Endothelial dysfunction in patients with spontaneous venous thromboembolism

Background and Objectives A high incidence of atherosclerotic lesions and cardiovascular events has been reported in patients with spontaneous venous thromboembolism. Endothelial dysfunction is an early marker of atherosclerosis and has predictive value for ischemic events. We have evaluated endothelial function in patients with a history of spontaneous venous thromboembolism.Design and Methods Patients with a history of symptomatic, objectively confirmed, spontaneous venous thromboembolism were included in a case-control study. Exclusion criteria were any known risk factors for cardiovascular diseases, other conditions associated with endothelial dysfunction, estro-progestinic therapy or pregnancy. Controls were age-(±5 years) and sex-matched subjects with the same exclusion criteria but without previous venous thromboembolism. Endothelial function was evaluated by the non-invasive measurement of flow-mediated vasodilation of the brachial artery and of plasma markers of endothelium activation; platelet activation parameters were also measured.Results Twenty-eight cases (8 females; mean age 59±15 years) and 28 controls (8 females; mean age 58±15) were studied. Flow-mediated vasodilation was 3.5±0.6% in cases (95% CIs: 2.2 to 4.8) and 5.7±0.6% (4.2 to 6.8) in controls (p=0.015). Brachial artery blood flow and hyperemic blood flow did not differ between the two groups. Plasma von Willebrand factor and soluble P-selectin levels were significantly higher in patients with venous thromboembolism, while plasma soluble CD40 ligand and urinary 11-dehydro-TxB2 levels were similar in cases and controls.Interpretation and Conclusions Patients with spontaneous venous thromboembolism have endothelial dysfunction, unlike age- and sex- matched controls. This finding suggests that spontaneous venous thromboembolism may be a condition associated with an enhanced risk of atherosclerosis

Guideline on carotid surgery for stroke prevention: updates from the Italian Society of Vascular and Endovascular Surgery. A trend towards personalized medicine

Background: This guideline (GL) on carotid surgery as updating of "Stroke: Italian guidelines for Prevention and Treatment" of the ISO-SPREAD Italian Stroke Organization-Group, has recently been published in the National Guideline System and shared with the Italian Society of Vascular and Endovascular Surgery (SICVE) and other Scientific Societies and Patient's Association. Methods: GRADE-SIGN version, AGREE quality of reporting checklist. Clinical questions formulated according to the PICO model. Recommendations developed based on clinical questions by a multidisciplinary experts' panel and patients' representatives. Systematic reviews performed for each PICO question. Considered judgements filled by assessing the evidence level, direction, and strength of the recommendations. Results: The panel provided indications and recommendations for appropriate, comprehensive, and individualized management of patients with carotid stenosis. Diagnostic and therapeutic processes of the best medical therapy, carotid endarterectomy (CEA), carotid stenting (CAS) according to the evidences and the judged opinions were included. Symptomatic carotid stenosis in elective and emergency, asymptomatic carotid stenosis, association with ischemic heart disease, preoperative diagnostics, types of anesthesia, monitoring in case of CEA, CEA techniques, comparison between CEA and CAS, post-surgical carotid restenosis, and medical therapy are the main topics, even with analysis of uncertainty areas for risk-benefit assessments in the individual patient (personalized medicine [PM]). Conclusions: This GL updates on the main recommendations for the most appropriate diagnostic and medical-surgical management of patients with atherosclerotic carotid artery stenosis to prevent ischemic stroke. This GL also provides useful elements for the application of PM in good clinical practice

Comparison and combination of a hemodynamics/biomarkers-based model with simplified PESI score for prognostic stratification of acute pulmonary embolism: findings from a real world study

Background: Prognostic stratification is of utmost importance for management of acute Pulmonary Embolism (PE) in clinical practice. Many prognostic models have been proposed, but which is the best prognosticator in real life remains unclear. The aim of our study was to compare and combine the predictive values of the hemodynamics/biomarkers based prognostic model proposed by European Society of Cardiology (ESC) in 2008 and simplified PESI score (sPESI).Methods: Data records of 452 patients discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. The ESC model and sPESI were retrospectively calculated and compared by using Areas under Receiver Operating Characteristics (ROC) Curves (AUCs) and finally the combination of the two models was tested in hemodinamically stable patients. All cause and PE-related in-hospital mortality and fatal or major bleedings were the analyzed endpointsResults: All cause in-hospital mortality was 25% (16.6% PE related) in high risk, 8.7% (4.7%) in intermediate risk and 3.8% (1.2%) in low risk patients according to ESC model. All cause in-hospital mortality was 10.95% (5.75% PE related) in patients with sPESI score ≥1 and 0% (0%) in sPESI score 0. Predictive performance of sPESI was not significantly different compared with 2008 ESC model both for all cause (AUC sPESI 0.711, 95% CI: 0.661-0.758 versus ESC 0.619, 95% CI: 0.567-0.670, difference between AUCs 0.0916, p=0.084) and for PE-related mortality (AUC sPESI 0.764, 95% CI: 0.717-0.808 versus ESC 0.650, 95% CI: 0.598-0.700, difference between AUCs 0.114, p=0.11). Fatal or major bleedings occurred in 4.30% of high risk, 1.60% of intermediate risk and 2.50% of low risk patients according to 2008 ESC model, whereas these occurred in 1.80% of high risk and 1.45% of low risk patients according to sPESI, respectively. Predictive performance for fatal or major bleeding between two models was not significantly different (AUC sPESI 0.658, 95% CI: 0.606-0.707 versus ESC 0.512, 95% CI: 0.459-0.565, difference between AUCs 0.145, p=0.34). In hemodynamically stable patients, the combined endpoint in-hospital PE-related mortality and/or fatal or major bleeding (adverse events) occurred in 0% of patients with low risk ESC model and sPESI score 0, whilst it occurred in 5.5% of patients with low-risk ESC model but sPESI ≥1. In intermediate risk patients according to ESC model, adverse events occurred in 3.6% of patients with sPESI score 0 and 6.65% of patients with sPESI score ≥1.Conclusions: In real world, predictive performance of sPESI and the hemodynamic/biomarkers-based ESC model as prognosticator of in-hospital mortality and bleedings is similar. Combination of sPESI 0 with low risk ESC model may identify patients with very low risk of adverse events and candidate for early hospital discharge or home treatment.

Walking-induced endothelial dysfunction predicts ischemic cardiovascular events in patients with intermittent claudication

Endothelial dysfunction, evaluated by flow-mediated dilatation (FMD), predicts adverse cardiovascular events in patients with intermittent claudication (IC). IC is an example of repeated ischemia/reperfusion injury that may contribute to the progression of vascular disease by worsening endothelial function, a trigger for acute cardiovascular events. The predictive value of effort-induced endothelial dysfunction for cardiovascular events in patients with IC has not been studied previously. The objective of this study was to assess whether exercise-induced endothelial dysfunction is predictive of adverse cardiovascular outcome in IC. In 44 patients with IC, we measured brachial artery FMD by B-mode ultrasonography at rest and 10 minutes after a maximal treadmill exercise. Treadmill exercise halved the FMD (from 3.5 +/- 0.6% to 1.45 +/- 0.46%, p < 0.05). After a follow-up period of 85 (72-98) months, a total of 20 major cardiovascular events occurred. In a multivariate analysis, a post-exercise reduction of brachial FMD > 1.3% was predictive for cardiovascular events. Maximal exercise-induced endothelial dysfunction is predictive of cardiovascular events in patients with IC

Peripheral arterial occlusive disease and ischemic disease of the lower limbs are not the same condition. A proposed unambiguous Italian terminology for defining Peripheral arterial disease of lower limbs and related clinical/therapeutic implications

Not require

Peripheral arterial occlusive disease and ischemic disease of the lower limbs are not the same condition. A proposed unambiguous Italian terminology for defining Peripheral arterial disease of lower limbs and related clinical/therapeutic implications

Not require

Effect on walking distance and atherosclerosis progression of a nitric oxide-donating agent in intermittent claudication

Background: Peripheral arterial disease (PAD) is almost invariably associated with a generalized atherosclerotic involvement of the arterial tree and endothelial dysfunction. Previous short-term studies showed improvement of vascular reactivity and walking capacity in PAD patients by measures aimed at restoring nitric oxide (NO) production. NO is also known to prevent the progression of atherosclerosis. We wished to assess whether the prolonged administration of an NO-donating agent (NCX 4016) improves the functional capacity of PAD patients and affects the progression of atherosclerosis as assessed by carotid intima-media thickness (IMT). Methods: This prospective, double-blind, placebo-controlled study enrolled 442 patients with stable intermittent claudication who were randomized to NCX 4016 (800 mg, twice daily) or its placebo for 6 months. The primary study outcome was the absolute claudication distance on a constant treadmill test (10% incline, 3 km/h). The main secondary end point was the change of the mean far-wall right common carotid artery IMT. Results: The increase of absolute claudication distance at 6 months compared with baseline was 126 ± 140 meters in the placebo-treated group and 117 ± 137 meters in the NCX 4016-treated group, with no significant differences. Carotid IMT increased in the placebo-treated group (+0.01 ± 0.01 mm; P =.55) and decreased in the NCX 4016-treated group (-0.03 ± 0.01 mm; P =.0306). Other secondary end points did not differ between the two treatments. Conclusions: Long-term NO donation does not improve the claudication distance but does reduce progression of atherosclerosis in patients with PAD. Further studies aimed at assessing whether long-term NO donation may prevent ischemic cardiovascular events are warranted. © 2012 Society for Vascular Surgery

Characteristics and clinical management of acute pulmonary embolism in real world: findings from TUSCAN-PE study

Acute pulmonary embolism (PE) remains one of the leading causes of mortality and morbidity in cardiovascular setting. Despite much information about clinical aspects and recommendations or clinical guidelines is available from literature, few data exist about the management of PE in real world of internal medicine scenario. Therefore the aim of the present study was to report on characteristics and management of PE patients admitted in this setting. TUSCAN-PE study was a multicenter, observational, retrospective, cohort study aimed to analyze data of PE patients admitted in Internal Medicine wards of Tuscany. Each center was invited to submit anonymously data of at least ten patients consecutively discharged for acute PE in 2012. Data were referred to demographic, clinical, instrumental, prognostic and therapeutic characteristics. A total of 452 patients from 28 Tuscan centers (60.2% F), with mean age 76.01±12.34 years, were enrolled. A total of 87% of patients was admitted from Emergency Department, but only 65.2% of patients with diagnosis of PE. Around one third of diagnoses of PE was performed by internists. In 14.8% of diagnoses was incidental. In 86% of patients, diagnosis was performed by computer tomography pulmonary angiography. Overall mortality was 9.5%, 5.75% being PE-related. Main risk factors enclosed recent respiratory tract infections (55.3%), immobility (42.25%), recent hospital admissions (33.6%) and cancer (30.3%). In 65.8% of patients, PE was associated with deep vein thrombosis. 16.6% of patients had a shock index ≥1 and 84.75% simplified pulmonary embolism severity index (PESI) score ≥1. A number of 51.5% of patients presented echocardiographic right heart dysfunction, 50.6% and 55.9% of patients presented increased values of troponins and natriuretic peptides, respectively. The following percentage, 6.5%, 71.1% and 22.4%, were defined as high, intermediate and low risk according to the European Society of Cardiology (ESC) criteria, respectively. Antithrombotic treatment was started in Internal Medicine wards in 60.6% of patients. 4.9% of patients were treated with systemic thrombolysis, 15.1% with intravenous unfractionated heparin, whereas low molecular weight heparins and fondaparinux were performed in 39.2% and 39.8% of patients, respectively. Vitamin K antagonists were prescribed in 52.1% of patients at hospital discharge. Fatal and non-fatal major bleedings occurred in 1.7% of patients. TUSCAN-PE study contributes to the knowledge of real life management of acute PE in the Internal Medicine setting