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Importance: Prior studies have observed an association between the burden of atherosclerotic vascular disease and the risk of venous thromboembolism (VTE). The association is not well described in peripheral artery disease (PAD) after lower extremity revascularization (LER)., Objective: To describe the risk of, factors associated with, and outcomes after VTE, as well as the association of low-dose rivaroxaban plus antiplatelet therapy with VTE after LER., Design, Setting, and Participants: This global, multicenter cohort study used data from the Vascular Outcomes Study of ASA (acetylsalicylic acid) Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD (VOYAGER PAD) randomized clinical trial, which enrolled patients from 2015 to 2018 with median follow-up of 28 months. Participants included patients with PAD undergoing LER. Patients with an indication for therapeutic anticoagulation were excluded. Data were analyzed from September 2020 to September 2021., Exposure: Randomization to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily; short-term clopidogrel was used at the discretion of the treating physician., Main Outcomes and Measures: Symptomatic VTE was a prespecified secondary outcome and prospectively collected., Results: Among 6564 patients (median [IQR] age, 67 [61-73] years; 4860 [74.0%] men), 66 patients had at least 1 VTE. The 3-year rate of VTE in patients receiving placebo was 1.7%, and the pattern of risk was linear (year 1: 0.5%; year 2: 1.1%). After multivariable modeling, weight (hazard ratio [HR], 3.04; 95% CI, 1.09-8.43), hypertension (HR, 2.11; 95% CI, 0.91-4.89), prior amputation (HR, 2.07; 95% CI, 0.95-4.53), and older age (HR, 1.81; 95% CI, 1.06-3.11) were associated with increased risk of VTE. VTE was associated with risk of subsequent mortality (HR, 7.22; 95% CI, 4.66-11.19). Compared with aspirin alone, rivaroxaban plus aspirin was associated with lower VTE risk (HR, 0.61; 95% CI, 0.37-0.998; P = .047), with benefit apparent early and sustained over time. This association was not modified by use of clopidogrel at randomization (without clopidogrel: HR, 0.55; 95% CI, 0.29-1.07; with clopidogrel: HR, 0.69; 95% CI, 0.32-1.48; P for interaction = .67)., Conclusions and Relevance: In this cohort study, there was continuous risk for VTE after LER in patients with PAD, with greater risk in patients who were older and had obesity and those with more severe PAD, as reflected by prior amputation. Low-dose rivaroxaban plus aspirin was associated with lower VTE risk compared with aspirin alone, with benefits apparent early and continued over time. The spectrum of venous and arterial thrombotic events and overall benefits of more potent antithrombotic strategies for prevention should be considered after LER for PAD.

Background: 31P-MR spectroscopy is a technique for undertaking a comprehensive evaluation of muscle metabolism. The goal of this study was to compare patients with mild and severe lower limb ischemia measured by 31P-MR spectroscopy at rest and during exercise., Methods: Sixteen non-diabetic mild peripheral arterial occlusive disease (PAOD) patients, 23 diabetic PAOD patients with severe ischemia and 19 healthy controls were examined by rest and dynamic 31P-MR spectroscopy with a 3T MR system equipped with an MR-compatible home-made pedal ergometer. Signal intensity ratios of phosphorous metabolites to the sum of all 31P intensities (Ptot) and pH were obtained at rest. The PCr drop (ΔPCr), time recovery constant of PCr (τPCr), pH at the end of the exercise (pHend), and mitochondrial capacity (Qmax) were calculated from dynamic MR spectra., Results: Diabetic PAOD patients with severe ischemia differed from controls in both rest (PCr/Pi, βATP/Ptot, pH) and dynamic (Qmax, pHend, τPCr) parameters. PAOD patients with mild ischemia differed from controls only in Qmax and pHend. Rest parameters of the nondiabetic PAOD patients did not differ from control values excluding rest pH which was higher in both patient groups., Conclusions: A combination of rest and dynamic 31P-MR spectroscopy can distinguish among all three groups of subjects. On the other hand, examination at rest is sufficient for differentiation between patient groups and verification of severe ischemia.

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.

Aim: The aim was to investigate the effect of micronized purified flavonoid fraction (MPFF; Daflon® 500 mg, Laboratoires Servier, France) versus placebo, on pain and quality of life (QoL) in patients with symptomatic chronic venous disease (CVD)., Methods: A large randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate treatment effects on vesperal oedema using water displacement volumetry (WDV). Other criteria were leg pain\heaviness assessed by Visual Analog Scale (VAS) and Quality Of Life Questionnaire (CIVIQ-20). Study treatments were administered once a day for 4 months. The tolerance to the study treatments was assessed based on spontaneously reported adverse events, coded using the MedDRA dictionary. The present post-hoc analysis focuses on the subgroup of symptomatic patients having a baseline VAS>4 cm., Results: The main study included 1137 patients classified C3 or C4 according to CEAP classification, with 592 in the symptomatic subgroup: 296 randomized to MPFF and 296 to placebo. Patient demographics and medical history were well-balanced at baseline. The main study was inconclusive on WDV for methodological reasons. In the symptomatic subgroup, MPFF treatment was associated with a greater reduction in VAS score than on placebo treatment (between-group difference =-0.5 cm; P=0.031) and greater improvement in CIVIQ score (between-group difference =3.1%; P=0.040)., Conclusion: A 4-month treatment with MPFF significantly reduced leg pain/heaviness and improved QOL when compared to placebo and was well tolerated.

Objectives: It has been demonstrated that the deleterious effect of smoking on the cardiovascular system is mediated through a decrease in protective HDL cholesterol. In addition, women are more sensitive to the negative effects of smoking, although the exact mechanism underlying this phenomenon is currently unknown. In this study, we evaluated whether smoking habits could modify the association of HDL cholesterol and apolipoprotein A1 (ApoA1) with reverse cholesterol transport (RCT), as measured by cholesterol efflux (CHE), in middle-aged women., Design: The study group consisted of 39 healthy middle-aged women, 21 non-smokers (age 51.8±2.5 years, BMI 25.1±2.8 kg/m2) and 18 smokers (age 50.5±3.2 years, BMI 24.8±3.5 kg/m2). In addition to all traditional cardiovascular risk factors, CHE from macrophages, labelled during a 48-hour incubation in a medium containing [14C] cholesterol, to plasma acceptors in study subjects was established as a marker of reverse cholesterol transport., Results: CHE was significantly higher in non-smokers than in smokers (14.22±1.75% vs. 13.17±1.33%; p<0.05). Smoking habit had no effect on the association of HDL with ApoA1 or HDL with CHE. However, in contrast to the strong association of ApoA1 with CHE in non-smokers (r=0.62; p<0.01), no such strong association was found in smokers (r=0.38; n.s.)., Main Findings and Conclusion: Based on our results, smoking can alter ApoA1-mediated reverse cholesterol transport in women.

Aim: The association between chronic venous disease (CVD) and atherosclerosis has been intensively investigated. Because data regarding cardiovascular disease in women are sparse, we evaluated the potential association between the symptoms of CVD and cardiovascular risk factors including markers of preclinical atherosclerosis in middle-aged women., Methods: A questionnaire for chronic lower limb venous insufficiency was completed by 902 women, aged 45-54 years, from the general population. At the same time, all women were examined for the presence of cardiovascular risk factors, including the ankle/brachial systolic blood pressure index (ABI) and carotid intima media thickness of the common carotid arteries measured by ultrasound. Differences in cardiovascular risk factors and markers of preclinical atherosclerosis between women with and without symptoms of CVD were evaluated., Results: Symptoms (cramps, aching, edema, disturbance of sleep) suggestive of CVD in the lower extremities were reported by 606 (67.2%) women and 114 (12.6%) reported that those symptoms were severe enough to limit their usual daily activities. A higher prevalence of ABI of less than 0.91 was observed in women with any (P=0.005) or severe (P=0.029) CVD symptoms. A significantly higher prevalence of the following were observed in women with any or severe CVD symptoms: coronary artery disease, history of diabetes mellitus, increased body mass index, waist circumference, serum triglycerides, serum C-reactive protein and lower serum HDL cholesterol., Conclusion: CVD symptoms were strongly associated with a higher prevalence of pathological values of ABI and several other manageable cardiovascular risk factors. These findings support the data that chronic venous disease might also indicate increased risk for atherosclerosis.

Patients with claudication have a high cardiovascular risk and, foremost, require an introduction of the appropriate procedures to stop the progression of the disease and to prevent cardiovascular events as if these were patients with a coronary or cerebrovascular disease. To manage the claudication-associated complaints, surgery and endovascular revascularization procedures, exercise therapy and vasoactive agents with proven clinical efficacy are used.

Background: The aim of the study was to assess the regression rate of persistent echogenic masses in patients with idiopathic deep venous thrombosis (DVT) who were after initial 6 months randomized to long-term anticoagulation treatment or to discontinuation of anticoagulation., Patients and Methods: We followed 168 patients with idiopathic DVT for two years since diagnosis. After 6 months of standard therapy (heparin/LMWH, warfarin with target INR 2-3) we randomized patients with persistent echogenic masses of over 20% of venous diameter to either discontinuation of warfarin or to continuation of warfarin for another 6 months. We evaluated the size of thrombotic masses with duplex ultrasound., Results: After 6 months of standard therapy complete regression was observed in 69 patients while in 99 patients echogenic masses persisted, with 71 patients maintaining an obstruction of at least 20% of venous cross-sectional area. 52 patients were randomized. 27 patients continued warfarin therapy and in 25 patients warfarin was discontinued. After discontinuation of warfarin a further trend to regression was seen in both groups. A significant difference in regression of thrombotic masses between the 6th and 12th month of follow up was seen in patients continuing to receive warfarin, both within the popliteal vein (2.81 +/- 1.56 vs. 2.10 +/- 1.67 mm, p < 0.05) and the femoral vein (3.95 +/- 2.74 vs. 2.30 +/- 1.34 mm, p < 0.05)., Conclusions: After 6 months of DVT treatment persistent echogenic masses can be found in almost two thirds of patients. Even after discontinuation of anticoagulation treatment echogenic masses further regress. However, the rate of regression in patients with deep venous thrombosis between the 6th and 12th month was greater in patients randomized to continue warfarin during this period than in patients without anticoagulation.

This first Czech version of guidelines formulated by the working group of mentioned medical associations is based on current literature and international guidelines. They are aimed mainly on clinical medicine and on incorporation of this treatment into the health care system according to WHO recommendations. They should serve to the treatment of tobacco dependence at any level: during any contact with the smoking patient (short intervention), in specialised centres or for the health care providers or health system itself.

Aim: Epidemiological data show that standard compression therapy for leg ulceration in chronic venous insufficiency (CVI) often fails to effectively improve patients' condition. This study assesses the contribution of Daflon 500 mg added to conventional therapy in the healing of hypostatic ulcers of CVI patients., Methods: Patients of about 65 years were included, with ulcers > or = 2 and > or = 10 cm diameter on 1 or 2 limbs, Doppler ankle/arm pressure index > 0.9, and no recent history of skin graft. Controls (n=68) remained on compression alone while the tested group (n=82) also received Daflon 500 mg 2 tablets/day during 6 months. Treatment could be stopped as soon as the reference ulcer appeared fully healed. Primary endpoints were the rate of healed ulcers and the time to complete healing assessed by planimetry/photography and clinical examination. Variations of the ulcer surface, appearance of the skin, and clinical symptoms of CVI were the secondary criteria., Results: Only 7% of Daflon 500 mg patients necessitated the full 6 month therapy. Whatever the lesion size, from W8 significantly more healed ulcers were observed under Daflon 500 mg (p=0.004), and the ulcer surface was more reduced (p=0.012). For large ulcers, the rate of healing was approximately 2-fold higher with Daflon 500 mg, and the percentage of ulcers healed before W24 was significantly higher (p=0.008). Heavy leg sensation was significantly improved by Daflon 500 mg from W4 (p < 0.05). No treatment-related side effects were reported and the acceptability was considered excellent by 85% of Daflon 500 mg patients., Conclusion: Six months of Daflon 500 mg in addition to compression significantly improve some clinical symptoms and accelerate the healing process in patients with ulcerous complications of CVI, with a good acceptability.

The authors present the technique of chemical lumbar sympathectomy by an anatomically new medial transdiscal approach. On a group of 80 operations they analyze the indication criteria, complications and results of this method. They compare the percutaneous technique of severing of the sympathetic nerve with the classical surgical approach. In 41 patients where a modified transdiscal approach was used the authors did not encounter any serious complications. Using thin needles (minimum 23-G) they recommend this method as an alternative of the classical approach of Kappis.

The authors present in their paper the possibility of thoracoscopic thoracic sympathectomy as the method of choice for reoperation of the thoracic sympathetic nerve 14 years after classical surgical upper chest sympathectomy, as the original effect had receded. They mention the possibility of reoperation of the sympathetic nerve with a subsequent favourable effect by the endoscopic method which reduces the risk of complications to a minimum.

1. Conservative therapy of critical limb ischaemia either supports the effect of revascularisation procedures (thrombolysis, PTA, surgical reconstruction) or is employed in cases where instrumental intervention is no more possible. As a longterm control programme, the conservative approach reduces the number of local and general vascular complications. 2. The main physiological principles of conservative treatment are as follows: improvement of driving pressure (limb dependency, slow walking, mild temporary hypertension induced by isometric contraction of forearm muscles), decrease of vascular resistance (exercise, reflex dilatation by body heating, pharmacological vasodilators, prostanoids), microcirculatory improvement (oxygen inhalation, full recommended doses of drugs), prevention of oedema (calcium blocking agents not to be administered) and prevention of tissue destruction (anabolic hormones). It is of utmost importance to start vigorous therapy without delay when symptoms or signs of incipient critical ischaemia are detected; this should be followed by a life-long control and treatment programme. 3. Early beginning of therapy makes it usually possible to control incipient critical ischaemia effectively. The long term control and treatment programme contributes to a significant drop of relapses and mortality.

Medical therapy of CLI is only indicated in patients unsuitable for vascular reconstruction or angioplasty. The approach includes early detection of subjects at risk, observation of physiological principles of therapy and long-term control. The finding of ankle pressure < or = 50 mmHg is of particular value in early detection because of high specificity with respect to CLI. Limb dependency increases skin flow in CLI while in patients with moderate ischaemia vasoconstriction occurs. Positioning of the limb thus contributes to therapeutical effect. Vasodilator substances increase foot blood flow only when administered to patients covered with blankets; improper administration may cause vasoconstriction. When a long-term control programme is established, the number of episodes of CLI decreases as compared to spontaneous course of disease. Rational use of available methods in early diagnosis and therapy considerably improves the prognosis of CLI.

The results obtained by analysis of pulse waves by means of Fourier harmonics in healthy subjects and patients with aortic insufficiency show good agreement between input impedance of the aorta and the initial segment of the femoral bed in both groups. This means that in this region there is no marked increase in impedance, which provides a favourable background for energy transfer (blood content) in the distal direction. Impedance in healthy subjects increases in vessels of the lower extremity. In patients with aortic insufficiency there is a marked decrease in amplitude of all higher harmonic frequencies. This practically means that the second harmonic is no longer the main accumulator of energy of the pulse wave as in healthy subjects, and the same is also true, to a proportionate degree, for the third, fourth and fifth harmonics.

In female patients with idiopathic oedema the capillary filtration rate and capillary diffusion capacity for I-131 were studied in lower-limb muscles and subcutaneous tissue. The capillary filtration rate averaged 0.276 ml/100 ml per minute, and the capillary diffusion capacity for I-131 averaged 9.8 mol/(mol/ml) per 100 g per minute in the gastroonemius muscle and 8.7 mol/(mol/ml) per 100 g per minute in the lower-limb subcutaneous tissue. All of these figures are statistically significantly higher than the corresponding control findings. The results are compatible with the concept of disturbed capillary permeability, and etiopathogenetic factor of idiopathic oedema.

The transcapillary escape rate of albumin was studied in 24 juvenile hypertensives and in 13 controls on the basis of the radioactivities determined in the blood during 60 min after i.v. injection of human 131I-labelled albumin. In addition, the central haemodynamics of all hypertensive subjects was examined at rest and during exercise. The patients were grouped according to their pressure during the investigation at rest. The group whose mean arterial pressure did not exceed 100 mmHg, thus being within the range of normotension, did not exhibit a significant deviation from controls. The group with mean arterial pressure exceeding this limit (corresponding to the range of borderline hypertension) showed a significantly higher escape rate of albumin (9.3 +/- 5.0%/h) than controls (5.2 +/- 1.6%/h). The albumin escape rate was significantly correlated to the mean pulmonary artery pressure during exercise but not to the remaining central haemodynamic parameters at rest or during exercise. No difference was seen in the magnitude of plasma volumes of juvenile hypertensives and controls. The findings suggest that secondary changes of capillary functions are present already in the early stages of hypertension.

Capillary functions in humans can be assessed by measuring capillary filtration and capillary diffusion capacity in the extremities. Examination of these two parameters supplements each other and renders it possible to evaluate capillary function from different aspects. As an example of practical use may serve the findings in patients with obliterating atherosclerosis of the lower extremities and in subjects with chronic venous insufficiency. The authors revealed a rised capillary diffussion capacity on obliterated extremities and a reduced capillary filtration in venous insufficiency. It is possible that in both instances these are manifestations of adaptational changes focused on the prevention of oedema formation and on a raised metabolism under conditions of an inadequate blood supply of tissues.