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Keywords = major adverse cardiovascular endpoint

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19 pages, 1025 KiB  
Article
Prediction of All-Cause Mortality and Cardiovascular Outcomes Using Ambulatory Arterial Stiffness and Ankle-Brachial Indices in Patients with Acute Myocardial Infarction: A Prospective Cohort Study
by Areti Koumelli, Konstantinos Konstantinou, Athanasios Sakalidis, Konstantinos Pappelis, Emmanouil Mantzouranis, Christina Chrysohoou, Petros I. Nihoyannopoulos, Dimitrios Tousoulis and Konstantinos Tsioufis
J. Clin. Med. 2025, 14(13), 4627; https://doi.org/10.3390/jcm14134627 - 30 Jun 2025
Viewed by 391
Abstract
Background/Objectives: The ankle-brachial index (ABI) is a non-invasive diagnostic tool for peripheral artery disease (PAD) and a marker of systemic atherosclerosis, predictive of cardiovascular (CV) events. The ambulatory arterial stiffness index (AASI), derived from 24-h blood pressure monitoring, also predicts CV morbidity [...] Read more.
Background/Objectives: The ankle-brachial index (ABI) is a non-invasive diagnostic tool for peripheral artery disease (PAD) and a marker of systemic atherosclerosis, predictive of cardiovascular (CV) events. The ambulatory arterial stiffness index (AASI), derived from 24-h blood pressure monitoring, also predicts CV morbidity and mortality, particularly stroke. However, their combined prognostic utility in acute myocardial infarction (AMI) remains underexplored. This study aimed to assess the predictive value of ABI and AASI in patients with AMI. Methods: We conducted a single-center observational cohort study including 441 consecutive patients with AMI (79% male; mean age 62 years). ABI was measured using an automated device, with ≤0.9 defined as abnormal. AASI was calculated from 24-h blood pressure recordings. The primary endpoint was a composite of all-cause and CV death and major CV events, assessed in-hospital and over a 3-year follow-up. Results: Median ABI was 1.10 (IQR 1.00–1.18); 10.4% had abnormal ABI. Abnormal ABI was associated with a threefold higher risk of in-hospital adverse events (OR 2.93, 95% CI: 1.48–5.81, p = 0.002). In Cox regression, abnormal ABI predicted long-term all-cause mortality (HR 2.88, 95% CI: 1.53–5.42, p = 0.001), independent of traditional risk factors. Each 0.1 increase in AASI was linked to a 21% higher risk of the composite outcome (p = 0.001) and 25% increased risk of recurrent AMI or urgent revascularization (p = 0.001). Conclusions: In this prospective cohort of patients with AMI, ABI and AASI were associated with adverse outcomes, suggesting their potential role in risk stratification. These exploratory findings require validation in larger, multicenter cohorts to assess their incremental prognostic value and generalizability. Full article
(This article belongs to the Section Cardiology)
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16 pages, 388 KiB  
Article
Interferon Gamma and Tumor Necrosis Factor Alpha Are Inflammatory Biomarkers for Major Adverse Cardiovascular Events in Patients with Peripheral Artery Disease
by Ben Li, Eva Lindner, Raghad Abuhalimeh, Farah Shaikh, Houssam Younes, Batool Abuhalimeh, Abdelrahman Zamzam, Rawand Abdin and Mohammad Qadura
Biomedicines 2025, 13(7), 1586; https://doi.org/10.3390/biomedicines13071586 - 29 Jun 2025
Viewed by 556
Abstract
Background/Objectives: Major adverse cardiovascular events (MACE)—including heart attacks and strokes—are the leading cause of death in patients with peripheral artery disease (PAD), yet biomarker research for MACE prediction in PAD patients remains limited. Inflammatory proteins play a key role in the progression of [...] Read more.
Background/Objectives: Major adverse cardiovascular events (MACE)—including heart attacks and strokes—are the leading cause of death in patients with peripheral artery disease (PAD), yet biomarker research for MACE prediction in PAD patients remains limited. Inflammatory proteins play a key role in the progression of atherosclerosis and may serve as useful prognostic indicators for systemic cardiovascular risk in PAD. The objective of this study was to evaluate a broad panel of circulating inflammatory proteins to identify those independently associated with 2-year MACE in patients with PAD. Methods: We conducted a prospective cohort study involving 465 patients with PAD. Plasma concentrations of 15 inflammatory proteins were measured at baseline using validated immunoassays. Patients were followed over a two-year period for the development of MACE, defined as a composite endpoint of myocardial infarction, stroke, or mortality. Protein levels were compared between patients with and without MACE using the Mann–Whitney U test. Cox proportional hazards regression was used to determine the independent association of each protein with MACE after adjusting for baseline demographic and clinical variables, including existing coronary and cerebrovascular disease. To validate the findings, a random forest machine learning model was developed to assess the relative importance of each protein for predicting 2-year MACE. Results: The mean age of the cohort was 71 years (SD 10), and 145 participants (31.1%) were female. Over the two-year follow-up, 84 patients (18.1%) experienced MACE. Six proteins were significantly elevated in PAD patients who developed MACE: interferon gamma (IFN-γ; 42.55 [SD 15.11] vs. 33.85 [SD 12.46] pg/mL, p < 0.001), tumor necrosis factor alpha (TNF-α; 9.00 [SD 5.00] vs. 4.65 [SD 4.29] pg/mL, p < 0.001), chemokine (C-X-C motif) ligand 9 (CXCL9; 75.99 [SD 65.14] vs. 5.38 [SD 64.18] pg/mL, p = 0.002), macrophage inflammatory protein-1 beta (MIP-1β; 20.88 [SD 18.10] vs. 15.67 [SD 16.93] pg/mL, p = 0.009), MIP-1δ (25.29 [SD 4.22] vs. 17.98 [SD 4.01] pg/mL, p = 0.026), and interleukin-6 (IL-6; 12.50 [SD 40.00] vs. 6.72 [SD 38.98] pg/mL, p = 0.035). After adjusting for all baseline covariates, only two proteins—TNF-α (adjusted HR 1.66, 95% CI 1.28–2.33, p = 0.001) and IFN-γ (adjusted HR 1.25, 95% CI 1.12–2.29, p = 0.033)—remained significantly and independently associated with 2-year MACE. These findings were corroborated by the random forest model, where TNF-α and IFN-γ received the highest importance scores for predicting 2-year MACE: (TNF-α: 0.15 [95% CI 0.13–0.18], p = 0.002; IFN-γ: 0.19 [95% CI 0.17–0.21], p = 0.001). Conclusions: From a panel of 15 proteins, TNF-α and IFN-γ emerged as inflammatory biomarkers associated with 2-year MACE in PAD patients. Their measurement may aid in cardiovascular risk stratification, helping to identify high-risk individuals who could benefit from early multidisciplinary referrals to cardiology, neurology, and/or vascular medicine specialists to provide intensified medical therapy. Incorporating these biomarkers into PAD management may improve systemic cardiovascular outcomes through more personalized and targeted treatment approaches. Full article
(This article belongs to the Special Issue Advances in Biomarker Discovery for Cardiovascular Disease)
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14 pages, 398 KiB  
Article
Efficacy and Safety of Low-Dose Rivaroxaban in High-Ischemic-Risk Patients with Chronic Coronary Syndrome: Rationale and Design of the DUTCH CCS Registry
by Abi Selvarajah, Dirk J. van der Heijden, Wouter S. Remkes, Jurriën M. ten Berg, Michael Magro, Clemens von Birgelen, Robert K. Riezebos, Ron Pisters, Martin E. W. Hemels, Saman Rasoul, Arnoud W. J. van ‘t Hof, Samer Somi, Jawed Polad, Pieter Hoogslag and Renicus S. Hermanides
J. Clin. Med. 2025, 14(13), 4401; https://doi.org/10.3390/jcm14134401 - 20 Jun 2025
Viewed by 408
Abstract
Background/Objectives: Despite progress in secondary prevention, people with chronic coronary syndrome (CCS) still face a residual risk of ischemic events. Antithrombotic therapy reduces this risk and helps stabilize chronic cardiovascular disease. Studies have shown that combining low-dose rivaroxaban with aspirin—an approach called [...] Read more.
Background/Objectives: Despite progress in secondary prevention, people with chronic coronary syndrome (CCS) still face a residual risk of ischemic events. Antithrombotic therapy reduces this risk and helps stabilize chronic cardiovascular disease. Studies have shown that combining low-dose rivaroxaban with aspirin—an approach called dual-pathway inhibition (DPI)—can lower this risk and reduce major adverse cardiovascular events (MACEs). However, researchers have not yet gathered enough real-world data to confirm the efficacy and safety of this strategy. The DUTCH CCS registry aims to collect real-world data on how effective and safe low-dose rivaroxaban combined with aspirin is for patients with CCS in The Netherlands. The study aims to provide insights into the outcomes, benefits, and risks of DPI in a real-world setting, beyond the scope of controlled clinical trials. Methods: The DUTCH CCS registry operates as a national, multicenter, prospective observational study. It enrolls 1000 patients with CCS who receive rivaroxaban (2.5 mg twice daily) and aspirin (80 mg or 100 mg once daily). The study targets individuals at high ischemic risk due to coronary artery disease (CAD) and follows a single-arm design. Researchers will measure the primary efficacy endpoint by tracking MACEs, clinically driven coronary, peripheral, or carotid revascularization, and stent thrombosis over one year. They will assess the primary safety endpoint by recording major bleeding events at one year. The team will collect data at both 3-month and 1-year follow-ups. Conclusions: As an observational study, this registry is not designed to establish causality. However, it seeks to improve our understanding of how DPI performs in real-world secondary prevention for CCS patients. The results may help update treatment guidelines and inform clinical decisions in everyday practice. Full article
(This article belongs to the Section Cardiovascular Medicine)
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11 pages, 954 KiB  
Article
Serum NT-ProBNP/Chloride Ratio Predicts Adverse Cardiovascular Outcomes in Patients with Acute Heart Failure
by Victor José Leal-Alcántara, Eder González-Macedo, Ana Cristina Maldonado-May, Alberto Santiago-Hernández, Eder Jonathan Amaro-Palomo, Sarai Hernandez-Pastrana, Anna Elisa Adib-Gracia, Rodrigo Gopar-Nieto, Daniel Sierra-Lara Martínez, José Luis Briseño-De la Cruz, Héctor González-Pacheco, Alexandra Arias-Mendoza and Diego Araiza-Garaygordobil
Biomedicines 2025, 13(6), 1493; https://doi.org/10.3390/biomedicines13061493 - 18 Jun 2025
Viewed by 493
Abstract
Background: Heart failure (HF) is a public health issue. It represents the second most common cause of hospitalization and the leading cause in individuals over 60 years old. Tools that predict adverse outcomes in patients with HF are needed. Objective: This study [...] Read more.
Background: Heart failure (HF) is a public health issue. It represents the second most common cause of hospitalization and the leading cause in individuals over 60 years old. Tools that predict adverse outcomes in patients with HF are needed. Objective: This study analyzed the prognostic role of the serum NT-proBNP/chloride ratio as a predictor of major cardiovascular events in patients with acute decompensated HF. Methods: Patients with a confirmed diagnosis of acute decompensated heart failure were retrospectively enrolled in the study; admission NT-proBNP/chloride ratio was used to stratify patients above or below the median (>/<83). The primary composite endpoint consisted of cardiovascular mortality, decompensated HF readmission, and unplanned emergency department visits. Results: A total of 197 individuals were included, of whom 100 (50.7%) were classified above and 97 (49.2%) below the median. Patients showing a high ratio had a lower LVEF (31 vs. 39%), a higher proportion of previous MI (30 vs. 15%), a lower diastolic blood pressure (73 vs. 80 mmHg), and higher BUN (38 vs. 23 mg/dL) and creatinine (1.6 vs. 1.1 mg/dL). After a follow-up period of 92 ± 3 days, 46 patients (23%) presented the primary endpoint; those with a high NT-proBNP/chloride ratio showed an increased risk (HR 3.18, 95% CI 1.55–6.52, p = 0.0015) of the primary endpoint. After multivariate analysis, only serum NT-proBNP/chloride ratio (p = 0.02) and diastolic pressure (0.037) remained significant. The area under the ROC curve for the NT-proBNP/chloride ratio for predicting the primary composite endpoint was significantly superior when compared with AUC for NT-proBNP or chloride alone. Conclusions: The serum NT-proBNP/chloride ratio is a novel, easy to use predictor of short- and medium-term cardiovascular events in patients with acute decompensated HF. Full article
(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches)
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11 pages, 568 KiB  
Article
Does Green Brazilian Propolis Extract Improve Functional Capacity in Symptomatic Chronic Coronary Disease?—A Pilot Randomized Trial
by Clara Salles Figueiredo, Luiz Carlos Santana Passos, Caio Rebouças Fonseca Cafezeiro, Rodrigo Morel Vieira de Melo, Tainá Teixeira Viana, Eduardo Jorge Gomes de Oliveira, Andresa Aparecida Berretta and Marcelo Augusto Duarte Silveira
Pharmaceuticals 2025, 18(6), 827; https://doi.org/10.3390/ph18060827 - 31 May 2025
Viewed by 780
Abstract
Background: Inflammation plays a critical role in the progression of coronary heart disease (CHD). Low-dose colchicine has shown promise in reducing cardiovascular events, and green Brazilian propolis extract (EPP-AF® (standardized Brazilian green propolis extract) was provided by Apis Flora Indl. Coml. Ltda, Ribeirão [...] Read more.
Background: Inflammation plays a critical role in the progression of coronary heart disease (CHD). Low-dose colchicine has shown promise in reducing cardiovascular events, and green Brazilian propolis extract (EPP-AF® (standardized Brazilian green propolis extract) was provided by Apis Flora Indl. Coml. Ltda, Ribeirão Preto, SP, Brazil), known for its anti-inflammatory properties, may offer additional therapeutic benefits. This pilot study aimed to evaluate whether six weeks of EPP-AF® supplementation improves functional capacity assessed by treadmill exercise testing. Methods: This was a randomized, double-blind, placebo-controlled pilot study conducted at a coronary disease clinic in Brazil. Patients aged ≥ 18 years with stable CHD receiving optimized medical therapy were randomized in a 2:1 ratio to receive either 200 mg of EPP-AF® or placebo twice daily for six weeks. The primary outcome was the change in treadmill exercise duration (in seconds). Secondary outcomes included total exercise time, functional capacity (measured in metabolic equivalents of task [METs]), high-sensitivity C-reactive protein (hs-CRP) levels, the Seattle Angina Questionnaire (SAQ), and the Canadian Cardiovascular Society (CCS) angina classification. Statistical analysis was performed on an intention-to-treat basis. Results: A total of 59 patients were randomized, with a median follow-up of 6.5 weeks. There was no significant difference in the primary endpoint between groups: the median change in treadmill test time was 39 s in the EPP-AF® group versus 30 s in the placebo group (p = 0.83). No improvements were observed in METs, hs-CRP levels, SAQ scores, or CCS class in the EPP-AF® group. No major adverse cardiovascular events occurred during the study. Conclusions: EPP-AF® did not improve functional capacity, inflammatory markers, or angina symptoms in patients with stable CHD compared to placebo. Full article
(This article belongs to the Special Issue Pharmacologically Active Compounds from Plants)
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13 pages, 6215 KiB  
Systematic Review
Peri-Procedural Continuation Versus Interruption of Anticoagulation for Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-Analysis
by Jacinthe Khater, Marco Frazzetto, Filippo Luca Gurgoglione, Jasim Hasan, Davide Donelli, Guilherme Attizzani and Bernardo Cortese
J. Clin. Med. 2025, 14(10), 3563; https://doi.org/10.3390/jcm14103563 - 20 May 2025
Viewed by 453
Abstract
Background/Objectives: Oral anticoagulation therapy (OAC) is crucial for reducing the risk of ischemic complications in patients with atrial fibrillation (AF). However, OAC also increases the risk of major bleeding events. The optimal management of OAC in patients with AF undergoing transaortic valve [...] Read more.
Background/Objectives: Oral anticoagulation therapy (OAC) is crucial for reducing the risk of ischemic complications in patients with atrial fibrillation (AF). However, OAC also increases the risk of major bleeding events. The optimal management of OAC in patients with AF undergoing transaortic valve implantation (TAVI) is unclear. This study aimed to compare the efficacy and safety of OAC interruption vs. continuation in patients with AF scheduled for TAVI. Methods: PubMed, EMBASE, and Cochrane were searched to include all pertinent randomized and observational studies. The primary endpoint was the occurrence of net adverse clinical events (NACE), a composite of all-cause death, major vascular complications, and major bleeding at 30-day follow-up. Secondary endpoints included all-cause death, cardiovascular death, major vascular complications, major bleeding, any bleeding, stroke, non-fatal myocardial infarction, and the need for red-packed blood transfusion. Results: A total of three studies and 2773 patients were included in the analysis (1314 were allocated to continuation of OAC therapy and 1459 to interruption of OAC therapy during TAVI). The two study groups experienced a similar rate of NACE (OR = 0.89 [95% CI 0.61 to 1.31], I2 = 77%, p = 0.56) compared to the OAC-interruption group. No significant differences were observed in the rate of all-cause death (p = 0.21), cardiovascular death (p = 0.35), major vascular complications (p = 0.84), major bleeding events (p = 0.47), total bleeding events (p = 0.62), or non-fatal MI (p = 0.55). Interestingly, the OAC-continuation group experienced a lower occurrence of stroke (OR = 0.62 [95% CI 0.39 to 0.97], I2 = 0%, p = 0.04) and the need for red packed blood cells (OR = 0.66 [95% CI 0.50 to 0.86], I2 = 20%, p < 0.01) compared to the OAC-interruption group. Conclusions: In patients with AF undergoing TAVI, there was no significant difference between interruption and continuation of OAC in terms of NACE, composite of all-cause death, major vascular complications, or major bleeding at 30-day follow-up. Of interest, the OAC-continuation group patients experienced lower rates of stroke and the need for blood transfusion. Full article
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19 pages, 2153 KiB  
Article
Relationship Between Level of Trimethylamine Oxide and the Risk of Recurrent Cardiovascular Events in Patients with Acute Myocardial Infarction
by Wenjun Ji, Bin Zhang, Jiahui Liu, Kaiyin Li, Jia Jia, Fangfang Fan, Jie Jiang, Xingang Wang and Yan Zhang
Nutrients 2025, 17(10), 1664; https://doi.org/10.3390/nu17101664 - 14 May 2025
Cited by 1 | Viewed by 545
Abstract
Background: This study investigated the value of trimethylamine oxide (TMAO) and its precursors in secondary prevention for patients with acute myocardial infarction (AMI). Methods: We retrospectively enrolled patients diagnosed with AMI. The associations of TMAO and its precursors with endpoint events were estimated [...] Read more.
Background: This study investigated the value of trimethylamine oxide (TMAO) and its precursors in secondary prevention for patients with acute myocardial infarction (AMI). Methods: We retrospectively enrolled patients diagnosed with AMI. The associations of TMAO and its precursors with endpoint events were estimated by Cox proportional hazards models. Results: During a median follow-up of 6.4 years, 319 (32.0%) major adverse cardiovascular event (MACE) occurred in the 996 patients enrolled. After adjusting for traditional risk factors, the risk of MACE, cardiac death, and recurrent MI increased by 28% (HR 1.28, 95% CI 1.10–1.49), 44% (HR 1.44, 95% CI 1.12–1.84), and 27% (HR 1.27, 95% CI 1.04–1.55), respectively, per one increment in ln-transformed TMAO. After adjustment for the levels of its precursors, the relationship between TMAO and MACE was still significant. Choline was associated with MACEs, all-cause mortality, cardiac death, and risk of recurrent MI after adjusting for the levels of the remaining metabolites, in addition to traditional risk factors. The overall ability to predict all-cause mortality was better for the choline model than for the TMAO model (continuous NRI 0.185, p = 0.007; IDI 0.030, p = 0.020). Mediation effect analysis showed that the mediating effect of TMAO on choline and the risk of all-cause mortality was 11.39% (95% CI 0.0209–0.2200, p = 0.016), suggesting the existence of a choline activity pathway that is independent of the TMAO pathway. Conclusions: TMAO and choline were associated with an increased risk of MACE in patients with AMI, and choline had better predictive power. Full article
(This article belongs to the Section Clinical Nutrition)
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16 pages, 3211 KiB  
Article
Evaluation of Mortality and Hospitalization Due to Decompensated Heart Failure and Appropriate Shocks in Reduced Ejection Fraction in Patients with an Implantable Cardioverter–Defibrillator According to a Novel Tissue Doppler Echocardiographic Method
by Gökhun Akkan, Tuncay Kiris, Fatma Esin and Mustafa Karaca
J. Clin. Med. 2025, 14(9), 3226; https://doi.org/10.3390/jcm14093226 - 6 May 2025
Viewed by 537
Abstract
Background/Objectives: Heart failure is a very common disease, and its incidence is increasing. Echocardiography is a non-invasive tool frequently used in the diagnosis and risk stratification of heart failure. In our study, we aimed to evaluate the risk of all-cause mortality, hospitalization due [...] Read more.
Background/Objectives: Heart failure is a very common disease, and its incidence is increasing. Echocardiography is a non-invasive tool frequently used in the diagnosis and risk stratification of heart failure. In our study, we aimed to evaluate the risk of all-cause mortality, hospitalization due to decompensated heart failure, and appropriate shocks in reduced ejection fraction patients (HFrEF) with an implantable cardioverter–defibrillator (ICD) according to a novel tissue Doppler echocardiographic parameter that reflects pulmonary capillary wedge pressure. Methods: A total of 320 HFrEF patients with ICD were included in the study between 1 February 2021 and 30 June 2023, from the cardiology outpatient clinic and cardiology ward. Using tissue Doppler, the peak systolic velocity (ST) at the free wall side of the tricuspid annulus and the peak systolic velocity (SM) at the lateral side of the mitral annulus were measured, and the ratio of ST to SM (ST/SM) was calculated. The inferior vena cava diameter (IVCDi) was measured during inspiration. These two values were multiplied to form the formula IVCDi × (ST/SM). Based on the IVCDi × (ST/SM) value, patients were divided into two groups: those with high values (>17, n = 144) and those with low values (≤17, n = 176). The primary endpoint of our study was all-cause mortality, and the secondary endpoint was major adverse cardiovascular events (MACE), including appropriate shocks, hospital admission due to acute heart failure decompensation, and mortality. Results: Long-term mortality was higher in the high IVCDi × (ST/SM) group compared to the low-value group (44% vs. 15%, p < 0.001). The MACE frequency was also higher in patients with high IVCDi × (ST/SM) values (71% vs. 30%, p < 0.001). In multivariable analysis, IVCDi × (ST/SM) was an independent predictor of both mortality (HR: 1.027, 95%CI: 1.009–1.046, p = 0.003), and MACE (HR: 1.018, 95%CI: 1.004–1.032, p = 0.013). Conclusions: We demonstrated that the IVCDi × ST/SM value, a novel tissue Doppler echocardiographic parameter, is an independent predictor of both long-term mortality and major adverse cardiac events (MACE) in HFrEF patients with ICD. This parameter may be valuable in identifying high-risk patients and optimizing their treatment management. Full article
(This article belongs to the Section Cardiology)
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15 pages, 891 KiB  
Article
The Association Between Peripheral Arterial Disease and Long-Term Bleeding Events in Patients with Acute Myocardial Infarction
by Soichiro Ban, Kenichi Sakakura, Hiroyuki Jinnouchi, Yousuke Taniguchi, Kei Yamamoto, Takunori Tsukui, Masashi Hatori, Taku Kasahara, Shun Ishibashi, Yusuke Watanabe, Masaru Seguchi and Hideo Fujita
J. Clin. Med. 2025, 14(9), 3183; https://doi.org/10.3390/jcm14093183 - 4 May 2025
Viewed by 497
Abstract
Background: Peripheral arterial disease (PAD) is associated with cardiovascular events in patients with acute myocardial infarction (AMI). However, there are limited reports regarding the association between PAD and bleeding events. In this study, we aimed to evaluate whether PAD is independently associated [...] Read more.
Background: Peripheral arterial disease (PAD) is associated with cardiovascular events in patients with acute myocardial infarction (AMI). However, there are limited reports regarding the association between PAD and bleeding events. In this study, we aimed to evaluate whether PAD is independently associated with an increased risk of major bleeding events, in addition to major adverse cardiovascular events (MACEs), in patients with AMI undergoing percutaneous coronary intervention (PCI). Methods: We included 1391 patients with AMI who underwent PCI and divided them into the PAD group (n = 210) and the non-PAD group (n = 1181). The primary endpoint was total bleeding events, defined as Bleeding Academic Research Consortium type 3/5. The secondary endpoint was MACE, defined as the composite of all-cause death, non-fatal myocardial infarction, and hospitalization for heart failure. Results: The median follow-up duration was 653 days. Total bleeding events were more frequently observed in the PAD group than in the non-PAD group (24.8% vs. 11.3%, p < 0.001). The multivariate Cox hazard analysis confirmed that PAD was significantly associated with total bleeding events (HR 1.509; 95% CI 1.056–2.156, p = 0.024) as well as MACEs (HR 2.152; 95% CI 1.510–3.066, p < 0.001) after controlling for confounding factors. Conclusions: PAD was independently associated with a higher risk of major bleeding and cardiovascular events in patients with AMI undergoing PCI. These findings suggest that PAD should be recognized as a critical factor in risk stratification for AMI and may affect individualized bleeding risk management strategies in patients with AMI. Full article
(This article belongs to the Section Cardiovascular Medicine)
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14 pages, 1605 KiB  
Article
Abnormal Plasma/Serum Magnesium, Copper, and Zinc Concentrations Associate with the Future Development of Cardiovascular Diseases
by Boyang Lin, Robin Alexander, Remi Fritzen, Sarah Mills, Alan J. Stewart and Colin McCowan
Nutrients 2025, 17(9), 1447; https://doi.org/10.3390/nu17091447 - 25 Apr 2025
Viewed by 911
Abstract
Background/Objectives: Cardiovascular diseases (CVDs) are the leading cause of global mortality. Major adverse cardiovascular events (MACEs)—such as acute myocardial infarction, stroke, and heart failure—are critical endpoints in the clinical research. The existing research has shown metal ions are important regulators of cardiovascular [...] Read more.
Background/Objectives: Cardiovascular diseases (CVDs) are the leading cause of global mortality. Major adverse cardiovascular events (MACEs)—such as acute myocardial infarction, stroke, and heart failure—are critical endpoints in the clinical research. The existing research has shown metal ions are important regulators of cardiovascular functioning, and defective metal handling may be associated with an increased risk of CVD. This study examines the association of the plasma/serum levels of magnesium, copper, and zinc with MACE incidence and the prevalence of circulatory system diseases, by using electronic health records from a subset of the Scottish population. Methods: We categorised individuals by high, low, or normal plasma/serum metal levels, and calculated the percentage of those who subsequently developed a MACE, identified using related International Classification of Diseases, 10th Revision codes from hospital admission records. Logistic regression was employed to analyse the association between pre-event metal ion levels and the development of specific circulatory system disease subgroups. Results: This study found abnormal magnesium, high copper, and low zinc were associated with a higher risk of developing MACEs. Low magnesium, high copper, or low zinc were associated with increased risks of various circulatory diseases, with specific variations, like low copper increasing venous and lymphatic disease risk. Conclusions: Our findings suggest abnormal plasma metal profiles are associated with the development of MACEs and circulatory disease events, underscoring the importance of monitoring plasma metal levels for cardiovascular risk management and prevention. Full article
(This article belongs to the Section Micronutrients and Human Health)
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17 pages, 4819 KiB  
Article
Low-Frequency Electrical Stimulation of the Auricular Branch of the Vagus Nerve in Patients with ST-Elevation Myocardial Infarction: A Randomized Clinical Trial
by Sofia Kruchinova, Milana Gendugova, Alim Namitokov, Maria Sokolskaya, Irina Gilevich, Zoya Tatarintseva, Maria Karibova, Vasiliy Danilov, Nikita Simakin, Elena Shvartz, Elena Kosmacheva and Vladimir Shvartz
J. Clin. Med. 2025, 14(6), 1866; https://doi.org/10.3390/jcm14061866 - 10 Mar 2025
Viewed by 1278
Abstract
Background: Despite the vast evidence of the beneficial effect of vagus nerve stimulation on the course of myocardial infarction confirmed in studies using animal models, the introduction of this method into actual clinical practice remains uncommon. Objective: The objective of our [...] Read more.
Background: Despite the vast evidence of the beneficial effect of vagus nerve stimulation on the course of myocardial infarction confirmed in studies using animal models, the introduction of this method into actual clinical practice remains uncommon. Objective: The objective of our study was to evaluate the effect of transcutaneous vagus nerve stimulation (tVNS) on in-hospital and long-term outcomes for patients with ST-elevation myocardial infarction. Materials and Methods: A blind, randomized, placebo-controlled clinical trial was conducted. The participants were randomly split into two groups. The Active tVNS group was subjected to stimulation of the tragus containing the auricular branch of the vagus nerve. The Sham tVNS group underwent stimulation of the lobule. Stimulation was performed immediately on admission before the start of the percutaneous coronary intervention (PCI). Then, tVNS continued throughout the entire PCI procedure and 30 min after its completion. The primary endpoints were hospital mortality and 12-month mortality. The secondary endpoints were in-hospital and remote non-lethal cardiovascular events. The combined endpoint consisted of major adverse cardiovascular events (MACEs)—recurrent myocardial infarction, stroke/TIA, and overall mortality. Results: A total of 110 patients were randomized into the Active tVNS group (n = 55) and the Sham tVNS group (n = 55). The incidences of hospital mortality, cardiogenic shock, and AV block 3 were statistically less common in the Active tVNS group than in the Sham tVNS group (p = 0.024*, p = 0.044*, and p = 0.013*, respectively). In the long-term period, no statistical differences were found in the studied outcomes obtained following the construction of Kaplan–Meyer survival curves. When comparing groups by total mortality, taking into account hospital mortality, we observed a tendency for the survival curves to diverge (Logrank test, p = 0.066). Statistical significance was revealed by the composite endpoint, taking into account hospital events (Logrank test, p = 0.0016*). Conclusions: tVNS significantly reduced hospital mortality (p = 0.024*), the level of markers of myocardial damage, and the frequency of severe cardiac arrhythmias in patients with acute myocardial infarction. In the long term, the prognostic value of tVNS was revealed by the composite endpoint major adverse cardiovascular events. Further studies with an expanded sample are needed for a more detailed verification of the data obtained to confirm the effectiveness of tVNS and allow an in-depth analysis of the safety and feasibility of its use in routine clinical practice. This clinical trial is registered with ClinicalTrials database under a unique identifier: NCT05992259. Full article
(This article belongs to the Special Issue Acute Coronary Syndromes: Focus on Precision Medicine)
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20 pages, 3616 KiB  
Review
Recent Advances in Coronary Chronic Total Occlusions
by Andreas Synetos, Leonidas Koliastasis, Nikolaos Ktenopoulos, Odysseas Katsaros, Konstantina Vlasopoulou, Maria Drakopoulou, Anastasios Apostolos, Soritios Tsalamandris, George Latsios, Konstantinos Toutouzas, Ioannis Patrikios and Constantinos Tsioufis
J. Clin. Med. 2025, 14(5), 1535; https://doi.org/10.3390/jcm14051535 - 25 Feb 2025
Cited by 1 | Viewed by 1611
Abstract
Coronary chronic total occlusions (CTOs) have been a point of interest of the medical community for the last decade. The natural history of CTOs was for a long time unknown, as the presence of a single CTO was the most frequent cause for [...] Read more.
Coronary chronic total occlusions (CTOs) have been a point of interest of the medical community for the last decade. The natural history of CTOs was for a long time unknown, as the presence of a single CTO was the most frequent cause for the exclusion of patients from randomized controlled trials (RCTs). Recent CTO RCTs have failed to show any benefit in terms of hard endpoints as major adverse cardiovascular events, but have shown a significant improvement in quality of life, as well in the frequency of angina; however, these studies are characterized by the limitation of the short duration of their follow-up period. Real-world data from observational studies indicate a significant improvement in cardiovascular death and overall mortality, suggesting that the results depend on the duration of the follow-up, and not on the procedure per se. The aim of the current review is to summarize all the existing RCTs, and to analyze the most important registries, as well as to present the current development of techniques to boost the successful interventional treatment of CTOs. Full article
(This article belongs to the Section Cardiology)
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14 pages, 913 KiB  
Article
Association of Opioid Prescription with Major Adverse Cardiovascular Events: Nationwide Cohort Study
by Tak-Kyu Oh, Hyoung-Won Cho and In-Ae Song
J. Clin. Med. 2025, 14(4), 1205; https://doi.org/10.3390/jcm14041205 - 12 Feb 2025
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Abstract
Background: This study aimed to investigate the association between opioid use and the incidence of major adverse cardiovascular events (MACEs). Methods: This study included adult patients who had received oral or transdermal opioids in 2016. The control group comprised individuals who [...] Read more.
Background: This study aimed to investigate the association between opioid use and the incidence of major adverse cardiovascular events (MACEs). Methods: This study included adult patients who had received oral or transdermal opioids in 2016. The control group comprised individuals who did not receive opioids in 2016 and was selected using a 1:1 stratified random sampling procedure. A MACE was defined as the occurrence of acute myocardial infarction, stroke, heart failure, or cardiovascular mortality. The primary endpoints were new MACEs and cardiovascular mortality, as evaluated from 1 January 2017 to 31 December 2021. Results: The study included 4,179,130 participants, of whom 1,882,945 (45.1%) were opioid users. After propensity score matching, 1,811,732 individuals (905,866 in each group) were included. Cox regression analysis revealed that the opioid user group had a 24% higher incidence of MACEs than the non-user group (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.23, 1.24; p < 0.001). Additionally, the opioid user group showed a 30% higher risk of cardiovascular mortality than the non-user group (HR: 1.30; 95% CI: 1.26, 1.35; p < 0.001). Conclusions: Opioid use was associated with an increased incidence of MACE and higher risk of cardiovascular mortality. Full article
(This article belongs to the Special Issue Pain Management: Current Challenges and Future Prospects)
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17 pages, 502 KiB  
Article
Role of C-Reactive Protein as a Predictor of Early Revascularization and Mortality in Advanced Peripheral Arterial Disease
by Giuseppe Di Stolfo, Mario Mastroianno, Michele Antonio Pacilli, Giovanni De Luca, Carlo Rosario Coli, Ester Maria Lucia Bevere, Gabriella Pacilli, Domenico Rosario Potenza and Sandra Mastroianno
J. Clin. Med. 2025, 14(3), 815; https://doi.org/10.3390/jcm14030815 - 26 Jan 2025
Viewed by 1068
Abstract
Background: Elevated high-sensitivity C-reactive protein (hsCRP) levels are associated with poor cardiovascular outcomes, particularly in patients with advanced peripheral arterial disease (PAD). This study aimed to assess the impact of hsCRP on clinical characteristics and long-term outcomes in a cohort of PAD patients. [...] Read more.
Background: Elevated high-sensitivity C-reactive protein (hsCRP) levels are associated with poor cardiovascular outcomes, particularly in patients with advanced peripheral arterial disease (PAD). This study aimed to assess the impact of hsCRP on clinical characteristics and long-term outcomes in a cohort of PAD patients. Methods: A total of 346 patients with advanced PAD were enrolled and stratified into two groups based on their median hsCRP level (Group 1: <0.32 mg/dL, Group 2: >0.32 mg/dL). The patients were followed for a mean of 102.70 ± 44.13 months. Their clinical characteristics, comorbidities, and long-term cardiovascular events, including myocardial and/or peripheral revascularization, ischemia, and death, were analyzed. This study evaluated two composite endpoints: major adverse cardiovascular events (MACEs) and major adverse peripheral events (MAPEs). MACEs comprised fatal cardiovascular events, cerebral ischemia, cardiac infarction, myocardial revascularization, acute peripheral arterial occlusion, and peripheral reperfusion. MAPEs included carotid reperfusion, acute peripheral arterial occlusion, and lower limb revascularization. Results: The patients in Group 2 had a higher body mass index, waist circumference, and waist–hip ratio compared to those in Group 1 (all p < 0.05). Inflammatory markers, including fibrinogen and the erythrocyte sedimentation rate, were significantly elevated in Group 2 (both p < 0.01). While the overall incidence of peripheral revascularization was similar between groups, these interventions occurred significantly earlier in Group 2 (28.24 ± 38.87 months vs. 67.04 ± 49.97 months, p = 0.004; HR: 2.015, 95% CI: 1.134–3.580, p = 0.017). The MAPEs were comparable in number, but occurred earlier in Group 2 (36.60 ± 37.35 months vs. 66.19 ± 48.18 months, p < 0.01; HR: 1.99, 95% CI: 1.238–3.181, p = 0.004). Similarly, the MACEs had an earlier onset in Group 2 (40.31 ± 38.95 months vs. 55.89 ± 46.33 months, p = 0.04; HR: 1.62, 95% CI: 0.983–1.987, p = 0.062). A total of 169 deaths were recorded during the follow-up. Group 2 exhibited a significantly higher mortality rate (56% vs. 42%, p < 0.01) and an earlier trend in mortality (76.58 ± 43.53 months vs. 84.86 ± 5.18 months), although this difference did not reach statistical significance (p = 0.22). Conclusions: Elevated hsCRP levels (>0.32 mg/dL) are associated with a worse clinical profile and earlier adverse events in patients with advanced PAD. Group 2 experienced significantly earlier peripheral revascularization, MACEs, and MAPEs. The mortality rates were also significantly higher, highlighting the prognostic value of hsCRP in this population. Full article
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12 pages, 979 KiB  
Article
Mid-Regional Pro-Adrenomedullin Is Associated with Adverse Cardiovascular Outcomes After Cardiac Surgery
by Ulrike Baumer, Niema Kazem, Andreas Hammer, Felix Hofer, Eva Steinacher, Lorenz Koller, Daniel Zimpfer, Martin Andreas, Barbara Steinlechner, Christian Hengstenberg, Alexander Niessner and Patrick Sulzgruber
J. Pers. Med. 2025, 15(2), 47; https://doi.org/10.3390/jpm15020047 - 26 Jan 2025
Viewed by 996
Abstract
Background: In the era of personalized medicine, tools for risk stratification after cardiovascular interventions are crucial to reduce mortality and morbidity, especially in the aging population. Biomarker-based approaches, in particular, have gained significant importance. Mid-regional pro-adrenomedullin (MR-proADM) represents an easily assessable biomarker that [...] Read more.
Background: In the era of personalized medicine, tools for risk stratification after cardiovascular interventions are crucial to reduce mortality and morbidity, especially in the aging population. Biomarker-based approaches, in particular, have gained significant importance. Mid-regional pro-adrenomedullin (MR-proADM) represents an easily assessable biomarker that mirrors cardiac function and fibrosis. Therefore, we aimed to investigate the prognostic potential of MR-proADM in patients undergoing elective cardiac surgery. Methods: Patients undergoing elective cardiac bypass and/or valve surgery were prospectively enrolled between May 2013 and August 2018. The primary endpoint was the composite of hospitalization for heart failure (HHF) or cardiovascular (CV) mortality. Results: In total, 500 patients (146 female [29.2%]; median age 69.8 years (IQR 60.6–75.5 years) were included. Individuals were stratified into risk categories based on their MR-proADM values (Low Risk ≤ 0.63 nmol/L, Intermediate Risk > 0.63 and ≤0.84, High Risk > 0.84). A significant increase in 5-year event rates for HHF/CV mortality in patients in the high-risk category (Low Risk 8.6% vs. High Risk 37.7%, p < 0.001) was observed. MR-pro ADM showed an independent association with HHF/ CV mortality (adjusted HR of 3.43, 95% CI 1.83–6.42; p < 0.001 comparing the High-Risk group to the Low-Risk group). Conclusions: MR-pro ADM was found to be a strong and independent predictor for HHF/CV mortality in patients undergoing elective cardiac surgery. Considering a personalized diagnostic and prognostic work-up, a standardized preoperative evaluation of MR-proADM levels might help to identify patients at risk for major adverse events and early re-hospitalization. Full article
(This article belongs to the Section Disease Biomarker)
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