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Ann Phlebology 2022; 20(2): 78-80

Published online December 31, 2022

https://doi.org/10.37923/phle.2022.20.2.78

© Annals of phlebology

The “C0s” Patient, What Do We Have to Know?

HaengJin Ohe, M.D., Ph.D.

Division of Vascular & Transplant, Department of Surgery, Seoul Paik Hospital, Inje University, Seoul, Korea

Correspondence to : HaengJin Ohe, 9 Mareunnae-ro, Jung-gu, Seoul 04551, Korea, Division of Vascular & Transplant, Department of Surgery, Seoul Paik Hospital, Inje University
Tel: 02-2270-0247, Fax: 02-2270-0017
E-mail: omarch@paik.ac.kr

Functional chronic venous disease (FCVD; C0 category of clinical manifestation, etiology, anatomic distribution, and pathophysiology classifications) is an underestimated syndrome that affects up to 20% of the general population. FCVD is based on the presence of venous symptoms without instrumental evidence of anatomical or morphological changes. The prevalence of FCVD is underestimated owing to a lack of awareness in Western countries. Given the inflammatory nature of FCVD, we speculate that noninvasive treatments including vasoactive drugs and elastic stockings would easily relieve C0 symptoms.

Keywords Chronic venous disease, Varicose vein, CEAP, C0, FCVD

The CEAP classification revised in 2020 classifies chronic venous disease into C (clinical manifestation), E (etiology), A (anatomic distribution), and P (pathophysiology). Among them, C was subdivided into categories C0-C6, and C0 was defined as “No visible or palpable signs of venous disease” (1).

The abovementioned CEAP classification, C0sEnAnPn, can be considered an objective situation without venous disease. However, since it relies on the patient’s subjective symptoms, scientific evidence of them is inevitably lacking and may lead to treatment confusion (2).

C0sEnAnPn patients were mentioned in several studies before the CEAP classification was developed in the mid-1980s, and the diagnosis of these patients in each study varied as follows (2-4):

  • Functional phlebopathy

  • Functional chronic venous disease (FCVD)

  • Varicose symptoms without varicose vein

  • Hypotonic phlebopathy

  • Phlebostatic syndrome

The prevalence of FCVD according to a few studies is reportedly 13.9∼19.7% in the general population (3-6): 13∼23% in the Polish Study; 15% in the San Diego Vein Study; 19.7% in the Belgium and Luxemburg subgroup of the Vein Consult Program; and >80% in the Vein Consult Program (of the latter, 20% were in the C0 category).

There are four types of epidemiology in the literature (2,3):

1. Hypotonic phlebopathy (HP) with subjective symptoms always present. This condition accounted for 26.83% of total HP cases;

2. Latent HP with subjective symptoms was referred intermittently (spring, summer, pregnancy, hard upright work). This condition accounted for 27.43% of the total number of HP cases;

3. Enhanced HP with subjective symptoms is continuously present during the examination period but occasionally in the past and is related to an identifiable cause, accounting for 29.89% of the total number of HP cases; and

4. Senile HP with subjective symptoms have been continuously documented since the sixth decade and never or occasionally in the past, accounting for 15.89% of the total number of HP cases.

The symptoms of FCVD primarily include heavy legs (74.39%), nighttime resting cramps, restless leg syndrome (29.26%), numbness, a burning sensation, achiness, and swelling (2,3).

The risk factors include family history (42.07%), obesity (37.19%), and constipation (29.26%). Hemodialysis and pregnancy are significant risk factors.

The scientific cause of these symptoms is venous wall tension caused by venous dilatation (prolonged standing position in a normal subject or venous incompetence in ill subjects) and hypoxia of the tunica media of the venous wall due to alteration of the vasa vasorum (2,7). These processes are triggered and modulated by various inflamma-tory cytokines (8). There is much evidence that the symptoms of FCVD improve greatly with conservative treatment that can reduce inflammatory reactions, including venoactive drugs (2,8,9) and compression therapy (10).

In 2016, the SYM Vein Consensus statement developed under the auspices of the European Venous Forum mentioned the pathophysiology, evaluation, and treatment of FCVD (2,11). The practical guidelines of the International Union of Angiology (IUA) suggested its pathophysiology, evaluation, and treatment according to scientific evidence in 2020 (12).

According to the practical guidelines of the IUA in 2020, treatments for FCVD can be summarized as follows (12):

  • Exclusion of non-venous cause of symptoms

  • Adaptation of lifestyle

  • Venoactive drugs

  • Topical venoactive drugs and topical heparinoids

  • Medical elastic stocking (ankle pressure 15∼20 mmHg)

The Vein Consult Program in 2012 reported that only 13% of C0 patients received lifestyle advice, while 8% were prescribed venoactive drugs (13). Due to a lack of awareness about C0 in the clinical field, many FCVD patients may be undertreated (13) or overtreated (14).

Although FCVD affects up to 20% of the general population, patients with FCVD are generally poorly treated. Given the inflammatory nature of CVD, we speculate that noninvasive treatment modalities to reduce inflammation may effectively control these symptoms.

  1. Lurie F, de Maeseneer MGR. The 2020 Update of the CEAP Classification: What is New? Eur J Vasc Endovasc Surg. 2020;59:859-60.
  2. Serra R, Andreucci M, de Caridi G, Massara M, Mastroroberto P, de Franciscis S. Functional chronic venous disease: a systematic review. Phlebology [Internet]. 2017 Oct 1 [cited 2022 Dec 13];32:588-92.
    Available from: https://journals.sagepub.com/doi/10.1177/0268355516686451?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed.
  3. Andreozzi GM, Signorelli SS, Pino L di. Varicose symptoms without varicose veins: the hypotonic phlebo-pathy, epidemiology and pathophysiology: the acireale project claudication treatment and pathophysiology View project [Internet].
    Available from: https://www.researchgate.net/publication/12134932.
  4. Andreozzi GM. Prevalence of patients with chronic venous disease-related symptoms but without visible signs (described as C0s in the CEAP classification): the Italian experience - Servier - PhlebolymphologyServier - Phlebolym-phology [Internet]. [cited 2022 Dec 21].
    Available from: https://www.phlebolymphology.org/prevalence-of-patients-with-chronic-venous-disease-related-symptoms-but-without-visible-signs-described-as-c0s-in-the-ceap-classification-the-italian-experience/.
  5. Langer RD, Ho E, Denenberg JO, Fronek A, Allison M, Criqui MH. Relationships Between Symptoms and Venous Disease: The San Diego Population Study. Arch Intern Med [Internet]. 2005 Jun 27 [cited 2022 Dec 14];165:1420-4.
  6. Vuylsteke ME, Colman R, Thomis S, Guillaume G, Degrande E, Staelens I. The influence of age and gender on venous symptomatology. An epidemiological survey in Belgium and Luxembourg. Phlebology [Internet]. 2016 Jun 1 [cited 2022 Dec 14];31:325-33.
  7. Nicolaides AN. Chronic Venous Disease and the Leukocyte-Endothelium Interaction: From Symptoms to Ulceration. 2016 Dec 11 [cited 2022 Dec 14];56(SUPPL. 1):11-9.
  8. Bush R, Comerota A, Meissner M, Raffetto JD, Hahn SR, Freeman K. Recommendations for the medical manage-ment of chronic venous disease: The role of Micronized Purified Flavanoid Fraction (MPFF): Recommendations from the Working Group in Chronic Venous Disease (CVD) 2016. Phlebology. 2017;32(1_suppl):3-19.
  9. Perrin M, Ramelet AA. Pharmacological Treatment of Primary Chronic Venous Disease: Rationale, Results and Unanswered Questions. Eur J Vasc Endovasc Surg. 2011;41:117-25.
  10. Blazek C, Amsler F, Blaettler W, Keo HH, Baumgartner I, Willenberg T. Compression hosiery for occupational leg symptoms and leg volume: a randomized crossover trial in a cohort of hairdressers. Phlebology. 2013;28:239-47.
  11. Venous symptoms: The SYM Vein Consensus statement developed under the auspices of the European Venous Forum | Lund University [Internet]. [cited 2022 Dec 14].
  12. Nicolaides A, Kakkos S, Baekgaard N, Comerota A, de Maeseneer M, Eklof B, et al. Management of chronic venous disorders of the lower limbs. Guidelines According to Scientific Evidence. Part II. Int Angiol [Internet]. 2020 Jun 1 [cited 2022 Dec 14];39:175-230.
  13. The “C0s” patient: Worldwide results from the vein consult program | Request PDF [Internet]. [cited 2022 Dec 14].
  14. Hong KP. Clinical efficacy of saphenous vein ablation in patients with CEAP C0-C1 chronic venous diseases. Annals of Phlebology [Internet]. 2021 Apr 30 [cited 2022 Dec 14];19:9-12.

Review Article

Ann Phlebology 2022; 20(2): 78-80

Published online December 31, 2022 https://doi.org/10.37923/phle.2022.20.2.78

Copyright © Annals of phlebology.

The “C0s” Patient, What Do We Have to Know?

HaengJin Ohe, M.D., Ph.D.

Division of Vascular & Transplant, Department of Surgery, Seoul Paik Hospital, Inje University, Seoul, Korea

Correspondence to:HaengJin Ohe, 9 Mareunnae-ro, Jung-gu, Seoul 04551, Korea, Division of Vascular & Transplant, Department of Surgery, Seoul Paik Hospital, Inje University
Tel: 02-2270-0247, Fax: 02-2270-0017
E-mail: omarch@paik.ac.kr

Abstract

Functional chronic venous disease (FCVD; C0 category of clinical manifestation, etiology, anatomic distribution, and pathophysiology classifications) is an underestimated syndrome that affects up to 20% of the general population. FCVD is based on the presence of venous symptoms without instrumental evidence of anatomical or morphological changes. The prevalence of FCVD is underestimated owing to a lack of awareness in Western countries. Given the inflammatory nature of FCVD, we speculate that noninvasive treatments including vasoactive drugs and elastic stockings would easily relieve C0 symptoms.

Keywords: Chronic venous disease, Varicose vein, CEAP, C0, FCVD

INTRODUCTION

The CEAP classification revised in 2020 classifies chronic venous disease into C (clinical manifestation), E (etiology), A (anatomic distribution), and P (pathophysiology). Among them, C was subdivided into categories C0-C6, and C0 was defined as “No visible or palpable signs of venous disease” (1).

The abovementioned CEAP classification, C0sEnAnPn, can be considered an objective situation without venous disease. However, since it relies on the patient’s subjective symptoms, scientific evidence of them is inevitably lacking and may lead to treatment confusion (2).

MAIN TEXT

C0sEnAnPn patients were mentioned in several studies before the CEAP classification was developed in the mid-1980s, and the diagnosis of these patients in each study varied as follows (2-4):

  • Functional phlebopathy

  • Functional chronic venous disease (FCVD)

  • Varicose symptoms without varicose vein

  • Hypotonic phlebopathy

  • Phlebostatic syndrome

The prevalence of FCVD according to a few studies is reportedly 13.9∼19.7% in the general population (3-6): 13∼23% in the Polish Study; 15% in the San Diego Vein Study; 19.7% in the Belgium and Luxemburg subgroup of the Vein Consult Program; and >80% in the Vein Consult Program (of the latter, 20% were in the C0 category).

There are four types of epidemiology in the literature (2,3):

1. Hypotonic phlebopathy (HP) with subjective symptoms always present. This condition accounted for 26.83% of total HP cases;

2. Latent HP with subjective symptoms was referred intermittently (spring, summer, pregnancy, hard upright work). This condition accounted for 27.43% of the total number of HP cases;

3. Enhanced HP with subjective symptoms is continuously present during the examination period but occasionally in the past and is related to an identifiable cause, accounting for 29.89% of the total number of HP cases; and

4. Senile HP with subjective symptoms have been continuously documented since the sixth decade and never or occasionally in the past, accounting for 15.89% of the total number of HP cases.

The symptoms of FCVD primarily include heavy legs (74.39%), nighttime resting cramps, restless leg syndrome (29.26%), numbness, a burning sensation, achiness, and swelling (2,3).

The risk factors include family history (42.07%), obesity (37.19%), and constipation (29.26%). Hemodialysis and pregnancy are significant risk factors.

The scientific cause of these symptoms is venous wall tension caused by venous dilatation (prolonged standing position in a normal subject or venous incompetence in ill subjects) and hypoxia of the tunica media of the venous wall due to alteration of the vasa vasorum (2,7). These processes are triggered and modulated by various inflamma-tory cytokines (8). There is much evidence that the symptoms of FCVD improve greatly with conservative treatment that can reduce inflammatory reactions, including venoactive drugs (2,8,9) and compression therapy (10).

In 2016, the SYM Vein Consensus statement developed under the auspices of the European Venous Forum mentioned the pathophysiology, evaluation, and treatment of FCVD (2,11). The practical guidelines of the International Union of Angiology (IUA) suggested its pathophysiology, evaluation, and treatment according to scientific evidence in 2020 (12).

According to the practical guidelines of the IUA in 2020, treatments for FCVD can be summarized as follows (12):

  • Exclusion of non-venous cause of symptoms

  • Adaptation of lifestyle

  • Venoactive drugs

  • Topical venoactive drugs and topical heparinoids

  • Medical elastic stocking (ankle pressure 15∼20 mmHg)

The Vein Consult Program in 2012 reported that only 13% of C0 patients received lifestyle advice, while 8% were prescribed venoactive drugs (13). Due to a lack of awareness about C0 in the clinical field, many FCVD patients may be undertreated (13) or overtreated (14).

CONCLUSION

Although FCVD affects up to 20% of the general population, patients with FCVD are generally poorly treated. Given the inflammatory nature of CVD, we speculate that noninvasive treatment modalities to reduce inflammation may effectively control these symptoms.

References

  1. Lurie F, de Maeseneer MGR. The 2020 Update of the CEAP Classification: What is New? Eur J Vasc Endovasc Surg. 2020;59:859-60.
  2. Serra R, Andreucci M, de Caridi G, Massara M, Mastroroberto P, de Franciscis S. Functional chronic venous disease: a systematic review. Phlebology [Internet]. 2017 Oct 1 [cited 2022 Dec 13];32:588-92. Available from: https://journals.sagepub.com/doi/10.1177/0268355516686451?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed.
  3. Andreozzi GM, Signorelli SS, Pino L di. Varicose symptoms without varicose veins: the hypotonic phlebo-pathy, epidemiology and pathophysiology: the acireale project claudication treatment and pathophysiology View project [Internet]. Available from: https://www.researchgate.net/publication/12134932.
  4. Andreozzi GM. Prevalence of patients with chronic venous disease-related symptoms but without visible signs (described as C0s in the CEAP classification): the Italian experience - Servier - PhlebolymphologyServier - Phlebolym-phology [Internet]. [cited 2022 Dec 21]. Available from: https://www.phlebolymphology.org/prevalence-of-patients-with-chronic-venous-disease-related-symptoms-but-without-visible-signs-described-as-c0s-in-the-ceap-classification-the-italian-experience/.
  5. Langer RD, Ho E, Denenberg JO, Fronek A, Allison M, Criqui MH. Relationships Between Symptoms and Venous Disease: The San Diego Population Study. Arch Intern Med [Internet]. 2005 Jun 27 [cited 2022 Dec 14];165:1420-4.
  6. Vuylsteke ME, Colman R, Thomis S, Guillaume G, Degrande E, Staelens I. The influence of age and gender on venous symptomatology. An epidemiological survey in Belgium and Luxembourg. Phlebology [Internet]. 2016 Jun 1 [cited 2022 Dec 14];31:325-33.
  7. Nicolaides AN. Chronic Venous Disease and the Leukocyte-Endothelium Interaction: From Symptoms to Ulceration. 2016 Dec 11 [cited 2022 Dec 14];56(SUPPL. 1):11-9.
  8. Bush R, Comerota A, Meissner M, Raffetto JD, Hahn SR, Freeman K. Recommendations for the medical manage-ment of chronic venous disease: The role of Micronized Purified Flavanoid Fraction (MPFF): Recommendations from the Working Group in Chronic Venous Disease (CVD) 2016. Phlebology. 2017;32(1_suppl):3-19.
  9. Perrin M, Ramelet AA. Pharmacological Treatment of Primary Chronic Venous Disease: Rationale, Results and Unanswered Questions. Eur J Vasc Endovasc Surg. 2011;41:117-25.
  10. Blazek C, Amsler F, Blaettler W, Keo HH, Baumgartner I, Willenberg T. Compression hosiery for occupational leg symptoms and leg volume: a randomized crossover trial in a cohort of hairdressers. Phlebology. 2013;28:239-47.
  11. Venous symptoms: The SYM Vein Consensus statement developed under the auspices of the European Venous Forum | Lund University [Internet]. [cited 2022 Dec 14].
  12. Nicolaides A, Kakkos S, Baekgaard N, Comerota A, de Maeseneer M, Eklof B, et al. Management of chronic venous disorders of the lower limbs. Guidelines According to Scientific Evidence. Part II. Int Angiol [Internet]. 2020 Jun 1 [cited 2022 Dec 14];39:175-230.
  13. The “C0s” patient: Worldwide results from the vein consult program | Request PDF [Internet]. [cited 2022 Dec 14].
  14. Hong KP. Clinical efficacy of saphenous vein ablation in patients with CEAP C0-C1 chronic venous diseases. Annals of Phlebology [Internet]. 2021 Apr 30 [cited 2022 Dec 14];19:9-12.
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Vol.21 No.2 Dec 31, 2023, pp. 53~98

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