Distribution and prevalence of reflux in the superficial and deep venous system in the general population – results from the Bonn Vein Study, Germany
Article Outline
Objective
Venous diseases are among the most frequent diseases in the general population of industrialized countries. The aim of this article is to investigate the population-based prevalence of pathologic reflux in superficial and deep leg veins, taking into account factors as gender, age, and clinical classification of venous disease.
Methods
In a population-based cross-sectional study, 3072 subjects aged 18 to 79 years (1350 male, 1722 female, response 59%) were enrolled from October 2000 through November 2001. A standardized interview was conducted to document phlebological history and clinical examinations including duplex sonography of selected superficial and deep leg veins. Pathological reflux was defined as being >500 ms. All participants where classified according to the CEAP classification.
Results
Using the highest clinical stage per participant, 9.6% where classified C0, 59.0% C1, 14.3% C2, 13.5% C3, 2.9% C4, and 0.7% C5-C6. A pathological reflux (>500 ms) was found in 35.3% (95% confidence interval [CI] 33.6-37.1) of subjects with 21.0% (95% CI 19.5-22.5) showing reflux in at least one superficial vein and 20.0% (95% CI 18.6-21.5) showing reflux in at least one deep vein. We observed significantly higher reflux prevalence for the superficial veins in women while for the deep veins reflux prevalence were significantly higher in men. Prevalence of reflux in the superficial veins markedly increases with age. In the deep venous system, no clear changes in reflux prevalence with age can be observed. For superficial veins, reflux prevalence is markedly higher with higher C-stages. For the deep veins, the proportion of refluxes is relatively constant in stages C0-C3 with a distinct increase of prevalence from stage C4 onward.
Conclusion
Our results show a high prevalence of reflux both for the superficial and the deep venous system. Reflux prevalence is associated with gender, age, and the clinical stage as measured by the CEAP classification. Further longitudinal studies are needed to clarify the relevance of pathological reflux in subjects with otherwise healthy veins.
Venous diseases are among the most frequent diseases in the general population of industrialized countries.1 In the pathophysiology of chronic venous diseases reflux, operationalized as prolonged time to valve closure, plays an important role. It is, however, not clear which reflux time actually represents a pathological prolongation. In the literature, both 500 ms and 1000 ms are used as threshold values for defining pathological reflux. In the Edinburgh Vein Study (EVS), not only prevalences of varicose veins and chronic venous disorders (CVD) were described but also prevalences of reflux in the superficial and deep venous system.2
The Bonn Vein Study (BVS) is a current epidemiological study on chronic venous diseases with study subjects randomly selected from population registries.3 The aim of this article is to investigate the prevalence of reflux in selected superficial and deep leg veins in the German general population, taking into account the factors gender, age and clinical classification.4, 5 We used both threshold values to define pathological reflux (>500 ms and >1000 ms).
Methods
Study design
The Bonn Vein Study (BVS) is described in detail by Rabe et al.3 This population-based cross-sectional study with a random sample of subjects selected from population registries was conducted in the city of Bonn and two rural communities from October 2000 through November 2001. The Bonn University ethics committee approved the study. Subjects were eligible if they were aged 18 to 79 years, of German nationality, and had sufficient German language skills. Persons with hemiparesis or leg amputations, severe illness, moribund patients, and patients with an inactivating systemic disease were excluded according to the study protocol. The response proportion was 59%. A total of 3072 subjects aged 18 to 79 years were enrolled and examined. The age and gender distribution of the participants was very similar to the overall German population and to the population studied in the German National Health Examination Survey in 1998.6
All participants filled in a standardized questionnaire including information on socio-demographic status, lifestyle, physical activity, medical history, and quality of life. Phlebologically trained investigators conducted standardized interviews on the specific phlebological history and performed clinical examinations including color-coded duplex sonography.
CEAP classification
All participants were classified according to the CEAP classification4, 5 and assigned a clinical stage (C0 – no visible or palpable signs of venous disease, C1 – telangiectases or reticular veins, C2 – varicose veins, C3 – edema caused by venous insufficiency, C4 – skin changes [pigmentation, eczema, lipodermatosclerosis, white atrophy], C5 – healed venous ulcer, and C6 – active venous ulcer) using the highest value for each participant in assigning a stage. The classification of C1-C6 was used only for changes of venous etiology. Details of the classification into the different clinical stages are summarised in Table I.
Table I. Description of the study population (N = 3016) included in prevalence analyses
| N | % | |
|---|---|---|
| Gender | ||
 Female | 1694 | 56.2 |
| Male | 1322 | 43.8 |
| Age | ||
| 18-39 y | 1013 | 33.6 |
| 40-59 y | 1128 | 37.4 |
| 60-79 y | 875 | 29.0 |
| Body mass index (kg/m2) | ||
| <20 | 43 | 1.4 |
| 20-24.9 | 1278 | 42.5 |
| 25-29.9 | 1153 | 38.3 |
| 30-34.9 | 508 | 16.9 |
| ≥35 | 26 | 0.9 |
| missing | 8 | |
| C stages of the CEAP classification | ||
| C0 | 290 | 9.6 |
| C1 | 1777 | 59.0 |
| C2 | 432 | 14.3 |
| C3 | 407 | 13.5 |
| C4 | 86 | 2.9 |
| C5-C6 | 22 | 0.7 |
| missing | 2 | |
| Place of residence | ||
| Urban | 1883 | 62.4 |
| Rural | 1133 | 37.6 |
Duplex sonography
The duplex sonographic examination was performed in B mode with 7.5-10 MHz and 7 MHz for the duplex (Esaote AU-5 Harmonic). During the examination, the participant stood on a tilt-table tilted 10° to the back from the upright position. Findings were stored using an optical storage medium. For duplex sonography of the proximal venous segments (femoral vein [FV], great saphenous vein [GSV]), the Valsalva maneuver was used as provocation maneuver, and we used distal manual compression and fast decompression for the distal venous segments (popliteal vein [PV], posterior tibial veins [PTV], great saphenous vein at knee level [GSV knee], and small saphenous vein [SSV]). In performing the Valsalva maneuver, the investigator monitored abdominal straining manually in a standardized way. The duration of each maneuver was 2 seconds minimum. Both reflux provocation maneuvers are routine in phlebological practice.7, 8, 9, 10, 11
Morphological and functional venous changes were measured at six standardized sites: FV and GSV in longitudinal section each 2 cm distal of the opening of the GSV into the FV; GSV in cross-section at the distal thigh immediately proximal to the epicondylus medialis femoris (GSV knee); PV and SSV in longitudinal section in the region of the knee fold at least 2 cm distal of the opening of the SSV into the PV; and PTV in cross section in the medial crural region at the transition between the distal to the medium third of the lower leg. GSV, GSV knee, and SSV were grouped as superficial veins (SV), and FV, PV, and PTV were grouped as deep veins (DV). It was not differentiated where the SSV joined the deep venous system. Each retrograde venous flow with duration of more than 500 ms was defined as pathological reflux and its duration in ms was documented. Due to the size of the monitor, the maximum reflux duration possible was 8 seconds.
In addition to prevalences of reflux single segments, we calculated the prevalence of continuous reflux in FV and PV as well as in GSV and GSV knee and other combinations and its influence as a risk factor for severe chronic venous insufficiency (CVI) (C4-C6).
Interobserver reliability
All four investigators who conducted the phlebological examinations took part in an interobserver reliability test. For these measurements, 10 patients were chosen from among the inpatients of the Bonn dermatology department. The results were as follows. For the CEAP classification, there was complete or almost complete agreement between the investigators with a kappa value between 0.85 and 1.00 for the different items. The investigation of the interobserver reliability for color-coded duplex sonography also showed almost complete agreement between investigators with a kappa value of 0.81.
Statistical analyses
For the calculation of reflux prevalence with a 95% confidence interval (95% CI), we dichotomized reflux times using the two threshold values of 500 ms12 and 1000 ms,13 which are both mentioned in the literature and used in clinical assessment. We calculated the age- and gender-specific prevalence for reflux both for the superficial and deep venous system and for the separate veins.
In calculating reflux prevalence for C stages of the CEAP classification, we chose the leg with the highest C stage for each participant. If the C stage was equal in both legs either the left or right leg was selected at random, using a random number generator (ranbin function of SAS version 9.1.3, SAS Institute Inc., Cary, NC). Variable sample sizes were used for the prevalence calculations, due to missing values for the reflux measurements in single veins.
To examine the association of reflux in single vein segments, vein systems and segment combinations with prevalence of severe CVI (C4-C6), we conducted logistic regression analyses. We calculated crude and adjusted odds ratios (OR) with their 95% CI. Adjustment was conducted for age and sex, both of which were associated with reflux and CVI in bivariate analyses.
Data analyses were performed using the statistical software SAS (version 9.1.3).
Results
Duplex sonography results were available and evaluable for 3016 participants. For a total of 109 participants, at least one measurement of a single vein was missing. The study population is described in Table I.
Distribution of reflux times
A total of 18,096 duplex sonographic results were collected for the superficial veins (Fig 1). One hundred twelve (0.6%) results with missing data on reflux time were excluded from the analysis; 16,881 (93.3%) of duplex results were inside the normal range of <500 ms. Five hundred twenty-four (2.9%) were between 500 ms and 2000 ms with 351 (1.9%) of these between 1000 and 2000 ms. Five hundred seventy-nine (3.2%) of results were above 2000 ms. A further classification of results in this range is not possible because in some cases, the Valsalva maneuver could not be performed for more than 2000 ms.
Fig 1.
Distribution of prolonged reflux times in the superficial venous system for 3016 participants and a total of 17,984 measurements. 93.3% of all findings were below 500 ms.
For the deep veins a total of 18,096 duplex results were collected. Thirty-three (0.6%) results with missing data on reflux time were excluded from the analysis. A total of 17301 (95.6%) of duplex results were inside the normal range of < 500 ms, and 684 (3.8%) were between 500 ms and 2000 ms with 178 (1.0%) of these between 1000 und 2000 ms (Fig 2). Seventy-eight (0.4%) were above 2000 ms. These results cannot be further classified due to the methodical limitation given above.
Fig 2.
Distribution of prolonged reflux times in the deep venous system for 3016 participants and a total of 18,063 measurements; 95.6% of all findings were below 500 ms.
Reflux prevalence
Table II shows the prevalences for a pathological reflux in the superficial and the deep venous systems for both threshold values (500 ms and 1000 ms). In the superficial venous system, the use of either one or the other threshold value leads to only marginal changes in prevalence, whereas the choice of threshold has a marked influence on prevalence values in deep veins.
Table II. Prevalence (95% CI) of pathologically prolonged reflux time (defined as >500 ms and >1000 ms) in the superficial and deep venous system for the population analyzed
| All veins | Superficial venous system | Deep venous system | |
|---|---|---|---|
| % (95% CI) | % (95% CI) | % (95% CI) | |
| Reflux >500 | 35.3(33.6-37.1) | 21.0(19.5-22.5) | 20.0(18.6-21.5) |
| Reflux >1000 | 23.3(21.8-24.9) | 18.8(17.4-20.2) | 7.2(6.3-8.2) |
Side-specific prevalence
On looking at the prevalence of reflux >500 ms separately for the right and left leg, no distinct differences in the overall picture can be seen (Table III). For the left leg, a tendency towards more pathologic refluxes in the deep venous system can be seen resulting from a slightly higher prevalence in the left FV.
Table III. Side and gender specific reflux prevalence in superficial and deep veins, reflux defined as time >500 ms
| Total | Right | Left | Male | Female | |
|---|---|---|---|---|---|
| N = 3016 | N = 3016 | N = 3016 | N = 1694 | N = 1322 | |
| % (95% CI) | % (95% CI) | % (95% CI) | % (95%CI) | % (95%CI) | |
| Venous systems | |||||
| Superficial | 21.0(19.5-22.5) | 13.3(12.1-14.5) | 13.7(12.5-15.0) | 17.7(15.7-19.9) | 23.5(21.5-25.7) |
| Deep | 20.0(18.6-21.5) | 11.2(10.1-12.4) | 12.4(11.3-13.7) | 23.1(20.9-25.5) | 17.6(15.8-19.5) |
| Single veins | |||||
| Great saphenous vein | 14.4(13.1-15.7) | 8.6(7.6-9.7) | 9.0(8.0-10.0) | 11.8(10.1-13.6) | 16.4(14.7-18.3) |
| Great saphenous vein, knee | 12.6(11.4-13.8) | 7.5(6.6-8.5) | 7.8(6.9-8.8) | 9.3(7.8-11.0) | 15.1(13.5-17.0) |
| Small saphenous vein | 3.5(2.9-4.2) | 2.1(1.6-2.6) | 1.9(1.4-2.4) | 3.5(2.6-4.6) | 3.5(2.7-4.5) |
| Femoral vein | 12.7(11.5-13.9) | 6.5(5.7-7.5) | 8.1(7.2-9.2) | 14.7(12.8-16.7) | 11.1(9.7-12.7) |
| Popliteal vein | 8.8(7.8-9.9) | 5.0(4.3-5.8) | 4.8(4.1-5.6) | 11.0(9.4-12.8) | 7.2(6.0-8.5) |
| Posterior tibial vein | 0.7(0.5-1.1) | 0.3(0.1-0.6) | 0.5(0.3-0.8) | 1.0(0.5-1.7) | 0.5(0.2-1.0) |
Age- and gender-specific prevalence
We observed significantly higher reflux prevalence for the superficial veins in women while for the deep veins reflux prevalence was significantly higher in men (Table III). For women, a reflux >500 ms was most frequently seen for the GSV (16.4% vs 11.8% in men) and the GSV knee (15.1% vs 9.3%), whereas for men refluxes were more frequent in the FV (14.7% vs 11.1 in women) and in the PV (11.0% vs 7.2%).
The prevalence of reflux in the superficial venous system markedly increases with age (Table IV). This increase is stronger in women than in men. In the deep venous system, no clear changes with age in reflux prevalence can be observed in either sex.
Table IV. Age- and gender-specific reflux prevalence in superficial and deep veins, reflux defined as time >500 ms
| 17-39 y | 40-59 y | 60-80 y | ||||
|---|---|---|---|---|---|---|
| % (95% CI) | % (95% CI) | % (95% CI) | ||||
| Male | Female | Male | Female | Male | Female | |
| N = 446 | N = 567 | N = 479 | N = 649 | N = 397 | N = 478 | |
| Venous systems | ||||||
| Superficial | 12.6(9.6-16.0) | 12.6(10.0-15.6) | 17.6(14.3-21.3) | 21.8(18.7-25.2) | 23.7(19.5-28.2) | 39.1(34.7-43.7) |
| Deep | 26.1(22.1-30.5) | 17.9(14.8-21.3) | 22.4(18.7-26.4) | 13.9(11.3-16.8) | 20.7(16.8-25.0) | 22.3(18.6-26.3) |
| Single veins | ||||||
| Great saphenous vein | 9.6(7.1-12.8) | 10.3(7.9-13.1) | 12.8(9.9-16.1) | 14.0(11.4-16.9) | 13.0(9.8-16.7) | 27.1(23.1-31.3) |
| Great saphenous vein, knee | 3.2(1.7-5.2) | 6.7(4.8-9.1) | 10.9(8.3-14.1) | 13.9(11.3-16.8) | 14.3(11.0-18.2) | 27.2(23.2-31.5) |
| Small saphenous vein | 2.2(1.1-4.1) | 1.1(0.4-2.3) | 2.9(1.6-4.9) | 3.3(2.0-4.9) | 5.6(3.5-8.3) | 6.7(4.7-9.4) |
| Femoral vein | 18.6(15.1-22.5) | 13.4(10.7-16.5) | 14.0(11.0-17.1) | 7.6(5.7-9.9) | 11.1(8.2-14.6) | 13.3(10.3-16.6) |
| Popliteal vein | 9.5(6.9-12.6) | 4.8(3.2-6.9) | 10.9(8.2-14.0) | 6.6(4.8-8.8) | 12.9(9.7-16.6) | 10.7(8.1-13.8) |
| Posterior tibial vein | 0.4(0.1-1.6) | 0.2(0-1.0) | 0.6(0.1-1.8) | 0.6(0.2-1.6) | 2.0(0.9-4.0) | 0.8(0.2-2.2) |
In looking at the separate veins, a distinct increase of reflux prevalence with age for the GSV, SSV, and PV can be observed in women. In men, there was only a trend towards higher prevalences with increasing age. In the FV, the prevalence for reflux was higher in the younger age groups in men, while no distinct differences were observed in women.
Prevalence by C of CEAP classification
For the superficial veins reflux prevalence is markedly higher with higher C-stages of the CEAP classification (Table V). The slightly lower frequency observed for stage C3 is due to the fact that participants with venous disease and edema, but without varicose veins, could also be included here. For the region of the deep veins, the proportion of pathological refluxes is relatively constant in stages C0-C3 with a distinct increase of prevalence from stage C4 onward. This tendency can also be observed when looking at single superficial and deep veins.
Table V. Prevalence of reflux according to C stage of the CEAP classification (N = 3014)
| C0 | C1 | C2 | C3 | C4 | C5-C6 | |
|---|---|---|---|---|---|---|
| N = 290 | N = 1777 | N = 432 | N = 407 | N = 86 | N = 22 | |
| % (95% CI) | % (95% CI) | % (95% CI) | % (95% CI) | % (95% CI) | % (95% CI) | |
| Venous systems | ||||||
| Superficial | 2.4(1.0-4.9) | 5.0(4.1-6.2) | 49.2(44.3-54.1) | 24.1(19.9-28.6) | 67.1(55.8-77.1) | 72.7(49.8-89.3) |
| Deep | 16.6(12.5-21.3) | 9.8(8.4-11.2) | 18.8(15.2-22.8) | 12.3(9.3-15.9) | 24.1(15.4-34.7) | 54.5(32.2-75.6) |
| Single veins | ||||||
| Great saphenous vein | 2.1(0.8-4.4) | 3.4(2.6-4.3) | 28.9(24.7-33.4) | 16.5(13.0-20.6) | 41.0(30.3-52.3) | 57.1(34.0-78.2) |
| Great saphenous vein, knee | 0.7(0.1-2.5) | 1.7(1.1-2.4) | 32.2(27.7-36.9) | 13.4(10.2-17.2) | 41.7(31.0-52.9) | 42.9(21.8-66.0) |
| Small saphenous vein | 0.0(0-1.3) | 0.6(0.3-1.1) | 8.6(6.2-11.7) | 3.0(1.5-5.1) | 12.9(6.6-22.0) | 22.7(7.8-45.4) |
| Femoral vein | 13.1(9.4-17.5) | 6.3(5.2-7.5) | 10.0(7.3-13.2) | 6.9(4.6-9.8) | 12.8(6.6-21.7) | 36.4(17.2-59.3) |
| Popliteal vein | 3.8(1.9-6.7) | 3.5(2.7-4.5) | 9.7(7.1-12.9) | 6.6(4.4-9.5) | 12.9(6.6-22.0) | 36.4(17.2-59.3) |
| Posterior tibial vein | 0.0(0-1.3) | 0.2(0.1-0.6) | 0.5(0.1-1.7) | 0.5(0.1-1.8) | 3.6(0.7-10.1) | 25.0(8.7-49.1) |
Table VI displays the crude and adjusted odds ratios (OR) for the associations of reflux in single vein segments, vein systems, and combinations of vein segments with severe CVI. Generally, strong associations can be observed, which are attenuated slightly by adjustment for age. Higher ORs are seen in the superficial vein system and single superficial vein segments. Stratification by sex reveals stronger associations between reflux and CVI in men than in women. This is especially pronounced in the FV.
Table VI. Crude and age-adjusted odds ratios with 95% CI for the association of reflux with severe CVI (C4-C6) (N = 2944) in the complete study group and stratified by sex
| N reflux All | Crude OR (95% CI) for severe CVI All | Adjusted OR (95% CI) for severe CVI | |||
|---|---|---|---|---|---|
| All | Men | Women | |||
| Venous systems | |||||
| Superficial | 437 | 13.96(8.98-21.70) | 9.83(6.25-15.45) | 10.43(5.51-19.75) | 11.41(5.78-22.50) |
| Deep | 369 | 3.19(2.04-5.01) | 3.31(2.07-5.30) | 4.88(2.55-9.35) | 2.17(1.06-4.42) |
| Thigh(GSV and FV) | 38 | 8.45(3.81-19.16) | 8.44(3.39-21.06) | 20.80(6.03-71.70) | 2.92(0.60-14.16) |
| Superficial axial(GSV and GSV knee) | 156 | 10.39(6.53-16.52) | 7.13(4.38-11.58) | 10.87(5.15-22.94) | 5.74(2.99-11.04) |
| Deep axial(FV and PV) | 20 | 13.50(5.07-35.93) | 11.25(3.52-35.90) | 17.29(4.31-69.37) | 3.86(0.38-39.57) |
| Single veins | |||||
| Great saphenous vein | 280 | 9.37(6.14-14.30) | 7.02(4.52-10.91) | 9.45(4.79-18.66) | 6.56(3.60-11.95) |
| Great saphenous vein, knee | 255 | 9.62(6.28-14.74) | 6.28(4.04-9.78) | 8.48(4.34-16.57) | 5.61(3.07-10.25) |
| Small saphenous vein | 73 | 8.07(4.33-15.04) | 5.82(3.01-11.25) | 5.73(2.22-14.75) | 5.87(2.33-14.75) |
| Femoral vein | 234 | 3.02(1.79-5.09) | 3.65(2.10-6.34) | 8.97(4.31-18.65) | 1.11(0.38-3.21) |
| Popliteal vein | 151 | 4.02(2.29-7.06) | 3.28(1.81-5.95) | 2.78(1.20-6.44) | 3.85(1.66-8.95) |
Influence of region of living and BMI
Region of living, rural or urban, had no influence on the prevalence of reflux. Higher body mass index (BMI) did not constantly increase the prevalence of reflux in the deep venous system. Prevalence of reflux in the FV was 12.8% in BMI 20-24.9 kg/m2, 12.8 in BMI 25-29.9 and 11.8 in BMI 30-34.9 subjects. In the PV, it was 8.5%, 9.9%, and 8.1%, respectively. In contrary, participants with BMI >30 showed a higher reflux prevalence in the saphenous veins. Prevalence of reflux in the GSV was 9.8% in BMI 20-24.9 kg/m2, 15.2% in BMI 25-29.9, and 24% in BMI 30-34.9 subjects. In the SSV it was 2.3%, 3.9%, and 5.7%, respectively.
Discussion
This article aims to examine the prevalence of pathological reflux in the superficial and deep veins of the lower limb in a population-based cross-sectional study. Our results show that reflux prevalence is high in the population both for the superficial and the deep venous system. We observed a noticeable association with gender, age, and C stage of the CEAP classification.
In looking at the results for reflux prevalence in the Edinburgh Vein Study2 and the BVS, it is conspicuous that in the Edinburgh Vein Study, the rate of refluxes seen in PV, GSV knee, and SSV was about twice as high as that seen in our study. The only vein for which we saw more reflux is the FV. Both studies used different participant's position during the examination. In the Edinburgh Vein Study, the participants were examined while in a diagonal position of a 45° and 30° on a tilted couch2 whereas we examined them in a standing position with a tilt of only 10°.
The question of optimum examination position during duplex sonography has been discussed in many studies.12, 14, 15, 16 In one of the first studies dating from 1989, van Bemmelen et al12 reported a higher specificity, when duplex sonographic reflux diagnostics were performed while the patient was standing. This was later confirmed by Araki et al,14 Masuda et al,16 and Labropoulos et al,15 and this is why we chose the standing position for duplex sonographic examination.
The inducement of sufficient blood flow is essential in obtaining meaningful duplex sonography results. The most common steps taken to ensure this are the Valsalva maneuver for proximal vein segments and for distal vein segments the use of manual compression distal of the vein segments to be examined.7, 8, 9, 10, 11 In their reflux diagnostics research, Masuda et al16 did not find any difference between Valsalva maneuvers and pressure cuffs for proximal vein segments in standing participants both with healthy veins or suffering from chronic venous insufficiency. In 1993, Araki et al14 published on equivalence between distal manual decompression, which is fast in performance, and decompression by pressure cuffs, which are more time-consuming, on the popliteal vein. Sarin et al17 also confirmed good repeatability for inducing reflux by manual compression and decompression.
In the Bonn Vein Study, we used the Valsalva maneuver as provocation maneuver for duplex sonography of the proximal venous segments (FV, GSV), and we used distal manual compression and fast decompression for the distal venous segments (PV, PTV, GSV knee, SSV). Both provocation maneuvers were conducted in a standardized manner, and on measuring interobserver reliability, we saw an almost complete agreement between the investigators. Distal manual compression was also used as provocation maneuver in the Edinburgh Vein Study18 if a sufficient blood flow could not be obtained by pressure cuff.
The cut-off value for the definition of a pathologically prolonged reflux time is an important question in reflux diagnostics. Our results show that reflux prevalence in the deep venous system is markedly influenced by the threshold value chosen, while there is only little influence on the prevalence of reflux in the superficial veins. This confirms the findings of the Edinburgh Vein Study.2 Only small differences could be found in the superficial venous system for a reflux duration of >0.5 or >1.0 seconds. In the deep venous system, prevalence of reflux was two to four times greater for reflux duration of >0.5 rather than >1.0 seconds. In some studies,19, 20 the duration of reflux was not defined. Most studies7, 21, 22, 23 define the threshold value for pathological reflux duration as 0.5 seconds according to the work of van Bemmelen.12 Other values defined as thresholds are 0.6 seconds,24 1 second,13 and 2 seconds.9, 11 Haenen et al8 und Labropoulos et al15 saw similar results in their prospective studies on healthy participants. Haenen et al8 defined a reflux of more than 1000 ms in proximal veins (FV, PV, GSV proximal) as pathological in a prospective study with 42 healthy participants while setting the threshold value for the distal veins (GSV distal, sural veins) at 500 ms. Labropoulos et al15 conducted a prospective study with 40 healthy participants and 45 patients suffering from chronic venous insufficiency (both groups were examined while standing) and had similar results. In this study, the threshold value for superficial and sural veins was established at 500 ms and for FV and PV at 1000 ms. Prospective studies are necessary to determine the best cut-off value for the prognosis of the development of venous disease.
We saw a higher prevalence of reflux for the FV in the left leg. In the Edinburgh Vein Study, 2 no difference in reflux prevalence was found between the right and left leg both in deep and superficial veins. The higher prevalence for the left leg, which our data show is probably associated with May-Thurner syndrome24, 25 with compression of the left common iliac vein by the right common iliac artery causing more frequent thromboses in the left leg.
It is noticeable that women show more reflux in superficial veins while the prevalence in deep veins is higher in men. This is confirmed by the results of the Edinburgh Vein Study.26 The differences in the superficial veins may be due to the fact that varicose veins were more frequent in our female population with 25.8% compared with men with 19.9%.3 Height may also influence reflux prevalence. In the Edinburgh Vein Study,2 height was related to reflux in men.
In superficial veins reflux prevalence shows a marked increase with age. This confirms the results of the Edinburgh Vein Study.2 However, we did not observe a consistent increase in reflux prevalence of the deep veins. While there was no change in the FV, an increase with an exposure-response relationship was seen for the PV.
Both in superficial and in deep veins, the prevalence of reflux is correlated with the C stage of the CEAP classification. In superficial veins, there is a distinct increase of reflux prevalence for both threshold values between stages C0 and C6 with the exception of stage C3. In C3 compared with C2, participants with venous disease and edema, but without varicose veins, are also included. Participants with advanced chronic venous diseases show a high rate of reflux in the superficial venous system with rates of about 67.1% to 72.7%. This is confirmed by results seen in other studies.20, 27, 28
The fact that only 49.2% of participants with stage C2 show pathological reflux in the superficial venous system is not surprising because we did not examine the whole of the superficial system but defined localizations only, thus isolated refluxes in lateral branches could not be accounted for. The Edinburgh Vein Study18 also shows that in 36.5% of cases with chronic venous insufficiency no reflux in the selected deep or superficial veins could be detected.
Many studies confirm the importance of reflux in superficial and deep veins for the development of the advanced stages of chronic venous insufficiency.13, 19, 21, 23, 26, 28 The most frequent comparison was between patients with known chronic venous insufficiency and healthy participants used as control group. Even in healthy subjects of other studies and also in our C0 and C1 participants, reflux can be demonstrated. In the Edinburgh Vein Study,2 reflux prevalence in healthy subjects varied between 5% and 10% in different vein segments. In our study, femoral vein reflux >0.5 seconds had a prevalence in C0 participants of 13.1%. This increased markedly only in the highest clinical stage. The cut-off value of 0.5 seconds may not be specific enough for this site.
Data from the Bonn Vein Study show that a pronounced increase of reflux prevalence in the deep veins is seen from CEAP stage 4 onwards. In stages C4 to C6, the rate of reflux for the deep venous system is 24.1% to 54.5%. These results are confirmed both in other studies13, 21, 23, 26, 28 and in the Edinburgh Vein Study18 where 44% of participants suffering from chronic venous insufficiency show reflux in the deep veins. The multivariate analysis revealed strong associations between reflux in superficial vein segments and severe CVI and slightly lower associations between reflux in deep vein segments and severe CVI. In the analysis of deep vein segments, stratification by sex points to an effect measure modification by sex, with stronger associations in men. This is especially pronounced in the femoral vein. However, the small number of subjects with reflux in the analysis of combined vein segments (ie, FV and PV) severely limits the precision of our results. A currently conducted follow-up of the BVS will shed more light on the prognostic value of superficial and deep vein reflux for the development of chronic venous disease.
In summary, our results show a high prevalence of reflux in the German general population both for superficial and deep veins. Reflux prevalence is associated with gender, age, and the clinical stage measured by the CEAP classification. Further longitudinal studies are needed to clarify the relevance of pathological reflux in subjects with otherwise healthy veins.
Author contributions
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Competition of interest: none.
PII: S0741-5214(08)00630-7
doi:10.1016/j.jvs.2008.04.029
© 2008 The Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
