By: Nick Morrison, MD, FACS, FACPh, RPhS Visit VeinGlobal at http://www.veinglobal.com/ for more presentations and videos on this topic, or for more information on venous disease news, education and research.

1. Nick Morrison, MD, FACS, FACPh, RPhS April 24, 2014
Should C2 Disease Classification Be
Broken Down Further?: Who
Progresses to C4?
Nick Morrison, MD, FACS, FACPh, RPhS April 24, 2014

2. Consultant, Research Grant - Sapheon
Educational Grant, MediUSA
Consultant, Merz
Scientific Advisory Board, VenX
Medical Director, Morrison Vein/Training Institute
Ballooning in Sedona, Arizona

3. Should C2 Disease Classification
Be Broken Down Further?
And should they be similarly
considered for treatment?
Are these patients really both C2?

4. Revision of the CEAP classification for chronic venous
disorders: Consensus statement
Varicose vein: Subcutaneous dilated vein 3 mm in diameter
or larger, measured in upright position. May involve
saphenous veins, saphenous tributaries or non-saphenous
superficial leg veins. Varicose veins are usually tortuous,
but tubular saphenous veins with demonstrated reflux may
be classified as varicose veins.
Eklof B, Rutherford RB, Bergan JJ, et al. J Vasc Surg 2004;40:1248–52
C2: Varicose Veins

5. Clinical, aetiological, anatomical and pathological classification
(CEAP): gold standard and limits
In the C2 class all kinds of varicose veins are summarized. Saphenous
veins in the interfacial space, accessory saphenous veins and
nonsaphenous tributaries may have different implications not only
for the severity of the disease but also for the risk of progression of
the disease, clinical symptoms and the choice of treatment. The
anatomical classification may add this information. However varicose
veins may have a small or a large diameter with implications for
clinical symptoms and for the choice of treatment option.
Rabe E, Pannier F. Phlebology 2012;27 Suppl 1:114–118.
C2: Varicose Veins

6. Prevalence of varicose veins and chronic venous insufficiency in
men and women in the general population: Edinburgh Vein Study.
Approximately one third of men and women aged 18–64 years had trunk varices.
Evans CJ, et al. J Epidemiol Community Health 1999;53:149–153
C2: Varicose Veins
What is the prevalence of varicose veins?
How about in older folks?
In a UK study, epidemiological risk factors for varicose veins in an elderly
population (avg:71yrs) was studied. The prevalence of trunk varices was 63.2
in men and 57.0% in women.
Clark A, et al. Phlebology 2010;25:236–240

7. Epidemiology of chronic venous disorders in geographically
diverse populations: results for the Vein Consult Program
UIP initiative large-scale, international, observational, prospective
survey carried out in 20 countries in 5 regions.
6,232 GPs screened 91,545 subjects
The results of the survey demonstrate that CVD is a global problem
that does not solely affect the Western world
Rabe E, et al. Int Angiol 2012;31(2):105-15
Are Varicose Veins a Problem for Western
Countries Only?
C2: Varicose Veins

8. Generic Health-related Quality of Life is Significantly Worse in
Varicose Vein Patients with Lower Limb Symptoms Independent
of Ceap Clinical Grade
Physical and mental HRQL is significantly worse in VV patients with lower limb
symptoms irrespective of the clinical stage of disease.
This observation confirms that VV are not primarily a cosmetic problem and
that NHS rationing of treatment to those with CEAP C4-6 disease excludes
many patients who would benefit from intervention in terms of HRQL.
Generic HRQL instruments also allow comparison with interventions for other
chronic conditions.
Darvall K, Bradbury A, et al. Eur J Vasc Endovasc Surg. 2012 Sep;44(3):341-4.
C2: Varicose Veins
Do Varicose Veins Make a Difference in
Quality of Life?

9. Relationship between clinical classification of chronic venous disease and
patient-reported quality of life: Results from an international cohort study
SF-36 Physical Component Summary scores and VEINES-QOL and VEINESSym
scores decreased significantly (ie, poorer QOL) with increasing CEAP class.
Kahn S, et al for VEINES Study Group. J Vasc Surg 2004;39:823-8.
Quality of life in patients with chronic venous disease: San Diego population
study
Chronic venous disease in the lower extremities has a substantial effect on
physical health aspects of quality of life but not on mental health
components.
Kaplan R, et al. J Vasc Surg 2003;37:1047-53.
C2: Varicose Veins
Do Varicose Veins Make a Difference in Quality of Life?

10. In an Italian study, the presence of symptoms correlated almost always positively with
both worsening of visible findings (P for trend < .001) and presence of hemodynamic
change in both genders.
Chiesa R, et al. J Vasc Surg 2007;46:433-30.
In UK women there was a significant relation between trunk varices and the symptoms
of heaviness or tension (P<0.001), aching (P<0.001), and itching (P<0.005).
Bradbury A, et al. BMJ 1999;318 :353-6.
It is possible to differentiate leg symptoms on the basis of CVD from other causes:
sensation of heavy or swollen legs, itching, impatient legs, or phlebalgia, worsened by
a hot environment or improved by a cold, not worsened by walking.
Carpentier P, et al. J Vasc Surg 2007;46:991-6.
C2: Varicose Veins
Question: What is the relationship between varicose veins
and symptoms?

11. C2: Varicose Veins
Question: What risk factors might help differentiate
patients with varicose veins?
The ascending severity of the classes was shown with the statistical
association of higher severity C classes with the age of the patient, a
history of previous deep vein thrombosis, the diameter class of the
most dilated varicose vein, venous symptoms, and the presence of a
corona phlebectatica.
Carpentier P, et al.J Vasc Surg 2003:37:827-33.

12. A Review of Familial, Genetic, and Congenital Aspects of Primary Varicose Vein Disease
It is apparent that there is a limited understanding of the complex underlying genetic
factors contributing to varicose vein formation. CVD is a complex, multifactorial disease,
and this needs to be considered in the planning of future genetic and epigenetic studies.
This approach has the potential to provide improved medical treatment for patients and
personalized, targeted preventive measures tailored to those identified to be at high risk
[and might also allow for treatment of specific patients at highest risk of disease
progression].
Anwar MA, Davies AH, et al. Circ Cardiovasc Genet 2012;5(4):460-6.
A Genetic Study of Chronic Venous Insufficiency
In families with affected patients with the D16S520 marker, there was evidence of
saphenofemoral junction reflux. The fact that there is linkage to a candidate marker for
the FOXC2 gene suggests there is a functional variant within, or in the vicinity of, which
predisposes to varicose veins.
Serra R, et al. Ann Vasc Surg 2012; 26: 636–642.
Question: What risk factors might help differentiate
patients with varicose veins?

13. Question: Can risk factors be modified to slow
progression of venous disease?
Risk factors for chronic venous disease: The San Diego Population
Study
Risk factors for venous disease: age, family history of venous disease,
and findings suggestive of ligamentous laxity (hernia surgery, flat feet)
are immutable, others can be modified, such as weight, physical
activity, and cigarette smoking. Overall, these data provide modest
support for the potential of behavioral risk-factor modification to
prevent chronic venous disease.
Criqui M, et al. J Vasc Surg 2007;46:331-7.

14. Oral Bacteria are a Possible Risk Factor for Valvular Incompetence in Primary
Varicose Veins
56 saphenous vein specimen (44 varicose veins and 12 control veins) were examined
for 7 periodontal bacteria.
Examination of the diseased vein specimens showed that 48% were positive for at
least one of 7 periodontal bacterial DNA. No bacteria were detected in the control
specimens.
Kurihara N, et al. Eur J Vasc Endovasc Surg 2007;34:102-106
So maybe we could study a large group of patients by first doing varicose vein
biopsies looking for periodontal bacteria and letting only the positive patients have
intervention for their C2 disorder.
Question: Can risk factors be modified to slow
progression of venous disease?

15. Incidence of Varicose Veins, Chronic Venous Insufficiency, and
Progression of the Disease in the Bonn Vein Study II (Abstract)
1978 (84.6% of Bonn I participants) reinvestigated
Participants with CEAP class C2 as a maximum at BVS I increased
to higher C classes in 19.8% (nonsaphenous varicose veins) and
in 31.8% (saphenous varicose veins).
Conclusions: These results show a high incidence of about 2%
for varicose veins and for CVI per year. During the same time,
the incidence of progression to higher C classes seems to be
very high.
Rabe E, et al. J Vasc Surg;51(3):791
Question: Do patients with varicose veins
progress to higher clinical stages?

16. Studies of the venous reflux progression
116 legs with 2 duplex and clinical exams a mean of 19 months apart
11.2% had progression of clinical stage, most from C2-C3
Approx. 30% had reflux progression
Labropoulos N, et al. J Vasc Surg 2005;41:291-5.
Venous vascular reflux in symptom-flee surgeons
Venous reflux was more frequently seen among symptom-free vascular
surgeons than normal individuals of a nonmedical vocation.
Labropoulos N, et al. J Vasc Surg 1995;22:150-4
Question: Do patients with varicose veins
progress to higher clinical stages?

17. UK: 36 patients waited a median time of 20 months for
intervention. We found a significant deterioration in this group
of patients.
Sarin D, Coleridge Smith PD, et al. J R Soc Med 1993;86:21-23.
Brazil: 92 women with GSV reflux followed for ̴3 yrs. Segmental
reflux declined and multi-segmental reflux increased. GSV reflux
worsens over time.
Engelhorn CA, Sallex-Cunha SX, et al. Phlebology 2012;27:25–32.
Question: Does venous function deteriorate in
patients waiting for varicose vein intervention?

18. Modelling the effect of venous disease on quality of life
Increasing clinical grade corresponded strongly with deterioration in disease specific
QoL (P < 0·001). The physical impairment seen with venous ulceration was comparable
with that seen in congestive cardiac failure and chronic lung disease.
Carradice D, et al. Br J Surg 2011; 98: 1089–1098
Towards an evidenced package of care for venous ulceration
$2500/year for unhealed ulcer – mostly for dressings
Bevis PM, Earnshaw JJ. Phlebology 2012;27:45–47
Questions: What happens with venous disease
progression?

19. The relevance of the natural history of varicose veins and refunded care
Bonn Vein Study
3072 participants from general population
C2 in 14.3%
VVs may progress from a symptomatic or asymptomatic C2 class to higher clinical
classes and CVI in a relevant percentage – up to 4% per year.
Quality of life (QOL) is also reduced in uncomplicated VV in C2 patients.
Conclusion
There is evidence that a high proportion of patients with uncomplicated VVs in the
clinical, aetiological, anatomical and pathophysiological classification (CEAP Clinical
Class 2) will progress to CVI if untreated.
VV patients with CVI (C3–C6) as well as those C2 patients with severe clinical
symptoms and impaired QOL due to CVD should be treated with ablation of the VVs
in a refunded care system.
Pannier F, Rabe E. Phlebology 2012;27 Suppl 1:23–26
Questions: What happens with venous disease
progression?

20. Costs of venous disease in UK, France, Germany 1.5-2% of total health care
expenditure
Bosanquet N, Franks P. Phlebology 1996; 11:6-9
Nurse-led varicose vein assessment and implementation of guidelines for
treatment [UK]
Objective: offer treatment only to those patients with skin changes and
ulcers in order to reduce the number of patients listed for surgery
Results: Surgery was considered necessary for 38% of those with varicose
veins. The remaining 62% were not listed for treatment. 53% fewer patients
were listed for surgery and the number on the waiting list had fallen by 62%.
Holdsworth J, et al. Phlebology 2004; 19: 69–71
Question: So how should we handle C2
patients?

21. Or we could adopt an entirely different way to look at varicose
veins:
Varicose veins may be “the price we pay” for an enhanced
ability to form [other] collateral vessels when necessary.
Rooke T, Felty C. J Vasc Surg: Venous and Lym Dis 2013
Question: So how should we handle C2
patients?

22. Question: So how should we handle C2
patients?
Mapping the future: Organizational, clinical, and research
priorities in venous disease
Assessment of reflux and symptomatic evaluation (ARSE)
This study proposes to evaluate the anatomic patterns of
reflux and hemodynamic parameters that most accurately
identify individual CEAP categories, forecast disease
progression to higher CEAP classes, and predict response
to therapy (quality of life, ulcer healing).
Meissner, et al. J Vasc Surg 2007;46(5):84S-93S.
OR…

23. There are many QoL instruments that have been validated
Generic QoL Disease-specific QoL
Short Form 36 AVVQ
EuroQol 5D VEINES-QOL
VEINES-SYM
CIVIQ
Question:
Insurers are desperately looking for ways to limit access to
care for C2 patients - so rather than have them arbitrarily cut
off funding for all C2 patients, what about combining the C2
classification with a QoL score and setting a clear standard by
which the necessity of treatment is judged?

24. Generic Health-related Quality of Life is Significantly Worse in Varicose Vein
Patients with Lower Limb Symptoms Independent of Ceap Clinical Grade
Physical and mental HRQL is significantly worse in VV patients with lower limb
symptoms irrespective of the clinical stage of disease.
This observation confirms that VV are not primarily a cosmetic problem and that NHS
rationing of treatment to those with CEAP C4-6 disease excludes many patients who
would benefit from intervention in terms of HRQL.
Generic HRQL instruments also allow comparison with interventions for other
chronic conditions.
Darvall K, Bradbury A, et al. Eur J Vasc Endovasc Surg. 2012 Sep;44(3):341-4.
Question:
Insurers are desperately looking for ways to limit access to
care for C2 patients - so rather than have them arbitrarily cut
off funding for all C2 patients, what about combining the C2
classification with a QoL score and setting a clear standard by
which the necessity of treatment is judged?

25. Question:
Insurers are desperately looking for ways to limit access to care for C2
patients - so rather than have them arbitrarily cut off funding for all C2
patients, what about combining the C2 classification with a QoL score and
setting a clear standard by which the necessity of treatment is judged?
The relevance of the natural history of varicose veins and refunded care
Bonn Vein Study
3072 participants from general population
C2 in 14.3%
VVs may progress from a symptomatic or asymptomatic C2 class to higher clinical
classes and CVI in a relevant percentage – up to 4% per year.
Quality of life (QOL) is also reduced in uncomplicated VV in C2 patients.
Conclusion
There is evidence that a high proportion of patients with uncomplicated VVs in the
clinical, aetiological, anatomical and pathophysiological classification (CEAP Clinical
Class 2) will progress to CVI if untreated.
VV patients with CVI (C3–C6) as well as those C2 patients with severe clinical
symptoms and impaired QOL due to CVD should be treated with ablation of the VVs
in a refunded care system.
Pannier F, Rabe E. Phlebology 2012;27 Suppl 1:23–26

26. Thank you for your kind attention
nickmorrison2002@yahoo.com