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Where does venous reflux start?
Where does venous reflux start? Nicos L a b r o p o u l o s , P h D , Athanasios D. G i a n n o u k a s , M D , Kostas Delis, M D , M. A s h r a f M a n s o u r , M D , Steven S. K a n g , M D , A n d r e w N. Nicolaides, MS, F R C S , J o h n Lumley, MS, F R C S , and William H . Baker, M D , 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 o f 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;26:736-42.)
The pathogenesis o f primary venous reflux and the etiologic mechanism o f morphologic changes in From the Division of Peripheral VascularSurgery, LoyolaUniversity Medical Center, Ma3~vvood, Ill. (Drs. Labropoulos, Mansour, Kang, and Baker); the AcademicVascular 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 AmericanVenous Forum, San Antonio, Tex., Feb. 20-24, 1997. Reprint requests: Nicos Labropoulos, PhD, DIC, LoyolaUniversity Medical Center, Department of Surgery,2160 S. First Ave., Maywood, IL 60153-3304. Copyright © 1997 by The Societyfor VascularSurgeryand International Society for Cardiovascular Surgery, North American Chapter. 0741-5214/97/$5.00 + 0 24/6/85267 736
the vein wall are largely unknown. The theory that suggests that valvular insufficiency is the principal cause for the development o f 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 o f valves, n The retrograde development o f reflux ~2 requires incompetence or absence o f 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 o f patients in w h o m saphenous reflux exists without SFJ or saphenopopliteal junction (SPJ) incompetence. 13,14 The
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Table I. Patient demographic data Group
No. of patients
M/F
No. of limbs
Mean age ++-SD (yr)
Age range (yr)
A B C Total
40 20* 501110
20/20 9/11 23/27 52/58
80 40 100 220
26.2 + 4 27.8 _+ 3 29.6 + 3
15-35 19-32 17-34
*Twenty-six limbs (65%) had prominent veins. tSixty-four limbs (64%) had varicose veins.
theory on the "weakening" o f 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 o f reflux in asymptomatic and early stages o f primary chronic venous disease (CVD) would increase our understanding about the development o f this disorder. Therefore, this study was conducted to identify the origin o f lower limb primary venous reflux in asymptomatic young individuals and to compare their patterns o f reflux with those seen in age-matched subjects with prominent or varicose veins.
PATIENTS A N D M E T H O D S 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 o f 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 o f 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 o f 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 M H z or 4.7 M H z linear
737
Table II. Distribution o f reflux in the three groups (n = 129) Group A Site of reflux S P D S+ P S+ D P+D S+P+D Total
Group B
Group C
No. of limbs
%
No. of limbs
%
No. of limbs
%
9 0 2 0 0 0 0 11
81.8 0 18.2 0 0 0 0 100
25 0 2 2 2 0 0 31
80.6 0 6.4 6.4 6.4 0 0 100
74 0 0 6 5 0 2 87
85.1 0 0 6.9 5.7 0 2.3 100
S, Superficial; P, perforator; D, deep.
array transducer (Ultramark 9 and H D I 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 o f 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 o f our results was performed by means of the unpaired Student t test for the difference of the means, X2 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 0.05. RESULTS Patients in all groups were comparable for age and sex (p > 0.2). The prevalence o f reflux was significantly higher in groups B (31 o f 40, 77%) and C (87 of 100, 87%) compared with group A (11 o f
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Labropoulos et al.
Table III. Distribution and extent of reflux in group A (n = 11") Site of reflux SFI + GSVak GSVbk LSVak SPJ LSV No. of limbs 1 % 9.1
Extent of reflux +
+ +
+ +
+ + +
2 18.2
4 36.4
1 0 0 0 9.1
+ 1 9.1
Table IV. Distribution and extent of reflux in group B (n = 26*) Total (%)
siu of
1 (9.1) 3 (27.6) 5 (45.5) 1 (9.1) 0 1 (9.1) 9 81.8
SFJ GSVak GSVbk
reflux
knee 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.
80, 14%; X2 = 44.9, p < 0.0001; and X2 = 93.2, p < 0.0001, 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 = 0.0089 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
+
+ +
+ +
LSVak
Total (%) + + +
+
SPJ LSV No. of 1
+ + 2
4
1
02
2
4
7 (23.1) 13 50) 13 (50)
+ +
+
2 (7.7)
+ + + 5 1 1
1 (3.8) 4 (15.4) 23
limbs %
GSVak, Above-knee segment of greater saphenous vein; GSVbk, below-knee segment of greater saphenous vein; LSVak, above-
Extent of reflux
3.8 7.7 15.4 3.8 0 7.7 7.7 11.5 19 3.8 3.8
88
*Two limbs (7.7%) had deep venous reflux; o n e i n 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.
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 < 0.0001) or group B (14 of 26, 54%; p < 0.0001), 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.
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T a b l e V. D i s t r i b u t i o n a n d e x t e n t o f reflux in g r o u p C (n = 64*) Site of reflux SFJ GSVak GSVbk LSVak SPJ LSV No. of limbs %
Total (%)
Extent of reflux +
+ +
+
+
+
+
+ + +
+ + +
+ +
+ +
+
0
4
10
1
0
+ 1
0
6.3
14.1
1.6
0
1.6
4
1
18
+ + 2
6.3
1.6
26.6
3.1
+ + 2 4.7
96.9
+
+ +
25 (39.1) 42 (65.6) 46 (71.9) 5 (7.8) 6 (9.4) 13 (20.3) 62
+
11
+ 1
+ 3
+ 2
+ + + 2
17.2
1.6
4.7
3.1
3.1
*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.
T a b l e V I . Overall prevalence o f superficial v e n o u s reflux in individual vein s e g m e n t s (n = 125) Site of reflux
No. of limbs
%
SFI GSVak GSVbk LSVak SPJ LSV
4i 69 85 8 8 18
32.8 55.2 68 6.4 6.4 14.4
SFI vs GSVak: X2 = 11.8, p = 0.0006. SFI vs GSVbk: X2 = 29.6, p < 0.0001. GSVak vs GSVbk: ×2 = 3.8, p = 0.051. GSVak + LSVak vs GSVbk + LSV: X2 = 14.2, p = 0.0002.
T h e results o f o u r s t u d y s h o w e d t h a t reflux can o c c u r in any vein s e g m e n t irrespective o f the disease stage. Such a finding is evidence against r e t r o g r a d e d e v e l o p m e n t o f reflux. I n fact, distal reflux was m o r e o f t e n f o u n d in t h e superficial, p e r f o r a t o r , a n d d e e p veins in all t h r e e g r o u p s , w h i c h indicates a possible a n t e g r a d e p r o g r e s s i o n o f the disease in a considerable n u m b e r o f patients. H o w e v e r , multifocal, asc e n d i n g , o r b o t h d e s c e n d i n g a n d a s c e n d i n g developm e n t o f reflux c o u l d occur, a n d t h e r e f o r e such questions o n the d e v e l o p m e n t o f reflux Can be ans w e r e d o n l y by prospective l o n g i t u d i n a l studies. T h e local d e v e l o p m e n t o f t h e disease w o u l d s u g g e s t t h a t t h e r e are susceptible sites, w h e r e wall changes, hem o d y n a m i c changes, o r b o t h o c c u r t o initiate reflux. F a m i l y history, a n d h e n c e a genetic c o m p o n e n t , is t h e s t r o n g e s t risk factor associated w i t h C V D . 29,34 O t h e r risk factors such as o c c u p a t i o n , p o s t u r e , o b e sity, a n d h e i g h t m i g h t p r e d i s p o s e the d e v e l o p m e n t o f reflux, b u t this association in m o s t studies has b e e n w e a k . 35-38
T h e distal part o f G S V a n d its tributaries were m o s t f r e q u e n t l y involved. A t this level, t h e p o s t e r i o r
T a b l e V I I . E x t e n t o f reflux in relation to n u m b e r o f v e n o u s s e g m e n t s involved in t h r e e different g r o u p s a n d u n i n v o l v e d contralateral limbs o f g r o u p B a n d C Reflux (n/%) Segmental Multisegmental Proximal Distal Group A Group B Group C Group B* Group C1"
9/81.8 12/46.2 3/4.7 3 5
2/18.2 14/53.8 61/95.3 2 18
3/27.3 8/30.8 10/15.6 1 4
Proximal + distal
7/63.6 1/9.1 9/34.6 9/34.6 14/21.9 40/62.5 3 1 11 8
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 o f L e o n a r d o ) was t h e m o s t c o m m o n site o f reflux a m o n g all veins, Clinically, varicosities are m o s t o f t e n seen in t h e m e d i a l a n d p o s t e r o m e d i a l aspect o f the calf, a n d o u r findings explain this observation. Several studies have s h o w n t h a t distal reflux is essential for d e v e l o p i n g signs a n d s y m p t o m s o f CVD. 14,25,27,39,40 Because t h e prevalence o f distal reflux was c o m p a r a b l e a m o n g the t h r e e g r o u p s , o t h e r factors, such as the e x t e n t , 14,27,4~ t h e pattern, 27,41-49 a n d t h e a m o u n t o f reflux, s°52 t h e t i m e t h a t the disease has b e e n present, s3 the rate o f disease p r o g r e s s i o n , s3 a n d t h e efficiency o f the calf muscle p u m p , a4 m a y be responsible for the d e v e l o p m e n t o f signs a n d s y m p t o m s o f C V D . I n d e e d , the prevalence o f c o m b i n e d p r o x i m a l a n d distal reflux was significantly increased in g r o u p C, whereas reflux c o n f i n e d to b o t h G S V a n d L S V was seen only in this g r o u p . D e e p v e n o u s reflux alone was u n c o m m o n . This finding was e x p e c t e d because o t h e r studies o n C V D
740
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Labropoulos et aL
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 6. 41-49 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 o f 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. The extent of
reflux is associated with the clinical severity in the
early stages of CVD. REFERENCES 1. Moore HD. Deep venous valves in the aetiology of varicose veins. Lancet 1951;2:7-10. 2. Cotton LT. Varicose veins: gross anatomy and development. Br J Surg 1961;48:589-98. 3. Sverjcar J, Prerovsky I, Linhart J, Krume J, Beckova B. Content of collagen, elastin and hexosamine in primary varicose veins. Clin Sci (Colch) 1963;24:325-30. 4. Zsoter T, Chronin RF. Venous distensibility in patients with varicose veins. Can Med Assoc J 1966;94:1293-7. 5. Zsoter T, Moore S, Keon W. Venous distensibility in patients with varicosities: in vitro studies. J Appl Physiol 1967;22: 505-8. 6. Jumkova Z, Milenkov C. Ultrastructural evidence for collagen degradation in the walls of varicose veins. Exp Mol Pathol 1982;37:37-47. 7. Psaila IV, Melhuish J. Viscoelastic properties and collagen content of the long saphenous vein in normal and varicose veins. Br J Surg 1989;76:37-40. 8. Clarke H, Smith SRG, Vasdelds SN, Hobbs JT, Nicolaldes AN. Role of venous elasticity in the development ofvaticose veins. Br J Surg 1989;76:577-80. 9. Maurel E, Azema C, Deloy J, Bouissou H. Collagen of the normal and varicose human saphenous vein: a biochemical study. Clin Claim Acta 1990;193:27-38. 10. Rose SS, Ahmed A. Some thoughts on the aetiology of varicose veins. J Cardiovasc Surg (Torino) 1986;27:534-43. 11. Venruri M, Bonavina L, Annoni F, Colombo L, Butera C, Perachia A. Biochemical assay of collagen and elastin in the normal and varicose vein wall. J Surg Res 1996;60:245-8. 12. Ludbrook J, Beale G. Femoral venous valves in relation to varicose veins. Lancet 1962;1:79-81. 13. Abu-Own A, Scurr JH, Coleridge Smith PD. Saphenous vein reflux without incompetence at the saphenofemoral junction. Br J Surg 1994;81:1452-4. 14. Labropoulos N, Leon M, Nicolaldes AN, Giannoukas AD, Volteas N, Chan P. Superficial venous insufficiency: correlation of anatomic extent of reflux with clinical symptoms and signs. J Vasc Surg 1994;20:953-8. 15. Mashiah A, Rose SS, Hod I. The scanning electron microscope in the pathology of varicose veins. Isr J Med Sci 1991; 27:202-6. 16. Rooke 2~/V, Sutor B, Heser JL. Compliance changes in venous insufficiency. Angiology 1993;44:777-83. 17. Porto LC, da Silveira PRM, de Carvalho JJ, Panico MDB. Conncctive tissue accumulation in the muscle layer in normal and varicose saphenous veins. Angiology 1995;46:243-9. 18. Maurel E, Azcma C, Deloy J, Bouissou H. Collagen of the normal and the varicose human saphenous vein: a biochemical study. Clin Chim Acta 1990;193:27-38. 19. Lengyel I, Acsady G. Histomorphological and pathobiochemical changes of varicose veins: a possible explanation of the development ofvaricosis. Acta Morphol Hung 1990;38: 259-67. 20. Bouissou H, Julian M, Pieraggi M-T, Maurel E, Thiers J-C, Louge L. Structure of healthy and varicose veins. In: Vanhoutte PM, editor. Return circulation and norepinephrine: an update. Paris: John Libbey Eurotext, 1991:139-50. 21. Gandhi Rift, Irizarry E, Nackman GB, Halpern VJ, Mulcare RJ, Tilson MD. Analysis of the connective tissue matrix and
JOURNAL OF VASCULARSURGERY Volume 26, Number 5
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36. 37. 38.
39.
proteolytic activity of primary varicose veins. J Vasc Surg 1993;18:814-20. Shields DA, Andaz SK, Satin S, Scurr JH, Coleridge Smith PD. Plasma elastase in venous disease. Br J Surg 1994;81: 1496-9. Travers JP, Brookes CE, Evans J, Baker DM, Kent C, Maldn GS, et al. Assessment of wall structure and composition of varicose veins with reference to collagen, elastin and smooth muscle cell content. Eur J Vasc Endovasc Surg 1996;11:230-7. Porter JM, Moneta GL, International Consensus Committee on Chronic Venous Disease. Reporting standards in venous disease: an update. J Vasc Surg 1995;21:635-45. Labropoulos N, Leon M, Nicolaldes AN, Sowade O, Volteas N, Ortega F, Chan P. Venous reflux in patients with previous deep venous thrombosis: correlation with ulceration and other symptoms. J Vasc Surg 1994;20:20-6. Satin S, Scurr JH, Coleridge Smith PD. Medial calf perforators in venous disease: the significance of outward flow. J Vasc Surg 1992;16:40-6. Labropoulos N, Dells K, Nicolaides AN, Leon M, Ramaswami G, Volteas N. The role of the distribution and anatomic extent of reflux in the development of signs and symptoms in chronic venous insufficiency. J Vasc Surg 1996; 23:504-10. van Bemmelen PS, Bedford G, Beach K, Strandness DE Jr. Quantitative segmental evaluation of venous valvular reflux with duplex ultrasound scanning. J Vasc Surg 1989;10:42531. Reagan B, Folse R, Lower limb venous dynamics in normal persons and children of patients with varicose veins. Surg Gynecol Obstet 1971;132:15-8. Negl~n P, Raju S. A comparison between descending phlebography and duplex Doppler investigation in the evaluation of reflux in chronic venous insufficiency: a challenge to phlebography as the "gold standard." J Vasc Surg 1992;16:68793. Welch HJ, Faliakou EC, McLaughlin RL, Umphrey SE, Belkin M, O'Donnell TF Jr. Comparison of descending phlebography with quantitative photoplethysmography, air plethysmography, and duplex quantitative valve closure time in assessing deep venous reflux. J Vasc Surg 1992;16:913-20. Valentin LI, Valentin WH, Mercado S, Rosario CJ. Venous reflux localisation: comparative study of venography and duplex scanning. Phlebology 1993;8:124-7. Baker SR, Bumard KG, Sommerville KM, Lea Thomas M, Wilson NM, Browse NL. Comparison of venous reflux assessed by duplex scanning and descending phlebography in chronic venous disease. Lancet 1993;341:400-3. Cornn-Thenard A, Boivin P, Buad JM, de Vincenzi I, Carpentier PH. Importance of the familial factor in varicose disease. I Dermatol Surg Oncol 1994;20:318-26. Ahramson JH, Hopp C, Epstein LM. The epidemiology of varicose veins: a survey in western Jerusalem. J Epidemiol Community Health 1981 ;35:213-7. Franks PJ, Wright DDI, McCollum CN. Epidemiology of venous disease: a review. Phlebology 1989;4:143-51. Callam MJ. Epidemiology of varicose veins [review]. Br J Snrg 1994;81:167-73. Robbins M, Frankel S, Nanchahal K, Williams M. DHA Project. Research programme: varicose veins treatments. National Health System, Health Care Evaluation Unit, University of Bristol, 1992:25-6. Gooley NA, Sumner DS. Relationship of venous reflux to the
Labropoulos et al. 741
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
site of venous valvular incompetence: implications for venous reconstructive surgery. J Vasc Surg 1988;7:50-9. Rosfors S, Lamke LA, Nordstrom E, Bygdeman S. Severity and location of venous valvular incompetence of distal valve function. Acta Clair Scand 1990;156:689-94. Labropoulos N. Relationship between anatomic extent of reflux and grade of chronic venous disease. Presented at the Second Pacific Vascular Symposium, ICamuela, Hawaii, Nov. 1996. Hanrahan LM, Araki CT, Rodriguez AA, Kechejian GJ, LaMorte WW, Menzoian JO. Distribution of valvular incompetence in patients with venous stasis ulceration. J Vasc Surg 1991;13:805q2. Shami SK, Satin S, Cheatle TR, Scurf JH, Coleridge Smith PD. Venous ulcers and the superficial venous system. J Vasc Surg 1993;17:487-90. Lees TA, Lambert D. Patterns of venous reflux in limbs with skin changes associated with chronic venous insufficiency. Br J Surg 1993;80:725-8. Myers KA, Ziegenbein RW, Zeng GH, Mathews PG. Duplex ultrasonography scanning for chronic venous disease: patterns of venous reflux. J Vasc Surg 1995;21:605-12. Labropoulos N, Leon M, Geroulakos G, Volteas N, Chan P, Nicolaides AN. Venous haemodynamic abnormalities in patients with leg ulceration. Am J Surg 1995;169:572-4. van Rij AM, Solomon C, Christie R. Anatomic and physiologic characteristics of venous ulceration. J Vasc Surg 1994; 20:759-64. Labropoulos N, Giannoukas AD, Nicolaides AN, Ramaswami G, Leon M, Burke P. New insights into the pathophysiologic condition of venous ulceration with color flow duplex imaging: implications for treatment? J Vasc Surg 1995;22:45-50. Welch HJ, Young CM, Semegran AB, Iafrati MD, Mackey WC, O'Donnell TF Jr. Duplex assessment of venous reflux and chronic venous insufficiency: the significance of deep venous reflux. J Vasc Surg 1996;24:755-62. Christopoulos D, Nicolaides AN, Szendro G. Venous reflux: quantification and correlation with clinical severity of chronic venous disease. Br J Surg 1988;75:352-6. Nicolaldes AN, Hussein MK, Szendro G, Christopoulos D, Vasdelds S, Clarke H. The relation of venous ulceration with ambulatory venous pressure measurements. J Vasc Surg 1993;17:414-9. Labropoulos N, Giannoukas AD, Nicolaides AN, Veller M, Leon M, Volteas N. The role of venous reflux and calf muscle pump fimction in nonthrombotic chronic venous insufficiency: correlation with severity of signs and symptoms. Arch Surg 1996;131:403-6. Labropoulos N. Lower limb haemodynamics in chronic venous dysfunction [thesis]. Senate House, University of London, January 1995. Christopoulos D, Nicolaides AN, CookA, Irvine A, Galloway JMD, Wilkinson A. Pathogenesis of venous ulceration in relation to the calf muscle pump function. Surgery 1989;106: 829-35. McMullin GM, Coleridge Smith PD, Scurr JH. Objective assessment of high ligation without stripping the long saphenous vein. Br J Surg 1991;78:1139-42. Satin S, Scurr JH, Coleridge Smith PD. Assessment of stripping the long saphenous vein in the treatment of primary varicose veins. Br J Surg 1992;79:889-93. Labropoulos N, Touloupalds E, Giannoukas All), Leon M, IGatsamouris A, Nicolaides AN. Recurrent varicose veins: in-
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vestigation of the pattern and extent of reflux with color flow duplex imaging. Surgery 1996;119:406-9. 58. Labropoulos N, Delis KT, Nicolaides AN. Venous reflux in symptom-free vascular surgeons. J Vasc Surg 1995;22:150-4. 59. Skladany M, Schanzer H. Increased arterial inflow in extremities with chronic venous insufficiency:an important and unappreciated hemodynamic parameter. Surgery 1996;120: 130-3.
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60. 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: 513-5.
Submitted Feb. 24, 1997; accepted Aug. 1, 1997.
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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 o f 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;26:736-42.)
The pathogenesis o f primary venous reflux and the etiologic mechanism o f morphologic changes in From the Division of Peripheral VascularSurgery, LoyolaUniversity Medical Center, Ma3~vvood, Ill. (Drs. Labropoulos, Mansour, Kang, and Baker); the AcademicVascular 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 AmericanVenous Forum, San Antonio, Tex., Feb. 20-24, 1997. Reprint requests: Nicos Labropoulos, PhD, DIC, LoyolaUniversity Medical Center, Department of Surgery,2160 S. First Ave., Maywood, IL 60153-3304. Copyright © 1997 by The Societyfor VascularSurgeryand International Society for Cardiovascular Surgery, North American Chapter. 0741-5214/97/$5.00 + 0 24/6/85267 736
the vein wall are largely unknown. The theory that suggests that valvular insufficiency is the principal cause for the development o f 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 o f valves, n The retrograde development o f reflux ~2 requires incompetence or absence o f 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 o f patients in w h o m saphenous reflux exists without SFJ or saphenopopliteal junction (SPJ) incompetence. 13,14 The
JOURNAL OF VASCULAR SURGERY Volume 26, Number 5
Labropoulos et al.
Table I. Patient demographic data Group
No. of patients
M/F
No. of limbs
Mean age ++-SD (yr)
Age range (yr)
A B C Total
40 20* 501110
20/20 9/11 23/27 52/58
80 40 100 220
26.2 + 4 27.8 _+ 3 29.6 + 3
15-35 19-32 17-34
*Twenty-six limbs (65%) had prominent veins. tSixty-four limbs (64%) had varicose veins.
theory on the "weakening" o f 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 o f reflux in asymptomatic and early stages o f primary chronic venous disease (CVD) would increase our understanding about the development o f this disorder. Therefore, this study was conducted to identify the origin o f lower limb primary venous reflux in asymptomatic young individuals and to compare their patterns o f reflux with those seen in age-matched subjects with prominent or varicose veins.
PATIENTS A N D M E T H O D S 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 o f 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 o f 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 o f 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 M H z or 4.7 M H z linear
737
Table II. Distribution o f reflux in the three groups (n = 129) Group A Site of reflux S P D S+ P S+ D P+D S+P+D Total
Group B
Group C
No. of limbs
%
No. of limbs
%
No. of limbs
%
9 0 2 0 0 0 0 11
81.8 0 18.2 0 0 0 0 100
25 0 2 2 2 0 0 31
80.6 0 6.4 6.4 6.4 0 0 100
74 0 0 6 5 0 2 87
85.1 0 0 6.9 5.7 0 2.3 100
S, Superficial; P, perforator; D, deep.
array transducer (Ultramark 9 and H D I 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 o f 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 o f our results was performed by means of the unpaired Student t test for the difference of the means, X2 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 0.05. RESULTS Patients in all groups were comparable for age and sex (p > 0.2). The prevalence o f reflux was significantly higher in groups B (31 o f 40, 77%) and C (87 of 100, 87%) compared with group A (11 o f
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Labropoulos et al.
Table III. Distribution and extent of reflux in group A (n = 11") Site of reflux SFI + GSVak GSVbk LSVak SPJ LSV No. of limbs 1 % 9.1
Extent of reflux +
+ +
+ +
+ + +
2 18.2
4 36.4
1 0 0 0 9.1
+ 1 9.1
Table IV. Distribution and extent of reflux in group B (n = 26*) Total (%)
siu of
1 (9.1) 3 (27.6) 5 (45.5) 1 (9.1) 0 1 (9.1) 9 81.8
SFJ GSVak GSVbk
reflux
knee 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.
80, 14%; X2 = 44.9, p < 0.0001; and X2 = 93.2, p < 0.0001, 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 = 0.0089 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
+
+ +
+ +
LSVak
Total (%) + + +
+
SPJ LSV No. of 1
+ + 2
4
1
02
2
4
7 (23.1) 13 50) 13 (50)
+ +
+
2 (7.7)
+ + + 5 1 1
1 (3.8) 4 (15.4) 23
limbs %
GSVak, Above-knee segment of greater saphenous vein; GSVbk, below-knee segment of greater saphenous vein; LSVak, above-
Extent of reflux
3.8 7.7 15.4 3.8 0 7.7 7.7 11.5 19 3.8 3.8
88
*Two limbs (7.7%) had deep venous reflux; o n e i n 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.
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 < 0.0001) or group B (14 of 26, 54%; p < 0.0001), 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.
JOURNAL OF VASCULAR SURGERY Volume 26, Number 5
Labropoulos et al. 739
T a b l e V. D i s t r i b u t i o n a n d e x t e n t o f reflux in g r o u p C (n = 64*) Site of reflux SFJ GSVak GSVbk LSVak SPJ LSV No. of limbs %
Total (%)
Extent of reflux +
+ +
+
+
+
+
+ + +
+ + +
+ +
+ +
+
0
4
10
1
0
+ 1
0
6.3
14.1
1.6
0
1.6
4
1
18
+ + 2
6.3
1.6
26.6
3.1
+ + 2 4.7
96.9
+
+ +
25 (39.1) 42 (65.6) 46 (71.9) 5 (7.8) 6 (9.4) 13 (20.3) 62
+
11
+ 1
+ 3
+ 2
+ + + 2
17.2
1.6
4.7
3.1
3.1
*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.
T a b l e V I . Overall prevalence o f superficial v e n o u s reflux in individual vein s e g m e n t s (n = 125) Site of reflux
No. of limbs
%
SFI GSVak GSVbk LSVak SPJ LSV
4i 69 85 8 8 18
32.8 55.2 68 6.4 6.4 14.4
SFI vs GSVak: X2 = 11.8, p = 0.0006. SFI vs GSVbk: X2 = 29.6, p < 0.0001. GSVak vs GSVbk: ×2 = 3.8, p = 0.051. GSVak + LSVak vs GSVbk + LSV: X2 = 14.2, p = 0.0002.
T h e results o f o u r s t u d y s h o w e d t h a t reflux can o c c u r in any vein s e g m e n t irrespective o f the disease stage. Such a finding is evidence against r e t r o g r a d e d e v e l o p m e n t o f reflux. I n fact, distal reflux was m o r e o f t e n f o u n d in t h e superficial, p e r f o r a t o r , a n d d e e p veins in all t h r e e g r o u p s , w h i c h indicates a possible a n t e g r a d e p r o g r e s s i o n o f the disease in a considerable n u m b e r o f patients. H o w e v e r , multifocal, asc e n d i n g , o r b o t h d e s c e n d i n g a n d a s c e n d i n g developm e n t o f reflux c o u l d occur, a n d t h e r e f o r e such questions o n the d e v e l o p m e n t o f reflux Can be ans w e r e d o n l y by prospective l o n g i t u d i n a l studies. T h e local d e v e l o p m e n t o f t h e disease w o u l d s u g g e s t t h a t t h e r e are susceptible sites, w h e r e wall changes, hem o d y n a m i c changes, o r b o t h o c c u r t o initiate reflux. F a m i l y history, a n d h e n c e a genetic c o m p o n e n t , is t h e s t r o n g e s t risk factor associated w i t h C V D . 29,34 O t h e r risk factors such as o c c u p a t i o n , p o s t u r e , o b e sity, a n d h e i g h t m i g h t p r e d i s p o s e the d e v e l o p m e n t o f reflux, b u t this association in m o s t studies has b e e n w e a k . 35-38
T h e distal part o f G S V a n d its tributaries were m o s t f r e q u e n t l y involved. A t this level, t h e p o s t e r i o r
T a b l e V I I . E x t e n t o f reflux in relation to n u m b e r o f v e n o u s s e g m e n t s involved in t h r e e different g r o u p s a n d u n i n v o l v e d contralateral limbs o f g r o u p B a n d C Reflux (n/%) Segmental Multisegmental Proximal Distal Group A Group B Group C Group B* Group C1"
9/81.8 12/46.2 3/4.7 3 5
2/18.2 14/53.8 61/95.3 2 18
3/27.3 8/30.8 10/15.6 1 4
Proximal + distal
7/63.6 1/9.1 9/34.6 9/34.6 14/21.9 40/62.5 3 1 11 8
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 o f L e o n a r d o ) was t h e m o s t c o m m o n site o f reflux a m o n g all veins, Clinically, varicosities are m o s t o f t e n seen in t h e m e d i a l a n d p o s t e r o m e d i a l aspect o f the calf, a n d o u r findings explain this observation. Several studies have s h o w n t h a t distal reflux is essential for d e v e l o p i n g signs a n d s y m p t o m s o f CVD. 14,25,27,39,40 Because t h e prevalence o f distal reflux was c o m p a r a b l e a m o n g the t h r e e g r o u p s , o t h e r factors, such as the e x t e n t , 14,27,4~ t h e pattern, 27,41-49 a n d t h e a m o u n t o f reflux, s°52 t h e t i m e t h a t the disease has b e e n present, s3 the rate o f disease p r o g r e s s i o n , s3 a n d t h e efficiency o f the calf muscle p u m p , a4 m a y be responsible for the d e v e l o p m e n t o f signs a n d s y m p t o m s o f C V D . I n d e e d , the prevalence o f c o m b i n e d p r o x i m a l a n d distal reflux was significantly increased in g r o u p C, whereas reflux c o n f i n e d to b o t h G S V a n d L S V was seen only in this g r o u p . D e e p v e n o u s reflux alone was u n c o m m o n . This finding was e x p e c t e d because o t h e r studies o n C V D
740
JOURNAL OF VASCULARSURGERY November 1997
Labropoulos et aL
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 6. 41-49 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 o f 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. The extent of
reflux is associated with the clinical severity in the
early stages of CVD. REFERENCES 1. Moore HD. Deep venous valves in the aetiology of varicose veins. Lancet 1951;2:7-10. 2. Cotton LT. Varicose veins: gross anatomy and development. Br J Surg 1961;48:589-98. 3. Sverjcar J, Prerovsky I, Linhart J, Krume J, Beckova B. Content of collagen, elastin and hexosamine in primary varicose veins. Clin Sci (Colch) 1963;24:325-30. 4. Zsoter T, Chronin RF. Venous distensibility in patients with varicose veins. Can Med Assoc J 1966;94:1293-7. 5. Zsoter T, Moore S, Keon W. Venous distensibility in patients with varicosities: in vitro studies. J Appl Physiol 1967;22: 505-8. 6. Jumkova Z, Milenkov C. Ultrastructural evidence for collagen degradation in the walls of varicose veins. Exp Mol Pathol 1982;37:37-47. 7. Psaila IV, Melhuish J. Viscoelastic properties and collagen content of the long saphenous vein in normal and varicose veins. Br J Surg 1989;76:37-40. 8. Clarke H, Smith SRG, Vasdelds SN, Hobbs JT, Nicolaldes AN. Role of venous elasticity in the development ofvaticose veins. Br J Surg 1989;76:577-80. 9. Maurel E, Azema C, Deloy J, Bouissou H. Collagen of the normal and varicose human saphenous vein: a biochemical study. Clin Claim Acta 1990;193:27-38. 10. Rose SS, Ahmed A. Some thoughts on the aetiology of varicose veins. J Cardiovasc Surg (Torino) 1986;27:534-43. 11. Venruri M, Bonavina L, Annoni F, Colombo L, Butera C, Perachia A. Biochemical assay of collagen and elastin in the normal and varicose vein wall. J Surg Res 1996;60:245-8. 12. Ludbrook J, Beale G. Femoral venous valves in relation to varicose veins. Lancet 1962;1:79-81. 13. Abu-Own A, Scurr JH, Coleridge Smith PD. Saphenous vein reflux without incompetence at the saphenofemoral junction. Br J Surg 1994;81:1452-4. 14. Labropoulos N, Leon M, Nicolaldes AN, Giannoukas AD, Volteas N, Chan P. Superficial venous insufficiency: correlation of anatomic extent of reflux with clinical symptoms and signs. J Vasc Surg 1994;20:953-8. 15. Mashiah A, Rose SS, Hod I. The scanning electron microscope in the pathology of varicose veins. Isr J Med Sci 1991; 27:202-6. 16. Rooke 2~/V, Sutor B, Heser JL. Compliance changes in venous insufficiency. Angiology 1993;44:777-83. 17. Porto LC, da Silveira PRM, de Carvalho JJ, Panico MDB. Conncctive tissue accumulation in the muscle layer in normal and varicose saphenous veins. Angiology 1995;46:243-9. 18. Maurel E, Azcma C, Deloy J, Bouissou H. Collagen of the normal and the varicose human saphenous vein: a biochemical study. Clin Chim Acta 1990;193:27-38. 19. Lengyel I, Acsady G. Histomorphological and pathobiochemical changes of varicose veins: a possible explanation of the development ofvaricosis. Acta Morphol Hung 1990;38: 259-67. 20. Bouissou H, Julian M, Pieraggi M-T, Maurel E, Thiers J-C, Louge L. Structure of healthy and varicose veins. In: Vanhoutte PM, editor. Return circulation and norepinephrine: an update. Paris: John Libbey Eurotext, 1991:139-50. 21. Gandhi Rift, Irizarry E, Nackman GB, Halpern VJ, Mulcare RJ, Tilson MD. Analysis of the connective tissue matrix and
JOURNAL OF VASCULARSURGERY Volume 26, Number 5
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36. 37. 38.
39.
proteolytic activity of primary varicose veins. J Vasc Surg 1993;18:814-20. Shields DA, Andaz SK, Satin S, Scurr JH, Coleridge Smith PD. Plasma elastase in venous disease. Br J Surg 1994;81: 1496-9. Travers JP, Brookes CE, Evans J, Baker DM, Kent C, Maldn GS, et al. Assessment of wall structure and composition of varicose veins with reference to collagen, elastin and smooth muscle cell content. Eur J Vasc Endovasc Surg 1996;11:230-7. Porter JM, Moneta GL, International Consensus Committee on Chronic Venous Disease. Reporting standards in venous disease: an update. J Vasc Surg 1995;21:635-45. Labropoulos N, Leon M, Nicolaldes AN, Sowade O, Volteas N, Ortega F, Chan P. Venous reflux in patients with previous deep venous thrombosis: correlation with ulceration and other symptoms. J Vasc Surg 1994;20:20-6. Satin S, Scurr JH, Coleridge Smith PD. Medial calf perforators in venous disease: the significance of outward flow. J Vasc Surg 1992;16:40-6. Labropoulos N, Dells K, Nicolaides AN, Leon M, Ramaswami G, Volteas N. The role of the distribution and anatomic extent of reflux in the development of signs and symptoms in chronic venous insufficiency. J Vasc Surg 1996; 23:504-10. van Bemmelen PS, Bedford G, Beach K, Strandness DE Jr. Quantitative segmental evaluation of venous valvular reflux with duplex ultrasound scanning. J Vasc Surg 1989;10:42531. Reagan B, Folse R, Lower limb venous dynamics in normal persons and children of patients with varicose veins. Surg Gynecol Obstet 1971;132:15-8. Negl~n P, Raju S. A comparison between descending phlebography and duplex Doppler investigation in the evaluation of reflux in chronic venous insufficiency: a challenge to phlebography as the "gold standard." J Vasc Surg 1992;16:68793. Welch HJ, Faliakou EC, McLaughlin RL, Umphrey SE, Belkin M, O'Donnell TF Jr. Comparison of descending phlebography with quantitative photoplethysmography, air plethysmography, and duplex quantitative valve closure time in assessing deep venous reflux. J Vasc Surg 1992;16:913-20. Valentin LI, Valentin WH, Mercado S, Rosario CJ. Venous reflux localisation: comparative study of venography and duplex scanning. Phlebology 1993;8:124-7. Baker SR, Bumard KG, Sommerville KM, Lea Thomas M, Wilson NM, Browse NL. Comparison of venous reflux assessed by duplex scanning and descending phlebography in chronic venous disease. Lancet 1993;341:400-3. Cornn-Thenard A, Boivin P, Buad JM, de Vincenzi I, Carpentier PH. Importance of the familial factor in varicose disease. I Dermatol Surg Oncol 1994;20:318-26. Ahramson JH, Hopp C, Epstein LM. The epidemiology of varicose veins: a survey in western Jerusalem. J Epidemiol Community Health 1981 ;35:213-7. Franks PJ, Wright DDI, McCollum CN. Epidemiology of venous disease: a review. Phlebology 1989;4:143-51. Callam MJ. Epidemiology of varicose veins [review]. Br J Snrg 1994;81:167-73. Robbins M, Frankel S, Nanchahal K, Williams M. DHA Project. Research programme: varicose veins treatments. National Health System, Health Care Evaluation Unit, University of Bristol, 1992:25-6. Gooley NA, Sumner DS. Relationship of venous reflux to the
Labropoulos et al. 741
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
site of venous valvular incompetence: implications for venous reconstructive surgery. J Vasc Surg 1988;7:50-9. Rosfors S, Lamke LA, Nordstrom E, Bygdeman S. Severity and location of venous valvular incompetence of distal valve function. Acta Clair Scand 1990;156:689-94. Labropoulos N. Relationship between anatomic extent of reflux and grade of chronic venous disease. Presented at the Second Pacific Vascular Symposium, ICamuela, Hawaii, Nov. 1996. Hanrahan LM, Araki CT, Rodriguez AA, Kechejian GJ, LaMorte WW, Menzoian JO. Distribution of valvular incompetence in patients with venous stasis ulceration. J Vasc Surg 1991;13:805q2. Shami SK, Satin S, Cheatle TR, Scurf JH, Coleridge Smith PD. Venous ulcers and the superficial venous system. J Vasc Surg 1993;17:487-90. Lees TA, Lambert D. Patterns of venous reflux in limbs with skin changes associated with chronic venous insufficiency. Br J Surg 1993;80:725-8. Myers KA, Ziegenbein RW, Zeng GH, Mathews PG. Duplex ultrasonography scanning for chronic venous disease: patterns of venous reflux. J Vasc Surg 1995;21:605-12. Labropoulos N, Leon M, Geroulakos G, Volteas N, Chan P, Nicolaides AN. Venous haemodynamic abnormalities in patients with leg ulceration. Am J Surg 1995;169:572-4. van Rij AM, Solomon C, Christie R. Anatomic and physiologic characteristics of venous ulceration. J Vasc Surg 1994; 20:759-64. Labropoulos N, Giannoukas AD, Nicolaides AN, Ramaswami G, Leon M, Burke P. New insights into the pathophysiologic condition of venous ulceration with color flow duplex imaging: implications for treatment? J Vasc Surg 1995;22:45-50. Welch HJ, Young CM, Semegran AB, Iafrati MD, Mackey WC, O'Donnell TF Jr. Duplex assessment of venous reflux and chronic venous insufficiency: the significance of deep venous reflux. J Vasc Surg 1996;24:755-62. Christopoulos D, Nicolaides AN, Szendro G. Venous reflux: quantification and correlation with clinical severity of chronic venous disease. Br J Surg 1988;75:352-6. Nicolaldes AN, Hussein MK, Szendro G, Christopoulos D, Vasdelds S, Clarke H. The relation of venous ulceration with ambulatory venous pressure measurements. J Vasc Surg 1993;17:414-9. Labropoulos N, Giannoukas AD, Nicolaides AN, Veller M, Leon M, Volteas N. The role of venous reflux and calf muscle pump fimction in nonthrombotic chronic venous insufficiency: correlation with severity of signs and symptoms. Arch Surg 1996;131:403-6. Labropoulos N. Lower limb haemodynamics in chronic venous dysfunction [thesis]. Senate House, University of London, January 1995. Christopoulos D, Nicolaides AN, CookA, Irvine A, Galloway JMD, Wilkinson A. Pathogenesis of venous ulceration in relation to the calf muscle pump function. Surgery 1989;106: 829-35. McMullin GM, Coleridge Smith PD, Scurr JH. Objective assessment of high ligation without stripping the long saphenous vein. Br J Surg 1991;78:1139-42. Satin S, Scurr JH, Coleridge Smith PD. Assessment of stripping the long saphenous vein in the treatment of primary varicose veins. Br J Surg 1992;79:889-93. Labropoulos N, Touloupalds E, Giannoukas All), Leon M, IGatsamouris A, Nicolaides AN. Recurrent varicose veins: in-
JOURNAL OF VASCULAR SURGERY
742
Labropouloset al.
November 1997
vestigation of the pattern and extent of reflux with color flow duplex imaging. Surgery 1996;119:406-9. 58. Labropoulos N, Delis KT, Nicolaides AN. Venous reflux in symptom-free vascular surgeons. J Vasc Surg 1995;22:150-4. 59. Skladany M, Schanzer H. Increased arterial inflow in extremities with chronic venous insufficiency:an important and unappreciated hemodynamic parameter. Surgery 1996;120: 130-3.
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60. 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: 513-5.
Submitted Feb. 24, 1997; accepted Aug. 1, 1997.
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