Chronic Venous Insufficiency

Abstract

HomeCirculationVol. 111, No. 18Chronic Venous Insufficiency Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBChronic Venous Insufficiency Robert T. Eberhardt, MD and Joseph D. Raffetto, MD Robert T. EberhardtRobert T. Eberhardt From Cardiovascular Medicine, Boston Medical Center (R.T.E.), Vascular Surgery, Boston VA Health System (J.D.R.), and Boston University School of Medicine (R.T.E., J.D.R.), Boston, Mass. Search for more papers by this author and Joseph D. RaffettoJoseph D. Raffetto From Cardiovascular Medicine, Boston Medical Center (R.T.E.), Vascular Surgery, Boston VA Health System (J.D.R.), and Boston University School of Medicine (R.T.E., J.D.R.), Boston, Mass. Search for more papers by this author Originally published10 May 2005https://doi.org/10.1161/01.CIR.0000164199.72440.08Circulation. 2005;111:2398–2409Chronic venous disease is often overlooked by primary and cardiovascular care providers because of an underappreciation of the magnitude and impact of the problem. The importance of chronic venous disease is related to the number of people with the disease and the socioeconomic impact of its more severe manifestations. Unfortunately, the literature concerning the prevalence and incidence of chronic venous disease has varied greatly because of differences in the methods of evaluation, criteria for definition, and the geographic regions analyzed. The most common manifestations of chronic venous disease are dilated cutaneous veins, such as telangiectases and reticular veins, and varicose veins. The term chronic venous insufficiency (CVI) describes a condition that affects the venous system of the lower extremities with venous hypertension causing various pathologies including pain, swelling, edema, skin changes, and ulcerations. Although the term CVI is often used to exclude uncomplicated varicose veins, varicose veins have incompetent valves with increased venous pressure leading to progressive dilation and tortuosity. We will use the term CVI to represent the full spectrum of manifestations of chronic venous disease.Varicose veins have an estimated prevalence between 5% to 30% in the adult population, with a female to male predominance of 3 to 1, although a more recent study supports a higher male prevalence.1 The Edinburgh Vein Study screened 1566 subjects with duplex ultrasound for reflux finding CVI in 9.4% of men and 6.6% of women, after age adjustment, which rose significantly with age (21.2% in men >50 years old, and 12.0% in women >50 years old).2 The San Valentino Vascular Screening Project found among the 30 000 subjects evaluated by clinical assessment and duplex ultrasound a prevalence of 7% for varicose veins and 0.86% for “symptomatic” CVI.3 As in previous studies, CVI was more common with increasing age, but there was no significant sex difference. The rate of varicose vein development may be estimated from the Framingham Heart Study, which found an annual incidence of 2.6% in women and 1.9% in men.4 Risk factors found to be associated with CVI include age, sex, a family history of varicose veins, obesity, pregnancy, phlebitis, and previous leg injury.5,6 There also may be environmental or behavioral factors associated with CVI such as prolonged standing and perhaps a sitting posture at work.6,7 Varicose veins have a significant impact on healthcare resources, with millions of people seeking medical attention for their cosmetic appearance annually. Although often minimized, the cosmetic consequences may adversely affect an individual’s quality of life and are associated with other manifestations.The more serious consequences of CVI such as venous ulcers have an estimated prevalence of ≈0.3%, although active or healed ulcers are seen in ≈1% of the adult population.8 It has been estimated that ≈2.5 million people have CVI in the United States, and of those, ≈20% develop venous ulcers.9 The overall prognosis of venous ulcers is poor, with delayed healing and recurrent ulceration being common.10 More than 50% of venous ulcers require prolonged therapy lasting >1 year.5 The socioeconomic impact of venous ulceration is dramatic, resulting in an impaired ability to engage in social and occupational activities, thus reducing the quality of life and imposing financial constraints. Disability related to venous ulcers leads to loss of productive work hours, estimated at 2 million workdays/year, and may cause early retirement, which is found in up to 12.5% of workers with venous ulcers.11 The financial burden of venous ulcer disease on the healthcare system is readily apparent: An estimated $1 billion is spent annually on the treatment of chronic wounds in the United States, or up to 2% of the total healthcare budget in all Western countries, and recent estimates place the cost of venous ulcer care at $3 billion annually.12,13Given the prevalence and socioeconomic impact of chronic venous disease, an understanding of the clinical manifestations, diagnostic modalities, and therapeutic options is warranted. This article reviews the clinical aspects of CVI with a focus on the diagnostic and therapeutic options.Venous PathophysiologyNormal Venous Anatomy and FunctionTo appreciate the pathophysiology of CVI, an understanding of the normal venous anatomy and function is necessary. The peripheral venous system functions as a reservoir to store blood and as a conduit to return blood to the heart. Proper functioning of the peripheral venous system depends on a series of valves and muscle pumps. Blood that enters into the lower-extremity venous system must travel against gravity and against fluctuating thoracoabdominal pressures to return to the central circulation in a person in an erect position.The veins of the lower extremity are divided into the superficial and deep venous system connected by a series of perforator veins.14,15 The superficial venous system is located above the muscular fascial layer. It comprises an interconnecting network of veins, which serve as the primary collecting system, and several truncal superficial veins, which function as a conduit to return blood to the deep venous system. The principal named superficial veins of the lower extremity are the short (or lesser) saphenous vein, which runs from the ankle typically to join the popliteal vein at the saphenopopliteal junction, and the great saphenous vein, which runs from the ankle to join the common femoral vein at the saphenofemoral junction. Other superficial veins, including the posterior arch, lateral accessory saphenous, and vein of Giacomini, also can develop pathology leading to CVI.The deep venous system is located below the muscular fascia and serves as collecting veins and the outflow from the extremity. The deep veins of the lower extremity consist of axial veins, which follow the course of the major arteries, and the intramuscular veins. Venous sinusoids within the leg muscles coalesce to form intramuscular venous plexi. Paired calf veins, which, corresponding to the axial arteries, merge to form a single large popliteal vein. The popliteal vein, on passing through the adductor canal, is subsequently known as the femoral (often called the superficial femoral) vein. The femoral vein is joined by the profunda femoris (or deep femoral) vein in the upper thigh to form the major outflow of the leg, the common femoral and eventually the external iliac vein. The superficial veins are connected to the deep venous system by a number of perforating veins in the thigh and leg that pass through anatomic fascial spaces.A series of bicuspid valves are located throughout the deep and superficial veins and ensures that blood moves in the cephalad direction, preventing the return of blood toward the feet while in the upright posture.14 The first of these lower-extremity valves is usually located in the common femoral vein or less commonly in the external iliac vein. The frequency of venous valves increases from the proximal to the distal leg to prevent an increase in pressure within the distal veins resulting from the effects of gravity. Perforating veins also contain one-way valves that prevent reflux of blood from the deep veins into the superficial system.The valves function in concert with venous muscle pumps to allow the return of blood against gravity to the heart.16 Contraction of the muscle pumps primarily in the calf, but also in the foot and thigh, and forces blood out of the venous plexi and up the deep venous system because of increased pressure within the fascial compartments. The valve system prevents blood from being forced distally within the deep venous system or through the perforator system into the superficial system. Immediately after ambulation, the pressure within the veins of the lower extremity is normally low (15 to 30 mm Hg) because the venous system has been emptied by the muscle pump function (Figure 1A). Relaxation of the muscle pump then allows blood to return to the deep venous system via arterial inflow through the superficial and the distal deep venous systems. With prolonged standing, the veins slowly fill and become distended, allowing the valves to open and eventually increase pressure that is directly related to the height of the column of blood. Contraction of the muscle pump will again empty the veins and reduce venous pressure. Download figureDownload PowerPointFigure 1. Illustrative ambulatory venous pressure measurements. (A) Normal venous pressure. The resting standing venous pressure is ≈80 to 90 mm Hg. The pressure drops with calf exercise to ≈20 to 30 mm Hg, or a >50% decrease. The return in pressure is more gradual, with refill taking >20 s. (B) Abnormal venous pressure with deep venous reflux. The drop in pressure with exercise is blunted (<50% decrease). The return in venous pressure to the resting level is rapid because of a short refill time (<20 s).Venous Pathophysiology and DysfunctionVenous pathology develops when venous pressure is increased and return of blood is impaired through several mechanisms.17 This can result from valvular incompetence of the axial deep or superficial veins, perforator valve incompetence, venous obstruction, or a combination of these. These factors are exacerbated by muscle pump dysfunction in the lower extremity. These mechanisms serve to produce venous hypertension particularly with standing or ambulation. Contributing to the macrocirculatory hemodynamic disturbances are alterations within the microcirculation.18,19 Unabated venous hypertension may result in dermal changes with hyperpigmentation, subcutaneous tissue fibrosis (“lipodermatosclerosis”), and eventual ulceration.With failure of the valves of the deep veins, normal blood volume is pumped out of the extremity, but refill occurs by both arterial inflow and pathological retrograde venous flow. The venous pressure immediately after ambulation may be slightly elevated or even normal, but veins refill quickly with the development of high venous pressure without muscle contraction (Figure 1B). Dysfunction of the valves of the deep venous system is most often a consequence of damage from previous deep vein thrombosis (DVT).20Dysfunction or incompetence of the valves in the superficial venous system also allows retrograde flow of blood and increased hydrostatic pressures. Valve failure may be primary the result of preexisting weakness in the vessel wall or valve leaflets, or secondary to direct injury, superficial phlebitis, or excessive venous distention resulting from hormonal effects or high pressure.17 Failure of valves located at the junctions of the deep and superficial systems, most notably at the saphenofemoral and saphenopopliteal junctions, allows high pressure to enter the superficial veins. In this situation, venous dilatation and varicose veins form and propagate from the proximal junction site down the extremity.High pressure also can enter the superficial system because of failure of the valves in the communicating perforator veins.21,22 Perforator valve incompetence allows blood to flow from deep veins backward into the superficial system and the transmission of the high pressures generated by the calf muscle pump. This local high pressure can produce excessive venous dilatation and secondary failure of superficial vein valves. As a result, a cluster of dilated veins develops at this site and appears to ascend up the leg. Clinically relevant perforator vein incompetence is typically associated with reflux of the deep and/or superficial venous system.21,22Obstruction of the deep veins may limit the outflow of blood, causing increased venous pressure with muscle contraction and secondary muscle pump dysfunction. Obstruction may occur because of an intrinsic venous process, such as previous DVT with inadequate recanalization or venous stenosis, or because of extrinsic compression, as in May-Thurner syndrome (compression of the left common iliac vein as it traverses between the right common iliac artery and the lumbosacral region). Venous outflow obstruction appears to play a more significant role in the pathogenesis of CVI and its clinical expression than previously appreciated.23Dysfunction of the muscle pumps leads to venous blood not being effectively emptied out of the distal extremity. This rarely occurs as a “primary” disorder with neuromuscular conditions or muscle wasting syndromes; however, clinically significant muscle pump dysfunction often occurs in the setting of severe reflux or obstruction. The immediate postambulatory venous pressure will be nearly as high as the pressure after prolonged standing. Muscle pump dysfunction appears to be a major mechanism for the development of superficial venous incompetence and its complications such as venous ulcers.24,25Changes in the hemodynamics of the large veins of the lower extremity are transmitted into the microcirculation and eventually result in the development of venous microangiopathy.18 Features of this microangiopathy include elongation, dilation, and tortuosity of capillary beds, thickening of basement membranes with increased collagen and elastic fibers, endothelial damage with widening of interendothelial spaces, and increased pericapillary edema with “halo” formation. The abnormal capillaries with increased permeability and high venous pressure leads to the accumulation of fluid, macromolecules, and extravasated red blood cells into the interstitial space. In addition to changes in the blood vessels and connective tissue, alteration in the lymphatic network and nervous system may occur. Fragmentation and destruction of microlymphatics may further impair drainage from the extremity, whereas dysfunction of local nerve fibers may alter regulatory mechanisms.Several mechanisms for the development of venous microangiopathy have been postulated, including fibrin cuff formation, growth factor trapping, and white blood cell trapping.18 The fibrin cuff theory involves the accumulation of fluid containing fibrin into the pericapillary space. This cuff with impaired fibrinolysis is speculated to increase the diffusion barrier, inhibit the repair process, and maintain the inflammatory process. A related mechanism is the trapping of growth factor by fibrin and other macromolecules, making them unavailable to facilitate healing. Another theory involves the trapping of white blood cells in the capillaries or postcapillary venules. The adhesion of white blood cells with activation releases inflammatory mediators and proteolytic enzymes with endothelial damage that may increase permeability or impede flow leading to occlusion.Clinical ManifestationsCVI represents a spectrum of conditions ranging from simple telangiectases or reticular veins to more advanced stages such as skin fibrosis and venous ulceration. It is important to realize that the same clinical manifestations may result from the varied pathogenic mechanisms (ie, incompetent valves alone, venous obstruction alone, muscle pump dysfunction alone, or a combination). The major clinical features of CVI are dilated veins, edema, leg pain, and cutaneous changes. Varicose veins are dilated superficial veins that become progressively more tortuous and larger (Figure 2A). They are prone to develop bouts of superficial thrombophlebitis. Edema begins in the perimalleolar (or gaiter) region but ascends up the leg with dependent accumulation of fluid. The leg pain or discomfort is described as heaviness or aching after prolonged standing and relieved by elevation of the leg. Edema presumably produces the pain by increasing intracompartmental and subcutaneous volume and pressure. There also may be tenderness along varicose veins from venous distention. Obstruction of the deep venous system may lead to venous claudication, or intense leg cramping with ambulation. Cutaneous changes include skin hyperpigmentation from hemosiderin deposition and eczematous dermatitis (Figure 2B). Fibrosis may develop in the dermis and subcutaneous tissue (lipodermatosclerosis). There is an increased risk of cellulitis, leg ulceration, and delayed wound healing (Figure 2C). Long-standing CVI also may lead to the development of lymphedema, representing a combined disease process. Download figureDownload PowerPointFigure 2. Manifestations of CVI. A, Uncomplicated varicose veins. B, Hyperpigmentation, dermatitis, and severe edema likely resulting from combined lymphedema. C, Active and healed venous ulcerations.The manifestations of CVI may be viewed in terms of a well-established clinical classification scheme. The CEAP—Clinical, Etiology, Anatomic, Pathophysiology—classification was developed by an international consensus conference to provide a basis for uniformity in reporting, diagnosing, and treating CVI (Table 1).26 The clinical classification has 7 categories (0 to 6) and is further categorized by the presence or absence of symptoms. The etiologic classification is based on congenital, primary, and secondary causes of venous dysfunction. Congenital disorders are those that are present at birth, although they may be recognized later in life, including the well-recognized Klippel-Trenaunay (varicosities and venous malformations, capillary malformation, and limb hypertrophy) and Parkes-Weber (venous and lymphatic malformations, capillary malformations, and arteriovenous fistulas) syndromes.27 The cause of primary venous insufficiency is uncertain, whereas secondary venous insufficiency is the result of an acquired condition. The anatomic classification describes the superficial, deep, and perforating venous systems, with multiple venous segments that may be involved. The pathophysiological classification describes the underlying mechanism resulting in CVI, including reflux, venous obstruction, or both. Validation of the CEAP classification system has often focused on the clinical classification.28 The classification is a valuable tool in the objective evaluation of CVI, providing a system to standardize CVI classification, with emphasis on the manifestations, cause, and distribution of the venous disease that is widely accepted.29TABLE 1. CEAP Classification of Chronic Venous DiseaseClassificationDescription/DefinitionC, Clinical (subdivided into A for asymptomatic, S for symptomatic) 0No venous disease 1Telangiectases 2Varicose veins 3Edema 4Lipodermatosclerosis or hyperpigmentation 5Healed ulcer 6Active ulcerE, Etiologic CongenitalPresent since birth PrimaryUndetermined etiology SecondaryAssociated with post-thrombotic, traumaticA, Anatomic distribution (alone or in combination) SuperficialGreat and short saphenous veins DeepCava, iliac, gonadal, femoral, profunda, popliteal, tibial, and muscular veins PerforatorThigh and leg perforating veinsP, Pathophysiological RefluxAxial and perforating veins ObstructionAcute and chronic Combination of bothValvular dysfunction and thrombusThere are limitations to the CEAP clinical classification, which is arbitrary and subjective with inadequate delineation of the categories. To complement the CEAP classification and further define the severity of CVI, a venous severity score was developed.30 The venous severity scoring provides a numeric score based on 3 components: the venous clinical severity score, the anatomic segment disease score, and the disability score. The venous clinical severity score consists of 10 attributes (pain, varicose veins, venous edema, skin pigmentation, inflammation, induration, number of ulcers, duration of ulcers, size of ulcers, and compressive therapy) with 4 grades (absent, mild, moderate, severe). The venous anatomic segmental score assigns a numerical value to segments of the venous system in the lower extremity that account for both reflux and obstruction. The venous disability score comes from the ability to perform normal activities of daily living with or without compressive stockings. The venous severity scoring has been shown to be useful to evaluate the response to treatment.31Diagnosis of CVIThe diagnosis of CVI is made via patient history and physical examination with the assistance of noninvasive testing. Invasive testing also may be used to establish the diagnosis, but it is typically reserved for assessing disease severity or when surgical intervention is being contemplated. A comprehensive overview of the methods to assess CVI may be found in a previously published consensus statement.32Physical ExaminationThe physical examination plays an important role in guiding therapy in CVI. Inspection and palpation may reveal visual evidence for chronic venous disease. The surface of the skin is examined for irregularities or bulges to suggest the presence of varicose veins. Hyperpigmentation, stasis dermatitis, atrophic blanche (white scarring at the site of previous ulcerations with a paucity of capillaries), or lipodermatosclerosis may be observed. The distribution of varicose veins may follow the course of the affected superficial vein, such as the great or short saphenous veins. Examination should include an evaluation of the patient in the upright posture to allow maximal distention of the veins and from multiple directions. The presence of edema and its severity are assessed. Edema is usually pitting; however, early evidence may be calf fullness or increased limb girth, so the calf muscle consistency should be assessed and measurement of the limb girth should be performed. Long-standing edema may become more resilient to palpation with “brawny” edema. Palpation also may reveal tenderness of the dilated veins. Active or healed ulcers are seen with more advanced disease. The venous ulcers usually occur in the medial supramalleolar area at the site of major perforating veins and the greatest hydrostatic pressure.A classic tourniquet (or Trendelenberg) test may be performed at bedside to help distinguish deep from superficial reflux.33 The test is performed with the patient lying down to empty the lower extremity veins. The upright posture is resumed after applying a tourniquet or using manual compression at various levels. In the presence of superficial disease the varicose veins will remain collapsed if compression is more proximal or cephalad to the point of reflux. With deep (or combined) venous insufficiency, the varicose veins will appear despite the use of the tourniquet or manual compression. Although useful to help determine the distribution of venous insufficiency, this test does not help determine the extent or severity of disease or provide information about the cause.The use of continuous wave Doppler has often been used to assist in the bedside evaluation.34 The presence and direction of flow in the veins (eg, common femoral vein) may be determined after maneuvers, such as the Valsalva maneuver or the sudden release of thigh or calf compression. Minimal signal should be detected toward the feet with these maneuvers. This technique also has been used to assess the great and short saphenous veins, although this is technically more difficult because of the lack of direct visualization. A limitation of this technique relates to the inability to insonate an individual vessel while flow is detected in any vessel within the path of the ultrasound beam. The lack of direct visualization of the vessels leaves uncertainty about the precise site of reflux.Differential DiagnosisThere is a broad differential for the common presenting complaint in limb swelling and discomfort seen with CVI. Acute venous problems such as DVT need to be excluded. Systemic causes of edema need to be considered such as heart failure, nephrosis, liver disease, endocrine disorders, or a side effect of a medication, such as calcium channel blockers, nonsteroidal antiinflammatory agents, and oral hypoglycemic agents. Other regional considerations include a ruptured popliteal cyst, soft tissue hematoma or mass, chronic exertional compartment syndrome, a gastrocnemius tear, or lymphedema. The use of examination findings and noninvasive testing allows for the proper diagnosis to be established.Noninvasive TestingVenous Duplex ImagingVenous duplex imaging is a well-established method to diagnosis DVT. The technique also is used to confirm the diagnosis of CVI and assess its etiology and severity.35,36 Venous duplex imaging combines B-mode imaging of the deep and superficial veins with pulsed Doppler assessment of flow. This provides information about the anatomic extent of disease involving the deep and superficial systems, as well as perforators. A standard venous duplex examination is performed to exclude DVT or venous obstruction. Venous compressibility complimented by flow characteristics is the key element of the examination to exclude thrombosis. The direction of flow may be assessed in a 30° reverse Trendelenberg position during provocative maneuvers, such as the Valsalva maneuver, or after augmenting flow with limb compression. The use of a cuff inflation-deflation method with rapid cuff deflation in the standing position is preferred to induce reflux.37The presence of reflux is determined by the direction of flow because any significant flow toward the feet is suggestive of reflux. The duration of reflux is known as the reflux time (replacing the commonly used valve closure time). A reflux time of >0.5 (or 1.0) second has been used to diagnosis the presence of reflux, although a more refined definition with a variable “cutoff” based on location has been suggested.38 The longer the duration of reflux or the greater the reflux time implies more severe disease. Other parameters such as the reflux velocity and even the calculated reflux volume have been used to assess the severity of reflux.39 These parameters, however, provide at best a semiquantitative assessment of the severity of disease. Importantly, there is a weak correlation of the severity of disease by duplex imaging with both plethysmographic techniques and clinical manifestations.Despite the limitation of the venous duplex reflux evaluation, it is considered the mainstay of the noninvasive evaluation of CVI. Venous duplex imaging may provide information about local valve function to construct an anatomic map of disease in terms of the systems and levels of involvement. This is often adequate information to help guide therapy, but if the contribution of the reflux to global hemodynamics is required, then further testing, such as plethysmographic techniques, may be considered.PhotoplethysmographyPhotoplethysmography (PPG) may be used to establish a diagnosis of CVI.40 Relative changes in blood volume in the dermis of the limb can be determined by measuring the backscatter of light emitted from a diode with a photosensor. A PPG probe is placed on the foot with maneuvers to empty the foot with calf muscle contraction. Then return of blood is detected by increased backscatter of light and the refill time may be calculated. The venous refill time is the time required for the PPG tracing to return to 90% of the baseline after cessation of calf contraction. The measure is not quantitative, but it has been shown to correlate with invasive measurements to diagnosis CVI.41 A venous refill time <18 to 20 seconds, depending on the patient’s position during the study, is indicative of CVI.40,41 A venous refill time >20 seconds suggests normal venous filling. The use of a tourniquet or low-pressure cuff allows for distinguishing superficial from deep venous disease. Correction of an abnormal refill time with a low-pressure thigh cuff is indicative of great saphenous vein disease. Failure to correct rapid venous refill time with a low-pressure cuff is indicative of deep venous disease. The test provides information about regional venous function, not about specific anatomic distribution. Although a shorter rapid refill time suggests more severe disease, there is a poor correlation of the severity of disease as assessed by other methods.32 Refill time depends on several factors, including the volume of reflux and the vessel diameter. The technique has been used to assess emptying of the venous system during calf muscle contraction and venous outflow.32 PPG may provide an assessment of the overall physiological function of the venous system, but it is most useful to determine the absence or presence of disease.Air PlethysmographyAir plethysmography (APG) has the ability to measure each potential component of the pathophysiological mechanisms of CVI—reflux, obstruction, and muscle pump dysfunction.42,43 Changes in limb volume are measured by air displacement in a cuff surrounding the calf during maneuvers to empty and fill the venous system. Venous outflow is assessed during rapid cuff deflation on an elevated limb that has a proximal venous occlusion cuff applied. The outflow fra