Prevalence of venous insufficiency in French adults of the SUVIMAX cohort. SUpplémentation en VItamines et Minéraux AntioXydants.

BACKGROUND: The symptoms of venous insufficiency of the lower limbs (VILL) include a feeling of heaviness in the legs, pain, and nocturnal cramps, which may be combined with organic disorders (varicose veins). The objective of this study was to determine the prevalence of VILL in terms of both varicose veins and functional symptoms in the participants of the SUVIMAX cohort, which is representative of the French population for the age range under consideration (women: 35-60; men: 45-60). METHODS: Information on the venous status of 3065 subjects in the SUVIMAX cohort were collected from three different sources: yearly systematic clinical examination (1994-1996), monthly follow-up by a telematic network (1994-1998) and non-specific questionnaire (1997). Two mutually exclusive populations were thus defined on medically diagnosed varicose veins and venous insufficiency and reported varicose veins and venous insufficiency. RESULTS: Venous insufficiency was medically diagnosed in 192 men (14.6%) and 584 women (33.6%), and varicose veins were diagnosed in 143 men (74.5%) and 317 women (54.2%) from this group. Prevalence reported symptoms of venous insufficiency and of varicose veins was 13.6% and 7.4% respectively in men and 28.2% and 12.4% in women. Sex, age, body mass index and number of pregnancies were found to be correlated with the risk of venous insufficiency. CONCLUSIONS: VILL is a very common disease in French adults both as varicose veins and as functional symptoms. Venotonics were the main type of treatment but not enough use is made of elastic compression stockings.     

Prevalence and risk factors of chronic venous insufficiency

Venous disease in the legs occurs very commonly in the general population in Western countries. Around one third of women have trunk varices. A lower prevalence has been observed in men but some recent surveys have suggested that the occurrence in men may be comparable to that in women. The prevalence increases with age but the incidence of new cases appears to be constant throughout adult life. Open venous ulcers occur in about 0.3% of the adult population and a history of open or healed ulceration occurs in around 1%. The etiology of chronic venous disease in the legs is unknown. A genetic predisposition may be present but evidence for this and for a mode of inheritance is lacking. There is some suggestion that prolonged standing may be a risk factor but studies are open to considerable bias. In women, obesity and previous pregnancy has been associated with the presence of varicose veins but the evidence is inconsistent. There have been few well-conducted studies examining diet and bowel habit as a risk factor. The risk of ulceration is related to the severity of varicosities and venous insufficiency, and is increased following deep vein thrombosis. Much further research is required to investigate the cause of this common condition in the general population.     

The influence of environmental factors in chronic venous insufficiency

The present article focuses on the prevalence and risk factors for varicose veins and the severe stage of chronic venous insufficiency (CVI). The evaluation was made by reviewing the results of specific well-designed studies performed on the general population (case-control studies, cross-sectional studies, and large case series). Data from the literature were compared with the results of a recent multicenter cross-sectional study in Poland, in which 40,095 individuals from 803 registers of primary care physicians were clinically examined and assigned a clinical CEAP class. Analysis of the associations between varicose veins or severe CVI prevalence and factors that are usually considered as representing a risk for the development of CVI was performed. In Poland, a prevalence of varicose veins and severe CVI (skin changes, leg ulcer) similar to that observed in the other developed countries was reported. It was more common in women, but female sex was not found to be a strong risk factor. Among the risk factors most closely associated with CVI were age, family history of varicose veins, and constipation, whatever the sex. This is in keeping with findings from recent epidemiologic studies. Obesity and lack of physical activity were strongly associated with CVI in women, more so than in men. The number of pregnancies (more than 2 pregnancies) significantly distinguished between women with and without CVI. Regarding these latter risk factors, the Polish results do not contradict the commonly held beliefs that are found in the literature. A modest association was found with female sex, previous injury in legs (DVT), and remaining in the standing position for a long time, although these parameters are usually among those mostly agreed as being risk factors. The role of the prolonged sitting position was not established. The Polish epidemiologic survey provided updated figures on the prevalence of and risk factors for varicose veins and severe CVI, using clear and globally accepted clinical definitions for the venous disease based on the CEAP classification.     

Haemostatic factors and risk of varicose veins and chronic venous insufficiency: Edinburgh Vein Study.

Despite much research, the aetiology of venous disease is still poorly understood. Since haemostatic factors are involved in the processes of fibrinolysis and platelet aggregation, it is conceivable that such processes may be implicated in the pathology of varicose veins and chronic venous insufficiency (CVI). The Edinburgh Vein Study examined 1566 men and women aged 18-64 years that were randomly selected from the lists of 12 general practitioners. Each subject completed a questionnaire, underwent a comprehensive clinical examination and had a blood sample taken for the analysis of plasma fibrinogen, tissue plasminogen activator (t-PA) and von Willebrand factor (vWF) antigens. Subjects with trunk varicose veins and those with CVI had higher levels of each haemostatic factor compared with those with no trunk varices and no CVI. Although unit increases in t-PA and vWF were initially associated with a significantly increased risk of CVI in men, and both factors with an elevated risk of trunk varices in women, multiple adjustment for age, smoking status and body mass index reduced the odds ratios to non-significance. However, this does not entirely rule out the possibility of a pathogenic role for haemostatic factors in venous disease, but rather indicates the need for further experimental and epidemiological studies.     

Varikose: Schönheitsfehler oder Erkrankung?

According to one's subjective appraisal varicose veins will be perceived as more or less disfiguring. About 60% of the population suffer from only minor variants of varicose veins which bear no risk to health. A certain percentage will develop progressive disease with the venous ulcer representing the worst variant of chronic venous insufficiency. As long as there is no progressive disease, therapeutic modalities also account for a superior cosmetic appearance. Endoluminal procedures in particular meet with the claim for a superior treatment result with respect to cosmetic outcome without diminution of efficiency. In case of progressive venous insufficiency appearance is of inferior importance. About 70% of venous ulcers are due to primary varicose veins. Surgery of all accessible superficial refluxing veins is important to prevent recurrence. Compression treatment is highly effective in preventing chronic venous insufficiency and in venous ulcer treatment. About 60% of venous ulcers heal within a 24-week treatment period.     

Risk factors for varicose veins.

AIM: To determine the prevalence of varicose veins in the German population and specify possible risk factors the data of the Duesseldorf/Essen civil servants study were analysed. METHODS: From December 1989 to July 1993 a total of 9 935 employees were recruited. All volunteers filled out a questionnaire regarding family history and risk factors and were clinically examined. Venous findings were classified and adapted to the CEAP-classification. For the analysis of risk factors only volunteers classified as CEAP-class 0 or as CEAP-class II were considered: 4 250 men, 10% belonged to CEAP-class II and 2 380 women including 16% CEAP-class II. RESULTS: In general, age and gender were the most relevant risk factors for varicose veins. Odds ratio age: male: 3.4 (95%-CI: 2.6-4.4), age female 6.5 (95%-CI: 5.0-8.5), gender 2.3 (95%-CI 1.9-2.7). In addition in females the most frequent risk factors were oral contraception and in both genders a predominately sitting posture at work. Regarding the family history, varicose veins by the mother was most frequent compared to varicose veins by the father or both. After adjusting for age and gender heridity became the most important risk factor with an odds ratio of 5.2 (95%-CI:3.7-7.3-4.50) in case of varicose veins present in both parents, followed by a standing posture at work 2.2 (95%-CI: 1.2-3.9). In contrast, smoking also reached a significant level, but with a decreased odds ratio of 0.66 (95%-CI: 0.57-0.77) indicating a protective effect. CONCLUSION: In addition to age and gender a family history of varicose veins is the most important risk factor in the total population. Despite significant influence of other risk factors their relevance for varicose veins in the investigated population is low either due to low frequencies or low odds ratios.     

The risk of maternal venous thromboembolism disease. Synopsis and definition of high-risk groups

Risk factors for venous thromboembolic disease, during pregnancy and post-partum, can be identified in as much as 75% of pregnant women, who present such an accident. Different risk factors are usually associated in the same women. Risk factors can be attribuated to the pregnant women (age over 35 years, overweight, varicose veins, smoking, previous deep venous thrombosis and/or pulmonary embolism) or to the conditions of the pregnancy (multiparity, immobilisation, hypertension and pre-eclampsia, cesarean delivery). Inherited or acquired biological thrombophilia enhance the risk of thrombosis but the magnitude of this effect in ante-partum, puerperium or post-partum depends on the nature of the abnormality. The analysis of all these risk factors and their cumulative effect enable classifying pregnant women into groups with very high risk, high risk or moderate risk for venous thromboembolism and to propose an adapted strategy to prevent the occurrence of such accidents.     

Incidence of varicose veins in Finland

BACKGROUND: Incidence of varicose veins in the population is unknown. The study aimed at estimating the incidence of varicose veins in complete cohorts of 40-60 year-olds in a general population. PATIENTS AND METHODS: The study was conducted in the city of Tampere, Finland. A validated questionnaire (with 93% sensitivity and 92% specificity) was used in a general population of 6874 individuals (aged 40, 50 or 60). Initially, 3065 of them had no varicose veins and 78% were followed-up for 5 years. RESULTS: 157 individuals reported new varicose veins during the follow-up. The overall incidence was 13.5 per 1000 person years (8.5 for men and 19.2 for women). Female sex was an independent and statistically significant risk indicator of varicose veins (adjusted odds ratio, OR 2.4). The incidence was significantly higher at the age of 50-55 years (OR 1.6). Higher body mass index seemed to be related to higher risk of new varicose veins (OR 1.2-1.8), but the association failed to reach statistical significance. The level of education did not affect the incidence. CONCLUSIONS: New varicose veins appear also in the middle-aged population, and the rate is linked with the female gender, especially at the beginning of the 6th decade.     

Superficial vein thrombosis: risk factors,diagnosis, and treatment

Superficial vein thrombosis (SVT) risk factors are close to those of venous thromboembolism (VTE). Diagnosis is made in a clinical setting but ultrasonography is useful to eliminate concomitant deep vein thrombosis (DVT). For SVT of the lower limbs, which is the main location, varicose veins represent the principal cause but underlying conditions (e.g.: autoimmune diseases, malignancy or thrombophilia) must be sought in idiopathic, migrant or recurrent SVT and in the absence of varicose veins. Concomitant DVT and pulmonary embolism can occur in approximately 15% and 5% respectively. Historical treatments consist of anti-inflammatory agents plus elastic stockings and, in case of varicose veins, thrombectomy and stripping. Other treatments (anticoagulants, vein ligation) were assessed to limit the VTE risk. A one-month prophylactic dose of low molecular weight heparin plus elastic stockings could be the appropriate strategy in most cases. Other studies are needed before definitive conclusions can be drawn.     

Increased mast cell infiltration in familial varicose veins: pathogenetic implications?

AIM: Increased infiltration of activated mast cells has been recently implicated in the pathophysiology of varicose veins. The aim of the present study was to investigate a possible association between mast cell infiltration of primary varicose veins and clinical features, which could clarify further varicose vein pathophysiology. METHODS: Seventeen patients, operated on for primary varicose veins and greater saphenous vein incompetence, participated in the study. Mast cells, distributed within the adventitia of grossly abnormal segments of the greater saphenous vein and calf varicosities removed during surgery, were identified and measured in stained tissue sections. The mast cell count, expressed as mast cells per 10 high-power fields, was subsequently associated with clinical features, including age, gender, body mass index, familial varicose veins, duration of varicose vein disease and relation to previous pregnancies, leg symptoms and findings on physical examination, clinical class and score of chronic venous insufficiency (CEAP classification). RESULTS: Patients with family history of varicose veins (n=7) had a significantly increased mast cell infiltration (median, interquartile range) of the abnormal venous segments (16, 8.4) in comparison with those (n=10) without such a history (9.2, 7.3), p=0.005. Mast cell infiltration had a significant inverse association with age (r= -0.49, p=0.046), but not with the remaining clinical features. CONCLUSION: Our findings support the hypothesis that the increased mast cell infiltration in varicose veins is not a consequence of venous hypertension. Furthermore, the increased mast cell infiltration in familial varicose veins implies a rather primary role and therefore the presence of a distinct pathophysiology. Further investigation testing the activity of mast cells in cases of family history might reveal another step in the pathogenic mechanism of varicose veins, leading to a more rational treatment.     

Persons with varicose veins have a high subsequent incidence of arterial disease: a population-based study in Tampere, Finland

The aim of this population research was to find out the risk of arterial disease (defined as angina pectoris, myocardial infarction, peripheral occlusive arterial disease, and cerebrovascular disease) and hypertension in persons with varicose veins. A 5-year follow-up study was conducted in Tampere, Finland. A validated questionnaire was used in 3 middle-aged cohorts (40, 50, and 60 year olds) in a general population of 6,874. In the follow-up study, 71% (n = 4,903) replied. The incidence of arterial disease and hypertension was studied in those with varicose veins and those without at the entry to the study. During the follow-up, new arterial disease occurred significantly more often in individuals with varicose veins. The incidence odds ratio was 2.0 (95% confidence interval, 1.5-2.7; n = 3,032), but the incidence odds ratio of new hypertension was 1.0 (95% confidence interval, 0.8-1.3; n = 2,915). Varicose veins are a risk indicator of arterial disease but not of hypertension. Varicose veins likely do not cause arterial disease, but they may have common causes that, however, are not related with hypertension.     

The relevance of the natural history of varicose veins and refunded care

Chronic venous disease (CVD) is one of the most common diseases in our population. Aside from venous symptoms like heaviness and pain, which are present in about 50% of the general population, signs of CVD include varicose veins (VVs), oedema, eczema, venous eczema, hyperpigmentation, white atrophy, lipodermatosclerosis and venous ulcers. The aim of this paper is to review current literature for the relevance of natural history of VVs in refunded care. Available papers on VVs, progression of the disease and complications were reviewed. Prevalence of VVs is high with more than 20% in the general population. Information on progression of uncomplicated VV to chronic venous insufficiency (CVI) is rare. However, most venous ulcers have a primary venous origin. The progression rate of VV to higher clinical stages reaches 4% per year. Among the risk factors are obesity and higher age. Quality of life (QOL) is also reduced in uncomplicated VV in C2 patients. In conclusion, there is evidence from the literature that a high proportion of patients with uncomplicated VVs in the clinical, aetiological, anatomical and pathophysiological classification (CEAP Clinical Class 2) will progress to CVI if untreated. VVs have a negative impact on QOL and clinical symptoms. VV patients with CVI (C3-C6) as well as those C2 patients with severe clinical symptoms and impaired QOL due to CVD should be treated with ablation of the VVs in a refunded care system.     

Epidemiology and pathogenesis of varicosities

Epidemiologic studies have shown that over 70% of the population in the Federal Republic of Germany have pathologic changes in the peripheral venous system, from which 5% require treatment. In the Basler Study, varicose veins were found in 26% of those 25 to 36 years of age and in 74% of those 65 to 74 years old. In earlier years, according to a questionnaire of the US National Health Survey there was a prevalence of varicose veins of 0.8% in men and 3.5% in women. In a similar study in the United Kingdom, the prevalence was 2.25%, in Denmark 2%. In contrast, in men of the Maori tribe, 36.3% had varicose veins while the women were affected in 47.4% as compared to 21.5% in the white male population and 40.4% in white women. According to the World Health Organization, varicosities are defined as saccular or cylindrical widened superficial veins where the widening may be circumscribed or segmental. In general, the dilatation of the veins is associated with tortuosities. There are various causes of primary varicose veins whereas secondary varicosities are usually due to a postthrombotic condition (Figure 1, Table 1). Primary varicose veins predominantly manifest themselves in the domain of the great saphenous vein and infrequently in the region of the lesser saphenous vein (Figure 2). Lateral branch varicosities are generally an isolated condition. Microvaricosities may appear as a network or arcade-like pattern of intradermal vessels (Figure 3) or reticular with a diffuse, small caliber network in the upper layers of the subcutis (Figure 4). Varicosities of the perforating veins occur subsequent to local incompetence.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the results of the curative treatment of varices using 3 scoring systems: clinical, Doppler and echographic]

There have been many studies reporting results of curative treatment of varicose veins. Four methodological errors are nevertheless often committed: groups of varicose vein patients not comparable with regard to the degree of venous dilatation; insufficient objective parameters; population inadequately followed up; retrospective studies. It was felt necessary to develop systems for the quantification of varicose disease. These systems provide three grades: a clinical grade, a Doppler grade and an ultrasonographic grade. Clinical grade essentially involves the maximum diameter of varicose veins found by palpation and expressed in millimetres. The Doppler grade takes into account the maximum duration of the reflux wave in compression-decompression manoeuvres. The ultrasonographic grade also involves the maximum diameter of the varicose system. These grades enable the numerical assessment of the results of curative treatment of varicose veins, as well as forming the basis for statistically satisfactory epidemiological surveys.     

Prevalence and risk factors of varicose veins in Japanese women

The prevalence and risk factors of varicose veins in Japan were investigated in 541 Japanese women. Varicose veins were defined as any dilated, tortuous, and elongated veins of the lower extremity and classified into four types. The total prevalence rate was 45%. Saphenous type was observed in 22%, segment type in 35%, reticular type in 28%, and web type in 16%. Varicose veins in Japan seem to be less common than in the United States and Europe but more prevalent than in Africa. Concerning risk factors for varices, age, sex, heredity, and childbirth were related to the incidence of varicosities, as reported by others. However, these risk factors were shown to differ according to type of varicose veins.     

What is the medical rationale for the treatment of varicose veins?

Varicose veins occur in up to one-third of Western populations and are associated with clinical manifestations ranging from asymptomatic, isolated varicose veins (C2 disease) to venous ulceration. While the development of less invasive treatment options, such as endovenous ablation and sclerotherapy, have been well accepted by patients they have led to increased utilization of scarce health-care resources. While few would argue with the treatment of acute complications such as superficial venous thrombosis and variceal haemorrhage, the role of interventional treatment in the management of lifestyle limiting symptoms and the prevention of disease progression may be debatable. Good-quality evidence does suggest that surgical management of varicose veins is associated with improved quality of life at costs below the thresholds of many Western health-care systems. However, the progression of isolated C2 disease to advanced chronic venous insufficiency occurs infrequently and the role of treatment to prevent such progression remains undefined at present.     

8-Epi-PGF2alpha and 6-oxo-PGF1alpha in human (varicose) veins: influence of age,sex, and risk factors

The isoprostane 8-epi PGF2alpha is a vasoconstrictive, mitogenic, proliferative, and mild proaggregatory agent. We examined 8-epi-PGF2alpha and 6-oxo-PGF1alpha from venous tissue derived from varicose (venous) surgery by means of a specific radioimmunoassay. A total of 336 samples from 82 patients (50 females, 32 males; aged 22-68 years) were examined. Tissue samples were classified according to normal, dilated, and varicose. Of these, 94 samples from 31 patients (20 females, 11 males; aged 29-64 years) with additional risk factors (cigarette smoking, hyperlipidemia, diabetes mellitus) were determined in the same way. Mean absolute values for 6-oxo-PGF1alpha are not significantly higher for dilated segments followed by varicose and intact samples. No significant age and sex differences can be monitored. Presence of risk factors, however, results in a significantly diminished 6-oxo-PGF1alpha, irrespective of morphology. 8-Epi-PGF2alpha again showed no age and sex dependence, its presence in varicose segments, however, was significantly (p<0.01) decreased. Risk factors resulted in a significantly increased 8-epi-PGF2alpha. These data indicate that the influence of risk factors on vasomodulatory (iso-)eicosanoids of human veins is more pronounced than the actual morphologic stage. Lower 8-epi-PGF2alpha in varicose veins may shift the venous tone toward vasodilatation and contribute to development and progression of varicosis.     

Quantitative proteomics analysis of varicose veins: Identification of a set of differentially expressed proteins related to ATP generation and utilization

Although morphological and anatomical studies indicate that varicose veins are characterized by venous wall weakening and subendothelial fibrosis, the exact underlying biochemical mechanism of their development remains unknown. Additionally, no quantitative proteomic study of venous proteins leading to decreased contractility of varicose veins has been reported to date. Therefore, to elucidate the molecular mechanism of altered vascular contractility, this study performed shotgun proteomic analysis to obtain protein expression profiles in patients with varicose veins. Stable isotope dimethyl labeling coupled with nanoLC-MS/MS revealed downregulation in 12 polypeptides, including myosin light chain kinase, creatine kinase B-type, ATP synthase, phosphoglycerate kinase, and pyruvate kinase. However, analyses of protein species associated with cytoskeletal assembly or with cellular morphology showed no clear up- or down-regulation. These results indicate that defects in ATP generation and utilization may account for the dysfunction of vascular smooth muscle following formation of varicose veins. Collectively, the severity of varicose veins depends on the regulatory roles of various protein factors in the metabolic coordination of physiological functions. This pilot study improves understanding of the pathogenesis of varicose veins and lays the foundation for further validation and clinical translation of biomarkers for targeted therapies in treating this disease.     

Varicose veins. Chronic venous insufficiency. Lower limbs venous ulcers. Point of view

PURPOSE: Lower limbs chronic venous disorders are still considered as a minor disease from a university hospital point of view, yet it is a very common problem, affecting the quality of life, generating disability, and expensive for healthcare resources. Its teaching is neither satisfactory nor easy to do. KEY POINTS: Apart from the fact that it rarely causes death, the complexity of venous anatomy and physiopathology, the lack of animal model, common practices lumping together visible varicose veins and chronic venous insufficiency, and moreover a certain carelessness in the vocabulary probably largely explain these difficulties. Our purpose is to discuss chronic venous disorders (varicose veins, chronic venous insufficiency, venous ulcers) on the basis of semantic, of anatomical, haemodynamic and clinical forms and finally of nosology.     

TGF-beta1 upregulation in the aging varicose vein

BACKGROUND: Although the etiology of venous insufficiency is not well understood, immune response and aging are beginning to emerge as contributing factors. Factors involved in tissue remodeling such as TGF-beta(1) also seem to play an important role in extracellular matrix production. The aim of this study was to explore the relationship between chronic venous insufficiency and TGF-beta(1) examining the latent/mature form of TGF-beta(1) and the presence of mast cells. Effects of age were also evaluated. METHODS: Saphenous veins were obtained from patients subjected to aortocoronary bypass (controls) and undergoing varicose vein surgery. These were immunolabeled using anti-LAP TGF-beta(1)/anti-TGF-beta(1) antibodies and subjected to Western blot. Mast cell population was identified by metachromatic staining. RESULTS: Latent TGF-beta(1) was significantly reduced in varicose veins from older subjects. In contrast, smooth muscle cells obtained from the varicosities showed intense levels. Mature TGF-beta(1) significantly differed between healthy and varicose veins. No mature TGF-beta(1) was detected in the cell cultures. Mast cell number and degranulation were increased with aging and varicose disease, colocalizing with the mature form of TGF-beta(1). CONCLUSION: Aging and varicose pathology induce dysregulation of TGF-beta(1) that could play an important role in the fibrous process, representing the final stages of venous insufficiency.