Venous disease is the most common cause of leg ulceration. Although compression therapy improves venous ulcer healing, it does not treat the underlying causes of venous hypertension. Treatment of superficial venous reflux has been shown to reduce the rate of ulcer recurrence, but the effect of early endovenous ablation of superficial venous reflux on ulcer healing remains unclear.

Chronic venous disease (CVD) is a prevalent condition that tends to worsen with age. Patients initially seek treatment to relieve symptoms of leg pain, discomfort, heaviness and swelling, all of which impact their quality of life. As the disease increases in severity to include varicose veins, skin changes, and venous ulcer, the demand for treatment increases while the quality of life further diminishes. The prevalence of CVD is highest in Western countries where it already consumes up to 2% of healthcare budgets. With the aging of the global population, the prevalences of CVD and severe CVD are projected to increase substantially, foretelling unsustainably large increases in the healthcare resources and costs needed to treat CVD patients in the coming decades. Effective venoactive drug treatments and ablation procedures are available that provide symptom relief, improve quality of life, slow disease progression, and promote ulcer healing. In addition, venoactive drug treatments may be highly cost-effective. However, there is evidence that physician awareness of CVD is suboptimal and that many patients with CVD are not being treated or referred to specialists according to established guidelines. To decrease this treatment gap and prevent unnecessary disease progression, international guidelines are available to help physicians consider CVD treatment options and refer patients when warranted. Improved disease awareness and appropriate early treatment may help reduce the coming burden of CVD. Funding: Servier.

Background: Valvular incompetence and reflux are common features of primary varicose veins, and have long been thought to be their cause. Recent evidence, however, suggests that changes in the vein wall may precede valvular dysfunction. Methods: A literature search was performed using PubMed and Ovid using the keywords ‘varicose vein wall changes’, ‘pathogenesis’, ‘aetiology’ and ‘valvular dysfunction’. Articles discussing the pathophysiology of complications of varicose veins, such as ulceration, recurrence, thrombophlebitis and lipodermatosclerosis, were excluded. Results and conclusion: Positive family history, age, sex and pregnancy are important risk factors for varicose vein formation. Areas of intimal hyperplasia and smooth muscle cell proliferation are often noted in varicose veins, although regions of atrophy are also present. The total elastin content in varicose as opposed to non-varicose veins is reduced; changes in overall collagen content are uncertain. Matrix metalloproteinases (MMPs), including MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9, and tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP-3 are upregulated in varicose veins. Activation of the endothelium stimulates the recruitment of leucocytes and the release of growth factors, leading to smooth muscle cell proliferation and migration. Dysregulated apoptosis has also been demonstrated in varicose veins. An understanding of the pathophysiology of varicose veins is important in the identification of potential therapeutic targets and treatment strategies.

High blood pressure is responsible for the modulation of blood vessel morphology and function. Arterial hypertension is considered to play a significant role in atherosclerotic ischaemic heart disease, stroke and hypertensive nephropathy, whereas high venous pressure causes varicose vein formation and chronic venous insufficiency and contributes to vein bypass graft failure. Hypertension exerts differing injurious forces on the vessel wall, namely shear stress and circumferential stretch. Morphological and molecular changes in blood vessels ascribed to elevated pressure consist of endothelial damage, neointima formation, activation of inflammatory cascades, hypertrophy, migration and phenotypic changes in vascular smooth muscle cells, as well as extracellular matrix imbalances. Differential expression of genes encoding relevant factors including vascular endothelial growth factor, endothelin-1, interleukin-6, vascular cell adhesion molecule, intercellular adhesion molecule, matrix metalloproteinase-2 and -9 and plasminogen activator inhibitor-1 has been explored using ex vivo cellular or organ stretch models and in vivo experimental animal models. Identification of pertinent genes may unravel new therapeutic strategies to counter the effects of pressure-induced stretch on the vessel wall and hence minimise its notable complications.