Pathophysiological Mechanisms of Chronic Venous Disease and Implications for Venoactive Drug Therapy

Abstract

Chronic venous disease (CVD) is a common pathology, with significant physical and psychological impacts for patients and high economic costs for national healthcare systems. Throughout the last decades, several risk factors for this condition have been identified, but only recently, have the roles of inflammation and endothelial dysfunction been properly assessed. Although still incompletely understood, current knowledge of the pathophysiological mechanisms of CVD reveals several potential targets and strategies for therapeutic intervention, some of which are addressable by currently available venoactive drugs. The roles of these drugs in the clinical improvement of venous tone and contractility, reduction of edema and inflammation, as well as in improved microcirculation and venous ulcer healing have been studied extensively, with favorable results reported in the literature. Here, we aim to review these pathophysiological mechanisms and their implications regarding currently available venoactive drug therapies.

The Importance of Ambulatory Venous Hypertension Should Be Revised

“…Increased sheer stress exerts load on the endothelium, which may lead to its damage (both functional and morphological); low sheer stress facilitates the formation of thrombi. Endothelial dysfunction leads to the aforementioned cascade of processes in microcirculation [2,22] and also in valves [23,24]. Chronic inflammation leading primarily to protection of the venous wall may, in the event of permanent stimuli, cause further dilatation of varicose veins and valvular insufficiency, and thus further increase of sheer stress.…”

“…We found no data for venous pressure in sitting position and small movements. We assessed this situation by photoplethysmography [2].…”

“…Nowadays venous hypertension has been generally recognized as the fundamental pathophysiological mechanism of development of chronic venous insufficiency [1][2][3]. In the standing and sitting positions, venous pressure in lower limbs is increased by hydrostatic pressure.…”

Early Stages of Chronic Venous Disease: Medical Treatment Alone or in Addition to Endovenous Treatments

“…CVD progresses as a result of a persistent inflammatory cycle that typically begins with abnormal venous flow due to venous hypertension and damaged venous valves. Aberrant hemodynamics and reflux activate the venous endothelium, leading to infiltration of activated leukocytes into the vein walls and surrounding tissues, where inflammatory cytokines and mediators are released [4]. These events, along with persistent vein dilatation, lead to further Options for management of patients at the early stages of CVD (C0s to C2) include venoactive drugs (VAD), which may be used alone or in conjunction with interventional treatment of varices such as sclerotherapy, surgery, or endovenous treatments [1].…”

“…Pharmacologically, MPFF has anti-inflammatory activities, reduces endothelial activation and leukocyte adhesion, and increases capillary resistance and integrity [4]. As a result of these effects, MPFF produces a number of significant clinical benefits in patients with CVD.…”