How Varicose Veins Form
Varicose veins develop through a combination of valvular incompetence and vein wall weakening, where genetic predisposition leads to loss of elasticity in the vein wall, causing valve leaflets to fail to close properly, which allows blood to flow backward (reflux) and creates increased pressure that progressively dilates and elongates the veins. 1
Primary Pathophysiologic Mechanisms
The exact sequence of events remains debated, but two interconnected processes drive varicose vein formation 1:
Valve Dysfunction
- In most cases, valvular dysfunction is presumed to result from loss of elasticity in the vein wall, with subsequent failure of the valve leaflets to fit together properly 1
- Rather than blood flowing from distal to proximal and superficial to deep as intended, incompetent valves allow blood to flow in reverse direction 1
- Recent evidence suggests vein wall dilation may actually precede valve dysfunction, with structural abnormalities and focal dilation in vein wall segments near valve junctions causing secondary valve incompetence 2
Vein Wall Deterioration
- With increased pressure on the affected venous system from reflux, the larger veins become elongated and tortuous 1
- The increase in vein wall tension augments expression and activity of matrix metalloproteinases (MMPs), which degrade extracellular matrix proteins and compromise the structural integrity of the vein wall 2
- MMPs also affect the endothelium and smooth muscle components, altering venous constriction and relaxation properties 2
Contributing Inflammatory Processes
Shear stress on venous endothelial cells due to reversed or turbulent blood flow triggers inflammation, which is an important etiologic factor for venous disease 1:
- Endothelial cell injury triggers leukocyte infiltration, activation, and inflammation, leading to further vein wall damage 2
- Patients with varicose veins have increased levels of interleukins, the most specific inflammatory markers of vascular wall inflammation that promote coagulation 3
- This superimposed inflammation and fibrosis leads to chronic and progressive venous insufficiency 2
Genetic and Risk Factor Context
Established risk factors include family history of venous disease, female sex, older age, and chronically increased intra-abdominal pressure 1, 4:
- The well-established genetic predisposition suggests this high prevalence (affecting up to 40% of adults) may reflect underlying biological mechanisms 5, 6
- Varicose veins are more common in obese people and women who have had more than two pregnancies 5
- Prolonged standing exacerbates the condition by increasing venous pressure 4
Clinical Implications
The progressive nature of this pathophysiology explains why symptoms typically worsen at the end of the day after prolonged standing and improve with leg elevation 1, 4. As the disease advances, the chronic venous hypertension can lead to skin changes including pigmentation, eczema, and lipodermatosclerosis 1, 4.