Elsevier

Annals of Epidemiology

Volume 15, Issue 3, March 2005, Pages 175-184
Annals of Epidemiology

The Epidemiology of Chronic Venous Insufficiency and Varicose Veins

https://doi.org/10.1016/j.annepidem.2004.05.015Get rights and content

Chronic venous disease is a common condition presenting to physicians in Western Europe and the United States. This article provides a comprehensive review of the published literature in the English language, from 1942 to the present, and focuses on the prevalence of chronic venous insufficiency and varicose veins, as well as the involved risk factors. Prevalence estimates vary widely by geographic location, with the highest reported rates in Western countries. Reports of prevalence of chronic venous insufficiency vary from < 1% to 40% in females and from < 1% to 17% in males. Prevalence estimates for varicose veins are higher, <1% to 73% in females and 2% to 56% in males. The reported ranges in prevalence estimations presumably reflect differences in the population distribution of risk factors, accuracy in application of diagnostic criteria, and the quality and availability of medical diagnostic and treatment resources. Established risk factors include older age, female gender, pregnancy, family history of venous disease, obesity, and occupations associated with orthostasis. Yet, there are several factors that are not well documented, such as diet, physical activity and exogenous hormone use, which may be important in the development of chronic venous disease and its clinical manifestations.

Introduction

Venous disease, including varicose veins and chronic venous insufficiency (CVI), is one of the most commonly reported chronic medical conditions and a substantial source of morbidity in the United States and the Western world 1, 2, 3, 4, 5, 6, 7, 8. Yet, little epidemiologic research has been conducted in the United States. Much of what we know about the prevalence and determinants of chronic venous disease is the result of studies conducted primarily in European populations. Estimates of disease occurrence vary widely by geographic region and disease classification. Several risk factors have been associated with the development of varicose veins, chronic venous insufficiency or both, which include older age, female gender, family history, obesity, and standing occupation. However, there are a number of other potential factors that may play a role in disease occurrence and progression which have not been well studied and warrant further investigation. In this review, we will summarize the epidemiologic literature with regard to varicose veins and one of the underlying causes of varicosities, chronic venous insufficiency. Additionally, we will discuss some of the major methodologic issues in studying chronic venous disease, which may provide some insight and guidance for future investigations.

In the lower extremities, deep and superficial veins occupy different compartments or chambers that are separated by the fascia overlying the muscles of the leg. The deep veins within the calf muscle converge to form the popliteal vein, which in turn becomes the femoral vein, then the common femoral vein, iliac vein, and finally the inferior vena cava. This is the main conduit for venous blood to return to the heart. In the lower extremities, the greater saphenous vein empties into the common femoral vein and the lesser saphenous vein empties into the popliteal vein. The superficial compartment is a low pressure chamber while the deep compartment is a high pressure chamber due primarily to the action of the calf muscle pumping venous blood back to heart. The pump of the calf muscle chamber is the gastrocnemius and soleus muscles. The chamber itself is an intricate network of unusually distensible and thin walled veins (sinuses) within these muscles. Perforator veins pierce the muscle fascia and connect the deep veins to the superficial venous system. Normally, upon contraction of the calf muscle (muscular systole), the valves of the perforating veins close to keep the high pressure of the deep veins from being transmitted to the superficial veins. When the calf muscle relaxes (muscular diastole) the pressure in the deep veins (and deep compartment) is temporarily lower than the pressure in the superficial venous system. Blood then flows from the superficial veins, through the perforator veins, to the deep veins within the calf muscle (Fig. 1A). The next muscle contraction will result in a closure of the perforator valves and the blood is again pumped proximally in the deep veins (9).

Chronic venous insufficiency occurs when normal venous blood transport is disturbed (Fig. 1B). The disruption can occur in the superficial or deep venous systems, the perforating veins or any combination of these (10). The prevailing theory emphasizes the role of valve reflux in the etiology of varicose veins and CVI. If the perforator valves become incompetent, the increased pressure of calf muscle contraction will flow through the incompetent perforator veins into the superficial venous system, thus converting it into a high pressure system. This “venous hypertension” is responsible for most venous pathology of the leg, including edema, lipodermatosclerosis, ulceration, and both spider telangiectasias and varicose veins.

While most experts agree that valve reflux is the principal determinant of varicose veins and CVI, there is no consensus as to whether primary valve incompetence is the initiating event in the pathogenesis of venous disease or that the incompetence is secondary to vein wall dilatation 10, 11, 12, 13, 14. Some evidence indicates that reflux is likely due to weakening of vein walls and subsequent venous dilatation resulting in incompetence of the valve (15). Investigations have suggested that the weakening of the vein wall was due to altered collagen composition and diminished elastin content 16, 17, 18, 19. An additional contributing mechanism may be due to chronic inflammation and the release of cytokines (10). Other potential causes of valve failure include damage to the valve cusps from thrombosis or physical trauma. Moreover, the fact that many patients with varicose veins have a significant family history of varicosities suggests a possible genetic predisposition contributing to valve incompetence.

The methods for reporting presence of varicose veins vary in epidemiologic investigations, resulting in a range of estimations of prevalence. Namely, case definitions may rely on reports of varicose veins by study participants, based on self-diagnosis or recall of a diagnosis by a physician, or on a standardized physical examination. For a time, the criteria used by the Basle Study for classification of varicose veins was the most comprehensive and most widely used among studies (20). The Edinburgh Vein Study, one of the largest studies of venous disease, employed Basle criteria to define classes of varicosities. Varicose veins were categorized based on location and sub-divided into grades based on severity: 1) trunk varices were defined as “dilated, tortuous trunks of the saphena magna or parva vein and their branches of the first or second order”; 2) reticular varices were “dilated, tortuous subcutaneous veins not belonging in the main trunk”; and 3) hyphenwebs were defined as “intradermal varices” (21). However, there are studies which do not include the latter category as part of their definition. Other studies have adapted criteria used by Arnoldi 22, 23 as “any dilated, tortuous, and elongated subcutaneous veins of the leg.” A more recently agreed upon criteria for classification expanded the Basle criteria to include criteria for: varicose veins, “dilated, palpable subcutaneous veins generally larger than 4 mm”; reticular veins, “dilated, non-palpable subdermal veins less than 4 mm”; or telangiectases, “dilated intradermal venules, less than 1 mm” (24).

Burnand (25) points out that “chronic venous insufficiency is a poorly defined term, and means a different set of symptoms and signs to different clinicians.” Some believe the term includes all venous disorders that are not acute (acute thrombosis, occlusion, or injury). Others hold to the traditional view that chronic venous insufficiency refers to venous disease that causes symptoms in the leg, including edema, hyperpigmentation, lipodermatosclerosis, and ulceration. Burnand excludes uncomplicated varicose veins. CVI criteria as defined by Basle were based on severity, the signs of which progressed from dilated subcutaneous veins and hyperpigmentation to ulceration (open or healed) (20). Belcaro and Nicolaides (26) assume that most chronic venous insufficiency is post-phlebitic, but add that other causes such as absence or incompetence of valves may be the initial cause of chronic venous insufficiency. Karch and Sumner (27) describe the clinical manifestations of chronic venous insufficiency as ranging from simple varicose veins and mild swelling to severe edema, induration, stasis, pigmentation, and ulcers. Thulesius (28) groups venous insufficiency and varicose veins together and defines venous insufficiency as “any abnormality of the peripheral venous system that reduces or impedes venous return… the spectrum of varicose veins is great; they can be an early sign of venous insufficiency, which could be treated to prevent disease progression, or they may be a late sign, appearing as dilated collaterals.” In this article, the authors hold with much of the above definitions. Chronic venous insufficiency usually begins with the commonest of symptoms of edema and varicose veins, and in more complicated cases, progresses to skin changes of stasis cellulitis and pigmentation, and finally lipodermatosclerosis and ulceration. Chronic venous occlusion more frequently results in a rapid evolution to the final skin changes previously mentioned.

Most recently, clinicians and researchers have relied upon use of Duplex ultrasonography to detect valve incompetence associated with chronic venous insufficiency 11, 29, 30, 31, 32. This technology has enabled diagnosis of functional disease (i.e., venous reflux and/or obstruction) in addition to visible manifestations. In 1994, a new classification system was developed for the evaluation of the severity of venous disease and has been widely accepted in the clinical and scientific communities. The Clinical, Etiologic, Anatomic, Pathophysiologic (CEAP) classification system includes not only the clinical symptoms of CVI, including pain, presence of varicose veins, edema, hyperpigmentation, and ulcer, but also considers the etiology (primary, secondary, or congenital in origin), anatomic distribution and position, and the pathogenic mechanism (venous reflux, obstruction, or both) and produces a score based on the severity of disease (33). The CEAP classification system was developed in an effort not only to incorporate use of Duplex scanning in diagnosis, but also to standardize evaluation for comparison of outcomes across clinical studies. Most recently, the Venous Severity Scoring (VSS) system was introduced in an effort to modify the CEAP assessment (34). The VSS system consists of three components, VCSS (venous clinical severity score), VSDS (venous segmental disease score), and VDS (venous disability score). Results from recent evaluations of both classification systems suggest that VSS is a valid method to categorize venous disease and an improvement over the CEAP classification in that it accounts for the dynamic changes in outcome with therapeutic management 35, 36.

Estimates as to the prevalence of varicose veins vary widely, from 2% to 56% in men and from < 1% to 73% in women (Table 1). The variation in prevalence may be explained in part by numerous factors unrelated to actual differences in population frequency. Study methodology, namely, variation in disease criteria, use of diagnostic imaging, and population composition with respect to age, race, gender, and geographic location accounts for some of the discrepancy in population estimates. Generally, prevalence is higher in more developed, industrialized countries than underdeveloped regions. Results published by Mekky et al. (37) and Beaglehole et al. 38, 39 illustrate this point. Mekky observed a more than five-fold difference in prevalence between England and Egypt. Beaglehole found significant differences in age-standardized prevalence rates of varicose veins among five different populations in the South Pacific. The Maoris and Pakehas of New Zealand possessed much higher rates compared with the atoll-dwelling Pukapuka and Tokelau Islanders. The San Diego Population Study, the first examination of chronic venous disease in a multi-ethnic study population, observed that the prevalence of visible varicose veins was highest among Hispanics (26.3%) and lowest among Asians (18.7%). However, trophic changes (ulcer, hyperpigmentation, edema, and lipodermatosclerosis) and functional disease were observed more frequently among non-Hispanic whites (40).

Prevalence estimates of CVI also vary, from < 1% to 17% in men and < 1% to 40% in women. These estimates are strongly dependent on the inclusion (or exclusion) of specific clinical features. Clearly, studies that limit classification to an active, visible, or healed ulcer typically report lower occurrences of CVI compared with those which include hyperpigmentation, eczema, and varicose veins as part of the clinical definition. Table 2 describes the prevalence of the more severe clinical manifestations of CVI, excluding varicose veins. The prevalence estimates obtained from recent studies, which establish a diagnosis of CVI though use of medical imaging to detect functional disease, tend to yield intermediate estimations 31, 32, 40.

Table 3 provides a summary of established and potential risk factors associated with chronic venous insufficiency and varicose veins based on current evidence. These conditions have similar risk profiles, however, instances where risk factors appear to differ between conditions and inconsistencies in the literature have been highlighted.

Epidemiologic studies describe familial aggregation of manifestations of venous disease, however, specific genes have yet to be identified 23, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50. In a study of 541 Japanese women, 42% of subjects with varicose veins reported a positive family history compared with just 14% of women without disease. This difference diminished with increasing age (45). More dramatic trends were observed in a Turkish study of elderly men and women. The overall risk ratio associated with a positive family history was approximately 4.4 (p = 0.001). However, in those aged 60 to 69 years the observed ratio associated with family history was 29.2, while in men and women aged 80 years and older a ratio of 2.0 was observed (42). Gourgou et al. (51) also observed that patients with CVI were significantly more likely to report a positive family history compared with control patients selected from general practices. Scott et al. (46) reported that patients with varicose veins were 21.5 times more likely to indicate a positive family history of varicose veins as compared with controls (p = 0.0001), but family history was not a significant factor in patients with CVI.

One must be careful in interpreting the results of such studies. Because varicosities are a fairly common phenomenon, a family history of disease will be reported by a vast majority of case and control subjects. Presumably, those with venous disease would be more aware of the occurrence of disease among family members than those without disease. Of interest in this regard, in an examination of misclassification bias based on a self-administered survey of varicose veins, the specificity associated with the questionnaire was poorer among those reporting a positive family history (0.83) compared with individuals with no reported family history (0.98). This suggests that an increased proportion of false positives were reported particularly among the subjects with a family history of varicose veins (52). A majority of studies rely on self-report of family history without validation by clinical examination of family members.

The preponderance of evidence indicates that prevalence of venous disease increases with increasing age 20, 23, 37, 40, 41, 43, 45, 53, 54, 55, 56, 57, 58, 59, 60. The magnitude of risk does appear to differ depending on classification criteria and estimates vary in published studies. The relationship is most likely the result of increased pressure on superficial veins due to the weakening of calf muscles coupled with the gradual deterioration of vessel walls over time. In a recently published article from the Edinburgh Vein Study, investigators reported that the prevalence of trunk, hyphenweb and reticular varices increased linearly with age (p ⩽ 0.001), although the latter two types were more common at any age. There was also a significant trend of increased prevalence of CVI with increasing age (p ⩽ 0.001) and this trend was more apparent in men compared with women (61). A survey of the prevalence of venous disease in the United States estimated that the prevalence of varicose veins among individuals younger than 30 years was less than 1% for men and less than 10% for women. However, in men and women aged 70 years and older the estimates increased substantially to 57% and 77%, respectively (48). In a dual case–control study of CVI and varicose veins, when comparing CVI cases with general surgical clinic controls, Scott et al. (46) observed a 6% increase in risk of CVI per 1 year increase in age (OR, 1.06; 95% CI, 1.03–1.09). However, the patients seen for varicose veins were significantly younger than the surgical clinic controls (OR, 0.96; 95% CI, 0.93–0.99). A prospective cohort study of 518 school children using Doppler ultrasonography and photoplethysmography reported that saphenous valve incompetence was detected in 3.1% of children aged 10 to 12 years. These children were examined again at age 14 to 16 and 12.3% were observed to have incompetence in either the long or short saphenous vein. Varicose veins were visible in 3.7% of the cohort at the end of the 4-year follow-up (62).

Varicose veins present more commonly in women compared with men 40, 41, 43, 45, 53, 54, 58, 59, 60, 63, 64, 65. Pregnancy is presumed to be a major contributory factor in the increased incidence of varicose veins in women (66). Evidence suggests that parous women have a higher incidence of varicose veins compared with nulliparous women, and that multiparous women have the highest risk. Dindelli et al. (44) reported in a study of risk factors for varicose veins in women during pregnancy, that a family history of varicose veins, increasing number of full term pregnancies, and increasing age were all significant risk factors in the development of varicose veins, while the extent of weight gain during pregnancy was not an independent risk factor.

Pregnancy is associated with a number of physiologic changes which likely contribute to the development of venous distension and potentially varicose veins. Early in pregnancy there is significant increase in blood volume which is primarily due to plasma volume expansion 67, 68. In addition, fetal growth and weight gain increase intra-abdominal pressure and central venous return 66, 69. The elevated pressure can result in valve failure and progression of varices. Relaxin, a hormone structurally similar to insulin and insulin-like growth factors (IGFs) and secreted by the corpus luteum relatively early in pregnancy, functions in relaxing pelvic ligaments and preparing the cervix for delivery. Recent studies have also shown relaxin to be a potent vasodilator contributing to increased pressure on venous valves in lower limbs 70, 71, 72, 73.

Elevated risk has also been speculated to be related to sex-steroid hormone concentrations, but the exact mechanism is unclear. Concentrations of both estrogen and progesterone increase dramatically at around the sixth week of pregnancy and continue to rise throughout. Estrogen has been shown to increase venous capacitance while increased levels of progesterone weaken blood vessel walls 71, 74, 75, 76.

While the occurrence of varicose veins is clearly more common in women, results with respect to CVI have not been as consistent. Some studies have shown the prevalence of CVI to be higher in men 21, 46, however, others have reported a higher prevalence in women 42, 53, 77 or no difference 20, 54, 60. Evans et al. (21) reported that the prevalence of CVI was higher in women until age 45 and then becomes more frequent in men. In the age group 55 to 64 years, the overall prevalence of CVI in men was more than double that in women (25.3% vs. 12.3%). Criqui et al. (40) observed a higher proportion of men with the visible trophic changes compared with women (7.8% vs. 5.3%), however, the prevalence of superficial or deep functional disease was higher in women (30% and 24.4%, respectively).

Most studies have shown that overweight and obese women are more likely to develop varicose veins 37, 41, 48, 59, 64, 78, 79, 80, 81. However, there is no consistent indication that this relationship holds true for men 57, 64, 82, 83. Seidell et al. (79) found that compared with referent, non-overweight women, moderately overweight women (BMI = 25.0–29.9 kg/m2) were more likely to report varicose veins (OR, 1.53; 95% CI, 1.21–1.94). Obese women (BMI ⩾ 30.0 kg/m2) were three times more likely to report the presence of varicose veins. No relationship between BMI and venous disease was observed among male subjects. Similarly, a study conducted among elderly men and women in Italy reported a highly statistically significant trend of increasing prevalence of varicose veins with increasing BMI among women (p-trend < 0.0001), but no relationship in men (p = 0.54). The gender difference in these studies, coupled with the fact that average body weight is higher in parous compared with nulliparous women cannot exclude the possibility that the observed associations between varicose veins development and obesity may be explained by a confounding effect of parity. This notion is supported by the results of Dindelli et al. (44) which show an increasing risk of venous disease associated with increasing number of births, but not overweight in multivariate analysis.

Obesity has not been consistently shown to be associated with CVI 46, 50, 51, 56. Gourgou et al. (51) observed an approximate 2-fold increase in likelihood of having CVI among obese subjects, however, after adjustment for other related factors this difference was no longer significant. Scott et al. (46) observed significantly higher prevalence of obesity among patients with CVI; however, case–control studies of obesity and chronic venous disease are limited in that this design does not establish a temporal sequence between exposure and disease. It is possible that patients with CVI and varicose veins are less physically active due to their condition and may be more prone to becoming overweight.

If a relationship with body weight and varicose veins truly exists, the mechanism may be similar to that proposed to explain pregnancy. Namely, overweight and obese women have significantly greater concentrations of total and bioavailable circulating estrogens than non-overweight women and this difference is more apparent after the menopause 84, 85, 86, 87. Increasing endogenous estrogen coupled with increased central adiposity would expand the intravascular volume that may result in mechanical impeding pressure on peripheral venous return.

The ergonomics and physical activity of an occupation may represent a contributing factor in the epidemiology of CVI and varicose veins. Most studies 30, 37, 41, 43, 55, 58, 63, 88, 89, but not all 53, 90, indicate that working in a position resulting in protracted orthostasis may increase the prevalence and severity of disease. Abramson et al. (58), in a community-based study of varicose veins conducted in Jerusalem among men and women aged 20 to 64 years, found that the prevalence of varicose veins was significantly higher among subjects who reported that they spent much of the work day standing. Women were more likely to report occupations requiring prolonged standing compared with men (31.4% vs. 13.6%). However, the observed prevalence ratio related to workplace posture (standing vs. sitting) was higher in men than in women (prevalence ratios, 1.88 and 1.53, respectively). Gourgou et al. (51) reported that CVI cases were 2.7 times more likely to report regular on the job standing for greater than 4 hours per day compared with controls after adjustment for physical activity, family history, smoking, alcohol abuse, and exposure to heat. Findings of retrospective and cross-sectional occupational studies should be interpreted with caution as both are prone to errors in exposure misclassification. In retrospective studies, subjects may not be able to accurately recall or summarize workplace posture over many years of work. Cross-sectional studies' reliance on posture at time of examination may not reflect the same posture at the time of development of venous disease.

It was Cleave (91) who first proposed that a diet deficient in fiber was a contributing factor to the development of varicose veins. Some studies that have examined dietary factors and venous disease have shown a high refined carbohydrate, low fiber “Western” diet increases risk of varicose veins. Cleave (91) and subsequently Burkitt 92, 93 postulated that constipation and increased intra-abdominal pressure contributed to obstruction of venous return. In an effort to lend credence to this hypothesis, studies have examined bowel habits including toilet posture and stool transit time as risk factors for varicose veins 30, 47, 53, 94, 95. Lee et al. (94) observed increased risk of saphenous trunk varices in men who reported that they strained at the initiation of a bowel movement. In women, there was a suggestion of an inverse relationship with defecation frequency and a positive one with straining at a bowel movement. However, fiber intake and stool transit time were unrelated to the prevalence or severity of varicose veins in men and women. Fowkes et al. (30) did not observe an association between fiber intake, transit time, and venous reflux. Of note, most studies of diet, CVI, and varicose veins have been limited to Caucasian populations. It may be important for future studies to examine the dietary habits of other racial and ethnic groups and a potential relationship with chronic venous disease.

A small number of studies have also examined associations with smoking, physical activity, oral contraceptives and hormone replacement therapy, and a history of diabetes, hypertension, traumatic injury to the extremities, and blood plasma levels of a number of hemostatic factors 30, 42, 46, 47, 50, 51, 60, 64, 74, 83, 96. Further examination of these factors is needed to clearly explicate their relationship with chronic venous disease.

Section snippets

Methodologic issues

There are several methodologic issues that must be addressed in epidemiologic studies of CVI and varicose veins. Although most of the cited studies are population-based, studies whose participants are drawn from vascular clinics or physicians' offices with varicose veins and/or CVI are subject to selection bias 46, 50, 51, 74. CVI is generally not a life-threatening condition, and superficial varicose veins may be treated electively and may not be covered by health insurance. Thus patients who

Future directions

Most epidemiologic research of varicose veins and CVI has been conducted outside the United States, primarily in the UK and other European countries. Earlier results published from the Framingham Heart Study (48) and Tecumseh Community Health Study (54) may not be generalizable as these study populations are not racially or ethnically diverse. However, recently reported results from the San Diego Population Study provide valuable insight into ethnic differences in the prevalence of disease (40)

References (103)

  • M.H. Meissner et al.

    Performance characteristics of the venous clinical severity score

    J Vasc Surg

    (2002)
  • T.E. Scott et al.

    Risk factors for chronic venous insufficiency: A dual case–control study

    J Vasc Surg

    (1995)
  • A.J. Lee et al.

    Lifestyle factors and the risk of varicose veins: Edinburgh Vein Study

    J Clin Epidemiol

    (2003)
  • F.N. Brand et al.

    The epidemiology of varicose veins: The Framingham Study

    Am J Prev Med

    (1988)
  • J. Laurikka et al.

    Misclassification in a questionnaire survey of varicose veins

    J Clin Epidemiol

    (1995)
  • G. Stansby

    Women, pregnancy, and varicose veins

    Lancet

    (2000)
  • I.M. Bernstein et al.

    Plasma volume expansion in early pregnancy

    Obstet Gynecol

    (2001)
  • A.B. Chapman et al.

    Temporal relationships between hormonal and hemodynamic changes in early human pregnancy

    Kidney Int

    (1998)
  • A.V. Ciardullo et al.

    High endogenous estradiol is associated with increased venous distensibility and clinical evidence of varicose veins in menopausal women

    J Vasc Surg

    (2000)
  • J.C. Seidell et al.

    Overweight and chronic illness-a retrospective cohort study, with a follow-up of 6–17 years, in men and women of initially 20–50 years of age

    J Chronic Dis

    (1986)
  • A. Iannuzzi et al.

    Varicose veins of the lower limbs and venous capacitance in postmenopausal women: Relationship with obesity

    J Vasc Surg

    (2002)
  • T.L. Cleave

    Varicose veins: Nature's error or man's?

    Lancet

    (1959)
  • A.J. Lee et al.

    Fiber intake, constipation, and risk of varicose veins in the general population: Edinburgh Vein Study

    J Clin Epidemiol

    (2001)
  • J.B. Richardson et al.

    Varicose veins in tropical Africa

    Lancet

    (1977)
  • M.J. Callam

    Prevalence of chronic leg ulceration and severe chronic venous disease in Western countries

    Phlebologie

    (1992)
  • M.J. Callam

    Epidemiology of varicose veins

    Br J Surg

    (1994)
  • G.H. White

    Chronic venous insufficiency

  • G. Madar et al.

    Varicose veins and chronic venous insufficiency, disorder or disease?

    Vasa

    (1986)
  • C.J. Evans et al.

    How common is venous disease in the population

  • C.J. Evans et al.

    Epidemiology of varicose veins. A review

    Int Angiol

    (1994)
  • N.L. Browse et al.

    Physiology and functional anatomy

  • J.L. Ballard et al.

    Pathogenesis of chronic venous insufficiency

  • G.H. Clarke et al.

    Venous wall function in the pathogenesis of varicose veins

    Surgery

    (1992)
  • N.L. Browse et al.

    Varicose veins: Pathology

  • J. Svejcar et al.

    Content of collagen, elastin, and water in walls of the internal saphenous vein in man

    Circ Res

    (1962)
  • J. Svejcar et al.

    Content of collagen, elastin, and hexosamine in primary varicose veins

    Clin Sci

    (1963)
  • M.A. Wali et al.

    Histopathological changes in the wall of varicose veins

    Int Angiol

    (2003)
  • P. Sansilvestri-Morel et al.

    Chronic venous insufficiency: Dysregulation of collagen synthesis

    Angiology

    (2003)
  • L.K. Widmer

    Peripheral Venous Disorders Basel III

    (1978)
  • C.J. Evans et al.

    Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study

    J Epidemiol Community Health

    (1999)
  • C.C. Arnoldi

    The aetiology of primary varicose veins

    Dan Med Bull

    (1957)
  • C.C. Arnoldi

    The heredity of venous insufficiency

    Dan Med Bull

    (1958)
  • K.G. Burnand

    The physiology and hemodynamics of chronic venous insufficiency

  • G. Belcaro et al.

    Chronic venous insufficiency and the post-phlebitic syndrome

  • L.A. Karch et al.

    Section on venous disease

  • O. Thulesius

    Physiologic observations on causes of varicose veins

  • F.G.R. Fowkes et al.

    Lifestyle risk factors for lower limb venous reflux in the general population: Edinburgh Vein Study

    Int J Epidemiol

    (2001)
  • C. Lionis et al.

    Chronic venous insufficiency. A common health problem in general practice in Greece

    Int Angiol

    (2002)
  • R.L. Kistner et al.

    Classification and diagnostic evaluation of chronic venous disease

  • S. Mekky et al.

    Varicose veins in women cotton workers. An epidemiological study in England and Egypt

    BMJ

    (1969)
  • Cited by (727)

    View all citing articles on Scopus
    View full text