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Context: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction.Objective: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction.Data Sources: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies.Study Selection: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality.Data Extraction: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease.Results: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women.Conclusion: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS. [ABSTRACT FROM AUTHOR]

Background: Telemedicine is increasingly used in several fields of healthcare, including vascular medicine. This study aimed to investigate the views of experts and propose clinical practice recommendations on the possible applications of telemedicine in vascular medicine. Methods: A clinical guidance group proposed a set of 67 clinical practice recommendations based on the synthesis of current evidence and expert opinion. The Telemedicine Vascular Medicine Working Group included 32 experts from Europe evaluating the appropriateness of each clinical practice recommendation based on published RAND/UCLA methodology in two rounds. Results: In the first round, 60.9% of clinical practice recommendations were rated as appropriate, 35.9% as uncertain, and 3.1% as inappropriate. The strongest agreement (a median value of 10) was reached on statements regarding the usefulness of telemedicine during the 2019 coronavirus disease (COVID-19) pandemic, its usefulness for geographical areas that are difficult to access, and the superiority of video calls compared to phone calls only. The lowest degree of agreement (a median value of 2) was reported on statements regarding the utility of telemedicine being limited to the COVID-19 pandemic and regarding the applicability of teleconsultation in the diagnosis and management of abdominal aortic aneurysm. In the second round, 11 statements were re-evaluated to reduce variability. Conclusions: This study highlights the levels of agreement and the points that raise concern on the use of telemedicine in vascular medicine. It emphasizes the need for further clarification on various issues, including infrastructure, logistics, and legislation.

Buerger's disease (BD) remains a debilitating condition and early diagnosis is paramount for its effective management. Despite many published diagnostic criteria for BD, selective criteria have been utilized in different vascular centers to manage patients with BD worldwide. A recent international Delphi Consensus Study on the diagnostic criteria of BD showed that none of these published diagnostic criteria have been universally accepted as a gold standard. Apart from the presence of smoking, these published diagnostic criteria have distinct differences between them, rendering the direct comparison of patient outcomes difficult. Hence, the expert committees from the Working Group of the VAS-European Independent Foundation in Angiology/Vascular Medicine critically reviewed the findings from the Delphi study and provided practical recommendations on the diagnostic criteria for BD, facilitating its universal use. We recommend that the 'definitive' diagnosis of BD must require the presence of three features (history of smoking, typical angiographic features and typical histopathological features) and the use of a combination of major and minor criteria for the 'suspected' diagnosis of BD. The major criterion is the history of active tobacco smoking. The five minor criteria are disease onset at age less than 45 years, ischemic involvement of the lower limbs, ischemic involvement of one or both of the upper limbs, thrombophlebitis migrans and red-blue shade of purple discoloration on edematous toes or fingers. We recommend that a 'suspected' diagnosis of BD is confirmed in the presence of a major criterion plus four or more minor criteria. In the absence of the major criterion or in cases of fewer than four minor criteria, imaging and laboratory data could facilitate the diagnosis. Validation studies on the use of these major and minor criteria are underway.

Even today thromboangiitis obliterans has disease features that remain misunderstood or underappreciated. The epidemiology, etiology and pathophysiology of the disease are still unclear. Biomarkers and disease activity markers are lacking, thus clinical assessment is difficult. We are still struggling to establish unique diagnostic, staging and treatment criteria. This is an academic-collaborative effort to describe the pathophysiology, the clinical manifestations, the diagnostic approach, and the challenges of management of patients with TAO. A systematic search for relevant studies dating from 1900 to the end of 2020 was performed on the PubMed, SCOPUS, and Science Direct databases. Given the intriguing nature of presentation of TAO, its management, to some extent is not only different in different regions of the world but also varies within the same region. Following this project, we discovered ambiguity, overlap and lack of clear-cut criteria for management of TAO. An international group of experts however came to one conclusion. They all agree that management of TAO needs a call for action for a renewed global look with multi-center studies, to update the geographical distribution of the disease and to establish a unique set of diagnostic criteria and a consensus-based guideline for best treatment based on current evidence.

Background: One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis., Management: Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic., Current Issues: The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments., Perspectives: There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) P revention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA)., Conclusion: The "PDA strategy" integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Aims: Since December 2015, the European/International Fibromuscular Dysplasia (FMD) Registry enrolled 1022 patients from 22 countries. We present their characteristics according to disease subtype, age and gender, as well as predictors of widespread disease, aneurysms and dissections., Methods and Results: All patients diagnosed with FMD (string-of-beads or focal stenosis in at least one vascular bed) based on computed tomography angiography, magnetic resonance angiography, and/or catheter-based angiography were eligible. Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46 ± 16 years (12% ≥65 years old), 86% were hypertensive, 72% had multifocal, and 57% multivessel FMD. Compared to patients with multifocal FMD, patients with focal FMD were younger, more often men, had less often multivessel FMD but more revascularizations. Compared to women with FMD, men were younger, had more often focal FMD and arterial dissections. Compared to younger patients with FMD, patients ≥65 years old had more often multifocal FMD, lower estimated glomerular filtration rate and more atherosclerotic lesions. Independent predictors of multivessel FMD were age at FMD diagnosis, stroke, multifocal subtype, presence of aneurysm or dissection, and family history of FMD. Predictors of aneurysms were multivessel and multifocal FMD. Predictors of dissections were age at FMD diagnosis, male gender, stroke, and multivessel FMD., Conclusions: The European/International FMD Registry allowed large-scale characterization of distinct profiles of patients with FMD and, more importantly, identification of a unique set of independent predictors of widespread disease, aneurysms and dissections, paving the way for targeted screening, management, and follow-up of FMD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Recent studies suggest the use of topical nitroglycerin (NTG) application in systemic sclerosis (SSc)-associated Raynaud phenomenon (RP). With the current study, we aimed to characterize for the first time the microvascular response to a NTG patch (Trinipatch ® 5 mg/24 h) applied to the hand dorsum in patients with SSc using Laser Doppler imaging (LDI) at baseline and following a cold challenge. The study included 21 patients with SSc and 13 controls. Blood flow was evaluated by LDI at the level of the fingertips and metacarpus. Microvascular morphology was evaluated by nailfold capillaroscopy (NC). LDI revealed decreased fingertip baseline perfusion and a stronger vasoconstrictor response to a cold challenge in patients with SSc versus control. Metacarpal application of a NTG patch led to an increase in blood flow and hand temperature in patients with SSc. Furthermore, NTG administration led to a faster reperfusion after cold challenge. Correlation analyses revealed that the magnitude of the vasodilatory response was inversely related to baseline fingertip perfusion and hand temperature, but unrelated to the number of capillaries/mm assessed using NC. In conclusion, we provide evidence of a vasodilatory reaction following NTG patch application in patients with SSc using LDI and a protective effect against cold challenge. The magnitude of the response to NTG was related to functional, but not structural features. Our results support a further evaluation of the NTG patch as a possible therapeutic agent in SSc-associated RP.

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH., Competing Interests: None declared., (Thieme. All rights reserved.)

It is now reported that coronavirus disease 2019 ICU patients are at increased risk of thrombosis. Expert opinion and scientific societies recommend a higher dose of low-molecular-weight heparin, but definitive data is lacking. We report our adapted thromboprophylaxis practice of low-molecular-weight heparin administration in coronavirus disease 2019 ICU patients. One-hundred six measurements in 19 ICU patients were collected. Despite enoxaparin 60 mg once daily, only two measurements of the trough anti-Xa were in the upper end of prophylactic range. Anti-Xa activity peaks increased significantly after administration, but all measurements were under the optimal prophylactic ranges. Despite an adapted protocol, three of the 19 patients (16%) developed venous thromboembolism. We show in coronavirus disease 2019 ICU patients, despite higher prophylactic low-molecular-weight heparin administration due to body mass index, anti-Xa activity was well below peak serum levels in our cohort of critically ill coronavirus disease 2019 patients. This evaluation suggests the need for rapid studies on adequate thromboprophylaxis in these patients., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

The term "microcirculation" refers to the terminal vascular network of the body, which includes arterioles, capillaries, venules as well as initial lymphatic vessels. Additionally, it insinuates to their unique function in thermoregulation, fluid balance, maintenance of cellular exchange, and metabolism. Disturbances of microvascular function were identified to precede macrovascular involvement in the presence of cardiovascular risk factors and is the hallmark of terminal disease stages like critical limb or acral ischemia. Nevertheless, despite its obvious significance in vascular medicine assessment of microvascular function became increasingly neglected in the clinical institutions during the last decades and seems to play a subordinary role in medical education. We therefore provide an overview over relevant and clinically practicable methods to assess microcirculation in vascular medicine with critical estimations of their pros and cons and their perspectives in the future.

Idiopathic chilblain is a relatively common yet poorly recognized acrosyndrome. This literature review aims to better understand and draw attention to this disorder. Chilblain is a localized inflammation of the skin that occurs on exposure to cold but non-freezing wet weather. It usually resolves spontaneously. The etiology is uncertain, but vasospasm seems to play a role in this abnormal reaction to cold. Diagnosis is most often based on clinical presentation, but a skin biopsy can be useful in dubious cases. In histology, dermal edema and an inflammatory infiltrate are usually present. A distribution of the infiltrate particularly around the eccrine gland is typical. Systemic symptoms and underlying autoimmune disease should be screened. Avoiding cold and keeping extremities warm is the first recommendation for management, as well as smoking cessation. Calcium channel blockers (in particular nifedipine) seems to be the treatment that has been most evaluated in chilblains. However, their effectiveness is not confirmed by all studies. Topical betamethasone is often used but its effect has not been confirmed by randomized clinical trials. Other treatments, such as pentoxifylline, hydrochloroquine and topical nitroglycerin have shown positive effects only in a reduced number of patients. Acupuncture seems to bring a benefit.

In Europe, the prevalence of abdominal aortic aneurysms (AAAs) in the elderly population (≥65 year old) has declined in the past decades to <4%. Aneurysmal degeneration of the aorta is a serious and potentially life-threatening vascular disease. Abdominal aortic aneurysms typically develop subclinically and often only become symptomatic when complicated by impending rupture. Most AAAs are discovered incidentally while investigating for an unrelated pathology. Ruptured AAA is the tenth leading cause of death in Belgium (0.32% of all deaths in 2014). Health-care providers have emphasized the importance of early detection of AAA and elective repair when the rupture risk outweighs operative risk (usual diameter threshold of 55 mm). Routine AAA screening programs, consisting of a single abdominal ultrasonography at the age of 65 years, aim to reduce the number of AAA-related deaths. Does population-based ultrasound screening for AAA achieve its objective and is it cost-effective? This literature review tries to answer these challenging questions.

The main goal of the present document is to provide a set of practical recommendations for ultrasound imagers who are interested in artery diseases or for physicians who intend to undertake vascular procedures. This is the first part of the work. It is dedicated to general principles of ultrasonography, cervicoencephalic, subclavian, aortoiliac and lower extremity arteries, abdominal aorta, and popliteal aneurysms. It also discusses miscellaneous items such as medial arterial calcinosis, arterial embolism, arteritis, arterial stents and bypasses, false aneurysms, aortic dissection, popliteal entrapment syndrome, and iliac endofibrosis.

Background: Pygmies living in the Central African rainforest with a traditional hunter-gatherer lifestyle have a low incidence of cardiovascular diseases. Because of progressive loss of traditional habitat and ancestral lands, some Pygmies have migrated to urban areas and adopt specific Bantu lifestyles such as increased salt consumption and a sedentary way of life. We tested the hypothesis that migrant Pygmies could present with hemodynamic and metabolic characteristics different from those of traditional in-situ Pygmies and possibly closer to those of Bantu farmers., Patients and Methods: The study included 148 Pygmies (94 traditional and 54 migrants) and 164 Bantus. Peripheral and central hemodynamics, aortic pulse wave velocity (PWV), and augmentation index corrected for heart rate (AIx) were measured, as well as fasting lipid profile. Urinary sodium and potassium excretion was also measured on a morning spot., Results: Compared to Bantus, Pygmies had lower height (even between men and women, but men were taller than women in the three groups), weight, waist and hip circumference, peripheral and central blood pressure, total, low-density lipoprotein, and high-density lipoprotein cholesterol and apolipoprotein B100 levels, sodium urinary excretion, and lower prevalence of the metabolic syndrome. By contrast, they had a higher waist-to-hip ratio, and higher triglycerides levels, as compared to Bantu farmers. PWV and AIx did not differ between Bantus and Pygmies. Compared to traditional in-situ Pygmies, migrant Pygmies were not taller when adjusted for sex, had lower brachial and central blood pressure, higher PWV (adjusted for mean arterial pressure, BMI, and sex), and higher apolipoprotein B100 levels. In the whole population, multivariable analysis revealed that PWV was independently associated with age, weight, height, mean arterial pressure, total cholesterol, and hip circumference, whereas AIx was independently related to age, sex, height, heart rate, diastolic blood pressure, and group (from Bantu farmers to Pygmies)., Conclusion: Comparisons between Bantus and Pygmies, and between migrant Pygmies and traditional in-situ Pygmies, showed mixed results, with favorable and deleterious hemodynamic and metabolic characteristics in all groups. This could be due to increased contacts between these populations, which blunt the expected differences and because the beneficial effects of the hunter-gatherer subsistence mode of traditional in-situ Pygmies are counterbalanced by unhealthy behavioral habits.

Regarding the clinical diagnosis of Raynaud's phenomenon and its associated conditions, investigations and treatment are substantial, and yet no international consensus has been published regarding the medical management of patients presenting with this condition. Most knowledge on this topic derives from epidemiological surveys and observational studies; few randomized studies are available, almost all relating to drug treatment, and thus these guidelines were developed as an expert consensus document to aid in the diagnosis and management of Raynaud's phenomenon. This consensus document starts with a clarification about the definition and terminology of Raynaud's phenomenon and covers the differential and aetiological diagnoses as well as the symptomatic treatment.

Lower limb vascular amputations represent serious problem in the vascular care. As a consequence of critical limb ischemia, often associated with diabetes, it is highly critical to health care service aiming at prevention of limb loss. Understanding of the nature and complexity of amputation scenario is paramount for the effective preventive strategy planning and implementation. Amputation incidence and data of the trends show high variability in the international reports. Variability is also remarkable in a more granular, regional comparison. Different calculation methods for incidence fraction, varying epidemiological, demographic features of the populations, different socio-economic, cultural backgrounds and disparity in vascular care are the main factors contributing to this variability in reports. Lower limb amputations can be considered as a valuable healthcare quality indicator with some limitations. One of these limitations is the lower actionability that corresponds to the reduced ability of health care providers to intervene influencing the burden of amputations. Lower limb vascular amputations represent a lifetime risk, therefore not only the effective revascularization is to be achieved but the importance of the early recognition of peripheral arterial disease, no delay in referral to special vascular care, effective vascular risk prevention and collaboration in multidisciplinary teams should be also emphasized.

Deep vein thrombosis (DVT) is a component of venous thromboembolism (VTE), the other being pulmonary embolism (PE). Its incidence is 1 to 2/1.000/year and nearly 1/100/year after 80 years. The major complication of DVT is PE which occurs in about 1/3 of cases, is often asymptomatic but can be fatal. Another common complication, occurring in 20-50 % of cases is the post-thrombotic syndrome (PTS) which is likely to alter the quality of life. Several issues remain unanswered when considering DVT. The optimal management of distal DVT versus proximal DVT is not well codified. The diagnostic approach to DVT is essential : it is based on the estimation of clinical probability, the possible use of D-dimer test and compression ultrasonography. The new direct oral anticoagulants (NOACs) have been proven effective in the phase 3 studies but when to use them and which to choose in the real life ? Wearing compression stockings to prevent the SPT is recommended: what is the definition of compression stockings and is there some evidence of their efficacy ? The purpose of this article is to provide some useful information to primary care physicians to address a DVT.

Background and Objective: Management of non-valvular atrial fibrillation (NVAF) focuses on the use of anticoagulation to mitigate the risk of stroke. Until recently, vitamin K antagonist (VKA) treatment was considered the standard of care, with the emergence of non-VKA oral anticoagulants (NOACs) shifting treatment practice. The objective of this study was therefore to assess the use of warfarin and the NOACs for stroke prevention in patients with NVAF from the perspective of a Belgian healthcare payer using a cost-effectiveness analysis and the efficiency frontier approach., Methods: A previously published Markov model was adapted to the Belgian healthcare setting. Clinical events modelled include ischaemic and haemorrhagic stroke, systemic embolism, intracranial haemorrhage, other major bleeding, clinically relevant non-major bleeding, myocardial infarction, cardiovascular hospitalisation and treatment discontinuations. Efficacy and bleeding data for warfarin and apixaban 5 mg twice daily were obtained from the ARISTOTLE trial, whilst those for other NOACs (rivaroxaban 20 mg once daily, dabigatran 110 mg twice daily, dabigatran 150 mg twice daily) were from published indirect comparisons. Acute medical costs were obtained from reimbursement payments made to Belgian hospitals, whilst long-term medical costs and utility data were derived from the literature. The efficiency frontier was calculated using total costs and quality-adjusted life-years (QALYs) as outcomes. Univariate and probabilistic sensitivity analyses were performed., Results: Warfarin and apixaban were the two optimal treatment choices, as the other three treatment alternatives including dabigatran 110 mg, dabigatran 150 mg switching to dabigatran 110 mg at the age of 80 years and rivaroxaban were extendedly or strictly dominated on the efficiency frontier. Apixaban was a cost-effective alternative vs warfarin at an incremental cost-effectiveness ratio of 7,212/QALY gained., Conclusions: Amongst NOACs, apixaban may be the most economically efficient alternative to warfarin in NVAF patients who are suitable for VKA treatment and eligible for stroke prevention in Belgium.

Objective: To describe the clinical findings and prevalence of patients with cryofibrinogenemia (CF) and to determine whether CF is associated with primary Raynaud's phenomenon., Methods: Between June 2006 and December 2009, 227 patients were tested for CF in a single university hospital. Forty-five patients with primary Raynaud's phenomenon were tested for CF., Results: A total of 117 patients with CF without cryoglobulinemia were included. The main clinical manifestations included skin manifestations (50%) and arthralgia (35%). There were 67 patients with primary CF and 50 patients with secondary CF. There was no significant difference in the mean concentration of the cryoprecipitate in primary CF as compared to the secondary form (172 ± 18.6 vs 192 ± 20.9 mg/dl, respectively; p = 0.41). Highest concentrations of cryoprecipitate were observed in those containing fibrinogen only as compared to cryoprecipitates containing fibrinogen and fibronectin (301 ± 43.5 vs 125 ± 10.6 mg/dl; p < 0.001). Patients having skin necrosis (n = 3) had significantly higher values of cryofibrinogen compared to those without necrosis (638 ± 105 vs 160 ± 10.2 mg/dl; p = 0.0046). Among the 45 patients with primary Raynaud's phenomenon, 36 had associated CF. There was no significant difference in the mean concentration of the cryoprecipitate in these patients compared to those with primary CF., Conclusion: There seems to be a significant correlation between cryofibrinogen concentration and the severity of the clinical signs, particularly when cryoprecipitate is composed of fibrinogen alone. CF might have a possible pathophysiological role in primary Raynaud's phenomenon.

Few studies are available with sufficient sample size to accurately describe the prevalence of low ankle-brachial index (ABI) in patients at 'non-high' cardiovascular (CV) risk. The aim of this study was to evaluate the prevalence of asymptomatic peripheral arterial disease (PAD), as determined by using ABI, in this patient population. A non-interventional, cross-sectional, pan-European study was conducted in patients with ≥1 CV risk factor in addition to age, evaluating the prevalence of asymptomatic PAD (ABI ≤ 0.90). Secondary objectives included assessing the prevalence and treatment of CV risk factors. Patients were consecutively recruited during scheduled visits to the physician's office, or were randomly selected by the physician from a list of eligible patients. Patients with diabetes were excluded as this condition was deemed to be a secondary prevention risk. 10,287 patients were enrolled (9,816 evaluable: mean age 64.3 years; 53.5% male). Prevalence of asymptomatic PAD was 17.8% (99% CI 16.84-18.83). Factors significantly associated with asymptomatic PAD included hypertension, age, alcohol intake, family history of coronary heart disease, low levels of high-density lipoprotein-cholesterol, and smoking (p < 0.0001). Patients treated with statins were significantly less likely to have asymptomatic PAD than those who were not (odds ratio 0.62; 95% CI 0.50-0.76; p < 0.0001). Asymptomatic PAD was highly prevalent in patients with non-high CV risk, the majority of whom would not typically be candidates for ABI assessment. These patients should be carefully screened, and ABI measured, so that therapeutic interventions known to diminish their increased CV risk may be offered.

Background: Lower extremity peripheral arterial disease (PAD) is a marker of widespread atherosclerosis. Individuals with PAD, most of whom do not show typical PAD symptoms ('asymptomatic' patients), are at increased risk of cardiovascular ischaemic events. American College of Cardiology/American Heart Association guidelines recommend that individuals with asymptomatic lower extremity PAD should be identified by measurement of ankle-brachial index (ABI). However, despite its associated risk, PAD remains under-recognised by clinicians and the general population and office-based ABI detection is still poorly-known and under-used in clinical practice. The Prevalence of peripheral Arterial disease in patients with a non-high cardiovascular disease risk, with No overt vascular Diseases nOR diAbetes mellitus (PANDORA) study has a primary aim of assessing the prevalence of lower extremity PAD through ABI measurement, in patients at non-high cardiovascular risk, with no overt cardiovascular diseases (including symptomatic PAD), or diabetes mellitus. Secondary objectives include documenting the prevalence and treatment of cardiovascular risk factors and the characteristics of both patients and physicians as possible determinants for PAD under-diagnosis., Methods/design: PANDORA is a non-interventional, cross-sectional, pan-European study. It includes approximately 1,000 primary care participating sites, across six European countries (Belgium, France, Greece, Italy, The Netherlands, Switzerland). Investigator and patient questionnaires will be used to collect both right and left ABI values at rest, presence of cardiovascular disease risk factors, current pharmacological treatment, and determinants for PAD under-diagnosis., Discussion: The PANDORA study will provide important data to estimate the prevalence of asymptomatic PAD in a population otherwise classified at low or intermediate risk on the basis of current risk scores in a primary care setting., Trial Registration Number: Clinical Trials.gov Identifier: NCT00689377.

For more than 50 years vitamin K antagonists (VKA) have been the gold standard for long-term oral anticoagulant treatment. New anticoagulants are now in extensive clinical development what will probably have a significant impact on daily practice in the near future. Compounds that specifically block activated factor X (FXa) or activated factor II (thrombin) have entered impressive phase III trials. Idraparinux is a long-active derivative from fondaparinux (synthetic pentasaccharide) and is administered subcutaneously. It inhibits indirectly FXa. Apixaban and rivaroxaban are small molecules that directly block FXa following oral administration. Dabigatran is another substance that is administered orally and directly inhibit thrombin. This article will review the potential interest of these new drugs in the modern antithrombotic care. In the meantime, we will briefly discuss two new tools that have been developed to optimalizing the classical VKA anticoagulation: anticoagulation clinics and point-of-care testing of INR that allows self-monitoring.

Right ventricular function is frequently abnormal in patients with systemic sclerosis, but whether this is related to pulmonary vascular complications of the disease is unclear. Standard echocardiography with tissue Doppler imaging was performed at rest and during exercise for the study of right ventricular function and pulmonary circulation in 25 consecutive systemic sclerosis patients and in 13 age-matched healthy controls. When compared with the controls, the patients had no difference in systolic right ventricular pressure gradient, but a decreased pulmonary flow acceleration time, and increased right ventricular free wall thickness and end-diastolic dimensions. At the tricuspid annulus, the E maximal velocity was decreased (8.9 +/- 4 versus 11.7 +/- 2.3 cm.s(-1)) and the isovolumic relaxation time corrected to RR interval was increased (6.5 +/- 2.9 versus 4.5 +/- 2.5%). The tissue Doppler imaging profile at the mitral annulus was similar in both groups. At exercise, 18 patients had a decreased maximum workload and cardiac output, no change in systolic right ventricular pressure gradient, but an increase in the slope of pulmonary artery pressure/flow relationships. These results suggest that patients with systemic sclerosis may present with latent pulmonary hypertension as a likely cause of right ventricular diastolic dysfunction, as revealed by stress echocardiography and tissue Doppler imaging.

Introduction: Assessment of pretest probability should be the initial step in investigation of patients with suspected pulmonary embolism (PE). In teaching hospitals physicians in training are often the first physicians to evaluate patients., Objective: To evaluate the accuracy of pretest probability assessment of PE by physicians in training using the Wells clinical model and to assess the safety of a diagnostic strategy including pretest probability assessment., Patients and Methods: 291 consecutive outpatients with clinical suspicion of PE were categorized as having a low, moderate or high pretest probability of PE by physicians in training who could take supervising physicians' advice when they deemed necessary. Then, patients were managed according to a sequential diagnostic algorithm including D-dimer testing, lung scan, leg compression ultrasonography and helical computed tomography. Patients in whom PE was deemed absent were followed up for 3 months., Results: 34 patients (18%) had PE. Prevalence of PE in the low, moderate and high pretest probability groups categorized by physicians in training alone was 3% (95% confidence interval (CI): 1% to 9%), 31% (95% CI: 22% to 42%) and 100% (95% CI: 61% to 100%) respectively. One of the 152 untreated patients (0.7%, 95% CI: 0.1% to 3.6%) developed a thromboembolic event during the 3-month follow-up period., Conclusion: Physicians in training can use the Wells clinical model to determine pretest probability of PE. A diagnostic strategy including the use of this model by physicians in training with access to supervising physicians' advice appears to be safe.

Dissection of a renal artery is rare and, in most cases, associated with underlying arterial diseases. Spontaneous renal artery dissection (RAD) is exceptional. We report the case of a young and otherwise healthy man with an isolated dissection of the right renal artery without any obvious origin. Diagnosis was made by angiography. He received medical treatment and rapidly recovered. Renal artery dissection can be misdiagnosed because its clinical presentation may be confusing. Selective renal angiography is essential to evaluate the extent of the dissection and the suitability for repair. Control of the hypertension and renal function preservation are the two main goals of the treatment. The place of surgical repair remains unclear because of the poor results on hypertension improvement and high complication rate.

The functional repertoire of T cells in abdominal aortic aneurysm (AAA) and the exact nature of aortic wall adaptive cellular immune responses still remains a matter of debate. In this study, we sought to determine whether type 1 or type 2 responses occur predominantly in human aneurysmal aortic lesions. We first examined the phenotype and cytokine secretion profile of T lymphocytes freshly isolated from aneurysmal aortic wall for comparison with their circulating counterparts using flow cytometry. We found that both populations of infiltrating CD4(+) and CD8(+)T cells displayed a unique activated memory phenotype. In addition, we identified the presence in human aneurysmal aortic lesion of CD4(+)T cells producing high levels of interferon (IFN)-gamma but not interleukin (IL)-4, reflecting their type 1 nature. Quantitative analysis of cytokine gene expression confirmed increased IFN-gamma transcript levels in infiltrating cells compared to controls. We next analysed aortic wall responses using LightCycler-based quantitative real-time reverse transcription-polymerase chain reaction. Compared to control non-diseased aortic samples, we demonstrated that whole AAA tissues exhibited high mRNA levels of IFN-gamma but not IL-4. Overexpression of the transcription factor T-bet in the absence of significant GATA-3 expression further assessed the type 1 polarization of aortic wall immune responses. These findings indicate that type 1 CD4(+)T cells predominate in human AAA lesions. This study has important implications for the pathogenesis of aneurysm disease. Through the production of IFN-gamma, T cells may indeed contribute to orchestrate extracellular matrix remodelling.

Testing for laboratory evidence of thrombophilia is now common but it has limited predictive value for the majority of unselected symptomatic patients. So when is testing indicated ? And which one? The term "thrombophilia" describes disorders of the haemostatic mechanisms which are likely to predispose to thrombosis. Thrombophilia may be heritable, acquired or mixed, resulting of the environment interacting with genetic background. To date, a limited number of genetic variants and other defects are proven to be independent risk factors for venous thromboembolism. These include antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden, the prothrombin gene mutation, hyperhomocysteinemia and antiphospholipid antibodies. There is no good evidence currently available to support the hypothesis that heritable thrombophilias increase the risk of arterial disease. But acquired or mixed thrombophilias such as hyperhomocysteinemia and antiphospholipid antibodies have been found in association with both venous and arterial thrombotic disorders. When testing for thrombophilia is indicated, especially in case of venous thromboembolism, it should include assays for heritable, mixed or acquired defects: deficiency of antithrombin, protein C or protein S, factor V Leiden and prothrombin G20210A mutations, elevated factor VIII, hyperhomocysteinemia and for antiphospholipid antibodies. Depending on the site of venous thrombosis, laboratory testing to exclude myeloproliferative disorders should be performed.

Atherothrombosis is a common physiopathologic process resulting in morbid or fatal ischemic events affecting the cerebral, coronary, or peripheral arterial circulation. Antiplatelet agents are effective in preventing recurrence of vascular events among patients with established vascular disease or with multiple risk factors. Aspirin was the most widely studied antiplatelet drug but the optimal dose remains difficult to define. This article summarizes new data on antiplatelet agents including aspirin, clopidogrel, dipyridamole and glycoprotein IIb/IIIa antagonists with the aim of giving practical recommendations in this very moving field of therapy.