Inferior vena cava-syndrome.

Inferior vena cava syndrome (IVCS) is caused by agenesis, compression, invasion, or thrombosis of the IVC, or may be associated with Budd-Chiari syndrome. Its incidence and prevalence are unknown. Benign IVCS is separated from malignant IVCS. Both cover a wide clinical spectrum reaching from asymptomatic to highly symptomatic cases correlated to the underlying cause, the acuity, the extent of the venous obstruction, and the recruitment and development of venous collateral circuits. Imaging is necessary to determine the underlying cause of IVCS and to guide clinical decisions. Interventional therapy has changed the therapeutic approach in symptomatic patients. This article provides an overview over IVCS and focuses on interventional therapeutic methods and results.

Microcirculatory assessment of vascular diseases.

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.

Superior vena cava syndrome.

The superior vena cava syndrome (SVCS) is caused by compression, invasion, and/or thrombosis of the superior vena cava and/or the brachiocephalic veins. Benign SVCS is separated from malignant SVCS. SVCS comprises a broad clinical spectrum reaching from asymptomatic cases to rare life-threatening emergencies with upper airway obstruction and increased intracranial pressure. Symptoms are correlated to the acuity and extent of the venous obstruction and inversely correlated to the development of the venous collateral circuits. Imaging is necessary to determine the exact underlying cause and to guide further interventions. Interventional therapy has widely changed the therapeutic approach in symptomatic patients. This article provides an overview over this complex syndrome and focuses on interventional therapeutic methods and results.

A randomized cross-over trial in patients suspected of PAD on diagnostic accuracy of ankle-brachial index by Doppler-based versus four-point oscillometry based measurements.

Background: For diagnosis of peripheral arterial occlusive disease (PAD), a Doppler-based ankle-brachial-index (dABI) is recommended as the first non-invasive measurement. Due to limitations of dABI, oscillometry might be used as an alternative. The aim of our study was to investigate whether a semi-automatic, four-point oscillometric device provides comparable diagnostic accuracy. Furthermore, time requirements and patient preferences were evaluated. Patients and methods: 286 patients were recruited for the study; 140 without and 146 with PAD. The Doppler-based (dABI) and oscillometric (oABI and pulse wave index - PWI) measurements were performed on the same day in a randomized cross-over design. Specificity and sensitivity against verified PAD diagnosis were computed and compared by McNemar tests. ROC analyses were performed and areas under the curve were compared by non-parametric methods. Results: oABI had significantly lower sensitivity (65.8%, 95% CI: 59.2%-71.9%) compared to dABI (87.3%, CI: 81.9-91.3%) but significantly higher specificity (79.7%, 74.7-83.9% vs. 67.0%, 61.3-72.2%). PWI had a comparable sensitivity to dABI. The combination of oABI and PWI had the highest sensitivity (88.8%, 85.7-91.4%). ROC analysis revealed that PWI had the largest area under the curve, but no significant differences between oABI and dABI were observed. Time requirement for oABI was significantly shorter by about 5 min and significantly more patients would prefer oABI for future testing. Conclusions: Semi-automatic oABI measurements using the AngER-device provide comparable diagnostic results to the conventional Doppler method while PWI performed best. The time saved by oscillometry could be important, especially in high volume centers and epidemiologic studies.

Erythromelalgia.

Erythromelalgia is a rare syndrome characterized by the intermittent or, less commonly, by the permanent occurrence of extremely painful hyperperfused skin areas mainly located in the distal extremities. Primary erythromelalgia is nowadays considered to be a genetically determined neuropathic disorder affecting SCN9A, SCN10A, and SCN11A coding for NaV1.7, NaV1.8, and NaV1.9 neuronal sodium channels. Secondary forms might be associated with myeloproliferative disorders, connective tissue disease, cancer, infections, and poisoning. Between the pain episodes, the affected skin areas are usually asymptomatic, but there are patients with typical features of acrocyanosis and/or Raynaud's phenomenon preceding or occurring in between the episodes of erythromelalgia. Diagnosis is made by ascertaining the typical clinical features. Thereafter, the differentiation between primary and secondary forms should be made. Genetic testing is recommended, especially in premature cases and in cases of family clustering in specialized genetic institutions after genetic counselling. Multimodal therapeutic intervention aims toward attenuation of pain and improvement of the patient's quality of life. For this purpose, a wide variety of nonpharmacological approaches and pharmacological substances for topical and systemic use have been proposed, which are usually applied individually in a step-by-step approach. Prognosis mainly depends on the underlying condition and the ability of the patients and their relatives to cope with the disease.

ESVM guidelines - the diagnosis and management of Raynaud's phenomenon.

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.

Nailfold capillaroscopy microscopy - an interdisciplinary appraisal.

Nailfold capillaroscopy is a method of great diagnostic value in the differential diagnosis of primary versus secondary Raynaud´s phenomenon, of systemic sclerosis versus other so called connective tissue diseases and of additional diagnostic value in other entities. Rheumatologists, dermatologists, and angiologists in Germany have convened in an interdisciplinary working group in which they synergistically combined their expertise to develop a common nomenclature and standards for the technical performance of nailfold capillary microscopy. The article gives an overview of historical and technical aspects of capillaroscopy, morphologic findings, and disease-specific patterns. It also provides a critical appraisal of its significance in the diagnosis and sequelae of these interdisciplinarily-managed diseases including its performance in children and gives an excursion in the potential perspectives of capillaroscopy in less common indications.

Thromboangiitis obliterans (Buerger's disease).

Thromboangiitis obliterans (TAO, Buerger's disease) is an inflammatory vascular disease affecting small and medium sized arteries and veins. It is characterized by segmental thrombotic occlusions by highly mononuclear cellular thrombi. Its occurrence and re-occurrence is closely related to tobacco use. Immunohistological examinations and the detections of various autoantibodies led to the new paradigm of an immunopathogenesis of TAO. Clinically it is characterized by distal ischemia syndromes in young people and high amputation rates. This article summarizes the disease characteristics, clinical features, and diagnostic and therapeutic approaches and focuses on new therapeutic options, i.e. stem cell derived therapies, immunoadsorption, and the endothelin-receptor-blocking agent bosentan.

G-protein coupled receptor auto-antibodies in thromboangiitis obliterans (Buerger's disease) and their removal by immunoadsorption.

BACKGROUND: Immunhistopathological and serological data favors an immunopathogenesis of thromboangiitis onliterans (TAO, Buerger's disease). Auto antbodies seem to play a major role. Immunoadsorption (IA) proved to be therapeutically effective. We focused on agonistic autoantibodies (agAAB) directed against G-protein coupled receptors (GPCR) and proved the hypothesis, that these agAAB might be present in TAO and that a five day course of IA might be able to eliminate these agAAB effectively. PATIENTS AND METHODS: Between December 2012 and May 2014 11 TAO-patients were treated by IA in a five day course. AgAAB-analysis was performed using specific ELISA techniques. RESULTS: AgAAB were detected in 9 out of 11 patients (81.8 %).Multiple agAAB were present in 7 patients (63.6 %). A clustering of agAAB directed against loop1 of the adrenergic α1-receptor and the endothelin-A-(ETA)receptor was identified, representing 72.7 % resp. 54.5 % of the patients. AgAAB directed against the angiotensin-1 (AT-1) epitope 1 or 2 were detected in 3 patients and agAAB directed against protease-activated receptor (PAR) loop1/2 were seen in 2 patients. AgAAB directed against ETA-receptor loop1 never appeared without agAAB directed against α1-receptor loop1. Immediately after a five day-course of IA agAAB were absent in 81.8 % of the total study group and in 77.8 % of all cases tested positive for agAAB before IA. CONCLUSIONS: AgAAB directed against GPCR were identified in TAO patients with a clustering of agAAB directed against α-1-adrenergic receptor loop1 and ETA-receptor loop1. AgAA were eliminated by IA in the majority of cases. We suggest that these agAA play an important role in the pathogenesis of TAO and that their elimination might be responsible for the positive therapeutic effects reported in patients treated with IA.

Comparison and evaluation of cardiac biomarkers in patients with intermittent claudication: results from the CAVASIC study.

BACKGROUND: Plasma concentrations of the peptides midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), and C-terminal endothelin-1 precursor fragment (CT-proET-1) are increased in various cardiovascular conditions. However, there is limited information about the association and comparative performance of these peptides in peripheral arterial disease (PAD). METHODS: The associations of MR-proADM, MR-proANP, and CT-proET-1 plasma concentrations with symptomatic PAD were investigated in the CAVASIC (Cardiovascular Disease in Intermittent Claudication) Study. Study participants were a male cohort of 238 patients with a diagnosis of intermittent claudication (IC) and 245 age- and diabetes-matched controls. Results were compared to those for N-terminal pro-B-type natriuretic peptide (NT-proBNP). RESULTS: Each increase of MR-proADM, MR-proANP, and CT-proET-1 by 1 SD was significantly associated with symptomatic PAD: odds ratio (OR) = 1.78 (95% CI, 1.41-2.25, P < 0.001), OR = 1.32 (95% CI, 1.06-1.66, P = 0.014), and OR = 1.80 (95% CI, 1.43-2.28, P < 0.001), respectively. The association remained significant for all 3 markers after additional adjustment for log C-reactive protein, serum creatinine, HDL cholesterol, and current smoking. When one adjusts for log NT-proBNP and excluding individuals with prevalent cardiovascular disease, MR-proADM and CT-proET-1 still predicted symptomatic PAD. Extended adjustment models including MR-proADM or CT-proET-1 showed significantly improved model fits compared to models including classical cardiac risk factors or NT-proBNP and led to significant reclassification (P < 0.05). CONCLUSIONS: This study in a male cohort of patients with IC and age- and diabetes-matched controls indicates a significant association of high MR-proADM, MR-proANP, and CT-proET-1 concentrations with PAD. MR-proADM and CT-proET-1 provide additive information in comparison to NT-proBNP. Moreover, MR-proADM and CT-proET-1 significantly predict PAD in those patients and controls free from prevalent CVD.

Incidence and predisposing factors of cold intolerance after arterial repair in upper extremity injuries.

OBJECTIVE: The purpose of this report was to present abnormal posttraumatic cold intolerance in patients that previously underwent repair of arterial injuries after civilian upper limb trauma in our institution. METHODS: All patients who underwent repair of arterial lesions after upper limb trauma since 1990 were reviewed, and clinical follow-up studies were performed. Patients were asked to complete the cold intolerance symptom severity (CISS) questionnaire to evaluate presence and severity of self-reported cold sensitivity, and the disabilities of arm, shoulder, and hand (DASH) questionnaire to analyze functional disability. Abnormal cold intolerance was defined as a CISS score over 30. Further analysis included evaluation of epidemiologic, clinical, and perioperative data for factors predisposing to abnormal cold intolerance. RESULTS: A total of 87 patients with previous repair of upper limb arterial injuries were eligible to answer the CISS and DASH questionnaires, and 56 patients (64%; 43 men; median age: 31.9 years) completed both. In our cohort, blunt trauma was the predominant cause of injury (n = 50; 89%). Accompanying lesions of nerves (n = 22; 39%) and/or orthopedic injuries (n = 36; 64%) were present in 48 patients (86%). After a median follow-up period of 5.5 years (range, 0.5-19.7), 23 patients (41% of 56) reported on abnormal cold intolerance. Patients with cold intolerance had worse functional results (as measured by the DASH questionnaire; mean ± SD, 42.7 ± 29.7 vs 11.5 ± 23.9; P < .001) when compared with patients without. Cold intolerance was more frequently seen in patients with previous nerve lesion (P = .027) and in proximal injuries (subclavian or axillary vs brachial or forearm arteries: P = .006), but was not correlated to gender, age, involvement of the dominant or nondominant arm, and the presence of ischemia, bone injury, or an isolated vascular injury. CONCLUSIONS: Abnormal cold intolerance is frequently seen in patients with a history of arterial repair in upper limb trauma. It is associated with significant functional impairment. Concomitant nerve injury and involvement of the subclavian or axillary artery are the major predisposing factors for development of cold intolerance after upper limb trauma.

[Functional vascular acrosyndromes]. / Funktionelle akrale Durchblutungsstörungen.

Vascular acrosyndromes are characterized by sparse, uniform clinical manifestations and a variety of possible pathomechanisms. The present article focuses on the functional entities. Raynaud phenomenon is based on cold- or stress-induced vasospasms of acral arteries. It is defined by the color changes of the skin, in the typical case white-blue-red (tricolore). The long fingers are most commonly affected. The etiology is unknown, and the pathophysiology is poorly understood. A distinction is made between primary and a secondary Raynaud phenomenon. The most important underlying diseases include collagenosis, primarily systemic sclerosis, and malignancies; furthermore, medications and drugs may promote vasospasm. Treatment is aimed at preventing or breaking the vasospasm, but has been only partially effective in doing so. Acrocyanosis is a vasospastic dystonic acral disorder that results in permanent reddish-livid discoloration, especially of the hands and feet. Secondary forms occur in collagenosis, malignancies, and myelodysplastic syndromes. The etiology and pathophysiology are virtually unknown. Targeted pharmacological intervention is not possible. Unlike all other vascular acrosyndromes, erythromelalgia is characterized by hyperemia. The primary form is a genetic sodium channelopathy, while secondary forms include malignancies, connective tissue diseases, and myelodysplastic syndromes. The symptoms are often distressing and disabling. Therapy requires a multimodal approach that includes both nonpharmacological and pharmacological strategies. Close interdisciplinary collaboration is essential for the management of this disease.

Raynaud's Phenomenon: A Vascular Acrosyndrome That Requires Long-Term Care.

BACKGROUND: Some 5-10% of the German population are affected by Raynaud's phenomenon (RP). In around 10-20% of cases RP arises from an underlying disease, most commonly a connective tissue disease. This review encompasses the diagnosis and differential diagnosis of RP and examines the efficacy of the currently available pharmaceutical and non-pharmaceutical treatment options. METHODS: We conducted a selective literature search in PubMed using the search terms "Raynaud's phenomenon", "Raynaud's syndrome," "vasospasm," "vascular acrosyndrome," and "systemic sclerosis," together with a search of the Cochrane Database of Systematic Reviews up to April 2020. RESULTS: Raynaud's phenomenon mainly affects the fingers or toes and is typically triggered by cold or emotional stressors. The most important diagnostic steps are demonstration of a tendency towards digital vasospasm, exclusion of occlusions in the afferent arteries and acral vessels, nail-fold capillaroscopy, and determination of autoantibody status. Tumor screening should be arranged in the presence of B symptoms or first manifestation of RP in old age. The onset of RP in childhood is a rare occurrence and points to a secondary origin. The principal options for treatment are protection against cold and administration of calcium antagonists, which reduces the occurrence of RP by around 20-40 %. The treatment of RP in patients with systemic sclerosis is described in the recommendations of the European League Against Rheumatism (EULAR). CONCLUSION: At onset or after years of latency, patients with Raynaud phenomenon may have an underlying disease (most commonly a connective tissue disease). Long-term specialist care is necessary for asymptomatic patients with risk factors and for those with clinically manifest symptoms of an underlying condition alike.

Elevated levels of serum PCSK9 in male patients with symptomatic peripheral artery disease: The CAVASIC study.

BACKGROUND AND AIMS: Peripheral artery disease (PAD) affects more than 200 million people worldwide. Increased low-density lipoprotein cholesterol (LDL-C)levels are a risk factor for PAD and the concentrations are influenced by proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 regulates the recycling of the LDL receptors to the cell membrane surface. Only a limited number of mostly small studies investigated the association between serum PCSK9 concentrations and PAD of different definition, which revealed contrasting results. METHODS: Serum PCSK9, lipoprotein(a) [Lp(a)] and other lipoprotein concentrations were measured in male participants of the CAVASIC study, a case-control study of 248 patients with intermittent claudication and 251 age and diabetes-matched controls. RESULTS: PAD patients had significantly higher PCSK9 concentrations when compared to controls (250 ± 77 vs. 222 ± 68 ng/mL, p < 0.001). Logistic regression analysis with adjustment for age revealed that an increase in PCSK9 concentrations of 100 ng/mL was associated with a 1.78-fold higher risk for PAD (95%CI 1.38-2.33, p = 1.43 × 10-5). The association attenuated, but was still significant when adjusting additionally for age, Lp(a)-corrected LDL cholesterol, HDL cholesterol, high-sensitivity-CRP, statin treatment, hypertension, diabetes mellitus and smoking (OR = 1.49, 95%CI 1.03-2.18, p = 0.035). The strongest association was observed when both PCSK9 concentrations were above the median and Lp(a) concentrations were above 30 mg/dL (OR = 3.35, 95%CI 1.49-7.71, p = 0.0038). CONCLUSIONS: Our findings suggest an association of higher PCSK9 concentrations with PAD, which was independent of other lipid parameters and classical cardiovascular risk factors.

Non-invasive diagnosis of deep vein thrombosis from ultrasound imaging with machine learning.

Deep vein thrombosis (DVT) is a blood clot most commonly found in the leg, which can lead to fatal pulmonary embolism (PE). Compression ultrasound of the legs is the diagnostic gold standard, leading to a definitive diagnosis. However, many patients with possible symptoms are not found to have a DVT, resulting in long referral waiting times for patients and a large clinical burden for specialists. Thus, diagnosis at the point of care by non-specialists is desired. We collect images in a pre-clinical study and investigate a deep learning approach for the automatic interpretation of compression ultrasound images. Our method provides guidance for free-hand ultrasound and aids non-specialists in detecting DVT. We train a deep learning algorithm on ultrasound videos from 255 volunteers and evaluate on a sample size of 53 prospectively enrolled patients from an NHS DVT diagnostic clinic and 30 prospectively enrolled patients from a German DVT clinic. Algorithmic DVT diagnosis performance results in a sensitivity within a 95% CI range of (0.82, 0.94), specificity of (0.70, 0.82), a positive predictive value of (0.65, 0.89), and a negative predictive value of (0.99, 1.00) when compared to the clinical gold standard. To assess the potential benefits of this technology in healthcare we evaluate the entire clinical DVT decision algorithm and provide cost analysis when integrating our approach into diagnostic pathways for DVT. Our approach is estimated to generate a positive net monetary benefit at costs up to £72 to £175 per software-supported examination, assuming a willingness to pay of £20,000/QALY.

Milestones in thromboangiitis obliterans: a position paper of the VAS-European independent foundation in angiology/vascular medicine.

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.

Lipedema-Pathogenesis, Diagnosis, and Treatment Options.

BACKGROUND: Lipedema is often unrecognized or misdiagnosed; despite an estimated prevalence of 10% in the overall female population, its cause is still unknown. There is increasing awareness of this condition, but its differential diagnosis can still be challenging. In this article, we summarize current hypotheses on its pathogenesis and the recommendations of current guidelines for its diagnosis and treatment. METHODS: This review is based on publications about lipedema that were retrieved by a selective search in the MEDLINE, Web of Science, and Cochrane Library databases. RESULTS: The pathophysiology of lipedema remains unclear. The putative causes that have been proposed include altered adipogenesis, microangiopathy, and disturbed lymphatic microcirculation. No specific biomarker has yet been found, and the diagnosis is currently made on clinical grounds alone. Ancillary tests are used only to rule out competing diagnoses. The state of the evidence on treatment is poor. Treatment generally consists of complex decongestive therapy. In observational studies, liposuction for the permanent reduction of adipose tissue has been found to relieve symptoms to a significant extent, with only rare complications. The statutory healthinsurance carriers in Germany do not yet regularly cover the cost of the procedure; studies of high methodological quality will be needed before this is the case. CONCLUSION: The diagnosis of lipedema remains a challenge because of the hetero - geneous presentation of the condition and the current lack of objective measuring instruments to characterize it. This review provides a guide to its diagnosis and treatment in an interdisciplinary setting. Research in this area should focus on the elucidation of the pathophysiology of lipedema and the development of a specific biomarker for it.

Guidance for the Management of Patients with Vascular Disease or Cardiovascular Risk Factors and COVID-19: Position Paper from VAS-European Independent Foundation in Angiology/Vascular Medicine.

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.

The fate of patients with intermittent claudication in the 21st century revisited - results from the CAVASIC Study.

Patients with intermittent claudication carry a high risk for cardiovascular complications. The TransAtlantic Inter-Society Consensus (TASC) Group estimated a five-year overall mortality of 30% for these patients, the majority dying from cardiovascular causes. We investigated whether this evaluation is still applicable in nowadays patients. We therefore prospectively followed 255 male patients with intermittent claudication from the CAVASIC Study during 7 years for overall mortality, vascular morbidity and mortality and local PAD outcomes. Overall mortality reached 16.1% (n = 41). Most patients died from cancer (n = 20). Half of patients (n = 22; 8.6%) died within the first five years. Incident cardiovascular events were observed among 70 patients (27.5%), 54 (21.2%) during the first five years. Vascular mortality was low with 5.1% (n = 13) for the entire and 3.1% for the first five years of follow-up. Prevalent coronary artery disease did not increase the risk to die from all or vascular causes. PAD symptoms remained stable or improved in the majority of patients (67%). In summary, compared to TASC, the proportion of cardiovascular events did not markedly decrease over the last two decades. Vascular mortality, however, was low among our population. This indicates that nowadays patients more often survive cardiovascular events and a major number dies from cancer.

High prevalence of circulating CD4+CD28- T-cells in patients with small abdominal aortic aneurysms.

OBJECTIVE: To assess the possible role of proinflammatory CD28- T cells in abdominal aortic aneurysms (AAAs). Animal studies and human tissue studies suggest a role for interferon (IFN)-gamma-producing T cells in the development and progression of AAAs. METHODS AND RESULTS: Fluorescence-activated cells sorter analysis of peripheral blood samples and measurement of AAA size using sonography were performed in 101 AAA patients and 38 healthy controls. Peripheral percentages of CD28- T cells of the CD3+CD4+ and the CD3+CD8+ were enriched in AAA patients with 7.8+/-8.8% and 41.9+/-15.7% compared with healthy controls with 2.2+/-6.1% and 24.9+/-15.5%, respectively (P=0.002 and P<0.001, respectively). Both CD4+CD28- and CD8+CD28- T cells produced large amounts of IFN-[gamma] and perforin. Patients with small AAAs (<4 cm) showed higher peripheral levels of CD4+CD28- T cells than those with larger AAAs (P=0.025). Immunohistological examinations revealed 39.1+/-17.2% CD4+CD28- and 44.0+/-13.8% CD8+CD28- in AAA tissue specimens with inflammatory infiltratestes. CONCLUSIONS: IFN-gamma- and perforin-producing CD28- T cells are present in the periphery and the vessel wall of a majority of AAAs. This observation in humans favors the concept of a T cell-mediated pathophysiology of AAAs, especially during the early development of AAAs.