Varicose veins: why they develop and how they form

Varicose veins are chronic dilation and tortuosity of the subcutaneous veins of the legs, leading to valve insufficiency and abnormal backflow. The veins lose tone, their cusps fail to close, intraluminal pressure increases, blood stagnates, and the wall gradually remodels. This is not a cosmetic issue: the disease impacts work capacity and quality of life, and in some patients, progresses to trophic skin changes and ulcers. [1]

According to population studies in Europe, signs of reflux in the superficial venous system are detected in approximately 20% or more adults, with the incidence increasing with age. The exact percentages vary across samples, but the trend is consistent. Guidelines also indicate a broader prevalence range for clinically significant varicose veins—from one-fifth to one-third of the adult population, depending on diagnostic criteria. [2]

The current understanding of the causes is based on three levels: genetic and constitutional predisposition, hormonal and systemic influences, and mechanical and behavioral stresses that contribute to chronic orthostatic overload of the veins and microinflammation of the wall. These levels do not "compete" but rather are cumulative: in a given individual, the disease occurs when individual vulnerability meets prolonged overload. [3]

Below, the leading causes and risk factors are discussed based on large epidemiological studies, genetic studies, and clinical guidelines from professional societies of vascular surgeons and phlebologists. [4]

How varicose veins form

The key event is venous valve failure and persistent metabolic shifts in the wall: increased pressure and shear stress activate the endothelium, triggering leukocyte infiltration and extracellular matrix remodeling. At the same time, the phenotype of venous smooth muscle cells changes from "contractile" to "synthetic." This makes the vein more compliant and prone to dilation. [5]

Matrix metalloproteinases, primarily MMP-2 and MMP-9, play a significant role: their increased activity is associated with collagen and elastin degradation, tissue inhibitor imbalance, vein dilation, and valve leaflet degradation. This perpetuates the "vicious cycle" of venous hypertension and reflux. [6]

In some patients, primary weakness of the valve wall and apparatus is genetically determined. In others, chronic orthostatic overload and localized damage to the valves develop first, followed by secondary molecular changes. Both scenarios are supported by histological and molecular observations. [7]

The result is persistent valve insufficiency in the main subcutaneous veins, perforators, or tributaries. Depending on the anatomy of the reflux, the disease manifests itself through various "pathways" of progression—from varicose vein networks to edema and skin changes. [8]

Genetics and congenital predisposition

A family history increases the risk. In cohort studies, the presence of varicose veins in first-degree relatives is associated with a higher likelihood of developing varicose veins in offspring, even after accounting for age and gender. The contribution of family factors to prevalence has also been confirmed by registry studies in Scandinavia. [9]

Rare variants with large effects have been described at the level of individual genes. Mutations in the FOXC2 gene are associated with primary venous valve insufficiency in both the superficial and deep veins. This gene is important for the development and maintenance of venous and lymphatic valves. [10]

Large population genomic studies have identified dozens of loci associated with the risk of varicose veins. The role of the mechanosensitive ion channel PIEZO1 is consistently confirmed: rare truncated variants increase the risk of varicose veins and the need for ablation, while some missense variants reduce the risk, making the molecule an attractive therapeutic target. [11]

Population-wide studies based on the UK Biobank demonstrated a causal relationship between increased height and the risk of varicose veins using Mendelian randomization. Height reflects both genetic and biomechanical determinants of the blood column, making tall stature an independent risk factor. [12]

Hormones, pregnancy and gender differences

Pregnancy is one of the most powerful factors: the growing uterus mechanically increases venous pressure, and hormonal changes increase the distensibility of the venous wall, which together lead to the development or progression of reflux. A meta-analysis of observational studies confirms a consistent association between pregnancy and varicose veins. [13]

Female gender is associated with an earlier onset and higher frequency of varicose veins, which is partly explained by pregnancy and hormonal profile. Changes in the expression of estrogen and progesterone receptors, which affect the tone and remodeling of the vein wall, have been detected in varicose vein tissue. [14]

Exogenous hormones require careful interpretation. Combined hormonal contraceptives increase the risk of venous thromboembolism and, in the presence of superficial venous disease, may increase the risk of thrombotic events. However, a direct causal relationship between contraception and the development of varicose veins has been limited and remains controversial. The decision to use them should take into account the individual's venous risk profile. [15]

During menopause, hormone therapy is associated with an increased risk of venous thromboembolism with oral forms, but the impact on varicose vein development itself remains unclear. The clinical significance for varicose vein prevention is low, and decisions are made based on the balance of benefits and risks for other indications. [16]

Age, height, body weight and physical activity

Age is a universal, non-modifiable factor: with increasing age, the proportion of patients with reflux and clinical manifestations increases. This reflects the accumulation of structural changes in the wall and valves. [17]

Growth as an independent risk factor has been confirmed genetically and epidemiologically: each additional “step” of growth increases the height of the hydrostatic column and the mechanical load on the valves, and is also associated with certain pathways of vascular wall development. [18]

Excess body weight increases venous hypertension, impairs the function of the myovenous pump, and is associated with more severe forms of chronic venous disease. The association with the onset of varicose veins is usually weaker than with their progression and skin changes, but the practical significance for symptom control is significant. [19]

Regular physical activity improves the function of the calf muscle-venous pump and reduces venous pressure during exercise. Low activity levels have been noted as a risk factor in some studies, although the evidence base here is less robust than for age, height, or pregnancy. [20]

Professional and behavioral stress

Prolonged standing and static work increase the risk of varicose veins and related hospitalizations. Prospective Danish studies and modern reviews in occupational medicine show that prolonged periods of standing, carrying heavy loads, and total static time are associated with a higher incidence of varicose veins. [21]

Sedentary work without breaks worsens venous congestion and symptoms, although the evidence for a direct causal role of sitting is weaker than for standing. It is practically important to break up static loads into short cycles of movement and use simple deloading techniques. [22]

Myths also need to be dispelled. Sitting cross-legged and wearing tight clothing do not cause varicose veins, although they may increase discomfort in those already affected. High heels reduce the effectiveness of the calf pump and increase residual volume, which may worsen symptoms, but there is no direct evidence that "heels cause varicose veins." [23]

The bottom line for practice: risk is formed by the accumulation of hours of standing and static poses without breaks, and not by the "pose" itself. Organizing work and microbreaks is more important than banning individual habits. [24]

Anatomical causes and types of reflux

The most common "pathway" of the disease is insufficiency of the saphenofemoral junction and the trunk of the great saphenous vein. Less commonly, the starting point is the saphenopopliteal junction with involvement of the small saphenous vein, as well as incompetent perforators and non-saphenous tributaries. The reflux map determines the clinical presentation and management. [25]

In addition to the superficial system, the deep and pelvic venous basins are important. Obstruction or post-thrombotic changes in the iliac and femoral veins, as well as pelvic venous reflux, can maintain or provoke varicose veins in the legs, especially with atypical localization on the posterolateral thigh and varicose veins in the buttocks and perineum. [26]

If a proximal source of congestion is suspected, an extended ultrasound examination is indicated, including an assessment of the respiratory phase of blood flow in the common femoral vein and, if necessary, visualization of the iliac and renal segments using transverse tomography. This is especially important in cases of asymmetric edema, recurrent varicose veins, and trophic disorders. [27]

Correct anatomical verification of the source of reflux is the key to choosing treatment and reducing the risk of recurrence after interventions. [28]

Secondary causes: post-thrombotic changes and pelvic reflux

Secondary varicose veins occur following deep vein thrombosis and post-thrombotic syndrome, or following compression syndromes of the iliac and renal circulation. Here, the combination of obstruction and reflux plays a leading role. Identifying and correcting the proximal cause is essential for success. [29]

Pelvic venous disorders in women of childbearing age can cause "top-down" reflux with drainage through inguinal collaterals and intersaphenous anastomoses. In such cases, "conventional" ablation of the trunks in the legs without addressing the pelvic component carries a high risk of recurrence. [30]

Varicose veins on the back of the thigh, buttocks, and vulvar varicose veins are used for diagnostic purposes. In questionable situations, targeted ultrasound leak points and, if necessary, additional imaging techniques are used. [31]

Algorithms for examination and treatment of this layer of causes are described in detail in modern guidelines and clinical reviews with an emphasis on individualization and a multidisciplinary approach. [32]

What's Proven and What's Not: A Brief Overview of the Gray Areas

Proven and confirmed: age, female gender through pregnancy mediator, tall stature, family history, static loads while standing, obesity as an accelerator of venous hypertension and progression. These factors are confirmed by several independent sources. [33]

Likely, but with variable strength of evidence: low physical activity, heavy physical labor, connective tissue structural features outside the established genetic variants. These associations are present in cohort and regression models, but are not always reproducible. [34]

The habit of sitting with one's legs crossed and wearing tight clothing have not been proven to cause varicose veins. These factors may exacerbate subjective symptoms but are not considered the primary cause of varicose veins. The issue of high heels remains clinically significant for symptoms, not for triggering the disease. [35]

Associations with cardiovascular events and other conditions continue to be studied. There are genetic and epidemiological signals linking varicose veins with thrombosis and even heart failure, but for practical prevention, these associations do not yet change the basic approaches to risk assessment. [36]

Practical consequences of causes: how to reduce the impact of risk factors

Reduce the overall static load: break up standing and sitting with active breaks every 30-60 minutes, use simple ankle exercises and calf raises to activate the calf pump. For workers who stand for long periods, medical-grade compression stockings are useful, based on the results of a personal selection. [37]

Weight management and regular moderate-intensity aerobic exercise improve venous return and reduce symptoms. In the presence of severe complaints and identified reflux, the question of interventional treatment is decided on an individual basis after reflux mapping using duplex ultrasound. [38]

During pregnancy, early implementation of non-drug measures is recommended: orthopedic unloading, gentle compression as indicated, occupational and rest hygiene, constipation prevention, and symptom monitoring. After childbirth, some varicose veins regress, but if symptoms persist, ultrasound follow-up is indicated. [39]

In cases of atypical varicose vein localization, repeated recurrences after correctly performed interventions, and severe asymmetry of edema, pelvic reflux and proximal obstruction should be excluded before deciding on retreatment "on the leg." This reduces the risk of ineffective procedures and recurrence. [40]

Table 1. Risk factors for varicose veins: modifiable and non-modifiable, strength of evidence

Category	Factor	The power of data	Comment
Non-modifiable	Age	High	Prevalence and severity increase with age
Non-modifiable	Gender: female	Medium-high	Pregnancy mediator and hormonal influences
Non-modifiable	Tall growth	High	Causality by Mendelian randomization
Non-modifiable	Family history	Medium-high	Consistent cohort data
Modifiable	Static standing at work	Medium-high	Association with risk and hospitalizations
Modifiable	Obesity	Average	More strongly associated with progression and skin changes
Modifiable	Low physical activity	Low-medium	Some studies show a link
Modifiable	High heels	Low	Affects symptoms, not the underlying cause

Source: Compendium of guidelines and research. [41]

Table 2. Genetic and molecular basis

Level	Example	Role
Rare variants	FOXC2	Development and maintenance of venous valves, relationship with primary valvular insufficiency
Rare variants	PIEZO1 shortened versions	High risk of varicose veins and need for ablation, mechanosensitive signaling
General options	Dozens of loci from GWAS	Pathways of vascular development, mechanosensation, and extracellular matrix
Molecular mechanisms	MMP-2, MMP-9	Matrix degradation, wall dilation, valve damage

Source: Genetic and Molecular Reviews. [42]

Table 3. Hormonal conditions and their effect on veins

State	Mechanisms	Clinical conclusion
Pregnancy	Mechanical increase in pressure, hormonal dilation	Frequent occurrence or progression, partial regression possible after childbirth
Combined contraception	Prothrombotic profile	Assess individually for superficial venous pathology
Menopausal hormone therapy	Increased risk of thrombosis with oral forms	The decision is based on other indications; a direct influence on the “occurrence of varicose veins” has not been proven

Source: meta-analyses and clinical guidelines. [43]

Table 4. Occupational and behavioral impacts

Impact	Association	Note
Long standing	Increased risk of varicose veins and hospitalizations	The more total hours, the higher the risk
Heavy carriers	Additional load on the venous system	Occurs in combination with standing
Sitting without breaks	Increased congestion, symptoms	More importance for symptoms than for initiation
Crossing legs, tight clothing	Not a reason	It may increase discomfort, but does not cause the disease.

Source: prospective studies and reviews. [44]

Table 5. Anatomical sources of reflux

Zone	Characteristic reflux	Clinical clues
Saphenofemoral junction and trunk of the great saphenous vein	Distal reflux along the trunk and tributaries	Typical varicose veins of the medial surface of the thigh and leg
Saphenopopliteal junction and small saphenous vein	Distal reflux along the posterior surface of the leg	Varicose veins of the back of the leg
Perforators	Localized reflux pockets	Local cone-shaped nodes and networks
Pelvic component	"From top to bottom" through inguinal collaterals and intersaphenous anastomoses	Varicose veins of the posterolateral thigh, buttocks, vulvar varicose veins

Source: Clinical guidelines and reviews. [45]

Table 6. Common myths and what the data says

Statement	Status	Comment
"Crossed legs cause varicose veins"	Myth	They are not the cause, but may increase discomfort.
"High heels cause varicose veins"	Exaggeration	Affects the calf pump and symptoms, the causal role for the disease has not been proven
"It's just cosmetics."	Wrong	Progression to skin complications and ulcers is possible.
"Only for women"	Wrong	The disease is also common in men, although female gender and pregnancy are important

Source: educational materials and research. [46]