Where does venous reflux start?

Transcription

1 Where does venous reflux start? Nicos Labropoulos, PhD, Athanasios D. Giannoukas, MD, Kostas Delis, MD, M. Ashraf Mansour, MD, Steven S. Kang, MD, Andrew N. Nicolaides, MS, FRCS, John Lumley, MS, FRCS, and William H. Baker, MD, Maywood, Ill.; and London, United Kingdom Purpose: This study was designed to identify the origin of lower limb primary venous reflux in asymptomatic young individuals and to compare patterns of reflux with agematched subjects with prominent or clinically apparent varicose veins. Methods: Forty age- and sex-matched subjects with no symptoms (age, 15 to 35 years; 80 limbs; group A), 20 subjects (age, 19 to 32 years; 40 limbs) with prominent but nonvaricose veins (n = 26 limbs; group B), and 50 patients (age, 17 to 34 years; 100 limbs) with varicose veins (n = 64; group C) were examined with color flow duplex imaging. All proximal veins (above popliteal skin crease), superficial, perforator, and deep, in the lower limb were examined in the standing position, and all the distal veins in the sitting position. Patients who had a documented episode of superficial or deep vein thrombosis, previous venous surgery, or injection sclerotherapy were excluded from the study. Results: The prevalence of reflux in group A was 14% (11 of 80), in group B 77% (31 of 40), and in group C 87% (87 of 100). In more than 80% of limbs in the three groups, reflux was confined to the superficial veins alone. Deep venous reflux or combined patterns of reflux were uncommon even in group C. Reflux was detected in all segments of the saphen0us veins and their tributaries. In the 125 limbs that had superficial venous incompetence, the below-knee segment of the greater saphenous vein was the most common site of reflux (85, 68%), followed by the above-knee segment of greater saphenous vein (69, 55%) and the saphenofemoral junction (41, 32%). Nonsaphenous reflux was rare (3, 2.4%). Reflux in the lesser saphenous vein (21, 17%) was seen in all groups, whereas involvement of both greater and lesser saphenous veins (8, 6.4%) was seen in group C alone. The incidence of multisegmental reflux was significantly higher in group C (61 of 64, 95%) than in group A (two of 11, 18%) or group B (14 of 26, 54%). The prevalence of distal reflux was comparable in all groups. Conclusions: Primary venous reflux can occur in any superficial or deep vein of the lower limbs. The below-knee veins are often involved in asymptomatic individuals and in those who have prominent or varicose veins. These data suggest that reflux appears to be a local or multifocal process in addition to or separate from a retrograde process. (J Vasc Surg 1997;26: ) The pathogenesis of primary venous reflux and the etiologic mechanism of morphologic changes in From the Division of Peripheral Vascular Surgery, Loyola University Medical Center, Ma3~vvood, Ill. (Drs. Labropoulos, Mansour, Kang, and Baker); the Academic Vascular Surgery Unit, Imperial College School of Medicine at St. Mary's, London (Drs. Giannoukas, Delis, and Nicolaides); and the Professorial Surgical Unit, St. Bartholomew's Hospital Medical School, London (Drs. Giannoukas and Lumley). Presented at the Ninth Annual Meeting of the American Venous Forum, San Antonio, Tex., Feb , Reprint requests: Nicos Labropoulos, PhD, DIC, Loyola University Medical Center, Department of Surgery, 2160 S. First Ave., Maywood, IL Copyright 1997 by The Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter /97/$ /6/ the vein wall are largely unknown. The theory that suggests that valvular insufficiency is the principal cause for the development of varicosities 1 has often been disputed. 2-9 In addition, wall dilatation 2 and varicosities were found below competent valves, ~ whereas in a recent study changes in the collagen and elastin content were found to have no correlation with the site and function of valves, n The retrograde development of reflux ~2 requires incompetence or absence of valves above the saphenofemoral junction (SFJ), which in turn causes dilatation and valvular incompetence sequentially in the greater saphenous vein (GSV) and its tributaries. This theory has been found to be inaccurate in a number of patients in whom saphenous reflux exists without SFJ or saphenopopliteal junction (SPJ) incompetence. 13,14 The

2 Volume 26, Number 5 Labropoulos et al. 737 Table I. Patient demographic data No. of No. of Mean age Age range Group patients M/F limbs ++- SD (yr) (yr) A 40 20/ B 20* 9/ _ C / Total / *Twenty-six limbs (65%) had prominent veins. tsixty-four limbs (64%) had varicose veins. theory on the "weakening" of the venous wall 2~ as the initiating factor of reflux has gained support in many functional, 7,8,13,14 morphologic, 2,6,1,15-17 and biochemical studies. 9,11,18-23 Identification of reflux in asymptomatic and early stages of primary chronic venous disease (CVD) would increase our understanding about the development of this disorder. Therefore, this study was conducted to identify the origin of lower limb primary venous reflux in asymptomatic young individuals and to compare their patterns of reflux with those seen in age-matched subjects with prominent or varicose veins. PATIENTS AND METHODS Forty subjects with no symptoms (group A), 20 individuals with prominent but nonvaricose veins (group B), and 50 patients with primary varicose veins (group C) were examined with color flow duplex imaging. The details of each group of patients are shown in Table I. Patients from group B had dilated nonvaricose veins that had been present from 5 months to 3 years. None of these veins were transiently dilated as a result of temperature change or exercise. These patients were referred for mild symptoms, such as ache along the length of the prominent veins or for a purely cosmetic reason in some women. We believe that these patients represent an intermediate stage of early CVD, and they therefore were an important group of this study. All patients in group C belonged to CVD class 2 (varicose veins alone, without edema, sldn changes, or ulceration). 24 To allow valid comparisons among the three groups, all patients were age- and sex-matched, and none were obese. Twenty-one additional patients (15 with CVD class 2 and six with class 0 or 1) who had a documented episode of superficial (three patients) or deep vein thrombosis (three patients), previous venous surgery (eight patients) or injection sclerotherapy (seven patients) were excluded from the study. All lower limb superficial, perforating, and deep veins from groin to ankle were examined with color flow duplex imaging using a 5 MHz or 4.7 MHz linear Table II. Distribution of reflux in the three groups (n = 129) Group A Group B Group C No. of No. of No. of Site of reflux limbs % limbs % limbs % S P D S + P S + D P+D S+P+D Total S, Superficial; P, perforator; D, deep. array transducer (Ultramark 9 and HDI 3000; ATL, Bothell, Wash.), as described previously. 25 The SFJ, common femoral vein, superficial femoral vein, the above-lmee segment of GSV, and a high termination of LSV were investigated in the standing position. The SPJ, popliteal vein, anterior/posterior tibial vein, peroneal vein, gastrocnemial vein, LSV, and the below-lmee segment of the GSV were studied in the sitting position. Transverse and oblique scanning was used to evaluate the perforator veins along the course of the saphenous veins, their tributaries, and in areas where prominent or varicose veins were present. Valvular integrity was determined by distal compression of the limb. Because inward and outward flow is often seen in these veins, 26,27 reflux was considered to be present when net flow direction was towards the superficial system. A normal valvular closure time in the standing position is about 0.5 seconds28; reflux was considered to be present only if the duration of retrograde flow on Doppler tracings was longer than 0.5 seconds. Depending on its extent, reflux was separated as proximal if confined to above-knee veins, distal if confined to below-knee veins, or both proximal and distal. Reflux was also defined as isolated in one venous valve, in a single venous segment (segmental), or in more than one venous segments (multisegmental). Statistical analysis of our results was performed by means of the unpaired Student t test for the difference of the means, X 2 test, and Fisher's exact test when the expected value in any of the cells was -<5. Statistical significance was set at a p value less than RESULTS Patients in all groups were comparable for age and sex (p > 0.2). The prevalence of reflux was significantly higher in groups B (31 of 40, 77%) and C (87 of 100, 87%) compared with group A (11 of

3 738 Labropoulos et al. November 1997 Table III. Distribution and extent of reflux in group A (n = 11") Total Site of reflux Extent of reflux (%) SFI + 1 (9.1) GSVak (27.6) GSVbk (45.5) LSVak (9.1) SPJ + 0 LSV (9.1) No. of limbs % GSVak, Above-knee segment of greater saphenous vein; GSVbk, below-knee segment of greater saphenous vein; LSVak, aboveknee segment of lesser saphenous vein. *Two limbs (18.2%) had deep venous reflux; one in the popliteal vein and one in the medial gastrocnemius vein. Presence of reflux is indicated with plus signs. Table IV. Distribution and extent of reflux in group B (n = 26*) siu of reflux Extent of reflux Total (%) SFJ (23.1) GSVak ) GSVbk (50) LSVak (7.7) SPJ (3.8) LSV (15.4) No. of limbs % *Two limbs (7.7%) had deep venous reflux; onein the common femoral vein and one in the medial gastrocnemius vein. Another limb (3.8%) had nonsaphenous reflux in a superficial posteromedial thigh vein arising from a vulvar vein. Presence of reflux is indicated with plus signs. 80, 14%; X 2 = 44.9, p < ; and X 2 = 93.2, p < , respectively). The overall contribution of reflux in the superficial, perforator, and deep veins is seen in Table II. Reflux confined to the superficial veins alone (108 of 129, 84%) or in combination with the perforator or deep veins (125 of 129, 97%) was most frequent in all three groups (superficial versus perforating or deep reflux, p = at least for all comparisons). Nonsaphenous superficial reflux was rare (three of 129, 2.4%). The prevalence of reflux in the deep or perforator veins alone or in any combination with the superficial system was less than 19.5% in each group. The overall prevalence of deep venous reflux was small (13 of 129, 10%) and was mainly confined distally (10 of 13, 77%). The prevalence of combined patterns of reflux among all limbs was also low (17 of 129, 13%). Fifteen incompetent perforator veins were detected in 10 limbs in groups B and C. Twelve perforator veins were found in the calf, one in the knee area, and two in the thigh. Among the contralateral limbs with no prominent or varicose veins, reflux was found in 36% (five of 14) and 50% (23 of 46), respectively (p = 0.53). The distribution and extent of reflux in the three groups are shown in Tables III, IV, and V. Many different patterns of extent of reflux were found. The pattern in group C was more complex than either group A or B. In limbs with segmental reflux alone, the below-knee segment of the GSV was most often involved. Overall, as seen in Table VI, reflux in the below-knee segment of the GSV was the most common site (85 of 125, 68%). Reflux in the posterior arch vein was detected in 80 limbs (64%). Incompetence was often detected in the above-knee segment of the GSV (55%), but only a third of limbs had SFJ involvement. Reflux in the LSV was less prevalent (14%), as was the contribution of the SPJ (6%). Combined incompetence in both the GSV and LSV was found only in group C (6%). The incidence of multisegmental reflux was significantly higher in group C (61 of 64, 95%) than in group A (two of 11, 18%; p < ) or group B (14 of 26, 54%; p < ), as seen in Table VII. The prevalence of multisegmental reflux in the contralateral limbs without prominent or varicose veins was also higher in group C (18 of 23, 78%) than in group B (two of five, 40%), but not statistically significant (p = 0.12). The prevalence of distal reflux was comparable in all groups (p > 0.2 for all comparisons). DISCUSSION Because the venous pressure in the lower limbs is increased due to hydrostatic reasons in the upright posture, it has been traditionally believed that reflux develops in a retrograde fashion. In primary venous disease, where the valves are intact, it could be assumed that incompetence or absence of the iliac and common femoral valves are the initiating factors for a retrograde development of reflux. Although such pathophysiologic events have been reported, 1,12,29 the majority of the literature counteracts this hypothesis. Many functional, 7,8,1s,14 morphologic, 2,6,1,1s-17 and biochemical 9,11,1s23 studies have shown that venous wall changes can occur in any segment irrespective of the site and function of the valves. Color flow duplex imaging, which is currently considered the method of choice for detecting venous reflux, 3 33 has enabled us to evaluate the early stages of CVD and enhance our understanding of its development.

4 Volume 26, Number 5 Labropoulos et al. 739 Table V. Distribution and extent of reflux in group C (n = 64*) Site of Total reflux Extent of reflux (%) SFJ (39.1) GSVak (65.6) GSVbk (71.9) LSVak (7.8) SPJ (9.4) LSV (20.3) No. of limbs % *Two limbs (3.1%) had superficial nonsaphenous venous reflux; one in a posterolateral thigh vein arising from the gluteal area and one in a vulvar vein. Presence of reflux is indicated with plus signs. Table VI. Overall prevalence of superficial venous reflux in individual vein segments (n = 125) Site of reflux No. of limbs % SFI 4i 32.8 GSVak GSVbk LSVak SPJ LSV SFI vs GSVak: X 2 = 11.8, p = SFI vs GSVbk: X 2 = 29.6, p < GSVak vs GSVbk: 2 = 3.8, p = GSVak + LSVak vs GSVbk + LSV: X 2 = 14.2, p = The results of our study showed that reflux can occur in any vein segment irrespective of the disease stage. Such a finding is evidence against retrograde development of reflux. In fact, distal reflux was more often found in the superficial, perforator, and deep veins in all three groups, which indicates a possible antegrade progression of the disease in a considerable number of patients. However, multifocal, ascending, or both descending and ascending development of reflux could occur, and therefore such questions on the development of reflux Can be answered only by prospective longitudinal studies. The local development of the disease would suggest that there are susceptible sites, where wall changes, hemodynamic changes, or both occur to initiate reflux. Family history, and hence a genetic component, is the strongest risk factor associated with CVD. 29,34 Other risk factors such as occupation, posture, obesity, and height might predispose the development of reflux, but this association in most studies has been weak The distal part of GSV and its tributaries were most frequently involved. At this level, the posterior Table VII. Extent of reflux in relation to number of venous segments involved in three different groups and uninvolved contralateral limbs of group B and C Reflux (n/%) Proximal + Segmental Multisegmental Proximal Distal distal Group A 9/81.8 2/18.2 3/27.3 7/63.6 1/9.1 Group B 12/ /53.8 8/30.8 9/34.6 9/34.6 Group C 3/4.7 61/ / / /62.5 Group B* Group C1" This is the only table in which the uninvolved contralateral limbs are being included. *Five contralateral limbs in group B had reflux in the absence of prominent veins. 1"Twenty-three contralateral limbs in group C had reflux in the absence of varicose veins. arch vein (vein of Leonardo) was the most common site of reflux among all veins, Clinically, varicosities are most often seen in the medial and posteromedial aspect of the calf, and our findings explain this observation. Several studies have shown that distal reflux is essential for developing signs and symptoms of CVD. 14,25,27,39,40 Because the prevalence of distal reflux was comparable among the three groups, other factors, such as the extent, 14,27,4~ the pattern, 27,41-49 and the amount of reflux, s 52 the time that the disease has been present, s3 the rate of disease progression, s3 and the efficiency of the calf muscle pump, a4 may be responsible for the development of signs and symptoms of CVD. Indeed, the prevalence of combined proximal and distal reflux was significantly increased in group C, whereas reflux confined to both GSV and LSV was seen only in this group. Deep venous reflux alone was uncommon. This finding was expected because other studies on CVD

5 740 Labropoulos et al November 1997 classes 4 to 6 that did not exclude patients with a past DVT have also reported a low prevalence of isolated dee p venous reflux, ranging from 2.1% to 15%. 27,42,46 However, the total contribution of deep venous reflux in this study was only 10% (13 of 129) in contrast to that reported (28% to 70%) in CVD classes 4 to On the other hand, the overall involvement of the superficial system was much higher than the deep in any CVD class (from 79% lowest reported prevalence in class 6 to 100% in class 2), 42-49'53 indicating that reflux originates most often in the superficial veins and contributes significantly in the development of signs and symptoms. SFJ and SPJ ligation with or without stripping of the GSV and LSV are the most common operations performed in patients with varicose veins. Recent studies have shown that ligation of the junctions without stripping results more often in residual or recurrent varicose veins. 5s-57 One reason for the higher failure rate of junctional ligation may be that saphenous reflux often exists in the absence of SFJ or SPJ incompetence. 13,14 Indeed, in our study about two thirds of the limbs had no SFJ or SPJ reflux. Because the prevalence of the SFJ and SPJ reflux is higher in CVD classes 4 to 6, 27,41,42,46 this may also indirectly indicate an ascending progression of venous reflux, as previously suggested) 3,58 Furthermore, in about 6% of the limbs reflux was detected in the above-knee segment of LSV with or without the involvement of SPJ, suggesting an additional reason of ligation failures. The prevalence of reflux was also high in the contralateral asymptomatic limbs of groups B and C, and this is in accord with the findings of previous reports.59,6 The distribution and extent of reflux was similar in these limbs, with a high prevalence of distal reflux and limited involvement of the SFJ and the SPJ, suggesting an ascending or multifocal process of reflux. CONCLUSION In young volunteers without symptoms and patients with early stages of CVD, the development of reflux appears to most often be a local process that can develop in any part of the lower limb venous system, particularly in the superficial veins and often in the below-knee segment of the GSV. This may indicate an ascending progression, multicentric progression, or both, of reflux in addition to or separate from gravitational retrograde development. Deep venous reflux alone or in combination with the superficial and perforator vein incompetence is uncommon in clinical class 0 to 2 patients. 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7 742 Labropoulos et al. November 1997 vestigation of the pattern and extent of reflux with color flow duplex imaging. Surgery 1996;119: Labropoulos N, Delis KT, Nicolaides AN. Venous reflux in symptom-free vascular surgeons. J Vasc Surg 1995;22: Skladany M, Schanzer H. Increased arterial inflow in extremities with chronic venous insufficiency: an important and unappreciated hemodynamic parameter. Surgery 1996;120: Bradbury AW, Brittenden J, Allan PL, Ruckley CV. Comparison of venous reflux in the ~.ffected and nonaffected leg in patients with unilateral venous ulceration. Br J Surg 1996;83: Submitted Feb. 24, 1997; accepted Aug. 1, N 'ow you can have easy access to research information with the 12-year cumulative author and subject index to Volumes 1-22 of Journal of Vascular Surgery. The Cumulative Index is your comprehensive reference guide, including a list of every article in the Journal from 1984 through All articles are indexed both by subject and by author. The Cumulative Index features: Offset and bold Subject Headings that make searching for subject entries easier Subject Entries containing complete article title, author(s), year of publication, volume, and page Author Entries listing author(s), article title, author-to-author referral, year of publication, volume, and page!~i~~~::~~,~i~:#~ : : 3: " ~ " "~:i; i ~ ~~ '"::~':~=. i ~ i~'::"./n v:::'~~:.'~:~:=~;!~!!i!/i~!il;~li~!~iii:i!! ::~'~ ~ i ~ i!~ii~i!iii!! ~v A Mosby I've indicated m F method of payment below. All prices include shipping. O $75.00 U.S O $85.60 Canada* 121 $80.50 International * Includes Canadian GST. Payment must accompany your order. O Check enclosed (U.S. funds, payable to Journal of Vascular Surgery) O MasterCard UI VISA O Discover Credit Card # Signature Name Institution Address City ZIP Country Exp. Date State ~" To order, just call Or return coupon to: Mosby-Year Book, inc. Journal Subscription Services ~-~ Outside the U.S.: Westline Industrial Dr. Fax: I 158 St. Louis, M U.S.A, "~... J