Thrombotic Cardiovascular Events Research Articles

E-Cigarettes induce expression of procoagulant tissue factor in cultivated human endothelial cells.

E-cigarettes (ECIG) are proposed as an alternative for regular tobacco users with less dangerous effects for health. Several studies demonstrated that ECIG exert deleterious cardiovascular effects and promote platelet dependent thrombosis. However, ECIG role on Tissue Factor-dependent thrombosis is still unknown. Dysfunctional endothelial cells (ECs) are known to express Tissue Factor (TF) on their surface. Aim of the present study was to investigate whether ECIG might promote TF expression in ECs, shifting them to a pro thrombotic phenotype. Human Umbilical Vein Endothelial Cells (HUVEC) were incubated with increasing doses of ECIG (commercially available and mix of propylene glycol/vegetable glycerine/nicotine 18mg/mL) up to 1.8mg/mL. TF gene expression and protein levels were assessed at different time points by Real Time PCR and Western Blot, respectively. TF surface expression and activity were also measured by FACS analysis and coagulation assay. Finally, NF-kB translocation was investigated as possible mechanism of action. Potential protective effects by Rosuvastatin were also investigated. ECIG significantly increased TF expression at both gene and protein levels in a time and dose dependent manner. Surface expression and procoagulant activity were increased as well. These phenomena appeared modulated by the NF-κB pathway. Rosuvastatin reduced ECIG effects on TF-mRNA. Although in vitro, we indicate that ECIG promote a pro thrombotic phenotype in ECs via expression of functional TF. Data of the present study permit to shed a brighter light on the still partially unresolved issue about the role of ECIG in development of cardiovascular diseases suggesting that they might represent a potential risk factor for thrombotic cardiovascular events.

Impact of sodium-glucose cotransporter 2 inhibitor on recurrence and cardiovascular outcomes after catheter ablation for atrial fibrillation in patients with heart failure

BackgroundThe impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on atrial fibrillation (AF) recurrence outcomes and adverse cardiovascular outcomes in heart failure (HF) patients after AF ablation is unknown. ObjectiveWe investigated whether SGLT2i reduces the risk of AF recurrence and adverse cardiovascular outcomes in HF patients after AF ablation. MethodsHF patients with AF undergoing catheter ablation between January 2017 and December 2022 from the China-AF Registry were included. Patients were stratified into 2 groups on the basis of the use of SGLT2i at discharge and were 1:1 matched by propensity score, with SGLT2i using (n = 368) and non-SGLT2i using (n = 368) in each group. The primary outcome was AF recurrence after a 3-month blanking period. ResultsDuring a total of 1315 person-years of follow-up, AF recurred in 83 patients (22.6%) in the SGLT2i group and 132 patients (35.8%) in the non-SGLT2i group. SGLT2i was associated with a lower risk of AF recurrence (adjusted hazard ratio, 0.56; 95% CI, 0.43–0.74; P < .001). The composite risk of cardiovascular death, thrombotic events, or cardiovascular hospitalization was significantly lower in the SGLT2i group compared with those without SGLT2i (adjusted hazard ratio, 0.58; 95% CI, 0.41–0.80; P = .001). Although there was a trend toward benefit, the differences in all-cause mortality, cardiovascular death, or thrombotic events were insignificant between the 2 groups. ConclusionThe use of SGLT2i was associated with a lower risk of AF recurrence and the composite outcome of cardiovascular death, thrombotic events, or cardiovascular hospitalization after catheter ablation for AF in patients with HF.

Beyond silence: evolving ultrasound strategies in the battle against cardiovascular thrombotic challenges.

Cardiovascular thrombotic events have long been a perplexing factor in clinical settings, influencing patient prognoses significantly. Ultrasound-mediated acoustic therapy, an innovative thrombolytic treatment method known for its high efficiency, non-invasiveness, safety, and convenience, has demonstrated promising potential for clinical applications and has gradually become a focal point in cardiovascular thrombotic disease research. The current challenge lies in the technical complexities of preparing ultrasound-responsive carriers with thrombus-targeting capabilities and high thrombolytic efficiency. Additionally, optimizing the corresponding acoustic treatment mode is crucial to markedly enhance the thrombolytic effectiveness of ultrasound-mediated acoustic therapy. In light of the current status, this article provides a comprehensive review of the research progress in innovative ultrasound-mediated acoustic therapy for cardiovascular thrombotic diseases. It explores the impact of technical methods, therapeutic mechanisms, and influencing factors on the thrombolytic efficiency and clinical potential of ultrasound-mediated acoustic therapy. The review places particular emphasis on identifying solutions and key considerations in addressing the challenges associated with this cutting-edge therapeutic approach.

Overview of dyslipidemia and metabolic syndrome in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) occur due to the abnormal proliferation of one or more terminal myeloid cell lines in peripheral blood. Subjects suffering from MPNs display a high burden of cardiovascular risk factors, and thrombotic events are often the cause of death in this population of patients. Herein, we provide a brief overview of dyslipidemia and metabolic syndrome and their epidemiology in MPNs and examine the common molecular mechanisms between dyslipidemia, metabolic syndrome, and MPNs, with a special focus on cardiovascular risk, atherosclerosis, and thrombotic events. Furthermore, we investigate the impact of dyslipidemia and metabolic syndrome on the occurrence and survival of thrombosis in MPN patients, as well as the management of dyslipidemia in MPNs, and the impact of MPN treatment on serum lipid concentrations, particularly as side/adverse effects reported in the context of clinical trials.

Clinical and Economic Implications of Hydroxyurea Intolerance in Polycythemia Vera in Routine Clinical Practice.

Background/Objectives: Polycythemia vera (PV) is a chronic hematologic neoplasm commonly treated with hydroxyurea (HU). We utilized the advanced digitalized database of Maccabi Healthcare Services to retrospectively investigate the clinical and economic implications of HU intolerance in the routine clinical care of PV patients in Israel. Methods: We collected data on demographics, physician visits, hospitalizations, laboratory results, medication purchases, cardiovascular and thrombotic events, mental health, economic outcomes, and mortality. Outcomes included cardiovascular and other thrombotic events, disease progression, mental health events, economic outcomes, and overall mortality. Results: Of the 830 patients studied, 3 (0.4%) were resistant to HU treatment, 318 (38.3%) were intolerant to HU treatment, and 509 (61.3%) were stable on HU treatment. The venous thrombosis rate was significantly higher among HU-intolerant compared to HU-stable patients (1.58 vs. 0.47 per 100 person-years [PY], respectively; p < 0.001). The rate of progression to myelofibrosis was 6 vs. 0.9 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively (p < 0.001), and the rate of progression to acute myeloid leukemia (AML) was 1.16 vs. 0.2 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively (p < 0.001). The phlebotomy requirement, mortality rate, and total hospitalization days among HU-intolerant patients were significantly higher than in HU-stable patients (p = 0.049, p < 0.001, p < 0.001, respectively). More mental health-related events were noted in HU-intolerant patients vs. HU-stable patients (p = 0.007), and the total healthcare cost ratio was 2.65 for the HU-intolerant patients compared with HU-stable patients. Conclusions: This study suggests that HU-intolerant patients are more likely to have worse outcomes than HU-stable patients, highlighting the need for the close monitoring of these patients for disease-related complications or progression.

Increased risk of new‐onset cardiovascular disease after COVID‐19: A systematic review and meta‐analysis of 14 cohorts

AbstractCardiovascular diseases (CVD) are common in long COVID, yet the associated risk remains uncertain. We aimed to quantify the risk of new‐onset cardiovascular diseases after COVID‐19. We searched PubMed, Embase, and Web of Science from inception up to October 2022. Cohort studies that provided information on the number, proportion, or relative risks (RR) of cardiovascular diseases after COVID‐19 were included. Paired reviewers independently screened studies, extracted data, and assessed the risk of bias. We performed random‐effects models meta‐analyses to calculate RR and corresponding 95% confidence interval (95%CI), and conducted subgroup analyses and meta‐regression to explore the potential risk factors. Absolute effects were calculated to facilitate interpretation. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess the certainty of evidence. Outcomes of interest were any CVD, major adverse cardiovascular events (MACE), arrhythmias, heart failure, myocarditis, and thrombotic events. Fourteen cohort studies with over 25.37 million participants were included. The results showed a 2.42 times higher risk of any CVD (RR = 2.42, 95% CI: 1.24–4.71; 51 more per 1000), a 95% higher risk of MACE (RR = 1.95, 95% CI: 1.59–2.40; 4 more per 1000), a 61% higher risk of arrhythmias (RR = 1.61, 95% CI: 1.42–1.83; 12 more per 1000), a 71% higher risk of heart failure (RR = 1.71, 95% CI: 1.33–2.21; 2 more per 1000), a 5 times higher risk of myocarditis (RR = 5.06, 95% CI: 3.78–6.77; 4 more per 1000), and a 2.49 times higher risk of thrombotic events (RR = 2.49, 95% CI: 1.22–5.06; 6 more per 1000) associated with COVID‐19. Besides, for thrombotic events, a statistically significant subgroup effect was observed in male participants compared to females (Pinteraction = 0.008). The certainty of evidence was high for myocarditis, but low or very low for other outcomes. The results clearly showed varying degrees of elevated new‐onset CVD risk in post‐COVID‐19 individuals. Additionally, our findings suggest that male patients face a higher risk of thrombotic events. However, the differences in pooled results between studies, and the over‐precision due to the large sample size of the included studies resulted in high heterogeneity of exceeding 90% in most outcomes, which led to low certainty of evidence.

Arterial thrombosis triggered by methotrexate-induced hyperhomocysteinemia in a systemic lupus erythematosus patient with antiphospholipid antibodies

Systemic lupus erythematosus (SLE) patients have an increased risk of cardiovascular disease and thrombotic events, and the presence of antiphospholipid antibodies further raises the risk of these complications. Here we report a case of a patient with SLE and triple positivity for antiphospholipid antibodies who developed a popliteal artery thrombosis in the context of a severe hyperhomocysteinemia after the introduction of methotrexate (MTX) treatment. MTX is one of the most prescribed medications for a wide spectrum of autoimmune diseases, including SLE. On the other hand, by interfering with folate metabolism, it may induce hyperhomocysteinemia, which, in turn, may increase the risk of vascular complications. Current recommendations suggest screening and, when possible, treating classical and disease-related cardiovascular risk factors in all lupus patients. Based on what observed in our case, we suggest a follow-up of homocysteine levels after the introduction of drugs capable of inducing hyperhomocysteinemia, such as MTX, in SLE patients at high cardiovascular risk.

Haemophilia and cardiovascular disease in Japan: Low incidence rates from ADVANCE Japan baseline data.

With the increasing life expectancy of people with haemophilia, the risk of cardiovascular disease (CVD) and thrombotic events has become a growing concern. Longitudinal studies on the incidence and risk factors of CVD in this population are limited, and optimal prevention and treatment strategies are yet to be established. This study aimed to present the baseline data of a prospective longitudinal study focusing on a subset of Japanese patients with haemophilia, specifically investigated the incidence, risk factors and treatment modalities for CVD and thrombotic diseases in people aged 40 years in Japan over 10 years through the ADVANCE Japan study. The ADVANCE Japan study is a prospective multicentre cohort study involving 600 adult individuals with haemophilia A/B aged 40 years in Japan. The primary endpoint was the incidence of CVD, with secondary endpoints encompassing anticoagulant use, mortality rates, and comparison with the general population. Baseline data from the 600 participants revealed that thrombotic events occurred in 13 individuals (2.2%), mostly in those with haemophilia A. Atrial fibrillation was observed in 11 participants (1.8%). Hypertension and dyslipidaemia were identified as the prevalent risk factors. Various prophylactic treatments were employed, and no severe bleeding events were observed during the study period. This study provides vital baseline data for a 10-year prospective investigation of CVD and thrombotic disease risk in people with haemophilia. These findings will contribute to refining prevention and treatment approaches and improving patients' quality of life.

PB1097 Cost of Major Thrombotic Cardiovascular Events (MTCVE) Among US Patients with and without End-Stage Kidney Disease (ESKD)

PB1097 Cost of Major Thrombotic Cardiovascular Events (MTCVE) Among US Patients with and without End-Stage Kidney Disease (ESKD)

A tissue-engineered model of the atherosclerotic plaque cap: Toward understanding the role of microcalcifications in plaque rupture.

Rupture of the cap of an atherosclerotic plaque can lead to thrombotic cardiovascular events. It has been suggested, through computational models, that the presence of microcalcifications in the atherosclerotic cap can increase the risk of cap rupture. However, the experimental confirmation of this hypothesis is still lacking. In this study, we have developed a novel tissue-engineered model to mimic the atherosclerotic fibrous cap with microcalcifications and assess the impact of microcalcifications on cap mechanics. First, human carotid plaque caps were analyzed to determine the distribution, size, and density of microcalcifications in real cap tissue. Hydroxyapatite particles with features similar to real cap microcalcifications were used as microcalcification mimics. Injected clusters of hydroxyapatite particles were embedded in a fibrin gel seeded with human myofibroblasts which deposited a native-like collagenous matrix around the particles, during the 21-day culture period. Second harmonic multiphoton microscopy imaging revealed higher local collagen fiber dispersion in regions of hydroxyapatite clusters. Tissue-engineered caps with hydroxyapatite particles demonstrated lower stiffness and ultimate tensile stress than the control group samples under uniaxial tensile loading, suggesting increased rupture risk in atherosclerotic plaques with microcalcifications. This model supports previous computational findings regarding a detrimental role for microcalcifications in cap rupture risk and can further be deployed to elucidate tissue mechanics in pathologies with calcifying soft tissues.

GDF-15 at admission predicts cardiovascular death, heart failure, and bleeding outcomes in patients with CAD.

We aimed to investigate the independent associations between growth differentiation factor 15 (GDF-15) level at admission and cardiovascular (CV) death, thrombotic events, heart failure (HF), and bleeding outcomes in patients with coronary artery disease (CAD). We measured the plasma concentrations of GDF-15 centrally in patients from the BIomarker-based Prognostic Assessment for patients with Stable angina and acute coronary Syndrome (BIPass) registry, which consecutively enrolled patients with CAD from November 2017 to September 2019 at five tertiary hospitals in China. The outcomes included CV death, thrombotic events [myocardial infarction (MI) and ischaemic stroke], HF events [acute HF during hospitalization and hospitalization for HF post-discharge (A/H HF) and cardiogenic shock], and bleeding outcomes [non-coronary artery bypass grafting-related major bleeding and clinically significant bleeding (CSB)] during the 12month follow-up period after hospitalization. Among 6322 patients with CAD {65.4% male, median age 63.7 [inter-quartile range (IQR)] 56.0-70.1years}, the median concentration of plasma GDF-15 at admission was 1091 (IQR 790.5-1635.0) ng/L. Higher concentrations of GDF-15 were associated with an increased risk of CV death [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.35-2.88, P<0.001], A/H HF (HR 2.69, 95% CI 1.92-3.77, P<0.001), cardiogenic shock (HR 1.46, 95% CI 1.04-2.05, P=0.029), and CSB (HR 1.48, 95% CI 1.22-1.79, P<0.001), but not for MI or stroke, after adjusting for clinical risk factors and prognostic biomarkers. Adding GDF-15 to the model with risk factors and biomarkers improved the net reclassification for CV death, A/H HF, cardiogenic shock, and CSB. In patients with CAD, admission levels of GDF-15 were associated with an increased 1year risk of CV death, HF, and bleeding outcomes, but not with thrombotic events. GDF-15 may be a prognostic biomarker for CV death, HF, and bleeding outcomes and could be used to refine the risk assessment of these specific clinical outcomes. ClinicalTrials.gov Identifier: NCT04044066.

The role of monocytes in thrombotic diseases: a review.

Cardiovascular and cerebrovascular diseases are the number one killer threatening people's life and health, among which cardiovascular thrombotic events are the most common. As the cause of particularly serious cardiovascular events, thrombosis can trigger fatal crises such as acute coronary syndrome (myocardial infarction and unstable angina), cerebral infarction and so on. Circulating monocytes are an important part of innate immunity. Their main physiological functions are phagocytosis, removal of injured and senescent cells and their debris, and development into macrophages and dendritic cells. At the same time, they also participate in the pathophysiological processes of pro-coagulation and anticoagulation. According to recent studies, monocytes have been found to play a significant role in thrombosis and thrombotic diseases of the immune system. In this manuscript, we review the relationship between monocyte subsets and cardiovascular thrombotic events and analyze the role of monocytes in arterial thrombosis and their involvement in intravenous thrombolysis. Finally, we summarize the mechanism and therapeutic regimen of monocyte and thrombosis in hypertension, antiphospholipid syndrome, atherosclerosis, rheumatic heart disease, lower extremity deep venous thrombosis, and diabetic nephropathy.

In-hospital mortality analysis in patients with acute cardiovascular pathology and co-infection with COVID-19: a registry of one site

Abstract Funding Acknowledgements Type of funding sources: None. Patients with cardiovascular pathology have a significantly higher risk of adverse events and death when complicated by concomitant COVID-19. The aim of this study was to analyze in-hospital mortality in pts with acute cardiovascular pathology (ACP) and a co-infection with COVID-19. 139 pts with ACP who were diagnosed with COVID-19 were examined. 69 (49.6%) pts had ACS (47 pts with AMI), 33 (23.7%) pts - hypertensive urgency, 24 (17.3%) pts - ADHF, 9 (6.5%) pts - tachysystolic paroxysm of atrial fibrillation, 2 (1.4%) pts - acute pulmonary embolism, and 2 (1.4%) pts - syncope. The average age was 67.9±12.7 y.o., 70 (50.4%) pts were male. Concomitant arterial hypertension was found in 87.1%, DM – 20.9%, CHF - 30.9%, COPD – 9.4% of pts, history of AMI – 20.1% and ischemic stroke – 9.4% of pts. In 79 (56.8%) pts COVID-19 was diagnosed and laboratory confirmed before hospitalization (hospitalized in 5.3±3.6 days after symptoms onset). 31 (22.3%) pts were diagnosed with COVID-19 upon admission, and 29 (20.9%) - during their stay in the hospital. 20 (15.6%) pts were vaccinated against COVID-19. The initial SpO2 level was 91.6±10.3%, while more than half of pts (53.2%) had SpO2&amp;lt;95% and almost every fourth (23.2%) patient had SpO2&amp;lt;90%. During the hospital period, 20 (14.4%) pts died. The mortality rate was 28.0% in pts with ADHF, 19.1% in pts with AMI and significantly less in pts hospitalized for unstable angina, hypertensive urgency or atrial fibrillation - 5.2% (p&amp;lt;0.05 in comparison with pts with AMI or ADHF). The main cause of death was the development of cardiopulmonary failure – 14 (70.0%) pts. 4 (20.0%) pts died from AMI complications, 1 - from pulmonary embolism and 1 - from acute ischemic stroke. Two critical periods of in-hospital mortality can be distinguished: 1 - the first two days of hospitalization (mainly complications of acute cardiovascular pathology and thrombotic events); 2 – from 7 to 10 days after hospitalization (development of multiple organ failure due to hypoxia and heart failure progression). The mortality rate of patients with ACP and COVID-19 was significantly higher than that of simultaneously hospitalized patients without comorbid respiratory infection (14.4% vs. 6.4%, p=0.012) and patients who were hospitalized before the pandemic (14.4% vs. 2.9%, p&amp;lt;0.001). Vaccinated patients were significantly less likely to develop acute kidney injury, acute hypoxic delirium, had higher average blood spO2, and less often required non-invasive ventilation. Only 1 vaccinated patient died from the development of cardiogenic shock against the background of anterior AMI and multivessel coronary artery disease (mortality – 15.7% in unvaccinated pts vs 5.0% in vaccinated, p=0.076). Co-infection with COVID-19 worsens treatment outcomes and in-hospital mortality of patients with ACP. Vaccination significantly reduces the likelihood of complications and tends to reduce mortality.

The Impact of Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies with and without Apheresis on Platelet Aggregation in Familial Hypercholesterolemia

Background and aimsIt is well known that elevated cholesterol is associated with enhanced platelet aggregation and patients suffering from familial hypercholesterolemia (FH) have a high risk of thrombotic cardiovascular events. Although decreasing cholesterol level is associated with attenuation of platelet hyperactivity, there are currently no data on the effect of convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9ab) on platelet reactivity in FH. The aim of the study was to analyse the impact of different therapies including PCSK9ab on platelet aggregation in FH.MethodsThis study enrolled all 15 patients treated in the University Hospital Hradec Králové for FH. PCSK9ab have been administered in 12 of 15 patients while 8 patients were also undergoing lipid apheresis. Blood samples from all patients including pre- and post-apheresis period were tested for platelet aggregation triggered by 7 inducers, and the effect of 3 clinically used drugs (acetylsalicylic acid, ticagrelor and vorapaxar) was compared as well.ResultsAlthough apheresis decreased the reactivity of platelets in general, platelet responses were not different between non-apheresis patients treated with PCSK9ab and apheresis patients (post-apheresis values) with the exception of ristocetin. However, when compared to age-matched healthy population, FH patients had significantly lower platelet aggregation responses to 4 out of 7 used inducers and higher profit from 2 out of 3 used antiplatelet drugs even after exclusion of FH patients regularly receiving conventional antiplatelet treatment.ConclusionThis study showed for the first time the suitability of PCSK9ab treatment for reduction of platelet reactivity in FH patients.

SOD2 in platelets: with age comes responsibility

SOD2 in platelets: with age comes responsibility

Analysis of in-hospital complications in patients with acute cardiovascular pathology and co-infection with COVID-19: a registry of one center

The aim – to analyze in-hospital mortality in pts with acute cardiovascular pathology (ACP) and a co-infection with COVID-19.Materials and methods. 139 pts with ACP who were diagnosed with COVID-19 were examined. 69 (49.6 %) pts had ACS (47 pts with AMI), 33 (23.7 %) pts – hypertensive urgency, 24 (17.3 %) pts – ADHF, 9 (6.5 %) pts – tachysystolic paroxysm of atrial fibrillation, 2 (1.4 %) pts – acute pulmonary embolism, and 2 (1.4 %) pts – syncope. The average age was 67.9±12.7 y.o., 70 (50.4 %) pts were male. Concomitant arterial hypertension was found in 87.1 %, DM – 20.9 %, CHF – 30.9 %, COPD – 9.4 % of pts, history of AMI – 20.1 % and ischemic stroke – 9.4 % of pts. In 79 (56.8 %) pts COVID-19 was diagnosed and laboratory confirmed before hospitalization (hospitalized in 5.3±3.6 days after symptoms onset). 31 (22.3 %) pts were diagnosed with COVID-19 upon admission, and 29 (20.9 %) – during their stay in the hospital. 20 (15.6 %) pts were vaccinated against COVID-19. The initial SpO2 level was 91.6±10.3 %, while more than half of pts (53.2 %) had SpO2 &lt; 95 % and almost every fourth (23.2 %) patient had SpO2 &lt; 90 %.Results and discussion. During the hospital period, 20 (14.4 %) pts died. The mortality rate was 28.0 % in pts with ADHF, 19.1 % in pts with AMI and significantly less in pts hospitalized for unstable angina, hypertensive urgency or atrial fibrillation – 5.2 % (p&lt;0.05 in comparison with pts with AMI or ADHF). The main cause of death was the development of cardiopulmonary failure – 14 (70.0 %) pts. 4 (20.0 %) pts died from AMI complications, 1 – from pulmonary embolism and 1 – from acute ischemic stroke. Two critical periods of in-hospital mortality can be distinguished: 1 – the first two days of hospitalization (mainly complications of acute cardiovascular pathology and thrombotic events); 2 – from 7 to 10 days after hospitalization (development of multiple organ failure due to hypoxia and heart failure progression). The mortality rate of patients with ACP and COVID-19 was significantly higher than that of simultaneously hospitalized patients without comorbid respiratory infection (14.4 % vs. 6.4 %, p=0.012) and patients who were hospitalized before the pandemic (14.4 % vs. 2.9 %, p&lt;0.001). Vaccinated patients were significantly less likely to develop acute kidney injury, acute hypoxic delirium, had higher average blood SpO2, and less often required non-invasive ventilation. Only 1 vaccinated patient died from the development of cardiogenic shock against the background of anterior AMI and multivessel coronary artery disease (mortality – 15.7 % in unvaccinated pts vs 5.0 % in vaccinated, p=0.076).Conclusions. Co-infection with COVID-19 worsens treatment outcomes and in-hospital mortality of patients with ACP. Vaccination significantly reduces the likelihood of complications and tends to reduce mortality.

EE81 The Budget Impact of Cangrelor for the Treatment of Patients Undergoing Percutaneous Coronary Intervention When Oral P2Y12 Inhibitors Are Not Feasible or Desirable in the UK

Cangrelor is an intravenous, direct-acting, reversible P2Y12 inhibitor indicated for the reduction of thrombotic cardiovascular events in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) who have not received an oral P2Y12 inhibitor prior to the PCI procedure, and in whom oral therapy with P2Y12 inhibitors is not feasible or desirable. The objective of this analysis is to estimate the UK budget impact of introducing cangrelor, for the ST-elevation myocardial infarction (STEMI) population in whom oral P2Y12 inhibitors are not feasible or desirable.

Abstract 15606: Diabetes is Associated With Increased Risk of Major Adverse Cardiovascular Events in Patients Covid-19: A Retrospective U.S. Multicenter Cohort Study

Introduction: Diabetes mellitus (DM) increases the risk of adverse outcomes in patients with COVID-19. Whether this is driven by a higher rate of thrombotic complications or cardiovascular events in patients with COVID-19 has rarely been explored. Methods: We analyzed a retrospective cohort of 6920 consecutive patients ≥ 18 years old with confirmed SARS-COV-2 polymerase chain reaction testing from March 2020 to April 2020 using a US multicenter registry. Main outcomes of interest were 30-day of adjudicated major adverse cardiovascular events (MACE), major arterial and venous thromboembolic (VTE) events, and symptomatic VTE. MACE included VTE, catheter related thrombosis, myocardial infarction, stroke, major adverse limb events, heart failure hospitalization, atrial fibrillation (AF), and myocarditis. Results: Of 1252 patients with DM, 49.4% were women, 50.9% were non-white, and 26.2% were Latinx. Mean BMI of patients with and without DM was similar (34.2 vs 33.4 kg/m2, p =0.91). Compared with patients without DM, those with DM were older (50.3±15.4 years. vs 39.6±19.7, p &lt;0.001), had higher rates of hypertension, AF, hospitalization (76.4% vs 23.1%, 5.0% vs 1.0% and 60.8% vs 28.4%, p &lt;0.001, respectively). Thirty days after COVID diagnosis, patients with DM had a higher rate of MACE (12.7% vs 3.9%, p &lt;0.001), major arterial or venous thromboembolism (8.5% vs 3.1%, p &lt;0.001), symptomatic VTE (6.5% vs 4.7%, p &lt;0.001 ), and death (11.9% vs 4.7%, p &lt;0.001) compared with patients without DM (Panel A). After adjusting for age, gender, hypertension, COVID-19 admission, peripheral artery disease, and coronary artery disease, patients with DM had increased risk of MACE (aOR 1.39 95% CI 1.09-1.78), but not of major adverse arterial or VTE events (aOR 1.24 95% CI 0.93-1.65), symptomatic VTE (aOR 1.34 95% CI 0.98-1.86), or death (aOR 1.13 95% CI 0.87-1.47) (Panel B). Conclusions: In patients with COVID-19, DM is independently associated with increased risk of MACE.

Thymic stromal lymphopoietin induces platelet mitophagy and promotes thrombosis in Kawasaki disease.

Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting infants and children. Activated platelets predispose patients to coronary artery structural lesions that may lead to thrombotic cardiovascular events. To discover potential proteins underlying platelet activation in KD, we conducted a protein chip assay of 34 cytokines and discovered thymic stromal lymphopoietin (TSLP) was aberrantly expressed, which remained elevated after intravenous immunoglobulin G (IVIG) treatment and during convalescence in KD patients in comparison to healthy controls. Enzyme-linked immunosorbent assay (ELISA) corroborated the upregulation of TSLP in KD patients, which was exacerbated in convalescent patients complicated with thrombosis. TSLP receptors on platelets were also significantly upregulated in KD patients complicated with thrombosis. Platelet activation, apoptosis, and mitochondrial autophagy (mitophagy) were increased in convalescence KD patients complicated with thrombosis. In vitro, TSLP induced platelet activation and platelet mitophagy in healthy blood donors, as observed in KD patients. TSLP, similar to mitophagy agonist carbonyl cyanide 3-chlorophenyl hydrazone (CCCP), promoted thrombosis, which was attenuated by the mitophagy inhibitor Mdivi-1. Co-immunoprecipitation in TSLP-treated platelets revealed TSLP receptor (TSLPR) bound to mitophagy regulators, Parkin and Voltage Dependent Anion Channel Protein 1 (VDAC1).Thus, our results demonstrated that TSLP induced platelet mitophagy via a novel TSLPR/Parkin/VDAC1 pathway that promoted thrombosis in KD. These results suggest TSLP as a novel therapeutic target against KD-associated thrombosis.

Defective efferocytosis of vascular cells in heart disease.

The efficient phagocytic clearance of dying cells and apoptotic cells is one of the processes that is essential for the maintenance of physiologic tissue function and homeostasis, which is termed “efferocytosis.” Under normal conditions, “find me” and “eat me” signals are released by apoptotic cells to stimulate the engulfment and efferocytosis of apoptotic cells. In contrast, abnormal efferocytosis is related to chronic and non-resolving inflammatory diseases such as atherosclerosis. In the initial steps of atherosclerotic lesion development, monocyte-derived macrophages display efficient efferocytosis that restricts plaque progression; however, this capacity is reduced in more advanced lesions. Macrophage reprogramming as a result of the accumulation of apoptotic cells and augmented inflammation accounts for this diminishment of efferocytosis. Furthermore, defective efferocytosis plays an important role in necrotic core formation, which triggers plaque rupture and acute thrombotic cardiovascular events. Recent publications have focused on the essential role of macrophage efferocytosis in cardiac pathophysiology and have pointed toward new therapeutic strategies to modulate macrophage efferocytosis for cardiac tissue repair. In this review, we discuss the molecular and cellular mechanisms that regulate efferocytosis in vascular cells, including macrophages and other phagocytic cells and detail how efferocytosis-related molecules contribute to the maintenance of vascular hemostasis and how defective efferocytosis leads to the formation and progression of atherosclerotic plaques.