Journal of Vascular and Endovascular Therapy

Description

The design of the study was multi centric and international, carried out in 23 countries over 2 years, in which 5,052 symptomatic patients assigned to classes C0 to C4 (on the basis of CEAP clinical classification) were enrolled. Patients were treated with micronized purified flavonoid fraction (MPFF*), consisting of 450 mg of micronized diosmin and 50 mg of flavonoids expressed in hesperidin over 6 months. In order to document changes in the quality of life of these patients during MPFF treatment, a new validated Quality of Life Questionnaire specific to CVI (CIVIQ) was used. The study also set out to gather epidemiologic data including the prevalence of venous reflux in symptomatic patients.

Congenital Malformations

Chronic Venous Disease (CVD) is common. Its manifestations include varicose veins; skin changes such as dermatitis, hyperpigmentation, and lipodermatosclerosis; and chronic leg ulcers. Recent advances in the understanding of its pathophysiology have shown how molecular mechanisms in the inflammatory cascade are involved in these diverse findings. Venous hypertension and associated fluid shear stress alterations on the endothelial surface may initiate this cascade and may lead to adverse changes in the venous wall, venous valves, and skin that can eventually result in varicose veins and in venous ulcers. Chronic venous insufficiency is a common primary care problem associated with significant morbidity and health care costs. The clinical spectrum of disease ranges from minor cosmetic concerns to severe fibrosing panniculitis and ulceration. Duplex Doppler ultrasonography may be the single best test to rule out deep venous thrombosis and other entities that can mimic CVI. Leg elevation and compression stockings are effective treatments for CVI; recalcitrant cases may require intermittent pneumatic compression. Topical antiseptics, antibiotics, enzymes, or growth factors offer no clear advantages in ulcer healing. Ulcer dressings remain a matter of convenience, cost, and physician judgment. The role of surgery in CVI appears to be limited. Chronic venous insufficiency affects approximately 5% and chronic leg ulcer approxi mately 1% of the adult population of developed countries. Not only do recent quality of life studies highlight major disability and social impairment but, since this is a condition characterized by chronicity and relapse, it gives rise to massive health care expenditure amounting in the UK to around £400 million per annum. Venous disease consumes 1-2% of the health care budgets of European countries. Imprecise disease classifications and codings impede the acquisition of accurate data but there is a compelling need for better quality socioeconomic data concerning this long-neglected health care problem.

Elevated Subcutaneous Flow

The elevated ambulatory pressure in the peripheral venous system of chronic venous insufficiency (CVI) patients manifests itself not only in the form of disturbed macrocirculation but also and particularly in microangiopathic changes. For this reason, it is closely correlated with trophic disorders of the skin and can ultimately lead to ulceration. Using microcirculation research techniques, we are able to provide clear evidence of a typical microangiopathy in chronic venous insufficiency. Fifty CVI patients in Widmer stages I, II, and III were examined with fluorescence video microscopy, intravital video capillaroscopy, transcutaneous oxygen partial pressure measurement, TcpO2and laser Doppler flowmetry. The effects of compression therapy with individually fitted compression stockings on capillary morphology were studied over a period of 4 weeks in 20 CVI patients in Widmer stages I and II. The capillary pressure was measured during simulated muscle contraction using a servo-null micropressure system. We periodically drew blood from the dorsalis pedis vein and a brachial vein of 11 healthy test persons and 8 patients with stage III CVI during experimental venous hypertension in order to evaluate the expression pattern of leukocyte adhesion molecules involved in inflammation: LFA-1 (CD11a), Mac-1 (CD11b), p150,95 (CD11c), CD18, VLA-4 (CD49d), and L-selectin (CD62L). In the same patients, we used immunohistochemical methods to examine clinically unaffected skin and the skin near an ulcer, focusing on the adhesion molecules ICAM-1, VCAM-1, and E-selectin. The microangiopathic changes observed with worsening clinical symptoms include a decrease in the number of capillaries, glomerulus-like changes in capillary morphology, a drop in the oxygen content (tcpO2) of the skin, increased permeability of the capillaries to low-molecular-weight substances, increased laser Doppler flux reflecting elevated subcutaneous flow, and diminished vascular reserve. These microangiopathic changes worsen in linear proportion to the clinical severity of chronic venous insufficiency. In patients with venous ulcerations, the baseline expression of LFA-1 and VLA-4 on lymphocytes, Mac-1 expression on the myeloid cell line, and L-selectin expression on all three cell lines was not significantly different from that in healthy controls. During orthostatic stress, there was a significant reduction in the expression of L-selectin in blood cells collected at foot level in the controls (p= 0.002), but not in the patients. Clinical improvement by compression therapy was accompanied by an increase in the number of nutritive capillaries, while the diameter of the capillaries and the dermal papillae was reduced. When ulcers healed in a short period (<6 weeks), we observed a concomitant increase in the number of capillaries (p< 0.05). Microangiopathy appears before trophic disorders of the skin develop. Even trophically normal skin areas may have dilated nutritive capillaries, an early sign of disturbed skin perfusion. These changes represent a plausible explanation for the development and to recurrency tendency of venous ulcers. The reduced expression of lymphocytic L-selectin in healthy controls during the orthostatic stress test may be an indication that the cells are activated by venous stasis. Clinically effective therapeutic measures improve the impaired microcirculation of the skin in the ankle area.