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Epidemiology of chronic venous disorders
https://t.me/med1917
EBERHARD RABE AND FELIZITAS PANNIER
10
10.1 Introduction 121
10.2 Early epidemiological studies 121
10.3 Epidemiologic studies based on the CEAP
classification 121
10.4 Prevalence of CVD 121
10.5 Prevalence of venous reflux 124
10.6 Prevalence of venous symptoms 124
10.1 INTRODUCTION
In recent decades, epidemiological studies of chronic venous
disorders (CVDs) were performed in many countries
worldwide. Most of these were focused on the prevalence
of varicose veins.
problems were noted. Dierent denitions for CVDs or for
chronic venous insuciency (CVI) and dierent age groups
were used in the various studies. In very few cases, the
investigated population was based on a random sample of
the general population.9 In many studies, only information
gathered from questionnaires was used. Clinical and duplex
evaluation were incorporated into the protocols only rarely,
and a few recent studies incorporated the CEAP classication into the study design.
the incidence of CVDs have been published.
1–8
By reviewing these data, some principal
9–15
Recently, longitudinal data on
16–19
10.2 EARLY EPIDEMIOLOGICAL STUDIES
Early studies reported the prevalence of varicose veins as
being from 1% to 73% in females and from 2% to 56% in
males, and of CVI being from 1% to 40% in females and
from 1% to 17% in males.1 e results varied by geographic
region and also by the methods used for evaluation. In
Western countries, varicose veins are reported to be
present in 25%–33% of female adults and 10%–20% of male
1,2,5,8
adults.
Framingham study was 2.6% in women and 1.9% in men.20
e prevalence of skin changes varied between 3% and 13%,
and active and healed ulcers varied between 1% and 2.7%
in the investigated populations. Established risk factors
for varicose veins were older age, a positive family history,
e incidence of varicose veins per year in the
10.7 Incidence of CVD and venous reflux 124
10.8 Progression of CVD 124
10.9 Risk factors associated with varicose veins
and chronic venous insufficiency 124
10.10 Summary 125
10.11 Clinical recommendations 125
References 126
female gender, multiple pregnancies, a standing occupation,
and obesity in females.
1,2,5,20
10.3 EPIDEMIOLOGIC STUDIES BASED
ON THE CEAP CLASSIFICATION
In the revised CEAP classication, precise venous denitions have been given.21 Telangiectasia is the conuence of
dilated intradermal venules of less than 1 mm in caliber.
Reticular vein is a dilated bluish subdermal vein, usually
1 mm to less than 3 mm in diameter. Varicose vein is a
subcutaneous dilated vein 3 mm in diameter or larger,
measured in the upright position. Edema is the perceptible increase in volume of uid in skin and subcutaneous
tissue, characteristically becoming indented with pressure. e term “chronic venous insuciency” implies a
functional abnormality of the venous system, and is usually
reserved for more advanced disease, including edema (C3),
skin changes (C4), or venous ulcers (C5–C6).
years, several studies have been published using the CEAP
classication (Table 10.1).
9–15
21
In recent
10.4 PREVALENCE OF CVD
10.4.1 The San Diego Population Study
Between 1994 and 1996, 2211 men and women between 40
and 79 years of age in San Diego, CA, were evaluated by
visual inspection and duplex ultrasound for manifestations
of CVD: telangiectasias, varicose veins, trophic changes,
and edema. A modied CEAP classication was applied
using the most severe clinical ndings and excluding C3.
13
121
122 Epidemiology of chronic venous disorders
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F
(%)
M
(%)
All
(%)
F
(%)
M
(%)
All
(%)
F
(%)
(%)
(%)
(%)
(%)
(%)
(%)
f
6.2 7.8 5.3
b
M
All
F
M
All
F
d
13.6 11.4 13.9 3.4 5.2 3.1 8.6 11.6 8.1
e h i
C0 C1 C2 C3 C4 C5 C6
M/F
M
(%)
All
(%)
F
(%)
M
(%)
All
(%)
F
(%)
M
(%)
All
(%)
size
Sample
Age
(years)
propor-
tion (%)
23.7 46.3 1.1 2.2 4.0 2.1 1.4 0.7 0.0 0.0
13.6 11.4 13.9
g
91,545 36.1 21.7 17.9 14.7 7.5 1.4 0.7
16.9
First
author
Table 10.1 Prevalence of chronic venous disorders C0–C6 (CEAP) in Western countries
(year) Country
USA 35.3/64.7 40–79 2211 19.0 33.6 11.0 51.6 43.6 55.9 23.3 15.0 27.7 5.8 7.4 4.9
13a
(2003)
Criqui
Poland 16.0/84.0 16–97 40,095 51.5 16.5 21.8 4.5 4.6 1.0 0.5
14a
(2003)
Jawien
Germany 43.9/56.1 18–79 3072 9.6 13.6 6.4 59.1 58.4 59.5 14.3 12.4 15.8 13.4 11.6 14.9 2.9 3.1 2.7 0.6 0.6 0.6 0.1 0.1 0.1
9a
(2003)
Rabe
France 67.7/32.3 Over 18 409 48.7
Italy 14.1/85.9 18–90 5187 22.7 36.0 20.6 64.8 33.4 69.9 29.4 29.3 29.4
10c
12c
(2004)
Carpentier
(2005)
Chiesa
Worldwide 31.6/68.4 50.6 ±
15a
(2012)
Rabe
Note: m: male; f: female.
Highest assigned clinical category.b Edema in the whole population.
All clinical categories listed.
Non-saphenous varicose veins.
Saphenous varicose veins.
Including C4–C6.
Including C0 + C1.
a
c
d
e
Including C4a only.i Including C4b–C6.
f
g
h
10.4 Prevalence of CVD 123
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A total of 19% were classied C0, 51.6% C1, 23.3% C2, and
6.2% C4–C6. Out of the whole population, 5.8% presented
with edema, 7.4% among men and 4.9% among women.
Prevalence of venous disease increased with age and in the
non-Hispanic white subpopulation. C1 and C2 were more
common in women than in men, but C4–C6 were more
common in men.
10.4.2 24-Cities Cohort Study, Italy
11,12
In this cross-sectional population study, 5247 participants
from 24 cities in the north, center, and south of Italy were
recruited during spring and summer 2003 by advertising
on television, in newspapers, and by leaets. e majority
of the participants were women (85.9%). All answered a
standardized questionnaire and were investigated clinically
and by duplex sonography. All clinical ndings were used
to dene the CEAP classes: 22.7% of the population was in
class C0, 64.8% C1, 43.0% C2, 13.6% C3, 3.4% C4a, and 8.6%
C4b–C6. CVI was dened as C1–C6. Risk factors for varicose veins were older age, living in southern Italy, number
of pregnancies, and positive family history.
10.4.3 Bonn Vein Study, Germany
9
Between November 2000 and March 2002, the German
Society of Phlebology performed the Bonn Vein Study in
the city of Bonn and two rural townships. e participants
were chosen from a random sample of the population registers. A total of 3072 participants (1722 women and 1350
men) between 18 and 79 years of age were investigated. All
participants answered a standardized questionnaire and
were investigated clinically and by duplex sonography by
four physicians trained in phlebology. e complete CEAP
classication was used. Within the clinical stages, the participants were classied according to the most severe clinical ndings.
Leg complaints consistent with symptoms of venous diseases, such as heaviness and a feeling of swelling, etc., were
present in 49.1% of the male population and 62.1% of the
female population. e prevalence increased with age. In
the 4 weeks preceding the investigation, 14.8% of the population experienced leg swelling: 7.9% of the men and 20.2%
of the women. Concerning the CEAP classication, only
9.6% of the population (13.6% men and 6.4% women) had
no signs of venous disorders (C0), while 59.1% (58.4% men
and 59.5% women) demonstrated telangiectasia or reticular
veins (C1) (Table 10.1).
Varicose veins without edema or skin changes (C2) were
present in 14.3% (12.4% men and 15.8% women) of the
population. At the time of investigation, 13.4% (11.6% men
and 14.9% women) had pretibial pitting edema (C3). Only
2.9% (3.1% men and 2.7% women) showed a C4 classication with skin changes such as eczema, pigmentation, or
lipodermatosclerosis. Only 0.6% had healed venous ulceration (C5), and 0.1% were aicted with active venous ulcers
(C6). Stages C2 and C3 had a signicantly higher prevalence
in the female population. e urban population showed a
higher frequency of CVI (C3–C6). e prevalence of stages
C2–C6 increased with age.
In a multivariate analysis adjusted for age and region of
living, risk factors for varicose veins were older age, female
gender, and number of pregnancies. Risk factors for CVI
were older age, obesity, and urban inhabitance.
10.4.4 The Polish Study
14
is cross-sectional, multicenter study involved 803 Polish
primary care physicians (general practitioners, internists,
and gynecologists). Fiy consecutive patients were selected
from their outpatient clinics. A total of 40,095 adults
between 16 and 97 years of age (mean age: 44.8 years) were
interviewed and clinically investigated. e majority were
women (84%). e clinical classication of CEAP (highest level) was used. CVI was diagnosed when any of the
stages C1–C6 was present. Leg complaints were reported in
up to 81% in the varicose vein group and up to 35% in the
varicose-free participants. A total of 10% of the population
presented with edema, 34.3% had varicose veins, and 1.5%
had active or healed venous ulcers. C0 was found in 51.1% of
the population, C1 in 16.5%, C2 in 21.8%, C3 in 4.5%, C4 in
4.6%, C5 in 1.0%, and C6 in 0.5%. Risk factors for varicose
veins were older age, number of pregnancies, positive family
history, and obesity. Female gender was not shown to be a
risk factor for varicose veins.
10.4.5 The French Study
10
In this cross-sectional study, a sub-population of a survey
concerning Raynaud’s phenomenon was used. A total of 409
participants (277 males and 132 females) were investigated
using a standardized questionnaire and clinical examination by trained vascular medicine professionals; 48.7%
were classied as C0 or C1. C2 was present in 23.7% of the
males and 46.3% of the females. C3 was found in 1.1% and
2.2%, respectively. A total of 4% of the men and 2.1% of the
women had skin changes (C4). Healed ulcers were found in
1.4% of the males and 0.7% of the females. No active ulcers
were reported.
Positive family history, advanced age, pregnancies and
height in women, and exercise frequency of less than once
a week in men were the main risk factors for varicose veins.
10.4.6 The Vein Consult Program
15
e most recent data derive from the Vein Consult
Program, a large, international observational prospective
survey that has been carried out on the initiative of the
Union Internationale de Phlébologie. A total of 6232 general
practitioners in Western, Central and Eastern Europe, Latin
America, and the Middle East screened 91,545 consecutive
patients clinically for the presence of CVDs. e mean age
was 50.6 years. A total of 16.4% of all participants showed an
asymptomatic C0 level and 19.7% had venous symptoms but
124 Epidemiology of chronic venous disorders
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no clinical signs of CVD (C0S). A total of 21.7% had reticular veins or telangiectasias, A total of 17.9% were on level C2,
14.7% C3, 7.5% C4, 1.4% C5, and 0.7% C6.
Even in the recent study protocols, there are still dif-
ferences concerning recruitment of the study population,
the age and sex distributions, and the denition of CVI
(Table 10.1). Only in three studies were the participants
investigated by duplex ultrasonography.
9,12,13
e method
of pitting edema assessment was mentioned only in the
Bonn Vein Study. is could explain the dierences in the
reported prevalence of C3, which varied between 1.1% and
14.9% (Table 10.1).
In the CEAP-based epidemiological studies, the reported
prevalence is similar for most of the classes (Table10.1).
C0 and C1 together are present in more than 60% of the
population (48.7%–70.6%). e prevalence of C2 is over
20% (17.9%–29.4%), with a higher number in women.
Skin changes due to venous diseases, including venous
ulcers, are reported in less than 10% of investigated individuals (3.6%–8.6%). e range of prevalence is from 0.6%
to 1.4% for healed ulcers and from 0% to 0.7% for active
9,10,12–15
ulcers.
10.5 PREVALENCE OF VENOUS REFLUX
In the pathogenesis of CVD, valve dysfunction and wall
dilation are followed by venous reux. In the Bonn Vein
Study, reux longer than 0.5 seconds was present in 21% of
the adult population (17.7% in men and 23.5% in women).22
A total of 20% of the adult population showed deep venous
reux (23.1% in men and 17.6% in women).22 Evans et al.
found similar results in the Edinburgh Vein Study.
23
10.6 PREVALENCE OF VENOUS
SYMPTOMS
e CEAP classication distinguishes symptomatic and
asymptomatic cases, with the symptoms being aching,
pain, tightness, sensation of skin irritation, heaviness,
muscle cramps, and others. Symptoms are typically exacerbated by heat or at the end of the day and relieved with leg
rest or elevation.21 Recent epidemiologic studies showed a
high prevalence of these symptoms in the general population being associated with, but not specic for, CVD.
the Bonn Vein Study, 56.4% of the participants claimed leg
symptoms assignable to CVD in the 4 weeks preceding the
investigation.30 Venous symptoms were more frequent in the
female population (62.1%) compared to the male population
(49.1%). e prevalence of symptoms increased with age and
with the clinical classes according to the CEAP classication.30 For participants in the San Diego Study, the prevalence of leg symptoms was higher when CVI trophic skin
changes were present. 24 In the varicose vein group, feeling
of heaviness was reported in 11.8% compared to 16.0% in
the trophic changes group. Similar dierences occurred for
sensation of swelling (19.1% vs. 35.7%), tired legs (18.3% vs.
21.1%), aching (25.5% vs. 29.1%), itching (8.7% vs. 13.1%),
24–2 9
In
and cramps (17.7% vs. 19.7%). Symptoms were more common in the female compared to the male population.
24
10.7 INCIDENCE OF CVD AND VENOUS
REFLUX
e incidence of CVD was assessed only in a few stud-
16,18 ,20
ies.
In the Framingham study, the incidence of varicose veins was 2.6% per year in women and 1.9% per year
in men.20 e incidence was comparable in all age groups.
In the Bonn Vein Study, we found an incidence for varicose
veins of 13.7% and for CVI of 13.0% aer a follow-up of 6.6
years.16 e incidence increased with age. In a follow-up
study of the Edinburgh Vein Study, Robertson etal. found a
13-year incidence of venous reux in the legs of 12.7% (95%
CI: 9.2%–17.2%) or 0.9% per year.18 e 13-year incidence of
reux was higher in the supercial veins at 8.8% compared
to the deep veins at 2.6%. No age and sex dierences were
found, but there was a higher incidence in obese participants and aer DVT.
18
10.8 PROGRESSION OF CVD
Recently, Lee etal. published the progression results of the
Edinburgh Vein Study.19 Aer a follow-up of 13.4 years,
57.8% of the participants (or 4.3% per year) showed a progression of venous disorders. A total of 31.9% of the participants who showed only varicose veins at baseline progressed
to CVI. Risk factors were family history of varicose veins
(odds ratio [OR]: 1.85, 95% CI: 1.14–1.30) and history of
DVT (OR: 4.10, 95% CI: 1.07–15.71). Overweight varicose
vein patients had a higher risk of developing CVI (OR: 1.85,
95% CI: 1.10–3.12).19 Participants of the Bonn Vein Study
with varicose veins from a symptomatic or asymptomatic
C2 class at baseline progressed to higher clinical classes in
up to 30% aer a follow-up of 6.6 years.17 ese data conrm the results from follow-up studies with patients on
the waiting list for varicose vein surgery. Brewster et al.
reported the follow-up results of 304 patients on a waiting
list for varicose vein surgery.31 Aer a mean waiting time
of 4 years, 64% reported a progression of the disease. A
total of 5.2% developed a supercial vein thrombosis while
waiting for the operation, 22% developed skin changes, and
12% developed venous leg ulcers. In a study of 116 limbs in
190 patients waiting for varicose vein surgery, Labropoulos
etal. reported 11.2% progression of the clinical stage aer a
median follow-up of 19 months.
32
Seven limbs progressed
from C2 to C3, four limbs from C3 to C4, and two limbs
from C4 to C6.
32
10.9 RISK FACTORS ASSOCIATED WITH
VARICOSE VEINS AND CHRONIC
VENOUS INSUFFICIENCY
e main risk factors associated with varicose veins are
advanced age, female gender, pregnancies, and positive
family history (Table 10.2).
10.11 Clinical recommendations 125
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Table 10.2 Association of risk factors with varicose veins
and chronic venous insufficiency
Risk factor VV CVI
Older age
Family history
Female gender
Pregnancies
Obesity
Oral contraceptives or hormone-replacement
therapy
Note: +: established; ±: uncertain; –: no association; CVI: chronic
venous insufficiency; VV: varicose vein.
+ +
+ +
+ ±
+ ±
± +
– –
10.9.1 Age
Older or advanced age was the most important risk factor
for varicose veins and CVI in all studies.
2-year incidence rate for varicose veins in the Framingham
study was 5.2% for women and 3.9% for men, resulting
in a steady increase in prevalence for varicose veins with
age.20 In the San Diego Study, older or advanced age as a
risk factorshowed a signicant OR of up to 2.42 for varicose
veins and up to 4.85 for CVI.13 In the Bonn Vein Study, older
age was the most important risk factor for varicose veins
and CVI. e ORs in the subgroup of age 70–79 years were
15.9 for varicose veins and 23.3 for CVI.
1,5,8–11, 13–15
9
e mean
10.9.2 Positive family history
A positive family history for varicose veins or venous diseases
is associated with a higher risk for varicose veins in several
1,8–10,14
studies.
veins were 2.1 in men and 2.3 in women, and for CVI were
1.4 (95% CI: 1.01–2.02) in men and 1.3 (95% CI: 0.92–1.74) in
women. is eect diminishes with age.33 Although heredity seems to be a risk factor for varicose veins, no responsible
genetic defects have been identied to date.
In the Bonn Vein Study, the ORs for varicose
conrmed parity as an independent risk factor for varicose
veins (OR: 2.0). In the Bonn Vein Study, the OR increased
with the number of pregnancies from 1.3 to 2.2. Neverpregnant women and men had similar prevalence rates for
varicose veins.35 Hormone-replacement therapy or oral contraceptives seem not to be risk factors for varicose veins or
CVI. In the Bonn Vein Study, we did not see a consistent
eect of hormone intake on varicose veins (OR: 0.9), but
there was a negative association with CVI (OR: 0.6).35 In a
5-year follow-up study, Jukkola etal.34 also demonstrated
that hormone-replacement therapy and oral contraceptives
did not increase the risk of varicose veins. Bérard etal.36
found a protective eect of hormone- replacement therapy
on the development of venous ulcers.
10.9.4 Obesit y
e role of obesity in varicose veins is controversial. In the
Framingham study, obesity with a body mass index (BMI)
greater than 27 kg/m2 increased the risk of varicose veins
in women but not in men.20 In the Bonn Vein Study, a BMI
greater than 30 kg/m2 increased the risk of varicose veins for
women (OR: 1.9), but not signicantly so. However, the risk
for CVI was increased signicantly for men and women (OR:
6.5 and 3.1, respectively).9 Iannuzzi and colleagues37 demonstrated a positive association of BMI greater than 30 kg/m2
with varicose veins in postmenopausal women (OR: 5.8).
Carpentier etal.10 did not nd an elevated risk for varicose
veins with obesity, but found a correlation with height in
women. In the Polish Study, obesity was a risk factor for
venous disease compared with participants withoutCVD.
14
10.9.5 Other risk factors
For other risk factors, such as smoking, hypertension,
physical activity, or constipation, the data are inconsistent.
Ifpositive, the risk seems to be low.
1,2,4,5,38,39
10.10 SUMMARY
10.9.3 Gender, pregnancies, and hormones
e prevalence of varicose veins is higher in women than in
men.1 In the San Diego Study, the OR for female gender as a
risk factor for varicose veins was 2.18, and in the Bonn Vein
Study, it was 1.5.
studies.
2,5,8
In contrast, there is no obvious gender dierence
for the prevalence of CVI. Chiesa etal.12 found a higher prevalence rate of edema (13.9% vs. 11.4%) but lower prevalence
rates of C4a (3.1% vs. 5.2%) and C4b–C6 (8.1% vs. 11.6%) in
women. Similar results were found in the Bonn Vein Study.9
In the San Diego Study, the OR for female gender and trophic changes was 0.65.13 e main cause of the gender dierences in varicose veins could be the number of pregnancies.
12
Chiesa etal.
found a higher OR for non-saphenous varicose
veins in women with previous pregnancies (OR: 1.11) than
that noted in nulliparous women (OR: 0.75). Jukkola etal.
9,13
Similar results could be shown in many
CVDs are among the most prevalent conditions in the
Western population, and venous symptoms such as heaviness of the legs, feeling of swelling, and pain during
standing are frequent complaints in the general population.
e prevalence of more severe chronic venous signs such as
eczema, pigmentation, and lipodermatosclerosis or venous
ulceration reaches around 5% in men and women. Varicose
veins can be found in more than 20% of the general population. Established risk factors for varicose veins are older
age, family history, female gender, and pregnancies. In CVI,
obesity plays an important additional role.
10.11 CLINICAL RECOMMENDATIONS
1. e prevalence of C0/C1 together is over 60% (48.7%–
34
70.6%), with varicose veins (C2) present in more than 20%
of the population (21.8%–29.4%). Skin changes resulting
126 Epidemiology of chronic venous disorders
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from venous disease, including venous ulcers, are present
in less than 10% of the population (3.6%–8.6%), with a
prevalence of between 0.6% and 1.4% for healed ulcers
and between 0% and 0.5% for active ulcers.
9,10,12–14
2. Relevant risk factors for varicose veins are:
a. Advanced age
b. Positive family history
9,13,2 0
9,10,14
c. Female gender
d. Multiparity
e. Obesity
3. Relevant risk factors for CVI are:
a. Advanced age
b. Positive family history
c. Obesity.
9,13
12,34
20
9,13
9
9,14
Guidelines 1.9.0 of the American Venous Forum on the epidemiology of chronic venous disorders
Grade of evidence
(A: high quality;
B:moderate quality;
No. Guideline
C:low or very low quality)
1.9.1 The prevalence of varicose veins in the adult population is more than 20%
(21.8%–29.4%).
1.9.2 About 5% (3.6%–9.6%) of the adult population has skin changes or ulcers due to
chronic venous insufficiency.
1.9.3 Active venous ulcers are present in 0.1%–0.7% of the adult population; 0.6%–1.4%
have healed ulcers.
1.9.4 Advanced age is a risk factor for varicose veins and chronic venous insufficiency. A
1.9.5 Positive family history, female gender, and multiparity are risk factors for varicose veins. A
1.9.6 Age and obesity are risk factors for chronic venous insufficiency. A
A
A
B
REFERENCES
●
= Key primary papers
●
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●
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●
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●
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●
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https://t.me/med1917
PART 2
https://t.me/med1917
Diagnostic Evaluations and Venous
Imaging Studies
11 Evaluation of hypercoagulable states and molecular markers of acute venous thrombosis 131
Diane M. Nitzki-George and Joseph A. Caprini
12 Duplex ultrasound scanning for acute venous disease 141
Timothy K. Liem
13 Duplex ultrasound scanning for chronic venous obstruction and valvular incompetence 151
Rafael D. Malgor and Nicos Labropoulos
14 Evaluation of venous function by indirect noninvasive testing (plethysmography) 165
Fedor Lurie and Thom W. Rooke
15 Direct contrast venography 169
Haraldur Bjarnason
16 Computed tomography and magnetic resonance imaging in venous disease 177
Terri J. Vrtiska and James F. Glockner
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