with coronary artery disease (CAD) are particularly vulnerable to the efficacy and adverse drug reactions, and may therefore particularly benefit from personalized medication. Drug–gene interactions (DGIs) occur when an individual’s genotype affects the pharmacokinetics and/or pharmacodynamics of a victim drug.ObjectivesThis study aimed to investigate the impact of cardiovascular-related DGIs on the clinical efficacy and safety outcomes in older patients with CAD.MethodsHospitalized older patients (≥ 65 years old) with CAD were consecutively recruited from August 2018 to May 2022. Eligible patients were genotyped for the actionable pharmacogenetic variants of CYP2C9, CYP2C19, CYP2D6, CYP3A5, and SLCO1B1, which had clinical annotations or implementation guidelines for cardiovascular drugs. Allele frequencies and DGIs were determined in the cohort for the 5 actionable PGx genes and the prescribed cardiovascular drugs. All patients were followed up for at least 1 year. The influence of DGIs on the cardiovascular drug-related efficacy outcomes (all-cause mortality and/or major cardiovascular events, MACEs) and drug response phenotypes of “drug-stop” and “dose-decrease” were evaluated.ResultsA total of 1,017 eligible older patients with CAD were included, among whom 63.2% were male, with an average age of 80.8 years old, and 87.6% were administrated with polypharmacy (≥ 5 medications). After genotyping, we found that 96.0% of the older patients with CAD patients had at least one allele of the 5 pharmacogenes associated with a therapeutic change, indicating a need for a therapeutic change in a mean of 1.32 drugs of the 19 cardiovascular-related drugs. We also identified that 79.5% of the patients had at least one DGI (range 0–6). The median follow-up interval was 39 months. Independent of age, negative association could be found between the number of DGIs and all-cause mortality (adjusted HR: 0.84, 95% CI: 0.73–0.96, P = 0.008), and MACEs (adjusted HR: 0.84, 95% CI: 0.72–0.98, P = 0.023), but positive association could be found between the number of DGIs and drug response phenotypes (adjusted OR: 1.24, 95% CI: 1.05–1.45, P = 0.011) in the elderly patients with CAD.ConclusionsThe association between cardiovascular DGIs and the clinical outcomes emphasized the necessity for the integration of genetic and clinical data to enhance the optimization of cardiovascular polypharmacy in older patients with CAD. The causal relationship between DGIs and the clinical outcomes should be established in the large scale prospectively designed cohort study.