Prothrombotic state, endothelial injury, and echocardiographic changes in non-active sarcoidosis patients.

Sarcoidosis is a multisystem inflammatory granulomatous disease of unknown cause that most commonly affects lungs and lymph nodes, with frequent yet asymptomatic cardiac involvement. The epidemiologically associated cardiovascular risk suggests an underlying prothrombotic state and endothelial dysfunction, currently understudied in the available literature. Therefore, we aimed to investigate prothrombotic plasma properties together with selected echocardiographic and laboratory biomarkers of cardiovascular injury in that disease. N = 53 patients with pulmonary sarcoidosis in clinical remission and N = 66 matched controls were assessed for inflammatory and endothelial injury biomarkers, plasma thrombin generation profile, and echocardiographic and lung function parameters. Sarcoidosis cases had impaired systolic and diastolic left ventricular function, higher concentrations of inflammatory markers, D-dimer and factor VIII activity compared to the controls. The coexistence of extrapulmonary disease was associated with elevated circulating vascular cell adhesion molecule 1, while cases with hypercalcemia had higher thrombomodulin concentration. Sarcoidosis was characterized by the unfavorably altered thrombin generation profile, reflected by the 16% higher endogenous thrombin potential (ETP), 24% increased peak thrombin concentration, and 12% shorter time to thrombin peak in comparison to the control group. ETP was higher in cases with proxies of pulmonary restriction, extrapulmonary-extracutaneous manifestation, and need for corticosteroids use. Despite the clinical remission, sarcoidosis is related to prothrombotic plasma properties and signs of endothelial injury, likely contributing to the higher risk of cardiovascular events. In addition, subclinical cardiac involvement may play an additional role, although further clinical and experimental studies are needed to verify these findings.

Posture commonly and considerably modifies stenosis of left common iliac and left renal veins in women diagnosed with pelvic venous disorder.

OBJECTIVE: Pelvic venous incompetence or pelvic congestion syndrome (commonly referred to as pelvic venous disorder [PVD]) is increasingly diagnosed, especially in multiparous women. This may be either primary or secondary to pelvic venous outflow obstruction-left common iliac vein (LCIV) or left renal vein (LRV) stenosis. Intravascular ultrasound (IVUS) examination performed in the supine position is commonly used for diagnosis of LRV and LCIV stenosis; however, body position may affect the cross-sectional area (CSA) of both of these veins during IVUS. The aim of the study was to test the hypothesis that postural changes may significantly affect the CSA of the LRV and LCIV. METHODS: A single-arm, single-center cohort study of women suffering from PVD was performed at a tertiary hospital in Poland. It comprised consecutive patients with either pelvic vein reflux or suggestion of LCIV or LRV obstruction but no signs of deep venous thrombosis. IVUS examination of the iliac veins, inferior vena cava, and LRV was performed in the supine position. IVUS of the LRV and LCIV was performed also with a Valsalva maneuver and with patients lying on the left side and standing. A 60% CSA reduction was used as a cutoff value between significant and nonsignificant vein stenosis. RESULTS: A total of 41 women were examined. Significant stenosis of the LRV was seen in 22 patients (55%) supine but in only 4 (10%) patients studied when lying on the left side and in 27 (67.5%) patients studied while standing. Significant stenosis of the LCIV was seen in 26 supine patients (63.4%), in 8 lying on the left side (19.5%), and in 10 (24.4%) standing. CONCLUSIONS: Postural changes dramatically affect CSA of the LCIV and LRV and thus the degree of stenosis in women diagnosed with PVD. Stenosis found in patients while supine often disappears when the position is changed to lying on the left side or to standing. Therapeutic decisions based on assessment of CSA reduction in the supine position are likely to be inadequate.

Atorvastatin and Conditioned Media from Atorvastatin-Treated Human Hematopoietic Stem/Progenitor-Derived Cells Show Proangiogenic Activity In Vitro but Not In Vivo.

Myeloid angiogenic cells (MAC) derive from hematopoietic stem/progenitor cells (HSPCs) that are mobilized from the bone marrow. They home to sites of neovascularization and contribute to angiogenesis by production of paracrine factors. The number and function of proangiogenic cells are impaired in patients with diabetes or cardiovascular diseases. Both conditions can be accompanied by decreased levels of heme oxygenase-1 (HMOX1), cytoprotective, heme-degrading enzyme. Our study is aimed at investigating whether precursors of myeloid angiogenic cells (PACs) treated with known pharmaceuticals would produce media with better proangiogenic activity in vitro and if such media can be used to stimulate blood vessel growth in vivo. We used G-CSF-mobilized CD34+ HSPCs, FACS-sorted from healthy donor peripheral blood mononuclear cells (PBMCs). Sorted cells were predominantly CD133+. CD34+ cells after six days in culture were stimulated with atorvastatin (AT), acetylsalicylic acid (ASA), sulforaphane (SR), resveratrol (RV), or metformin (Met) for 48 h. Conditioned media from such cells were then used to stimulate human aortic endothelial cells (HAoECs) to enhance tube-like structure formation in a Matrigel assay. The only stimulant that enhanced PAC paracrine angiogenic activity was atorvastatin, which also had ability to stabilize endothelial tubes in vitro. On the other hand, the only one that induced heme oxygenase-1 expression was sulforaphane, a known activator of a HMOX1 inducer-NRF2. None of the stimulants changed significantly the levels of 30 cytokines and growth factors tested with the multiplex test. Then, we used atorvastatin-stimulated cells or conditioned media from them in the Matrigel plug in vivo angiogenic assay. Neither AT alone in control media nor conditioned media nor AT-stimulated cells affected numbers of endothelial cells in the plug or plug's vascularization. Concluding, high concentrations of atorvastatin stabilize tubes and enhance the paracrine angiogenic activity of human PAC cells in vitro. However, the effect was not observed in vivo. Therefore, the use of conditioned media from atorvastatin-treated PAC is not a promising therapeutic strategy to enhance angiogenesis.

Myocardial Injury is More Common than Deep Venous Thrombosis after Vascular Surgery and is Associated with a High One Year Mortality Risk.

OBJECTIVE/BACKGROUND: Venous thromboembolism (VTE) has been considered the dominant major life threatening vascular complication after non-cardiac surgery, but recent studies have shifted the emphasis toward myocardial injury after non-cardiac surgery (MINS) as a common adverse event in the peri-operative setting. The aim of the present study was to compare the incidence and influence on mortality of two dominant venous and arterial events in the peri-operative period by prospectively screening a consecutive cohort of patients undergoing vascular surgery. METHODS: This was a sub-study of Vascular Events In Non-cardiac Surgery Patients Cohort Evaluation (VISION), the main objective of which was to evaluate major peri-operative complications after non-cardiac surgery. Patients undergoing vascular surgery had their blood collected to measure the Roche fifth generation high sensitivity troponin T (hsTnT) assay before and four times after surgery (6-12 h post-operatively, on the first, second, and third day following the procedure). MINS was defined as an elevated post-operative hsTnT ≥65 ng/L or an hsTnT ≥20 to <65 ng/L with an absolute change of ≥5 ng/L that was judged to be due to ischaemia. All patients underwent ultrasound venous compression testing for deep vein thrombosis (DVT) before, 4, and 7 days after surgery and follow-up was performed by telephone 30 days and 1 year after surgery. RESULTS: In total, 164 consecutive patients were included in this sub-study. MINS was diagnosed in 39 patients (23.8%) and DVT in four patients (2.4%). The 1 year mortality was higher in MINS (9/39 [23.1%]) than non-MINS patients (9/125 [7.2%]; p = .006). None of the patients who developed DVT died in the first year after surgery. CONCLUSION: MINS is a common complication after vascular surgery. It occurs more frequently than DVT and is associated with high 1 year mortality.

Impaired responsiveness to clopidogrel and aspirin in patients with recurrent stent thrombosis following percutaneous intervention for peripheral artery disease.

Patients with peripheral artery disease (PAD) following peripheral percutaneous transluminal angioplasty (PTA) with stent implantation are prone to stent thrombosis despite treatment with aspirin and clopidogrel. Impaired clopidogrel responsiveness is associated with increased risk of ischemic events in patients following coronary stent implantation. We sought to assess platelet responsiveness to clopidogrel and aspirin in patients with PAD and recurrent stent thrombosis. Platelet aggregation induced by 5 and 20 µmol/l adenosine diphosphate (ADP) and 0.5 mmol/l arachidonic acid (AA), together with platelet reactivity index (PRI) and serum thromboxane B(2) (TXB(2)), were determined in 11 patients with PAD and a history of stent thrombosis (mean, 3.1 ± 1.14) after PTA and in 15 patients with PAD with no such history, also in 11 controls with coronary artery disease (CAD) and previous stent thrombosis. Platelet aggregation to 5 µmol/l ADP was higher in subjects with PAD and stent thrombosis than in those without stent thrombosis (p = 0.0003) and CAD subjects (p = 0.002). Aggregation induced by 20 µmol/l ADP was higher in PAD group with stent thrombosis than in PAD subjects without thrombosis (p = 0.004). The PAD group with stent thrombosis had higher AA-induced platelet aggregation than CAD controls (p = 0.007) and serum TXB(2) concentrations higher than PAD group without thrombosis (p = 0.002) and CAD group (p = 0.02). Concluding, platelet responsiveness to clopidogrel and aspirin is impaired in patients with PAD and recurrent stent thrombosis following PTA, as compared with similar individuals with CAD, and PAD with no history of stent thrombosis. This indicates that atherosclerosis burden affects platelet function and might contribute to stent thrombosis following percutaneous intervention in peripheral arteries.

[Polish guidelines for the prevention and treatment of venous thromboembolism. 2012 update]. / Polskie wytyczne profilaktyki i leczenia zylnej choroby zakrzepowo-zatorowej. Aktualizacja 2012.

The overall objective of the Polish guidelines for the prevention and treatment of venous thromboembolism is to increase patient benefit and safety by appropriate prevention and treatment of deep vein thrombosis and pulmonary embolism as well as proper management of the complications associated with antithrombotic and thrombolytic therapy. These guidelines apply to adult trauma, cancer, surgical, and medical patients as well as those at increased risk of venous thromboembolism. Specific recommendations have been formulated for pregnant women, patients requiring surgery while receiving long-term oral anticoagulant treatment, and patients undergoing regional anesthesia and/or analgesia. We chose to update the existing Polish guidelines with the use of the most recent high-quality international guidelines that we identified and adjusted the final product to Polish cultural and organizational setting. We based our recommendations primarily on the 9th edition of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines on Antithrombotic Therapy and Prevention of Thrombosis, the European Society of Cardiology Guidelines on the Diagnosis and Management of Acute Pulmonary Embolism, the 3rd edition of the American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines on Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy, the ACOG practice bulletin on thromboembolism in pregnancy (Number 123), and Guidance from the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis on the Duration of Anticoagulant Therapy after a First Episode of Unprovoked Pulmonary Embolus or Deep Vein Thrombosis, as well as two other Polish practice guidelines on the prophylaxis and treatment of venous thromboembolism and the management of patients treated with oral direct inhibitors of factor X or factor II. To make recommendations regarding specific management issues that had not been addressed in other guidelines, or whenever the panel members felt they needed additional information to reach the decision, we also consulted the authors of guidelines developed by other professional societies and organizations as well as additional sources of evidence. For each adapted recommendation, we explicitly assessed its relevance and applicability in the context of the healthcare system in Poland. When necessary, we explicitly stated the rationale for modification of the previously published recommendations and judgements about the values and preferences we assumed. The information regarding reimbursement of drugs mentioned in the recommendations was added in chapters 6-9 and 13 and approved by the National Health Fund. The final version of the practice guidelines was officially approved by the scientific societies and institutions listed at the beginning of the document.