© Borgis - New Medicine 3/2007, s. 74-78
*Iwona Sudoł-Szopińska1, Krzysztof Błachowiak2, Piotr Koziński, MD3
Overview of risk factors of chronic venous disease
1Department of Ergonomy, Central Institute for Labour Protection - National Research Institute, Warsaw, Poland
2Department of General Surgery "B” and Multi-Trauma with Gastroenterological and Endocrinological Surgery Unit, Provincial Hospital, Poznań, Poland
3Department of Medical Radiology, Central Clinic of the Medical Military Institute, Warsaw, Poland
In the European countries venous diseases pose a serious social problem – as many as 35% of the professionally active population, 50% of pensioners, and every second female suffer from this disease. Chronic venous disease (CVD) is one of the most frequently occurring forms of venous diseases, particularly in developed countries; it is thought to concern 1/3 of the population.
Although a correlation between selected risk factors, e.g. age, obesity or deep vein thrombosis, and clinical stage of CVD was found in a number of studies, there is still controversy about the real aetiopathogenesis of CVD. It is still open to discussion whether only hereditary factors are responsible for the development of CVD or, quite to the contrary, environmental factors including lifestyle and type of work performed are at the source of the disease. This paper presents a review of literature on the following risk factors for the development of CVD: obesity, lack of physical activity, dietary habits including constipation, pregnancy, genetic factors as well as prolonged sedentary or upright position while performing work tasks.
Venous diseases constitute a serious social problem. In Europe 35% of the working population, 50% of the retired and every other woman suffer from this condition. Chronic venous disease (CVD) is the most frequent one and according to different authors (Evans et al. 1999) it is present in one third of the population, including 40-60% of women and 15-30% of men. Therefore the social and economic costs of CVD in Western Europe are extremely high, due to the incidence of the disease, costs of its diagnostics and treatment as well as work absence (Nicolaides 2000). Lower leg (shank) ulceration is the greatest medical as well as economical problem in the course of CVD. It is estimated that expenses related to this treatment reach 1-3% of the health service budget (Evans et al. 1999; Jawien 2003). In the UK the cost of treatment for leg ulcers is 400-600 million pounds per year. Research done in Germany in 1980 demonstrated that the costs of treatment for varicose veins, superficial thrombophlebitis and deep vein thrombosis were 660 m euros, whereas in 1990 they reached 1 billion euros. In addition, in the USA (Tsai et al. 2005) the analysis of admission of patients requiring hospitalisation showed that among 100 thousand patients 92 were admitted due to CVD. The average hospitalisation period was 7 days and the average cost of hospitalisation and treatment was 13 900 US dollars.
The symptoms of chronic venous disease include pain, feeling of fatigue, leg heaviness, tingling sensation, itching of the skin of the legs, muscle cramps at night, leg oedema, dilation of small intradermal blood vessels (telangiectasia), dilation and prominence of subcutaneous veins (small – reticular or feeder veins, and large – varicose veins) and dermal changes: discolouration of the skin of the shanks (haemosiderosis – dermite ocre), lipodermatosclerosis, stasis dermatitis (eczema) and lower leg ulcers (Nicolaides 2000; Kalodiki and Nicolaides 2002; Jawien 2003). The CEAP classification, established in 1994 by the Ad Hoc Committee of American Venous Forum, presents a wide spectrum of possible CVD symptoms (Agus et al. 2005). This classification is commonly used by clinical physicians to evaluate the stage of CVD.
A multifactor aetiology of CVD is well documented and consists of two main factors: weakening of the venous wall (flaccidity, loss of elasticity) and impaired functions of the valves (Giannoukas et al. 2002). However, the aetiopathogenesis of the disease still remains unknown (Pistorius 2003; Sansilvestri-Morel et al. 2003). The question whether only genetic factors are responsible for CVD development or, to the contrary, the main reason for the disease is environmental factors including lifestyle and type of work is still controversial. This question is substantiated by statistical data indicating that CVD in the developing countries occurs with higher incidence (on average 50% of women in Western Europe) than in countries where civilisation progress is slowed down (e.g. only 0.1% of women living in the villages of New Guinea).
A great number of different studies have analysed the influence of many factors on the prevalence of CVD, especially the form which is manifested by varicose veins.
Effects of age and sex
The connection between CVD and age is emphasised in the majority of publications. For instance, it is thought that the incidence of varicose veins increases with age. A study performed among school children aged 10-12 indicated that 10% of them had small varicose veins and during the next 4 years the percentage of children with these changes increased to 30% (Nelsen et al. 1991; Mota-Capitao et al. 1995; Fowkes 1996; Jawien 2003).
In a study performed among 1566 citizens of the UK aged 18-44 (Evans 1999) the presence of varicose veins was found in 40% of men and 32% of women (p Ł 0.01). Their incidence increased significantly with age (p Ł 0.001) and for the age group 18-24 years it was 11.5%, whereas for the age group 55-64 years it was 55.7%. In the oldest group, 55-64 years, varicose veins were found more frequently in men (25.2%) than in women (12.3%). In general, in the study group below 35 years CVD was extremely rare in women and there were no cases of CVD in men. In the analysed age group, 18-44 years, CVD was found in 9% of men and 7% of women (p Ł 0.05). Differences regarding sex were not statistically significant for separately analysed individual stages of CVD degree (p> 0.05). In the majority of cases the observed changes were slightly advanced – degree I in the CEAP classification – and included varicose veins in the drainage area of the great and small saphenous veins. A statistically significant difference with regard to the prevalence of pathologic changes in women and men (p Ł 0.01) was observed only regarding this stage of CVD. Less advanced forms of CVD (varicose veins outside the saphenous veins, reticular veins and telangiectasia) were observed with high incidence, namely in 80% of the subjects. In the study group among other symptoms the presence of oedema (in 7.4% of men and with significantly higher frequency in women – 16%) was found and its incidence increased linearly with age. Ulcers were observed only in 10 subjects.
According to the majority of authors CVD is more frequent in women (incidence for women ranging from 0.1% in New Guinea to 60.5% in the Czech Republic, and for men from 5.1% in New Guinea to 56% on the Cook Islands (Fowkes et al. 2001)) although with age the predominance of women vanishes and the incidence of advanced CVD (namely ulcers) is higher in men (Jawien 2003). Therefore, the higher incidence of CVD in women still remains controversial, especially taking into account analyses indicating that the majority of studies showing a higher incidence of CVD in women did not regard a defined age group. Moreover, it is possible that such statistics are connected with the fact that women participate more frequently in epidemiological studies (Kurz et al. 1999; Jawien 2003). The analysis of results of the questionnaire regarding venous complaints (Evans et al. 1999) indicated that only 10% of men and 17% of women admitted that they had been diagnosed with varicose veins in the past, whereas in the clinical study which followed the questionnaire more numerous changes were seen in men. Namely a great number of authors do not confirm the role of a female factor as being significant with regard to the incidence of CVD, and they show similar results or even higher prevalence in men (Beaglehole et al. 1975; Evans et al. 1999). In The Basle Study (Fowkes 2001) varicose veins in men were found in 56% of cases and in women in 55% cases; in The Edinburgh Vein Study (Ewans et al. 1999), varicose veins in men were observed in 39.7% and women in 32.2% (p Ł 0.01), whereas in New Guinea CVD was observed in 0.1% of women and 5.1% of men (Fowkes 1996).
Among environmental factors affecting CVD development, especially varicose veins, the following are mentioned: pregnancy, hormonal changes, dietetic habits, obesity, physical activity, working in a standing or sitting position, tight clothes, atmospheric pressure. A positive correlation was also seen between the presence of varicose veins and chronic constipation with increased rectal tenesmus, weight lifting, presence of inguinal hernia or haemorrhoids (Comu-Thenard et al. 1994).
The most important factors in CVD pathogenesis are: a chronic standing position, obesity, constipation, pregnancy, varicose veins in the family and a history of thrombosis (e.g. almost 30% of fractures lead to lower leg thrombosis and its consequences (Jawien 2003; Jawien et al. 2003). However, it was not proven unambiguously whether any of these factors played a dominant role in CVD pathogenesis (Cesarone et al. 2002). At the same time many factors (such as CVD duration, the value of arterial blood pressure, the number of pregnancies, presence of cardiovascular disease) decrease the statistical significance of CVD when the age of subjects has been taken into account, although there are data presented above that the prevalence of CVD increases with age (Mota-Capitao et al. 1995).
In a study performed in Switzerland – The Basle Study (Fowkes et al. 2001) – with subjects working in the chemical industry, varicose veins were observed in 56% of men and 55% of women. Varicose veins in the small and great saphenous veins were present in 20% of men and 11% of women, whereas reticular veins and/or telangiectasia were seen in 36% of men and 44% of women. Moreover, the study performed in former Czechoslovakia with women working in a supermarket (Stvirtnova et al. 1991) showed the presence of: reticular veins in 15.4%, telangiectasia in 30.7%, varicose veins in the branches of VSM and VSP in 14.4%. In a study performed in Edinburgh (Ewans et al. 1999) reticular veins and telangiectasia in women were observed with similar frequency, namely 18% of cases.
In women working in Western countries the prevalence of varicose veins reaches 29%, whereas globally varicose veins are found in 17-20% (Cesarone et al. 2002). The highest incidence is among people working in industry and the presence of new cases of CVD is strictly connected with burdens in the work environment. This is indirectly proven by the fact that the incidence of CVD among people over 80 years is lower (Stvirtnova et al. 1991; Krijnen et al. 1997; Cesarone et al. 2002). There are no unambiguous opinions regarding the relationship between working in a chronically standing or sitting position and CVD. Some authors confirm such a relationship (Fowkes 2001; Cesarone et al. 2002); nonetheless, there are data which do not confirm the influence of such work on CVD development (Stvirtnova et al. 1991; Fowkes 2001). The Edinburgh Vein Study (Evans 1999) even indicated a reverse relationship between prolonged sitting time and the prevalence of CVD (namely, lower prevalence of CVD and varicose veins), but the opposite effect with regard to prolonged standing position (higher prevalence of CVD and varicose veins). Taking the above into account it should be assumed that a standing position is not the main or the only factor affecting CVD development, although it might be contributory. An example might be the low prevalence of CVD in the African population, also working in a standing position (Fowkes 2001), or prevalence of CVD in women working in operating theatres and in laundries (3), which is 76%, namely it is significantly higher than in the general population of women working in different parts of industry. In this case the factors for CVD include, apart from a chronic, usually static standing position, high temperature, and lifting heavy people or things.
The relationship between obesity and CVD has not been determined unambiguously. A study performed at Straub Clinic and Hospital in Hawaii (Jawien 2003) demonstrated a strong correlation between BMI (Body Mass Index) and the clinical stage of CVD in 272 studied subjects. The Edinburgh Vein Study (Evans 1999) indicated a correlation between the presence of varicose veins in the drainage area of the saphenous veins and BMI only in women, and this relationship concerned all stages of CVD. Therefore obesity cannot be recognised as a risk factor for CVD, although probably in predisposed people it accelerates the progress of disease. The fat tissue may have a negative effect on oestrogen metabolism (Cesarone et al. 2002). Moreover, it is possible that compression of the veins inside the abdominal cavity due to the increased amount of extraperitoneal fat may lead to increased venous pressure and the development of varicose veins. Obese patients definitely belong to the group with a high risk of CVD as well as deep vein thrombosis and its consequences in the form of secondary varicose veins.
Another study (Ducimetiere 1981) demonstrated a relationship between varicose veins and body weight gain as well as between smoking cigarettes and hypertension. In men with varicose veins the stage of atheromatous lesions, namely the risk of cardiovascular diseases, was higher than in men without varicose veins. These results indicate that increased physical activity and the control of body weight may prevent the development not only of varicose veins but also of arterial atheromatosis. Coexistence of these two illnesses may indicate that the development of these pathologies is affected by different combinations of factors connected with lifestyle, diet and hormonal changes.
A relationship between diverticular disease and varicose veins which had been indicated suggested that a low-fibre diet and constipation may play a role in the development of varicose veins, in the mechanism of compression of faecal masses present in the caecum on the iliac veins or due to constipation with increased rectal tenesmus leading to increased intraabdominal pressure (so-called Burkitt´s hypothesis) which after years may lead to venous lumen dilation (Fowkes et al. 2001; Cesarone 2002; Jawien 2003). Due to constipation veins may become more sensitive to blood stagnation in the lower leg vessels and resulting venous hypertension. The Edinburgh Vein Study (Evans 1999) confirmed a relationship between constipation and the presence of CVD, although only in the case of men. The relationship between constipation and the presence of varicose veins was demonstrated in a study performed among the citizens of Sicily; however, on the other hand, a study performed in Israel did not confirm this relationship in men and only a slight relationship between constipation and the presence of varicose veins in women (Fowkes et al. 2001). Another study (Jawien 2003) additionally quotes J.J. Malet´s hypothesis according to which the low vitamin E diet present in Western countries may play a role in the aetiology of varicose veins. This diet may have an adverse effect on the venous walls in periods of higher requirement for this vitamin, e.g. during pregnancy.
The results of many authors confirmed that in women who gave birth twice or more the risk of varicose vein development is 20-30% higher than in women who never gave birth or only once (Fowkes et al. 2001). On the other hand, other studies (Evans et al. 1999; Fowkes et al. 2001; Jawien 2003) did not show a significant relationship between the number of pregnancies and the development of varicose veins. In addition, only in a few trials confirming the relationship between pregnancy and varicose veins was the analysis performed taking age into account (Fowkes et al. 2001).
Evans et al. (Evans et al. 1991) showed a relationship only between the number of pregnancies and the presence of reticular veins and telangiectasia. Jawien et al. (Jawien et al.) demonstrated CVD symptoms in more than Ľ of pregnant women. Telangiectasia, reticular veins and varicose veins were the most prominent. A statistically significant relationship between their incidence and the number of pregnancies was demonstrated. A history of two or more pregnancies was a differentiating factor between women with and without CVD.
The direct reason why pregnancy influences the development of varicose veins remains unknown. The effect of uterine compression on the iliac veins is disputed as varicose veins usually develop in the first trimester of pregnancy. In addition, varicose veins often disappear after childbirth (Fowkes et al. 2001). This fact, by contrast, may indicate the influence of progesterone, released from the corpus luteum, on the development of varicose veins to a larger extent than the pressure exerted by a growing uterus on the iliac veins and the inferior vena cava (Jawien 2003). Progesterone has relaxing properties on the smooth muscles present in the venous walls, and consequently muscles are more prone to deformation and are more susceptible.
However, on the other hand, in non-Western countries, where the number of pregnancies is high, venous diseases are less frequent when compared to European countries or North America. At the same time, in Western countries multiparas are not the youngest women and the age, as it is known, plays a vital role in the development of CVD. Taking the above into account, pregnancy should be considered as a risk factor for CVD, but together with other risk factors (Jawien 2003).
Although there are only a few data, including unambiguous ones, the genetic factor is still considered as one of the most important with regard to aetiopathogenesis of CVD (Cesarone et al. 2002; Pistorius 2003). Based on the anamnesis data it is thought that this factor is present in 70-80% of cases of CVD (Pistorius 2003). Other studies (Cornu-Thenard et al. 1994) indicated that the risk of development of varicose veins in children is 90% if both parents suffered from CVD; however, when only one parent was ill, the risk of CVD reaches 62% in girls and 25% in boys. If none of the parents suffered from CVD, the risk of development of this disease is only 20% in the progeny. The genetic background of this illness is substantiated by the changes observed in people with varicose veins such as disorganisation of smooth muscle cells and extracellular elements of the matrix in the venous walls, deficiency of collagen type III, which is responsible for elasticity of the venous walls, and transformation of the protein matrix in the walls of the great and small saphenous veins leading to a change in their mechanical properties (Sansilvestri-Morel et al. 2002). However, the concept of genetic background of the disease is not confirmed in trials, few unfortunately, with twins, including a study recently conducted in France which discussed the influence of a hereditary lifestyle and typical inheritance (gene transmission) on the development of CVD (Pistorius 2003). In this study genotypes of all members of a few families were determined, where varicose veins were autosomally dominantly inherited; consequently, a potential location of a gene (different in each family) responsible for inheritance of this disease was determined. The research of this team will be continued with other families burdened with CVD. The molecular background of this disease still remains (disregarding the preliminary results of the above study) unexplained, although the opinion that different genes are responsible for CVD inheritance is predominant. Identification of families where CVD is transmitted autosomally, dominantly, and deeper knowledge regarding pathophysiology of varicose vein disease is likely to bring us closer to finding out about a gene or genes responsible for this illness. Such a phenotype-genotype analysis will be necessary if studies show the presence of single or multiple genetic mutations.
A great number of studies have confirmed the correlation between development of CVD and different risk factors such as age, obesity, limb injury or DVT (Scott et al. 1995; Jawien 2003; Jawien et al. 2003). Moreover, a typical picture of a person suffering from varicose veins was established: a young woman, with a positive anamnesis of DVT and varicose veins in the family. Despite studies indicating a higher incidence of CVD among women (Fowkes 1996) Evans (Evans et al. 1999) observed more cases of CVD in men. He claimed that it is likely that currently observed changes regarding lifestyle, emerging new jobs, and new risks/ environmental risk factors have affected the change in the incidence of CVD among women and men. However, so far there has been no convincing evidence that any of the factors mentioned, such as prolonged standing position, tight underwear, dietetic habits and constipation, obesity or genetic factors, was responsible for the development of the disease in men. It is only known that the frequency of CVD increases with age, and the number of pregnancies, which is a risk factor for CVD in women, is decreasing, which in general may also contribute to higher incidence of CVD in men (Evans et al. 1999; Fowkes et al. 2001). The members of the VEINES study programme, evaluating topics related to CVD comprehensively, concluded that evidence presented in the literature is sufficient to recognise only pregnancy and obesity as factors affecting the development of varicose veins (Kurz et al. 1999).
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