Classification Of Chronic Venous Disease Research Articles

A variant of the castor zinc finger 1 (CASZ1) gene is differentially associated with the clinical classification of chronic venous disease

Recent reports have suggested a reproducible association between the rs11121615 SNP, located within an intron of the castor zinc finger 1 (CASZ1) gene, and varicose veins. This study aimed to determine if this variant is also differentially associated with the various clinical classifications of chronic venous disease (CVD). The rs11121615 SNP was genotyped in two independent cohorts from New Zealand (n = 1876 controls /1606 CVD cases) and the Netherlands (n = 1626/2966). Participants were clinically assessed using well-established CVD criteria. The association between the rs11121615 C-allele and varicose veins was validated in both cohorts. This was strongest in those with higher clinical severity classes and was not significant in those with non-varicose vein CVD. Functional analysis of the rs11121615 variant demonstrated that the risk allele was associated with increased enhancer activity. This study demonstrates that the CASZ1 gene associated C-allele of rs11121615 has a significant, reproducible, association with CVD (CEAP C ≥ 2 meta-odds ratio 1.31, 95% CI 1.27–1.34, P = 1 × 10−98, PHet = 0.25), but not with non-varicose vein (CEAP C1, telangiectasia or reticular veins) forms of venous disease. The effect size of this association therefore appears to be susceptible to influence by phenotypic heterogeneity, particularly if a cohort includes a large number of cases with lower severity CVD.

Does the heel-rise test explain functional capacity in venous insufficiency?

Introduction Individuals with chronic venous insufficiency (CVI) have muscle pump dysfunction and reduced functionality. However, studies are inconsistent in proving whether a particular test can assess muscle functional capacity. Therefore, the aim of this study was to evaluate whether the heel-rise test (HRT) is able to explain functional capacity in patients with CVI. Materials and methods Subjects with CVI aged between 20 and 59 years old were selected for this study. All participants were classified by means of the Clinical Anatomy Etiology Pathophysiology Classification of Chronic Venous Disease (CEAP). The HRT and the shuttle walk test (SWT) were performed. Descriptive statistics, Spearman correlation, linear models and regression variance analysis (one-way ANOVA) were used for data analysis. Significance was set at alpha ≤ 5%. Results 79 subjects were included in the study (38.79 ± 1.34 years). The HRT was able to explain functional capacity only in individuals aged between 50-59 years (R2 = 0.60, p = 0.0001). The heel-rise test was not sensitive to detect differences between the CEAP classes analyzed (p > 0.05). Conclusion The HRT was able to explain functional capacity in individuals aged between 50-59 years, and it can be applied in clinical practice for the functional evaluation of patients with CVI with mild severity in this age range.

Body Mass Index and Primary Chronic Venous Disease – A Cross-sectional Study

This study aims to investigate whether overweight and obesity are related to the clinical (C) category of clinical, etiologic, anatomic and pathophysiologic (CEAP) classification of chronic venous disease (CVD). A cross-sectional study. The study was conducted in Serbia, in the year 2011. Men and women aged >18 years, consecutively coming to venous specialists because of venous problems in the legs, were included in the study. Patients demographic, anthropometric and clinical data were collected. For the analysis, univariate and multivariate logistic regressions were used. The study comprised 1116 subjects with primary CVD, 384 (34.4%) men and 732 (65.6%) women. Among them 464 (41.6%) were normal-weight patients (body mass index (BMI) < 25.0 kg m(-2)), 476 (42.7%) were overweight (BMI = 25.0-29.9 kg m(-2)) and 176 (15.8%) were obese (BMI ≥ 30.0 kg m(-2)). According to multivariate analysis, the CEAP C category of CVD was significantly more advanced in overweight and obese patients, the association being more pronounced in obese. Compared groups did not differ in the presence of venous reflux. In univariate analysis, venous obstruction was related to overweight and obesity but this association did not substantially affect the relationship between obesity and CEAP C categories of CVD. The CEAP C categories of CVD were significantly related to overweight and obesity, and this association was independent of age, sex and some other postulated risk factors.

Detecting the Association Between Residual Thrombus and Post-thrombotic Classification of Chronic Venous Disease with Range Regression

This paper addresses a clinical hypothesis detected by the method of range regression, a new statistical method portraying the clinical response via the range of an explanatory variable. For patients with iliofemoral deep venous thrombosis, it has long been clinically suspected that residual thrombus affects the quality of life after catheter-directed thrombolysis. However, such important medical experience has not been validated or scientifically quantified by experimental or observational data. In clinical practice, this association may directly affect the duration of thrombolytic therapy or other attempts at clot removal. In this study, we develop a new regression model to identify how the quantity of clot lysed affects the clarification of chronic venous disease after catheter-directed thrombolysis (a correlated index on postthrombotic quality of life). Bridging clinical insight with statistics by means of medical records of 62 IFDVT patients, the new method reveals that residual thrombus significantly and substantially affects post-thrombotic clarification of chronic venous disease. The conclusion of the new method is confirmed by a conventional logistic regression method when 50% thrombus removal is treated as a categorization threshold. This new approach is applicable to analyze other clinical or medical variables on the treatment of venous diseases.

Detecting the Association Between Residual Thrombus and Post-thrombotic Classification of Chronic Venous Disease with Range Regression

Detecting the Association Between Residual Thrombus and Post-thrombotic Classification of Chronic Venous Disease with Range Regression

Medical Treatment of Chronic Venous Insufficiency

Chronic venous insufficiency (CVI) of the lower extremities is a complicated disorder that affects the productivity and well-being of millions of people worldwide. Management requires careful differential diagnosis and a systematic long-term multidisciplinary care effort directed toward realistic goals within the context of the patient’s lifestyle. Patients suffering from any class of the Clinical, Etiological, Anatomical, Pathophysiological (CEAP) classification of chronic venous disease (CVD) may be symptomatic (C0s-C6s). Leg heaviness, discomfort, itching, cramps, pain, paresthesia and oedema (C3) are the most frequent manifestations of CVD and a major reason for medical consultation. The standard treatments for venous disease of the lower limb include compression bandaging and stocking as well as surgical removal of varicose veins. Drugs for the venous system were initially called phlebotonics as they were believed to act on venous tone. They are still largely used in the symptomatic treatment of CVI and to make patients more comfortable. Phlebotropic drugs, in their modern form, are aimed at a wide range of processes. They are naturally occurring, seminatural or synthetic substances, some of them combining two or more active principles to improve the efficacy. Most of these belong to the flavonoid family (such as diosmine, esperidine, troxoerutine, oxoerutine, etc.) and others are capillary protecting substances as escine, centella asiatica, bilberry anthocyanosides. Flavonoid drugs have been widely used in the management of the symptom of venous disease for many years and have recently been studied in some detail to assess their effects on the microcirculation. Phlebotropic drugs are widely prescribed and marketed in Italy, France, Germany and other parts of Europe. Their mechanisms of action vary, but their main property is activation of venous and lymphatic return. The effects of phlebotropic drugs on physiological parameters such us venous tone, venous haemodynamics, capillary permeability and lymphatic drainage have been studied by many well-conducted randomized, double-blind clinical trials. In particular, phlebotropic drugs participate in the heamodynamic re-equilibrium of the microvascular system consisting in reducing capillary permeability by increasing its resistance with the consequent reduction of interstitial fluid. A series of drugs have been recently introduced for the treatment of severe CVI (CEAP 4/5/6), as co-adjuvants. They are antithrombotic drugs (sulodexide, heparan sulfate, defibrotide) and vasodilators (pentoxifyllin and prostaglandin E1) for their specific action on endothelial alterations and blow flow patterns, and on microthrombi and their oxygen barrier effect.

Recommended reporting standards for endovenous ablation for the treatment of venous insufficiency: Joint Statement of the American Venous Forum and the Society of Interventional Radiology

Sanjoy Kundu, MD, FRCPC, FCIRSE, FASA, Fedor Lurie, MD, Steven F. Millward, MD, FRCPC, FSIR, Frank Padberg Jr, MD, Suresh Vedantham, MD, Steven Elias, MD, Neil M. Khilnani, MD, William Marston, MD, John F. Cardella, MD, FSIR, FACR, Mark H. Meissner, MD, Michael C. Dalsing, MD, Timothy W.I. Clark, MD, FSIR, and Robert J. Min, MD, MBA, FSIR, Toronto and Peterborough, Ontario, Canada; Honolulu, Hawaii; Newark and Englewood, NJ; Saint Louis, Mo; New York, NY; Chapel Hill, NC; Springfield, Mass; Seattle, Wash; and Indianapolis, Ind

Comparison of new continuous measurements of ambulatory venous pressure (AVP) with conventional tiptoe exercise ambulatory AVP in relation to the CEAP clinical classification of chronic venous disease

Quantitative measurements of chronic venous insufficiency (CVI) are sensitive in detecting the presence of CVI but have low specificity in differentiating clinical severities of CVI as defined by the CEAP classification. One possible reason for this is measurement techniques do not assess variables that reflect hemodynamic changes that occur during normal exercise. Our aim was to compare the association of variables determined from a new technique, continuous ambulatory venous pressure monitoring (CAVPM), and those of conventional AVP measurement with the clinical severity of chronic venous insufficiency in patients with primary venous reflux. Fifty-four limbs of 49 patients with CVI and 15 healthy controls were studied. CVI clinical severity was classified according to CEAP as C2&C3 (mild disease), C4 (moderate disease), and C5&C6 (severe disease). All participants underwent duplex ultrasound scanning to rule out the presence of reflux in the control group and to confirm it in the patient groups. Conventional AVP measurements, including 90% refilling time (RT90), were compared with the new CAVP variables of mean walking pressure (MWP) and percentage fall in walking pressure (%FWP). Data were analyzed by analysis of variance using the Kruskal-Wallis test, and comparisons between groups were performed using Mann-Whitney tests. Discriminant analysis was used to determine the ability of a test to classify limbs into clinical classes. Conventional AVP measurements could not differentiate between the control group and the presence of mild disease (P = .56) but did differentiate between controls and severe disease as well as mild and severe disease (P < .001). RT90 detected differences between controls and reflux groups (P < .001) but not between moderate (C4) and severe (C5&C6) clinical groups (P > .5). MWP and %FWP showed significant differences between all clinical severities and controls (P < .001). In the assessment of CVI, mean walking pressure and percent fall in walking pressure are more reliably associated with anatomic distribution of reflux and clinical severity of CVI than the gold standard investigations of conventional AVP and RT90.

Daflon 500 mg: Symptoms and Edema

Patients suffering from any class of the Clinical, Etiological, Anatomical, Pathophysiological (CEAP) classification of chronic venous disease (CVD) may be symptomatic (C0s-C6s). Leg heaviness, discomfort, itching, cramps, pain, paresthesia, and edema (C3) are the most frequent manifestations of CVD and a major reason for medical consultation. Daflon 500 mg (micronized purified flavonoid fraction [MPFF]) is an effective treatment for symptoms and edema in CVD as demonstrated in several randomized controlled studies. A 2-month, double-blind study in 40 patients established the superiority of Daflon 500 mg over placebo with regard to symptoms and objective signs. This was confirmed in another double-blind, placebo-controlled trial (2 months' treatment, 160 patients), and in the Reflux assEssment and quaLity of lIfe improvEment with micronized Flavonoids (RELIEF) study. The latter included 5,052 patients in 23 countries, using a visual analog scale for evaluating pain, leg heaviness, cramps, and a sensation of swelling. All symptoms showed significant and progressive improvement. The quality-of-life results (scores on the ChronIc Venous Insufficiency quality of life Questionnaire [CIVIQ]) paralleled those of symptoms. The decrease in the ankle and calf circumferences was significantly greater (p < 0.001) in the group of patients treated with Daflon 500 mg in two studies, and correlated well with the improvement in the sensation of swelling (p < 0.001). This was confirmed with more sophisticated measurement techniques as in the RELIEF study or in a trial assessing edema with an optoelectronic volumeter in 20 patients. A further double-blind, randomized, controlled study established a statistically significant difference in favor of Daflon 500 mg in comparison with diosmin, both on symptoms and edema. The therapeutic efficacy of Daflon 500 mg on CVD symptoms and edema has been demonstrated in double-blind, randomized, controlled studies. Further studies using a new approach may define the most precise and validated methodology for application in future research in phlebology.

Relationship between clinical classification of chronic venous disease and patient-reported quality of life: results from an international cohort study

Objectives The CEAP ( clinical, etiologic, anatomic, pathophysiologic) clinical classification for chronic venous disease (CVD) is based on physician-evaluated clinical signs of CVD. The relationship between CEAP clinical classification and patient-perceived quality of life (QOL) has not been evaluated, but is important for the selection and interpretation of outcomes in clinical studies of patients with CVD. The purpose of this study was to evaluate whether CVD, as classified with CEAP, is related to patient-reported QOL, and to identify patient characteristics associated with CEAP class and QOL that need to be considered when interpreting outcomes in CVD. Methods The Venous Insufficiency Epidemiologic and Economic Study (VEINES) population is an international cohort of 1531 patients with CVD recruited in Belgium, France, Italy, and Canada. At the baseline visit patients were categorized into one of seven CEAP clinical categories on the basis of a clinical examination, and completed standardized generic (Short-Form Health Survey, 36 items [SF-36]) and venous disease–specific (QOL [VEINES-QOL] and symptom severity [VEINES-Sym]) QOL questionnaires. Multivariate analyses were used to examine the relationship between CEAP class and QOL. Results The proportion of patients in the seven CEAP classes (class 0-6) was 3.8%, 13.3%, 24.1%, 12.8%, 36.4%, 7.3%, and 2.3%, respectively. In univariate analyses, SF-36 Physical Component Summary scores and VEINES-QOL and VEINES-Sym scores decreased significantly (ie, poorer QOL) with increasing CEAP class. Multivariate analyses controlling for age, sex, country, education, body mass index, years since CVD onset and comorbid conditions confirmed findings for VEINES-QOL and VEINES-Sym ( P < .0001 and P < .0001, respectively). Conclusions Physician-evaluated clinical category, based on the CEAP classification, predicts patient-reported QOL and symptom severity in CVD.

Sequelae after limb-sparing surgery with major vascular resection for tumor of the lower extremity

Purpose: Limb-sparing procedures have recently replaced amputations as the treatment for tumors invading major vessels of the lower extremity. Major arteries must be reconstructed for limb salvage. The veins are not usually reconstructed. This study was undertaken to investigate the sequelae such as chronic venous disease after venous resection for tumors. Methods: Ten patients who underwent limb-sparing surgery for a tumor of the lower extremity or retroperitoneum that required major vascular resection were studied. The median follow-up period was 48 months. After combined resection of a major artery and vein, arterial reconstruction was performed. The veins were not reconstructed. The resected veins included the inferior vena cava (n = 2), the external iliac and common femoral veins (n = 3), the superficial femoral vein (n = 3), and the popliteal vein (n = 2). The main outcome measures were clinical classification of chronic venous disease in 10 patients and air plethysmography in seven patients. Results: Clinical classification was C0A in 6 patients, C3A in 1 patient, C3S in 2 patients, and C4S in 1 patient. Venous claudication with uncontrollable edema was observed in two patients with C3S disease. Pain and itching with inflammatory skin changes were observed in one patient with C4S disease. These three patients had undergone resection of the femoral vein, including the deep femoral vein along with proximal adductor muscles. Air plethysmography revealed that the ejection fraction was significantly lower and the residual volume fraction was significantly higher in the three patients with symptoms than in symptom-free patients. Conclusions: Significant chronic venous disease was observed in the patients who underwent combined resection of the femoral vein, the deep femoral vein, and the adductor muscles for a tumor. (J Vasc Surg 2001;33:694-9.)

Venous bypass and valve reconstruction: long-term efficacy.

Palma and Esperon described the first femoro-femoral cross-over bypass for iliac vein obstruction in 1958, and Kistner performed the first valve reconstruction for deep vein reflux in 1968. Such surgical development has stimulated better diagnostic methods that now form the foundation for a classification of chronic venous disease, and surgery has been supported by, and sometimes replaced by, the rapid progress in endovascular procedures with angioplasty and stenting. The ability now exists to relieve obstruction and repair reflux in the deep veins, and the results in the successful cases demonstrate the improvement that follows correction of the physiologic abnormalities. The detail in workup required to achieve an accurate diagnosis that is adequate enough to guide surgical treatment in these cases has set a new standard for the diagnosis of chronic venous disease that incorporates the clinical state, etiology, pathophysiology and anatomic distribution of the venous problem, and is incorporated in the CEAP (clinical, etiologic, anatomic, pathophysiologic) classification. The challenge at this time is to produce a reliable set of data that demonstrate the results of treatment in patients with chronic venous disease by conventional methods of bandaging, rest and elevation as well as specific surgical correction of venous obstruction and reflux and to follow these cases over a significant period of time.

Classification of Chronic Venous Disease

Classification of Chronic Venous Disease

Diagnosis of Chronic Venous Disease of the Lower Extremities: The “CEAP” Classification

To test a new classification of chronic venous disease (CVD)--based on clinical, etiologic, anatomic, and pathophysiologic data (the CEAP system)--in a series of patients by using objective tests to establish all diagnoses. The CEAP classification was applied to 102 extremities in 70 consecutive patients with CVD. Diagnoses were based on objective testing with continuous-wave Doppler studies, duplex scanning, plethysmography, venous pressure, and phlebography, which were applied selectively (the more invasive methods were reserved for cases of greater severity). Use of this classification provided an organized categorization of the key elements of the venous abnormalities in each case and clarified the interrelationships among the clinical manifestations, cause of the process, and anatomic distribution of involvement. For example, in this series of 102 extremities, 79% had primary venous disease, 18% had secondary disease, and 3% had congenital abnormalities. Ulcers were found in 7% of extremities with primary CVD and 44% with secondary CVD. Of the cases with ulceration, 43% were due to primary incompetence and 57% to postthrombotic disease. Reflux was the pathophysiologic problem in 86% of the total series and in 80% of ulcer cases. Similar relationships can be delineated for cases with varicose veins, edema, or skin changes. Study of the specific facets of the CEAP classification provided precise information about the cause and the effect of venous abnormalities that could be compared with cases in other series. Use of the CEAP classification with diagnoses determined by objective testing accurately identifies categories of CVD. The objective date provide a clear description of the abnormalities in each case and may be used for analyses of meaningful relationships between categories of CVD. Adoption of this objective method of classifying CVD will facilitate interinstitutional studies.