Assessment of arterial stiffness in patients with chronic lower extremity venous disease: An observational study.

OBJECTIVES: Arterial stiffness is associated with major adverse cardiovascular events. Chronic venous insufficiency (CVI) is severe form of chronic venous disease (CVD). The aim of this study is to investigate arterial stiffness by cardio-ankle vascular index (CAVI) in patients with CVI. METHODS: This observational and cross-sectional study involved 87 subjects with CVI and 86 healthy subjects. All subjects underwent ultrasonography examination. CAVI was measured by VaSera-1000 CAVI instrument. RESULTS: High density lipoprotein cholesterol (HDL) was significantly lower in patients with CVI than controls (46.83 ± 9.25 mg/dl vs 51.33 ± 11.13 mg/dl, p = 0.004). Body mass index (BMI) was significantly higher in CVI patients than controls (28.53 ± 4.10 kg/m(2) vs 26.37 ± 5.16 kg/m(2), p = 0.003). Ankle brachial index (ABI) was significantly lower in patients with CVI compared to controls (1.08 ± 0.08 vs 1.14 ± 0.11, p < 0.001). CAVI was significantly higher in patients with CVI than controls (7.94 ± 1.37 vs 6.73 ± 1.16, p < 0.001). Mean arterial pressure (MAP) was significantly higher in patients with CVI than control group (105.41 ± 10.77 mmHg vs 99.70 ± 11.17 mmHg, p = 0.001). CAVI (p < 0.001, Odds ratio (OR) = 2.033, 95% Confidence interval (CI) = 1.493-2.768), ABI (p = 0.003, OR = 0.003, 95% CI = 0.001-0.137), female sex (p < 0.001, OR = 3.949, 95% CI = 1.613-9.663), and HDL (p < 0.001, OR = 0.923, 95% CI = 0.883-0.964) were the independent predictors of CVI. A CAVI value > 7.9 had a sensitivity 64.4% and a specificity of 94.7% for predicting the presence of CVI in ROC analysis (area under curve = 0.791, 95% CI = 0.723-0.849, p < 0.001). CONCLUSION: CAVI is independently increased in CVI patients. Therefore CVI may be accepted a form of vascular sclerosis and vascular system should be evaluated in continuum not isolated.

A new method for the assessment of venous insufficiency in primary varicose veins using near-infrared spectroscopy.

PURPOSE: Patients with chronic venous insufficiency (CVI) were evaluated from the aspect of ambulatory venous function using near-infrared spectroscopy (NIRS). METHODS: Seventy-two primary varicose veins of 59 patients (varicose group) and 20 normal limbs of 13 volunteers (normal group) were studied. The affected limbs of the patients were divided into three groups according to the classification advocated by an International Consensus Committee in 1995: mild CVI with class 2 or 3 (50 limbs); moderate CVI with class 4 (11 limbs); and severe CVI with class 5 or 6 (11 limbs). All of the patients underwent a treadmill walking test, during which NIRS was applied. Oxygenated hemoglobin (OxyHb) and deoxygenated hemoglobin (DeoHb) were continuously measured by NIRS during exercise. The ambulatory venous retention index (AVRI) obtained from serial changes in DeoHb was assessed comparatively in the four groups (normal and mild to severe CVI). In addition, 19 limbs in 13 patients were evaluated with air plethysmography for comparison with the data obtained by NIRS. RESULTS: Two distinct patterns of DeoHb change were observed. During exercise, the DeoHb level decreased in the normal group as a result of calf muscle contraction, whereas in the varicose group the DeoHb level rose because of an apparent venous reflux into the calf muscles. AVRI studies demonstrated a significant difference (p < 0.0001) among groups. Although there was no apparent relationship between AVRI and ejection fraction, AVRI showed a significant correlation with the venous filling index (r = 0.61) and a weak correlation with the residual volume fraction (r = 0.41). CONCLUSION: NIRS is useful for accurately assessing ambulatory venous dysfunction in patients with primary varicose veins.

A new method for the assessment of tissue hemoglobin oxygenation in patients with chronic venous insufficiency.

Venous incompetence often leads to ulceration of the skin of the lower limb due to a disturbance of skin microcirculation. We investigated 10 healthy subjects and 18 patients with chronic venous insufficiency by means of a fast scanning reflection photometer and determined noninvasively the hemoglobin oxygen saturation (S(HB)) and the relative concentration of hemoglobin (C(HB)) in the skin of the forefoot and at the calf, 10 cm proximal of the inner malleolus during positional changes. In supine position no significant differences were found. During sitting and standing S(HB) dropped and was significantly lower in patients at both locations (calf, standing, patients 22.2 +/- 10.6% vs controls 48.2 +/- 13.5%, P < 0.001). C(HB) increased in patients during standing from 0.71 to 2.13 +/- 0.33 aU (in controls from 0.69 to 1.49 +/- 0.28 aU, P < 0.001). Activation of the muscle pump decreased C(HB) and increased S(HB) in patients and in controls. After the movements were stopped, S(HB) decreased again and fell to the initial low values eight times faster in patients (7.4 +/- 5.3 vs 57.5 +/- 19.6 sec, P < 0.001). C(HB) increased four times faster in patients (7.2 +/- 6.1 vs 29.9 +/- 13.6 sec). In sitting and standing positions hemoglobin oxygenation in the skin of the lower limb was markedly reduced in patients, but normal perfusion conditions were restored in supine position, indicating reversibility of the changes. Reflection oxymetry seems a valuable tool for the assessment of chronic venous insufficiency. The substantially reduced oxygenation of dermal hemoglobin in standing patients may contribute to the development of venous ulcers.

Double-blind, double-dummy, randomized, multi-centre clinical assessment of the efficacy, tolerability and dose-effect relationship of sulodexide in chronic venous insufficiency.

A multi-centre study was carried out in 476 patients with chronic venous insufficiency to compare the efficacy, tolerability and dose-effect relationship of sulodexide given orally as either capsules or as a new, enteric-coated tablet formulation. Three comparable groups of patients each with chronic venous insufficiency of thrombotic or varicose aetiology received during 60 consecutive days either sulodexide 250 LRU (= 25 mg) capsules twice daily, 50 mg sulodexide enteric-coated tablets twice daily or 100 mg sulodexide enteric-coated tablets once daily, according to a double-blind, double-dummy, randomized design. Doppler and echoduplex examinations, supine and standing peripheral venous pressure, specific symptoms and signs, peripheral haemodynamics and safety haematology and haematochemistry were monitored monthly. The results showed that peripheral venous pressure improved to a clinically relevant and statistically significant extent in all groups and symptoms and signs were rapidly and significantly relieved. These effects were dose-related, as in both cases the recovery was faster and greater with the 100 mg per day dose however administered. Both the thrombotic and varicose aetiologic sub-groups benefited from treatment to approximately the same extent. Mild to moderate gastro-intestinal adverse experiences occurred in 48 patients evenly split between groups but spontaneously disappeared within 72 hours, none leading to treatment withdrawal. No clinically relevant modifications of peripheral haemodynamics or of safety haematology and haematochemistry was observed. The haemocoagulation parameters failed to exhibit appreciable variations. While the known clinical usefulness of sulodexide 250 LRU (= 25 mg) capsules twice daily was confirmed in this trial, the enteric-coated tablets, 50 mg twice daily or 100 mg once daily, were shown to have greater efficacy and similar tolerability to the standard formulation and dose.