Arterial Vascular Events Research Articles

Hyperhomocysteinemia in Adult Patients: A Treatable Metabolic Condition.

Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for various significant medical conditions, yet controversy persists around its assessment and management. The diagnosis of disorders afffecting homocysteine (Hcy) metabolism faces delays due to insufficient awareness of its clinical presentation and unique biochemical characteristics. In cases of arterial or venous thrombotic vascular events, particularly with other comorbidities, it is crucial to consider moderate to severe HHcy. A nutritional approach to HHcy management involves implementing dietary strategies and targeted supplementation, emphasizing key nutrients like vitamin B6, B12, and folate that are crucial for Hcy conversion. Adequate intake of these vitamins, along with betaine supplementation, supports Hcy remethylation. Lifestyle modifications, such as smoking cessation and regular physical activity, complement the nutritional approach to enhance Hcy metabolism. For individuals with HHcy, maintaining a plasma Hcy concentration below 50 μmol/L consistently is vital to lowering the risk of vascular events. Collaboration with healthcare professionals and dietitians is essential for developing personalized dietary plans addressing the specific needs and underlying health conditions. This integrated approach aims to optimize metabolic processes and reduce the associated health risks.

Coronary Artery and Peripheral Vascular Disease in a Patient with Poorly Differentiated Thyroid Cancer Treated with the Tyrosine Kinase Inhibitor Lenvatinib

A subset of patients with differentiated thyroid carcinoma develop radioiodine refractory (RAIR) incurable disease, which typically has a poor prognosis. The multitargeted tyrosine kinase inhibitor lenvatinib has demonstrated significant improvements in progression-free survival in RAIR thyroid cancers compared to placebos. However, in the phase III SELECT trial of the drug in thyroid cancer, 5.4% of patients on lenvatinib experienced arterial thromboembolic events, with 2.7% experiencing severe grade ≥3 toxicities associated with arterial vascular events. This case study reports a patient with metastatic poorly differentiated follicular thyroid cancer who developed significant obstructive coronary artery disease following initiation of lenvatinib treatment, despite no predisposing cardiovascular risk factors apart from a remote smoking history. The possibility of developing coronary or peripheral artery disease should be considered in patients who are on targeted therapies, such as lenvatinib, even in the absence of traditional cardiovascular risk factors. In addition, baseline cardiac risk assessment and early treatment should be pursued to minimize interruptions to potentially lifesaving cancer therapy.

Abdominal aortic calcification in patients newly diagnosed with essential thrombocythemia.

Although atherosclerosis is likely to be involved in the development of arterial thrombotic events in patients with essential thrombocythemia (ET), abdominal aortic calcification (AAC) has rarely been investigated. We evaluated the prevalence and clinical relevance of AAC at the time of ET diagnosis. This retrospective study included patients newly diagnosed with ET who underwent abdominal computed tomography (CT) at the time of diagnosis between January 2002 and December 2021 at Chungnam National University Hospital, Daejeon, Korea. CT images were reviewed and an aortic calcification score was assigned. Of the 94 patients (median age, 62 yr; range, 18‒90 yr), AAC was detected in 62 (66.0%). AAC was most commonly mild (33.0%), followed by moderate (22.7%) and severe (5.3%). Old age [odds ratio (OR), 34.37; 95% confidence interval (CI), 12.32‒95.91; P＜0.001] was an independent risk factor for AAC. The patients with AAC had a higher WBC count (11.8±4.7 vs. 9.7±2.9×109/L, P=0.017), higher neutrophil-to-lymphocyte ratio (4.3±2.7 vs. 3.1±1.5, P=0.039), and higher JAK2V617F positivity (81.5% vs. 58.8%, P=0.020) compared to those without AAC. AAC was an independent risk factor for arterial thrombotic vascular events that occurred before or at diagnosis of ET (OR, 4.12; 95% CI, 1.11‒15.85; P=0.034). AAC is common in patients with ET and is associated with arterial thrombotic events.

Evaluation of erythrocytapheresis compared to phlebotomy in polycythaemia vera patients

IntroductionPolycythaemia vera patients can present with arterial or venous vascular occlusive events such as thrombosis or cardiovascular disease; disease-related symptoms may significantly impact on the quality of life. The aim of this study was to evaluate the efficacy and safety of erythrocytapheresis compared to phlebotomy in the treatment of polycythaemia patients. MethodsThis study reports the findings of a retrospective analysis of 40 polycythaemia vera patients diagnosed according to published guidelines and treated either with erythrocytapheresis or phlebotomy over a four-year period. The goal of treatment was to reduce blood volume and red blood cell count to near normal levels as both of which may attenuate the symptoms and complications associated with polycythaemia. Patients were treated by applying a mathematical model. ResultsUsing the model, 28 erythrocytapheresis procedures were performed. Blood laboratory values (red blood cell count, haemoglobin count and haematocrit level) were significantly reduced in patients treated with erythrocytapheresis. Moreover, among treated patients, erythrocytapheresis resulted in less work absenteeism and reduced costs due to lost production, with a lower overall procedure cost in comparison to phlebotomy. ConclusionThis model can assist in selecting the proper treatment modality for individual patients. Especially for those with high blood volumes and high achievable haematocrit levels (delta), erythrocytapheresis offers a more efficient method in red blood cell depletion compared to phlebotomy thereby, potentially reducing the number of treatment procedures required for the induction of polycythaemia vera patients as well as the interval between procedures during the maintenance phase.

Race and Ethnicity With Atherosclerotic Cardiovascular Disease Outcomes Within a Universal Health Care System: Insights From the CARTaGENE Study.

It remains unclear whether racial and ethnic disparities for atherosclerotic cardiovascular disease (ASCVD) persist within universal health care systems. We aimed to explore long-term ASCVD outcomes within a single-payer health care system with extensive drug coverage in Québec, Canada. CARTaGENE (CaG) is a population-based prospective cohort study of individuals aged 40 to 69 years. We included only participants without previous ASCVD. The primary composite endpoint was time to the first ASCVD event (cardiovascular death, acute coronary syndrome, ischemic stroke-transient ischemic attack, or peripheral arterial vascular event). The study cohort included 18,880 participants followed for a median of 6.6 years (2009 to 2016). The mean age was 52 years, and 52.4% were female. After further adjustment for socioeconomic and cardiovascular factors, the increase in ASCVD risk for South Asians (SAs) was attenuated (hazard ratio [HR], 1.41; 95% confidence interval [CI], 0.75, 2.67), whereas Black participants' risk was lower (HR, 0.52; 95% CI, 0.29, 0.95) compared with White participants. After similar adjustments, there were no significant differences in ASCVD outcomes among the Middle Eastern, Hispanic, East-Southeast Asian, Indigenous, and mixed race-ethnicities participants and the White participants. After adjustment for CV risk factors, the risk of ASCVD was attenuated in the SA CaG participants. Intensive risk-factor modification may mitigate the ASCVD risk of the SAs. Within a universal health care context and comprehensive drug coverage, the ASCVD risk was lower among Black compared with White CaG participants. Future studies are needed to confirm whether universal and liberal access to health care and medications can reduce the rates of ASCVD among the Black population.

Cardiovascular risk in myositis patients compared with the general population.

We aimed to evaluate cardiovascular (CV) risk in patients with idiopathic inflammatory myopathies (IIM) compared with healthy controls (HC) and to assess its association with disease-specific features. Ninety IIM patients and 180 age-/sex-matched HC were included. Subjects with a history of CV disease (angina pectoris, myocardial infarction and cerebrovascular/peripheral arterial vascular events) were excluded. All participants were prospectively recruited and underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition. The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE) and its modifications. Compared with HC, IIM patients had a significantly higher prevalence of traditional CV risk factors, carotid artery disease (CARD), abnormal ABI and PWV. After propensity score matching (using traditional CV risk factors), the prevalence of CARD and pathological PWV remained significantly higher in IIM than HC. No significant difference in SCORE was observed. The most unfavourable CV risk profile was observed in patients with necrotizing myopathy, especially in statin-induced anti-HMGCR+ patients. The calculated CV risk scores by SCORE, SCORE2 and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to CIMT and the presence of carotid plaques. SCORE was demonstrated to be most inaccurate in predicting CV risk in IIM. Age, disease activity, lipid profile, body composition parameters and blood pressure were the most significant predictors of CV risk in IIM patients. Significantly higher prevalence of traditional risk factors and subclinical atherosclerosis was observed in IIM patients compared with HC.

The particularities of hemostasis in patients with non-ST elevation myocardial infarction and some comorbidities

The formation of an obstructive thrombus within an artery remains a major cause of mortality and morbidity worldwide. [1] Despite effective inhibition of platelet function by modern antiplatelet therapies, these agents fail to fully eliminate atherothrombotic risk. This may well be related to extensive vascular disease, beyond the protective abilities of the treatment agents used. However, recent evidence suggests that residual vascular risk in those treated with modern antiplatelet therapies is related, at least in part, to impaired fibrin clot lysis. Along these lines, thrombosis is the result of several changes in local homeostasis: endothelial dysfunction, changes in the fibrinolytic system, increased content of some coagulation factors, decreased natural inhibitors, platelet hyperactivity [2] [3]. In this review, we attempt to shed more light on the role of hypofibrinolysis in predisposition to arterial vascular events. We provide a brief overview of the coagulation system followed by addressing the role of impaired coagulation, anticoagulation, and fibrinolysis in acute vascular conditions, including coronary artery disease. We also discuss the prognostic implications of coagulation biomarkers regarding arterial thrombotic events, addressing, in particular, people who are exposed to metabolic risks (hyperlipidemia, hypertension, and diabetes). We conclude that affecting coagulation appears to contribute to residual thrombosis risk in individuals with arterial disease on antiplatelet therapy, and targeting proteins in the fibrinolytic and coagulant system represents a viable strategy to improve outcomes in this population. Future work is required to refine the antithrombotic approach by modulating pathological abnormalities in the fibrinolytic and anticoagulant system and tailoring the therapy according to the need of each individual

Arterial Complications following Total Knee Arthroplasty (TKA): A Systematic Review and Proposal for Improved Monitoring.

Total knee arthroplasty (TKA) is a common operation and is becoming more common due to population aging and increasing BMI. TKA provides excellent improvement in quality of life but carries risk of arterial complications in the perioperative period. This systematic review aims to provide a greater understanding of the incidence of such complications, and time taken to diagnose arterial injury. PubMed, Medline, Ovid SP and EMBASE databases were searched with the following MeSH keywords: 'complication', 'vascular injury', 'ischaemia', 'spasm', 'thrombosis', 'pseudoaneurysm', 'transection', 'pulse', 'ABPI OR ABI', 'Doppler', 'amputation'. All arterial vascular events in the perioperative state of the total knee replacement were included. Records were independently screened by two reviewers, and data was extracted according to a pre-determined proforma. Overall incidence and time to diagnosis was calculated for complications. Systematic review registration PROSPERO: CRD42018086643. No funding was received. Twelve studies were selected for inclusion. A total of 3325 cases of arterial complications were recorded across all studies, and were divided into three categories, pseudoaneurysms (0.06%); ischaemia and thrombosis (0.17%); haemorrhage and arterial transections (0.07%). Time taken to reach the diagnosis for each complication was longest in the ischaemia and thrombosis group (6.8 days), followed by pseudoaneurysm (3.5 days) and haemorrhage and transections (3.0 days). TKA post-operative vascular complications are rare, but when they do occur they lead to limb and life threatening complications. This should be discussed with patients during the consent process. Current times to diagnosis represent missed opportunities to recognise arterial injury and facilitate rapid treatment of the complication. A very low threshold for seeking specialist input should be adopted, and any concern for vascular injury, such as unexplained perioperative bleeding, absent lower limb pulses in the post-operative period or unexplained severe pain should warrant immediate review by a vascular surgeon, and in centres where this is not possible, immediate blue-light transfer to the closest vascular centre.

Vascular Involvement in Behcet's Disease: An Evaluation of 147 Cases and Literature Review.

Behcet's disease (BD) is characterized by systemic vasculitis with inflammation that can affect various body organs. In BD, vasculitis primarily manifests with venous involvement, distinguishing it from other forms of systemic vasculitis. We retrospectively analyzed the demographic and clinical characteristics of 147 patients diagnosed with vascular BD in our center. Vascular BD cases accounted for 25.0% (147 out of 589) of all BD patients. A statistically significant correlation was found between gender and vascular involvement that was seen predominantly in males (76.9%). In 71 patients, a vascular event developed during follow-up for BD, while in 76 patients the disease was diagnosed after the occurrence of a vascular event (51.7%). The most common vascular event was deep vein thrombosis in the lower extremities (69.4%). Arterial involvement was primarily observed in the pulmonary arteries (12.9%). Patients with lower extremity deep vein thrombosis tended to be younger, while those with pulmonary artery involvement were typically older. Overall, veins were affected 4.5 times more frequently than arteries. The prevalent type of venous involvement was deep vein thrombosis in the lower extremities. Thrombotic events in BD cannot be solely attributed to abnormalities in thrombotic factors. The treatment of thrombotic events in BD remains contentious, with anticoagulant efficacy being debated and immunosuppressive therapy representing the primary treatment approach. Behcet's disease should be considered when a young male patient presents with an arterial or venous vascular event, especially if it is recurrent.

Clinical and Pathologic Characteristics of Essential Thrombocythemia (ET) Patients Harboring Calreticulin (CALR) Mutations

Introduction: Calreticulin (CALR) mutations comprise of a significant proportion of essential thrombocythemia (ET) patients. The frequency, types and clinical characteristics of ET patients with CALR mutations have not been widely studied. Moreover, ET patients with calreticulin (CALR) mutations are reported to have different characteristics and complications as compared to ET patients with other mutations. Methods: We studied clinical characteristics and type of CALR mutations in ET patients diagnosed and managed at our center. Data were collected retrospectively from electronic health records and patients' files. We collected information on age, gender, presentation symptoms, history and development of vascular complications during follow up, risk category, blood counts at diagnosis, type of CALR mutation, therapy received, and any association of mutations with clinical and laboratory parameters. Results: Twenty patients were diagnosed with ET harboring CALR mutations with a median age of 51 years (range 25-66); 14 (70%) were males. The diagnosis was made in most patients because of an incidental finding of high platelet count and only 3 (15%) had symptoms at diagnosis. One patient presented with limb ischemia at diagnosis while 3 patients had prior history of arterial vascular events. Majority of the patients were in the low-risk category (65%), while 5 (25%) patients had high-risk disease at diagnosis. Seventeen (85%) patients were treated with aspirin, 15 (75%) with hydroxyurea, and 3 with anagrelide. Median platelet count at diagnosis of ET was 960 x 109 (range 463-1584; reference 150-400). Eight (40%) patients had platelet counts above 960 x 109 at presentation. Table 1 shows the genetic variants, frequency and the type of CALR mutations. Two patients had mutations of uncertain significance in the CALR gene. After a median follow up of 48 months (range 2-204), only one patient developed thrombosis (pulmonary embolism); this patient also had arterial thrombosis previously. One patient with type 2 mutation progressed to myelofibrosis (MF) and remains alive on ruxolitinib and regular blood transfusions after 84 months of follow up post MF diagnosis. One 56-year-old male patient underwent surgery for coronary artery disease and severe aortic stenosis and died of hemothorax and multiple complication. Vascular events in 3 of the 4 patients occurred in those with type-2 mutations. Conclusions: Majority of ET patients harboring CALR mutations were males and presented without symptoms with incidental diagnosis, and had low risk disease. Type 1 and 2 mutations occurred with almost equal frequency. Vascular complications were infrequent after diagnosis and only one patient developed thrombosis during follow up. These finding are consistent with other studies of ET with CALR mutations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The new 2022 ESC Guidelines on Cardio-oncology and their impact on the Acute Cardiovascular Care Society.

In this perspective piece on the recently published ESC Guidelines on Cardio-oncology and the Consensus Statements from the Acute Cardiovascular Care Association, we summarize key learning points regarding the management of acute cardiovascular disease in patients with cancer. This document outlines where other pre-existing ESC Guidelines can be applied to the management of acute cardiovascular disease in patients with cancer while simultaneously highlighting important gaps in knowledge that require further research. Cancer and cardiovascular disease share common risk factors and often co-exist, especially in older patients. In addition, patients with cancer undergoing active treatment are exposed to multiple, potentially cardiotoxic drugs, which may manifest as a variety of cardiovascular events, including left-ventricular systolic dysfunction and heart failure, arrhythmias, hypertension, or acute venous and arterial vascular events. Knowledge about potential causative cancer therapeutics is necessary for rapid recognition and management to improve cardiovascular outcomes and guide ongoing cancer treatment. Specifically, the importance of rapidly interrupting culprit cancer drugs is highlighted, as well as instituting standard guideline-based therapies for conditions such as acute heart failure and acute coronary syndromes [ST-elevation myocardial infarction and high-risk non-ST-elevation acute coronary syndrome (ACS)]. Given the high prevalence of thrombocytopenia and increased bleeding risk in patients with cancer, we are provided with platelet cut-offs for the use of different antiplatelet agents and anticoagulants for patients with ACS and atrial arrhythmias. In contrast, given the hypercoagulable milieu of cancer, we are provided information regarding types of anticoagulants, drug-drug interactions, and duration of anticoagulation in patients with acute venous thromboembolism, as well as for atrial fibrillation. They also discuss the diagnostic and treatment strategies for the unique cardiotoxicities seen with novel cancer therapeutics such as immune checkpoint inhibitors and chimeric receptor antigen T-cell therapy. Last, but not least, the authors emphasize that the care of these patients requires close collaboration between cardiology and oncology to maximize both cardiovascular and cancer outcomes.

Cardiovascular Risk in Myositis Patients Compared to the General Population: Preliminary Data From a Single-Center Cross-Sectional Study.

BackgroundIdiopathic inflammatory myopathies (IIM) are associated with systemic inflammation, limited mobility, and glucocorticoid therapy, all of which can lead to metabolism disturbances, atherogenesis, and increased cardiovascular (CV) risk. The aim of this study was to assess the CV risk in IIM patients and healthy controls (HC), and its association with disease-specific features.MethodsThirty nine patients with IIM (32 females; mean age 56; mean disease duration 4.8 years; dermatomyositis: n = 16, polymyositis: n = 7, immune-mediated necrotizing myopathy: n = 8, anti-synthetase syndrome: n = 8) and 39 age-/sex-matched HC (32 females, mean age 56) without rheumatic diseases were included. In both groups, subjects with a history of CV disease (angina pectoris, myocardial infarction, cerebrovascular, and peripheral arterial vascular events) were excluded. Muscle involvement, disease activity, and tissue damage were evaluated (Manual Muscle Test-8, Myositis Intention to Treat Activity Index, Myositis Damage Index). Comorbidities and current treatment were recorded. All participants underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition (by densitometry and bioelectric impedance). The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE, charts for the European population) and its modifications.ResultsCompared to HC, there was no significant difference in IIM patients regarding blood pressure, ABI, PWV, CIMT, and the risk of fatal CV events by SCORE or SCORE2, or subclinical atherosclerosis (CIMT, carotid plaques, ABI, and PWV). The calculated CV risk scores by SCORE, SCORE2, and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to the results of carotid plaque presence and CIMT; however, none of them was demonstrated to be significantly more accurate. Other significant predictors of CV risk in IIM patients included age, disease duration and activity, systemic inflammation, lipid profile, lean body mass, and blood pressure.ConclusionsNo significant differences in CV risk factors between our IIM patients and HC were observed. However, in IIM, CV risk was associated with age, disease duration, duration of glucocorticoid therapy, lipid profile, and body composition. None of the currently available scoring tools (SCORE, SCORE2, mSCORE) used in this study seems more accurate in estimating CV risk in IIM.

Prothrombotic role of antiphospholipid antibodies in a patient with sickle cell disease

<abstract> <p>Sickle cell disease (SCD) is a common inherited condition in African, Caribbean, and Mediterranean countries. SCD is a hematologic disorder caused by a well-characterized point mutation in the β-globin gene, which produces an abnormal hemoglobin S that results in the sickling of red blood cells in deoxygenated conditions. Patients with SCD display a “hypercoagulation state” leading to an increased risk of severe venous and arterial thrombotic vascular events. Herein we report a case of severe thrombotic complications in a patient with SCD who showed high antiphospholipid antibodies (APA) levels during vascular occlusions.</p> </abstract>

A Wireless Near-Infrared Spectroscopy Device for Flap Monitoring: Proof of Concept in a Porcine Musculocutaneous Flap Model.

Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are highly sensitive for detecting malperfusion. However, the clinical utility and user experience are limited by the wired connection between the sensor and bedside console. This wire leads to instability of the flap-sensor interface and may cause false alarms. We present a novel wearable wireless NIRS sensor for continuous fasciocutaneous free flap monitoring. This waterproof silicone-encapsulated Bluetooth-enabled device contains two light-emitting diodes and two photodetectors in addition to a battery sufficient for 5 days of uninterrupted function. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. Devices were tested in four flaps using three animals. Both devices produced very similar tissue oxygen saturation (StO2) tracings throughout the vascular clamping events, with obvious and parallel changes occurring on arterial clamping, arterial release, venous clamping, and venous release. Small interdevice variations in absolute StO2 value readings and magnitude of change were observed. The normalized cross-correlation at zero lag describing correspondence between the novel NIRS and T.Ox devices was >0.99 in each trial. The wireless NIRS flap monitor is capable of detecting StO2 changes resultant from arterial vascular occlusive events. In this porcine flap model, the functionality of this novel sensor closely mirrored that of the T.Ox wired platform. This device is waterproof, highly adhesive, skin conforming, and has sufficient battery life to function for 5 days. Clinical testing is necessary to determine if this wireless functionality translates into fewer false-positive alarms and a better user experience.

Association of Tyrosine Kinase Inhibitors with Vascular Adverse Events: A Cohort Study Using Pooled Electronic Health Record

IntroductionTyrosine Kinase Inhibitor (TKI)-associated vascular adverse events (VAE) have emerged as one of the challenges in the management of chronic myeloid leukemia (CML). Available knowledge on association of TKIs with VAE mostly comes from randomized clinical trials but there are concerns about comprehensiveness of the reported data. This is because different trials have relied on differing definitions to capture VAE. It is generally considered that TKI-associated VAE reported in clinical trials are underestimates. In this retrospective cohort study, we used a clinical informatics approach to collect data on CML pts from multiple, distinct electronic health records across several different healthcare systems and report on the prevalence of VAE in CML cohorts treated on different TKIs.MethodsExplorys Enterprise Performance Management (EPM) is a HIPAA-compliant database containing de-identified clinical data on 50 million pts from 26 healthcare networks comprising 360 hospitals since 1999. As this database is HIPAA-compliant, IRB approval was waived by Cleveland Clinic IRB. In this study, we used the EPM database's “power search” tool to create CML cohort and then identified VAE events occurring after TKI initiation using specific temporal relationships. Power searches for data extraction relies on associating clinical informatics standard ontologies that includes Current Procedural Terminology (CPT) (for procedures), International Classification of Diseases 9th edition (ICD-9) and 10th edition (for diagnoses), logical observation identifiers names and codes (LOINC) (for laboratory information), Medical Subject Headings (MeSH) (for medical topics), RxNorm (for pharmacy information), and Systematized Nomenclature for Medicine - Clinical Terms (SNOMED-CT) (for medical terms). We created temporal attributes linking the CML cohort to outcome of interest (VAE) using SNOMED-CT diagnosis for VAE (included coronary, cerebrovascular and peripheral arterial disease, venous thrombosis among others) and subsequently mapping it with RxNorm (all anticoagulants or antiplatelet agents in clinical use for the study time period) and CPT codes (use of inferior vena cava filter or thrombectomy). All generated quantitative data using EPM database are rounded to the nearest 10 for the purposes of de-identification.ResultsUsing Explorys, we identified a total of 2750 CML pts who were treated with imatinib, 680 pts with dasatinib, 600 pts with nilotinib and 870 pts with 2 or more TKI's. Of the five TKIs, we excluded bosutinib and ponatinib from analysis because of low pt numbers (<100). Baseline demographic characteristics showing overall distribution of atherosclerotic disease in CML pts treated with these three TKIs are shown in Table 1. Of note, there was a high prevalence of coronary arteriosclerosis in these TKI-treated cohorts - 29% in imatinib cohort, 28% in nilotinib group and 22% in pts who received dasatinib. A total of 780 VAE (28%) were identified after initiation of imatinib - 19% (520/2750) of them were arterial events and 9.5% (260/2750) were venous. Following initiation of nilotinib, 160 VAE occurred with a prevalence rate of 26.6% - 18.3% (110/600) of them were arterial and 8.3% (50/600) were venous. After starting dasatinib, 150 VAE was identified with a prevalence rate of 22% - 14.7% (100/680) of them were arterial events and 7.4% (50/680) were venous. In CML pts treated with 2 or more TKIs, the prevalence of VAE was highest at 36.8% (320/870) - 24.1% (210/870) were arterial and 12.6% were venous events.Conclusions:In this population based study of CML pts using clinical informatics approach, we report a much higher rate of VAE, both arterial and venous in TKI cohorts compared to that reported in clinical trials. Ontology based linking of CML with outcomes of interest and cross confirmation with subsequent anticoagulation treatment received ensures accuracy of the reported events using this approach. Arterial vascular events ranged from 15-20% whereas venous events were reported in the range of 8-9% for the three TKIs examined. Surprisingly high rates of VAE noted in the imatinib cohort could be the result of lead time bias because of earlier introduction of imatinib. Additional analysis of this cohort is underway to characterize this association. [Display omitted] DisclosuresGerds:Incyte: Consultancy; CTI BioPharma: Consultancy. Advani:Takeda/ Millenium: Research Funding; Pfizer: Consultancy. Majhail:Sanofi: Honoraria; Anthem, Inc.: Consultancy. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees.

Platelet bound complement split product (PC4d) is a marker of platelet activation and arterial vascular events in Systemic Lupus Erythematosus

Platelet-bound complement activation products (PC4d) are associated with thrombosis in Systemic Lupus Erythematosus (SLE). This study investigated the effect of PC4d on platelet function, as a mechanistic link to arterial thrombosis. In a cohort of 150 SLE patients, 13 events had occurred within five years of enrollment. Patients with arterial events had higher PC4d levels (13.6 [4.4–24.0] vs. 4.0 [2.5–8.3] net MFI), with PC4d 10 being the optimal cutoff for event detection. The association of arterial events with PC4d remained significant after adjusting for antiphospholipid status, smoking, and prednisone use (p = 0.045). PC4d levels correlated with lower platelet counts (r = −0.26, p = 0.002), larger platelet volumes (r = 0.22, p = 0.009) and increased platelet aggregation: the adenosine diphosphate (ADP) concentration to achieve 50% maximal aggregation (EC50) was lower in patients with PC4d 10 compared with PC4d < 10 (1.6 vs. 3.7, p = 0.038, respectively). These results suggest that PC4d may be a mechanistic marker for vascular disease in SLE.

Fibrinolysis in Acute and Chronic Cardiovascular Disease.

The formation of an obstructive thrombus within an artery remains a major cause of mortality and morbidity worldwide. Despite effective inhibition of platelet function by modern antiplatelet therapies, these agents fail to fully eliminate atherothrombotic risk. This may well be related to extensive vascular disease, beyond the protective abilities of the treatment agents used. However, recent evidence suggests that residual vascular risk in those treated with modern antiplatelet therapies is related, at least in part, to impaired fibrin clot lysis. In this review, we attempt to shed more light on the role of hypofibrinolysis in predisposition to arterial vascular events. We provide a brief overview of the coagulation system followed by addressing the role of impaired fibrin clot lysis in acute and chronic vascular conditions, including coronary artery, cerebrovascular, and peripheral vascular disease. We also discuss the role of combined anticoagulant and antiplatelet therapies to reduce the risk of arterial thrombotic events, addressing both efficacy and safety of such an approach. We conclude that impaired fibrin clot lysis appears to contribute to residual thrombosis risk in individuals with arterial disease on antiplatelet therapy, and targeting proteins in the fibrinolytic system represents a viable strategy to improve outcome in this population. Future work is required to refine the antithrombotic approach by modulating pathological abnormalities in the fibrinolytic system and tailoring therapy according to the need of each individual.

Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS).

The comparative cardiovascular risk profiles of available hormone therapies for the treatment of prostate cancer is not known. We queried the U.S. Food and Drug Administration Adverse Event Reporting System, a retrospective, pharmacovigilance database, for cardiovascular adverse event reports in men with prostate cancer receiving gonadotropin releasing hormone (GnRH) agonists, GnRH antagonists, androgen receptor antagonists, and/or androgen synthesis inhibitors from January 2000 to April 2020. Cardiovascular adverse events accounted for 6,231 reports (12.6%) on hormone monotherapy and 1,793 reports (26.1%) on combination therapy. Arterial vascular events were reported most commonly, followed by arrhythmias, heart failure, and venous thromboembolism. Compared to GnRH agonists, GnRH antagonists were associated with fewer cardiovascular adverse event reports as monotherapy (adjusted reporting odds ratio [ROR]=0.70 [95% CI 0.59-0.84], p <0.001) and as combination therapy (ROR=0.47 [0.34-0.67], p <0.0001), driven by reductions in arterial vascular events. Second generation androgen receptor antagonists and abiraterone were associated with more reports of hypertension requiring hospitalization (ROR=1.21 [1.03-1.41], p=0.02 and ROR=1.19 [1.01-1.40], p=0.03, respectively), and more heart failure events when used in combination with GnRH antagonists (ROR=2.79 [1.30-6.01], p=0.009 and ROR=2.57 [1.12-5.86], p=0.03). In this retrospective analysis of a pharmacovigilance database, arterial vascular events were the most commonly reported cardiovascular adverse events in men on hormone therapy for prostate cancer. GnRH antagonists were associated with fewer reports of overall cardiovascular events and arterial vascular events than GnRH agonists. Additional study is needed to identify optimal strategies to reduce cardiovascular morbidity among men with prostate cancer receiving hormone therapy.

The incidence and risk factors for venous thromboembolic events in patients with psoriasis and psoriatic arthritis

ObjectivesThe risk of arterial vascular events is increased in patients with psoriatic disease (PsD), however, limited information exists about the risk of venous thromboembolism (VTE) in these patients. We assessed the incidence and risk factors for VTE in patients with PsD. MethodsA multicentre cohort study was conducted involving patients with PsD followed prospectively from 1994 to 2020. Information about VTE, including pulmonary embolism (PE) and deep venous thrombosis (DVT), was obtained from provincial hospitalization databases. The incidence rate and cumulative probability of developing VTE were computed. Cox proportional hazards models were used to assess the association between risk factors, including comorbidities and disease-related factors, and the first VTE. ResultsA total 2,433 patients with PsD were analysed with 26 incident VTE (7 DVT alone, 12 PE alone, and 7 both PE and DVT). The incidence rates of the first VTE, DVT, and PE were 12, 6.5, and 8.8 events per 10,000 patient-years, respectively. The cumulative proportion of individuals developing VTE was 4.6% by 80 years of age. Independent predictors for VTE included older age, diabetes mellitus, and corticosteroid usage (all p<0.05). ConclusionOlder patients with PsD, those with diabetes, and those using corticosteroids are at a higher risk of developing VTE. Risk stratification of patients with these identified risk factors for VTE will allow for more individualized patient management and improved medication selection.

Abstract 14603: Arterial Vascular Events in Men With Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS)

Introduction: Hormone therapy has been associated with adverse cardiovascular events including arterial vascular events in men with prostate cancer. It is unclear if the risk of arterial vascular events varies by type of hormone therapy used. Methods: The Food and Drug Administration’s Adverse Event Reporting System (FAERS) was used to compare arterial vascular event reporting in men receiving hormone therapy from 01/01/2000 to 04/30/2020 for prostate cancer. Therapies evaluated were gonadotrophin-releasing hormone (GnRH) agonists (i.e. leuprolide), GnRH antagonists (i.e. degarelix), androgen receptor (AR) antagonists (i.e. bicalutamide) and abiraterone. Arterial vascular events included coronary artery disease, myocardial infarction, ischemic stroke, peripheral vascular disease, and hypertension requiring hospitalization. Polytomous logistic regression (adjusted for age, need for hospitalization, and event reporting source) was performed for non-GnRH agonists as compared to GnRH agonists. Results: Among 34,466 events reported during the study period on single agent therapy, 10.6% were arterial vascular events (5.9% hypertension requiring hospitalization, 2.3% coronary artery disease or myocardial infarction, 2.1% ischemic stroke, and 0.3% peripheral vascular disease). Median age of those with reported arterial vascular events was 76 years (IQR 70 - 82). Arterial vascular events were reported less commonly in men receiving AR antagonists (adjusted reporting odds ratio [ROR] 0.7 [95% CI 0.7-0.8], p&lt;0.0001), abiraterone (ROR 0.9 [0.8-0.98], p=0.02), and GnRH antagonists (ROR 0.9 [0.7-1.1], p=0.15) as compared to those receiving GnRH agonists. Conclusion: Arterial vascular events are reported more commonly in men receiving GnRH agonists for prostate cancer as compared with other types of hormone monotherapy. Use of non-GnRH agonists may reduce the risk of adverse cardiovascular events on hormone therapy in men with prostate cancer.