Reflux probability in saphenous veins of women with different degrees of chronic venous insufficiency

Métodos: Um total de 1.184 membros inferiores de 672 mulheres foram estudados pela ultra-sonografia vascular com Doppler colorido e avaliados pela classificação clínica, etiológica, anatômica e patológica (CEAP). As extremidades foram agrupadas de acordo com a gravidade da insuficiência venosa em graus leve (CEAP C1-C2), moderado (CEAP C3) e grave (CEAP C4-C6). Para avaliar a classificação clínica CEAP na predição do padrão de refluxo, utilizou-se o Teorema de Bayers. Para avaliar associação entre classificação clínica CEAP e padrões de refluxo com ou sem comprometimento das junções das safenas, utilizou-se o teste qui-quadrado (p < 0,05).


Introduction
Presence of chronic venous insufficiency (CVI) is easily identified by the symptoms present by the patient and by inspection of lower limbs.Physical examination can provide information about presence, location and extension of valve insufficiency.However, accurate identification of reflux sources in the venous system is only possible through investigation by complementary diagnostic means.Such complementary information is important for diagnosis improvement, for treatment planning, as well as for a better understanding of the disease natural history.Color-flow Doppler ultrasound (CFDU) is able to accurately identify distribution and extension of venous reflux.This examination has become a choice method for peripheral venous assessment. 1,2DU allows identification of reflux patterns and preoperative mapping for varicose vein surgery.Presence of reflux in the saphenofemoral junction (SFJ) and saphenopopliteal junction (SPJ) is important data for surgical planning.Recent studies carried out with CFDU showed that, in most patients with CVI, SFJ and SPJ are competent.[5][6][7] By adopting the clinical, etiologic, anatomic and pathologic classification (CEAP), it was possible to study specific groups of patients with the same evolution stage of CVI.Such approach allows a more precise definition of the guidelines to treat these patients. 8is study aims at identifying probability of different reflux patterns in great saphenous veins of women with varied degrees of CVI and assessing whether SFJ and SPJ impairment is associated with clinical severity of venous insufficiency.

Method
Only female patients were included in the study, with signs or symptoms of CVI, primary etiology, resulting from valve insufficiency (reflux), consecutively assessed by CFDU.
Male patients were excluded, as well as women with previous history of deep venous thrombosis or varicose vein surgery and women with CVI resulting from congenital vascular malformation.
This study was approved by the Research Ethics Committee in human beings of Pontifícia Universidade Católica do Paraná (PUCPR) under protocol number 876.

Clinical assessment
Lower limbs were clinically classified when the examination was performed by the vascular sonographer, according to CEAP classification 8

Color-flow Doppler ultrasound assessment
The patients were assessed using a color-flow Doppler ultrasound device Siemens, ® model Elegra, ® initially to exclude recent or previous venous thrombosis, with the patient in a supine position, through cross-sectional ultrasound sections in B mode and maneuvers of vein compressibility, using low frequency transducers (5 MHz).
The study of great and short saphenous veins was performed with the patient standing erect, with high frequency transducer (7 MHz), to obtain vein images in longitudinal ultrasound sections in B mode.With the aid of color-flow imaging, reflux was assessed using Valsalva's maneuver and manual muscle compression distal to the transducer.Quantification of reflux of saphenous veins was based on van Bemmelen's criteria, 9 with peak reflux equal or higher than 30 cm/s being considered significant or upper reflux duration longer than half a second.

Assessment of reflux patterns in great and short saphenous veins
Based on detection of reflux in great and short saphenous veins, six reflux patterns were identified: 4 -Perijunctional reflux pattern: characterized by reflux in the SFJ or SPJ, drained by tributary veins of the SFJ or SPJ, with maintenance of valve competence in the main saphenous vein.
-Proximal reflux pattern: characterized by reflux in the SFJ or SPJ and in the main saphenous vein, originated directly from the femoral or popliteal veins through the SFJ or SPJ, drained by superficial tributary veins or perforating vein in the topography of the leg and thigh, with maintenance of valve competence in the rest of the saphenous vein.
-Distal reflux pattern: characterized by absence of reflux in the SFJ or SPJ and in the proximal main saphenous vein.Presence of reflux in the saphenous vein until the perimalleolar region, caused by superficial tributary vein or perforating vein in the topography of the leg or thigh.
-Segmental reflux pattern: characterized by a single segment of the saphenous vein with reflux, in the topography of the leg and/or thigh, with no involvement of the SFJ or SPJ, caused and drained by tributary or perforating vein.
-Multisegmental reflux pattern: characterized by two or more segments of the saphenous vein with reflux in the topography of the leg and/or thigh.This reflux pattern is subdivided into multisegmental with reflux in the SFJ or SPJ and multisegmental with no reflux in the SFJ or SPJ.
-Diffuse reflux pattern: characterized by reflux in the whole main saphenous vein extension, from the SFJ or SPF to the perimalleolar region.

Statistical analysis
To assess CEAP clinical classification in predicting reflux patterns, Bayes' theorem was used, with the aim of estimating probability for each reflux pattern, according to clinical classification.Probabilities for each reflux pattern, as well as conditional classifications of mild, moderate or severe for each reflux pattern were estimated by results in the study sample.
The chi-square test was used to evaluate the association between CEAP clinical association and reflux patterns with and without SFJ or SPJ involvement.P values ≤ 0.05 were defined as statistically significant.

Results
A total of 1,184 lower limbs were assessed in 672 female patients, aged between 17-87 years, mean of 41 years.Of the 1,184 lower limbs assessed, 601 were right, 583 were left and 158 were bilateral examinations.
Among limbs with reflux, presence of reflux in the SFJ was identified in only 12.67%.Considering the association between the CEAP classification and SFJ insufficiency, there was statistically significant difference (p = 0.0009) between presence of SFJ reflux and later stages of the disease.The percentage of great saphenous veins with SFJ reflux was lower in cases with mild CEAP classification (10.65%), increasing in cases of moderate (17.95%) and severe (25%) classification.

Short saphenous vein assessment
Among 1,184 limbs assessed, 79.81% had no short saphenous vein reflux.In lower limbs with short saphenous vein reflux, 41% had segmental reflux pattern.
Among cases with reflux, presence of SPJ impairment was identified in only 5.66%.Considering the correlation between CEAP classification and SPJ insufficiency, there was a statistically significant difference (p = 0.0006) between SPJ insufficiency and later stages of CVI.The percentage of short saphenous veins with SPJ reflux was lower in limbs with mild CEAP classification (4.19%), increasing in cases of moderate (8.06%) and severe (17.86%) classification (Table 5).

Discussion
CVI is a prevalent disease with relevant social consequences, accounting for high costs with treatment and absenteeism, especially in cases of venous ulcer.It is estimated to affect about 5-20% of the adult population in developed countries; of these, 3.6% are cases of active or healed venous ulcer. 10,11e most widely used classification for CVI clinical assessment is the CEAP classification.Stratification of patients in different clinical classes allows specific populations with CVI to be studied with regard to their peculiarities.However, issues related to the origin of reflux in the superficial venous system and the relationship between CVI clinical severity and reflux sources still have to be better investigated.
The Edinburg Vein Study assessed, among the general population, 1,566 people aged between 18-64 years, of whom 124 had complaints compatible with CVI.Prevalence of the disease in this population was 9.4% in women and 6.6% in men, and approximately 1/3 of these patients had independent reflux in the superficial venous system.Also in that study, the higher CVI severity, the higher the incidence of reflux. 12DU is considered the choice method to assess venous reflux, since it allows detecting and measuring reflux, providing anatomic and functional details of veins, as well as identifying reflux patterns, their main sources and draining points, and allowing venous screening. 13All those characteristics allow the patient to have both individualized diagnosis and treatment.
Venous reflux can originate from valve insufficiency in communication points between the deep and superficial venous system (SFJ, SPJ and direct perforating veins) or from independent reflux sources, such as pudendal, perineal, gluteal and indirect perforating veins (with no direct communication with saphenous veins).Labropoulos et al. 13 assessed the superficial venous system of 860 patients using CFDU and observed presence of reflux in superficial tributary veins originated form independent source of refluxes of saphenous veins in 9.7% of cases.
In a similar study, Seidel et al. 14 studied the sources of superficial reflux of 1,712 patients with normal saphenous veins and found 43% of independent reflux of saphenous veins.According to the authors, a likely explanation for the higher incidence of reflux in relation to the previous study could be related to the individual characteristics of assessed populations.
In this study, sources of independent reflux of great and short saphenous veins were assessed, as well as their relation with CVI severity, therefore without any attempt of identifying independent sources of reflux.Reflux patterns were identified in short and great saphenous veins and SFJ and SPJ impairment as direct sources of reflux.
Identification of reflux patterns in saphenous veins allows individual diagnosis and treatment for different CVI classes.However, there is no standardization in the literature as to how superficial reflux can be identified.Based on the classification adopted in this study, independent segmental reflux was the most frequently found, both in the great (35%) and short (8%) saphenous vein.Such data are corroborated by Labropoulos et al.'s findings, 5 who identified 68% of reflux located in infrapatellar segments of the great saphenous vein, followed by 55% of reflux located in suprapatellar segments of the great saphenous vein.SFJ and SPJ incompetence, according to those authors, was detected in 32 and 6% of assessed limbs, respectively.
As to SFJ and SPJ involvement in the genesis of saphenous vein reflux, Jutley et al., 6 in a retrospective study of 223 limbs of 176 patients with primary varicose veins, found SFJ and SPJ incompetence in 30 and 9%, respectively.On the other hand, Wills et al. 15 studied 315 limbs of 188 patients with complaints of CVI and found greater involvement of SFJ and SPJ in, respectively, 63 and 19% of lower limbs.However, it should be stressed that, in the study by Wills et al., patients with previous treatment of lower limb varicose veins (38%) were included.
Abu-Own et al., 16 in a study of 190 limbs, and Cooper et al., 17 in a study of 706 limbs, reported change in SFJ in 67 and 54% of cases, respectively.In both studies, patients of both genders were assessed, mean age of 48 and 50 years, with primary varicose veins.
In the present study, SFJ and SPJ impairment in 1,184 assessed limbs was, respectively, 12.6 and 5.6%.Explanation for the lower incidence of SFJ and SPJ reflux could be related to selection of populations in different studies.In selection criteria, only women were included, with primary CVI, no history of varicose vein surgery or deep venous thrombosis.Therefore, a specific population of patients was studied, different from other authors who selected mixed populations of women, men, patients with previous history of thrombosis or surgery, among other factors. 5,6,15e results of this study show that, different from what was thought, reflux in the superficial venous system is not predominantly originated from the SFJ and SPJ, but in most cases in independent or multiple segments, along the whole extension of saphenous vein, caused by tributary veins or direct perforating veins.It was observed that, as CVI worsens clinically, the probability of SFJ and SPJ reflux increases, since there was a significant difference in prevalence of SFJ and SPJ insufficiency in later stager of the disease.
In this study, only 2.37% (n = 28) of lower limbs were in more advanced stages of CVI (CEAP classes C 4 , C 5 and C 6 ).Prevalence of lower limbs in CEAP C classes 4 , C 5 and C 6 found in this study corroborates the findings in the literature, which report prevalence of 1 to 3.6% of active or healed venous ulcer cases in patients with CVI. 10,11wever, despite that large difference as to prevalence of lower limbs in CEAP classes C 1 , C 2 and C 3 , statistical analysis showed a tendency of greater probability of SFJ and SPJ reflux in more advanced stages of venous disease. 10,11e findings of this research reinforce the need of individual approach to different CVI degrees in specific populations.Women in different clinical classes can present peculiar characteristics when compared between themselves or with male populations.Women with any degree of CVI should have a segmental reflux screened in CFDU examination, since this pattern has the highest probability of being responsible for clinical findings.In addition, the low probability of SFJ and SPJ reflux has a great preservation potential of saphenous veins in patients with indication of varicose vein surgery.
in seven clinical classes: C 0 = absence of visible or palpable signs of venous disease; C 1 = telangiectasia or reticular vein; C 2 = varicose veins; C 3 = edema; C 4 = skin changes resulting form venous disease (pigmentation, eczema, lipodermatosclerosis); C 5 = skin changes with healed ulcer; C 6 = skin changes with active ulcer.To evaluate association between SFJ and SPJ insufficiency and CVI clinical severity, lower limbs were divided into three evolutionary stages: mild (CEAP classes C 1 and C 2 ), moderate (CEAP class C 3 ) and severe (CEAP classes C 4 to C 6 ), based on natural history of CVI, similar to the classification suggested by Porter et al.8 Probability of finding segmental reflux in the great saphenous vein in classes C 1 , C 2 , C 3 , C 4 , C 5 and C 6 is, respectively, 30.21, 35.97, 38.10, 42.86, 28.57 and 28.57% (Table If clinical class is C 1 , then the probability the patient has of presenting short saphenous vein reflux is 92.01%.If it is C 2 and C 4 , the probability of the patient presenting segmental reflux pattern in the short saphenous vein is 10.25% and 19.05%, respectively.If clinical class is C 3 , then the probability the patient has of presenting distal reflux in the short saphenous vein is 10.26%.For classes C 5 and C 6 , the patient has the same probability of presenting diffuse and distal reflux and absence of reflux (28.57%).