Chronic venous diseases: features of pathogenesis and rational approaches to therapy
Maksimov M.L.1, Ermolaeva A.S.2, Voznesenskaya A.A.2, Starodubtsev A.K.2
1 Kazan State Medical Academy — branch of Russian Medical Academy of Continuous Professional Education
2 Sechenov University, Moscow
Chronic venous disease (CVD) of the lower extremities is a rather common pathology affecting up to 50% of the adult population, among which lower extremity varicose vein disease (LEVVD) is the most common vascular disease. Previously it was believed that the cause of LEVVD is the failure of venous valves and reflux. Nevertheless, data from ultrasound and histological studies indicate that valve pathologies may be preceded by structural and functional changes in the venous wall. These changes, on the one hand, are a response to the violation of hemodynamics in the veins, and on the other — provoke further slowing of blood flow, blood congestion and stretching of the vein wall. A vicious circle, underlying the varicose transformation, is formed. The review presents current ideas about the mechanisms of the development of this process.
The article presents the issues of conservative treatment of CVD. The place and tasks of pharmacotherapy in the treatment of patients with CVD, namely the administration of phlebotonics, are considered. They provide a systemic effect aimed at improving the function of the venous and lymphatic systems. When received by courses, they improve the quality of life of patients and slow down the progression of the disease.
Key words: varicose disease, chronic venous insufficiency, pathogenesis, compliance, venotonic effect, phleboprotectors, Aescusan.
For citation: Maksimov M.L., Ermolaeva A.S., Voznesenskaya A.A., Starodubtsev A.K. Chronic venous diseases: features of pathogenesis and rational approaches to therapy // RMJ. Medical Review. 2018. № 4. P. 25–29.
References
1. Мубаракшина О.А., Сомова М.Н., Дронова Ю.М. Применение препаратов экстракта конского каштана в практике лечения хронических заболеваний вен // Терапия. 2017. №6. С.114–120 [Mubarakshina O.A., Somova M.N., Dronova Ju.M. Primenenie preparatov jekstrakta konskogo kashtana v praktike lechenija hronicheskih zabolevanij ven // Terapija. 2017. №6. S.114–120 (in Russian)].
2. Золотухин И., Селиверстов Е., Шевцов Ю. и др. Распространенность хронических заболеваний вен: результаты популяционного эпидемиологического исследования // Флебология. 2016. №4. С.119–125 [Zolotuhin I., Seliverstov E., Shevcov Ju. I dr. Rasprostranennost’ hronicheskih zabolevanij ven: rezul’taty populjacionnogo jepidemiologicheskogo issledovanija // Flebologija. 2016. №4. S.119–125 (in Russian)].
3. Evans C.J., Fowkes F.G., Ruckley C.V., Lee A J. Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study // J Epidemiol Community Heal. 1999. Vol. 53. №3. P.149–153.
4. Langer R.D., Ho E., Denenberg J.O. et al. Relationships between symptoms and venous disease: the San Diego population study // Arch Intern Med. 2005. Vol. 165. №12. P.1420–1424.
5. Chiesa R., Marone E.M., Limoni C. et al. Chronic venous insufficiency in Italy: the 24-cities cohort study // Eur J Vasc Endovasc Surg. 2005. Vol. 30. №4. P.422–429.
6. Jawien A., Grzela T., Ochwat A. Prevalence of chronic venous insufficiency in men and women in Poland: multicenter cross-sectional study in 40095 patients // Phlebology. 2003. Vol. 18. P.110–121.
7. Шевела А.И., Новиков П.Б., Серяпина Ю.В. Применение компрессионных изделий у пациентов с хроническими заболеваниями вен: оценка безопасности и эффективности // Флебология. 2017. №1. С.47–52 [Shevela A.I., Novikov P.B., Serjapina Ju.V. Primenenie kompressionnyh izdelij u pacientov s hronicheskimi zabolevanijami ven: ocenka bezopasnosti i jeffektivnosti // Flebologija. 2017. №1. S.47–52 (in Russian)].
8. Савельев В.С., Гологорский В.А., Кириенко А.И. и др. Флебология: Руководство для врачей / Под ред. В.С. Савельева. М., 2001. С.438, 647 [Savel’ev V.S., Gologorskij V.A., Kirienko A.I. i dr. Flebologija: Rukovodstvo dlja vrachej / Pod red. V.S. Savel’eva. M., 2001. S.438, 647 (in Russian)].
9. Белоусова О.В., Белоусов Е.А., Белоусов П.Е., Белоусова Е.В. Медико-социальное досье пациентов отделения сосудистой хирургии, страдающих варикозной болезнью вен нижних конечностей // Молодой ученый. 2016. №2. С.326–330 [Belousova O.V., Belousov E.A., Belousov P.E., Belousova E.V. Mediko-social’noe dos’e pacientov otdelenija sosudistoj hirurgii, stradajushhih varikoznoj bolezn’ju ven nizhnih konechnostej // Molodoj uchenyj. 2016. №2. S.326–330 (in Russian)].
10. Ассоциация флебологов России. Российские клинические рекомендации по диагностике и лечению хронических заболеваний вен // Флебология. 2013. Т.2(2). С.47 [Associacija flebologov Rossii. Rossijskie klinicheskie rekomendacii po diagnostike i lecheniju hronicheskih zabolevanij ven // Flebologija. 2013. Т.2(2). S.47 (in Russian)].
11. Naoum J.J., Hunter G.C., Woodside K.J., Chen C. Current Advances in the Pathogenesis of Varicose Veins // Journal of Surgical Research. 2007. Vol. 141(2). P.311–316.
12. Lim C.S., Davies A.H. Pathogenesis of primary varicose veins // The British Journal of Surgery. 2009. Vol. 96(11). P.1231–1242.
13. Pfisterer L., König G., Hecker M., Korff T. Pathogenesis of varicose veins — lessons from biomechanics // Vasa. 2014. Vol. 43(2). P. 88–99.
14. Segiet O.A., Brzozowa M., Piecuch A. et al. Biomolecular mechanisms in varicose veins development // Annals of Vascular Surgery. 2015. Vol. 29(2). P.377–384.
15. Krysa J., Jones G.T., van Rij A.M. Evidence for a genetic role in varicose veins and chronic venous insufficiency // Phlebology. 2012. Vol. 27(7). P.329–335.
16. Шадрина А.С. Золотухин И.А., Филипенко М.Л. Молекулярные механизмы развития варикозной болезни нижних конечностей // Флебология. 2017. №2. С.71–75 [Shadrina A.S. Zolotuhin I.A., Filipenko M.L. Molekuljarnye mehanizmy razvitija varikoznoj bolezni nizhnih konechnostej // Flebologija. 2017. №2. S.71–75 (in Russian)].
17. Badier-Commander C., Couvelard A., Henin D., Verbeuren T., Michel J-B., Jacob M-P. Smooth muscle cell modulation and cytokine overproduction in varicose veins. An in situ study // The Journal of Pathology. 2001. Vol. 193(3). P.398–407.
18. Варикозное расширение вен нижних конечностей без хронической венозной недостаточности (Клинические рекомендации) http://phlebology-sro.ru/upload/iblock/7de/klinicheskie-rekomendatsii-minzdrava-rf-po-vrv-bez-khvn-_2017_.pdf. [Varikoznoe rasshirenie ven nizhnih konechnostej bez hronicheskoj venoznoj nedostatochnosti (Klinicheskie rekomendacii) http://phlebology-sro.ru/upload/iblock/7de/klinicheskie-rekomendatsii-minzdrava-rf-po-vrv-bez-khvn-_2017_.pdf (in Russian)].
19. Committee Writing, Wittens C., Davies A.H. et al. Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS) Eur J Vasc Endovasc Surg. 2015. Vol. 49(6). P.678–737.
20. Gloviczki P., Comerota A., Dalsing M. et al. The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. Journal of vascular surgery. Vol. 53. №16S. P.2–48.
21. Nelson E.A., Bell-Syer S.E. Compression for preventing recurrence of venous ulcers // Cochrane Database Syst Rev. 2012. Vol. 8:CD002303.
22. Vandongen Y.K., Stacey M.C. Graduated compression elastic stockings reduce lipodermatosclerosis and ulcer recurrence // Phlebology. 2000. Vol. 15. P.33–37.
23. McDaniel H.B., Marston W.A., Farber M.A. et al. Recurrence of chronic venous ulcers on the basis of clinical, etiologic, anatomic, and pathophysiologic criteria and air plethysmography // J Vasc Surg. 2002. Vol. 35(4). P.723–728.
24. Mayberry J.C., Moneta G.L., Taylor L.M., Jr., Porter J.M. Fifteen-year results of ambulatory compression therapy for chronic venous ulcers // Surgery 1991. Vol. 109(5). P.575–581.
25. Dinn E., Henry M. Treatment of venous ulceration by injection sclerotherapy and compression hosiery: A 5-Year study // Phlebology 1992. Vol. 7(1). P.23–26.
26. Kiev J., Noyes L.D., Rice J.C., Kerstein M.D. Patient compliance with fitted compression hosiery monitored by photoplethysmography. Arch Phys Med Rehabil. 1990. Vol. 71(6). P. 376–379.
27. Finlayson K., Edwards H., Courtney M. The impact of psychosocial factors on adherence to compression therapy to prevent recurrence of venous leg ulcers // J Clin Nurs. 2010. Vol. 19(9–10). P.1289–1297.
28. Jull A.B., Mitchell N., Arroll J. et al. Factors influencing concordance with compression stockings after venous leg ulcer healing // J Wound Care. 2004. Vol. 13(3). P.90–92.
29. Ito T., Kukino R., Takahara M. et al. The wound/burn guidelines — 5: Guidelines for the management oflower leg ulcers/varicose veins // Japanese Journal of Dermatology. 2011.Vol. 121(12). P.2431–2448.
30. Майнсков А.В., Киселева Т.Л., Колхир В.К. и др. Лекарственные средства растительного происхождения в терапии хронической венозной недостаточности. М.: МОКБ Марс, 1999. 42 с. [Majnskov A.V., Kiseleva T.L., Kolhir V.K. i dr. Lekarstvennye sredstva rastitel’nogo proishozhdenija v terapii hronicheskoj venoznoj nedostatochnosti. M.: MOKB Mars, 1999. 42 s. (in Russian)].
31. Богачев В.Б., Голованова О.В., Кузнецов А.Н., Ершов П.В. Особенности лечения начальных форм хронических заболеваний вен. Российский научно-практический тематический журнал: Стационарзамещающие технологии // Амбулаторная хирургия. 2014. 3–4. С.15–20 [Bogachev V.B., Golovanova O.V., Kuznecov A.N., Ershov P.V. Osobennosti lechenija nachal’nyh form hronicheskih zabolevanij ven. Rossijskij nauchno-prakticheskij tematicheskij zhurnal: Stacionarzameshhajushhie tehnologii // Ambulatornaja hirurgija. 2014. 3–4. S.15–20 (in Russian)].
32. Pittler M.H., Ernst E. Horse chestnut seed extract for chronic venous insufficiency // Cochrane Databse of Systematic Reviews. 2012. Issue 11. Art. No: CD003230.
33. Suter A., Bommer S, Rechner J. Treatment of patients with venous insufficiency with fresh plant horse chestnut seed extract: a review of 5 clinical studies // Adv ther. 2006. Vol. 23(1). P.179–190.
34. Siebert U., Brach M, Sroczynski G, Berla K. Efficacy, routine effectiveness, and safety of horsechestnut seed extract in the treatment of chronic venous insufficiency. A meta-analysis of randomized controlled trials and large observational studies // Int Angiol. 2002. Vol. 21(4). P.305–315.
35. Joseph J. Naoum, Glenn C. Hunter. Pathogenesis of Varicose Veins and Implications for Clinical Management // Vascular. 2007. Vol. 15(5). P.242–249.
36. Sirtori CR. Aescin: pharmacology, pharmacokinetics and therapeutic profile // Pharmacol Res. 2001. Vol. 44. P.183–193.
37. Perrin M., Ramelet A-A. Pharmacological Treatment of Primary Chronic Venous Disease: Rationale, Results and Unanswered Questions // Eur J Vasc Endovasc Surg. 2011. Vol. 41. P. 117–125.
38. Diehm C., Trampisch H.J., Lange S., Schmidt C. Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency // Lancet. 1996. Feb 3. Vol. 347(8997). P. 292–294.
2. Золотухин И., Селиверстов Е., Шевцов Ю. и др. Распространенность хронических заболеваний вен: результаты популяционного эпидемиологического исследования // Флебология. 2016. №4. С.119–125 [Zolotuhin I., Seliverstov E., Shevcov Ju. I dr. Rasprostranennost’ hronicheskih zabolevanij ven: rezul’taty populjacionnogo jepidemiologicheskogo issledovanija // Flebologija. 2016. №4. S.119–125 (in Russian)].
3. Evans C.J., Fowkes F.G., Ruckley C.V., Lee A J. Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study // J Epidemiol Community Heal. 1999. Vol. 53. №3. P.149–153.
4. Langer R.D., Ho E., Denenberg J.O. et al. Relationships between symptoms and venous disease: the San Diego population study // Arch Intern Med. 2005. Vol. 165. №12. P.1420–1424.
5. Chiesa R., Marone E.M., Limoni C. et al. Chronic venous insufficiency in Italy: the 24-cities cohort study // Eur J Vasc Endovasc Surg. 2005. Vol. 30. №4. P.422–429.
6. Jawien A., Grzela T., Ochwat A. Prevalence of chronic venous insufficiency in men and women in Poland: multicenter cross-sectional study in 40095 patients // Phlebology. 2003. Vol. 18. P.110–121.
7. Шевела А.И., Новиков П.Б., Серяпина Ю.В. Применение компрессионных изделий у пациентов с хроническими заболеваниями вен: оценка безопасности и эффективности // Флебология. 2017. №1. С.47–52 [Shevela A.I., Novikov P.B., Serjapina Ju.V. Primenenie kompressionnyh izdelij u pacientov s hronicheskimi zabolevanijami ven: ocenka bezopasnosti i jeffektivnosti // Flebologija. 2017. №1. S.47–52 (in Russian)].
8. Савельев В.С., Гологорский В.А., Кириенко А.И. и др. Флебология: Руководство для врачей / Под ред. В.С. Савельева. М., 2001. С.438, 647 [Savel’ev V.S., Gologorskij V.A., Kirienko A.I. i dr. Flebologija: Rukovodstvo dlja vrachej / Pod red. V.S. Savel’eva. M., 2001. S.438, 647 (in Russian)].
9. Белоусова О.В., Белоусов Е.А., Белоусов П.Е., Белоусова Е.В. Медико-социальное досье пациентов отделения сосудистой хирургии, страдающих варикозной болезнью вен нижних конечностей // Молодой ученый. 2016. №2. С.326–330 [Belousova O.V., Belousov E.A., Belousov P.E., Belousova E.V. Mediko-social’noe dos’e pacientov otdelenija sosudistoj hirurgii, stradajushhih varikoznoj bolezn’ju ven nizhnih konechnostej // Molodoj uchenyj. 2016. №2. S.326–330 (in Russian)].
10. Ассоциация флебологов России. Российские клинические рекомендации по диагностике и лечению хронических заболеваний вен // Флебология. 2013. Т.2(2). С.47 [Associacija flebologov Rossii. Rossijskie klinicheskie rekomendacii po diagnostike i lecheniju hronicheskih zabolevanij ven // Flebologija. 2013. Т.2(2). S.47 (in Russian)].
11. Naoum J.J., Hunter G.C., Woodside K.J., Chen C. Current Advances in the Pathogenesis of Varicose Veins // Journal of Surgical Research. 2007. Vol. 141(2). P.311–316.
12. Lim C.S., Davies A.H. Pathogenesis of primary varicose veins // The British Journal of Surgery. 2009. Vol. 96(11). P.1231–1242.
13. Pfisterer L., König G., Hecker M., Korff T. Pathogenesis of varicose veins — lessons from biomechanics // Vasa. 2014. Vol. 43(2). P. 88–99.
14. Segiet O.A., Brzozowa M., Piecuch A. et al. Biomolecular mechanisms in varicose veins development // Annals of Vascular Surgery. 2015. Vol. 29(2). P.377–384.
15. Krysa J., Jones G.T., van Rij A.M. Evidence for a genetic role in varicose veins and chronic venous insufficiency // Phlebology. 2012. Vol. 27(7). P.329–335.
16. Шадрина А.С. Золотухин И.А., Филипенко М.Л. Молекулярные механизмы развития варикозной болезни нижних конечностей // Флебология. 2017. №2. С.71–75 [Shadrina A.S. Zolotuhin I.A., Filipenko M.L. Molekuljarnye mehanizmy razvitija varikoznoj bolezni nizhnih konechnostej // Flebologija. 2017. №2. S.71–75 (in Russian)].
17. Badier-Commander C., Couvelard A., Henin D., Verbeuren T., Michel J-B., Jacob M-P. Smooth muscle cell modulation and cytokine overproduction in varicose veins. An in situ study // The Journal of Pathology. 2001. Vol. 193(3). P.398–407.
18. Варикозное расширение вен нижних конечностей без хронической венозной недостаточности (Клинические рекомендации) http://phlebology-sro.ru/upload/iblock/7de/klinicheskie-rekomendatsii-minzdrava-rf-po-vrv-bez-khvn-_2017_.pdf. [Varikoznoe rasshirenie ven nizhnih konechnostej bez hronicheskoj venoznoj nedostatochnosti (Klinicheskie rekomendacii) http://phlebology-sro.ru/upload/iblock/7de/klinicheskie-rekomendatsii-minzdrava-rf-po-vrv-bez-khvn-_2017_.pdf (in Russian)].
19. Committee Writing, Wittens C., Davies A.H. et al. Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS) Eur J Vasc Endovasc Surg. 2015. Vol. 49(6). P.678–737.
20. Gloviczki P., Comerota A., Dalsing M. et al. The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. Journal of vascular surgery. Vol. 53. №16S. P.2–48.
21. Nelson E.A., Bell-Syer S.E. Compression for preventing recurrence of venous ulcers // Cochrane Database Syst Rev. 2012. Vol. 8:CD002303.
22. Vandongen Y.K., Stacey M.C. Graduated compression elastic stockings reduce lipodermatosclerosis and ulcer recurrence // Phlebology. 2000. Vol. 15. P.33–37.
23. McDaniel H.B., Marston W.A., Farber M.A. et al. Recurrence of chronic venous ulcers on the basis of clinical, etiologic, anatomic, and pathophysiologic criteria and air plethysmography // J Vasc Surg. 2002. Vol. 35(4). P.723–728.
24. Mayberry J.C., Moneta G.L., Taylor L.M., Jr., Porter J.M. Fifteen-year results of ambulatory compression therapy for chronic venous ulcers // Surgery 1991. Vol. 109(5). P.575–581.
25. Dinn E., Henry M. Treatment of venous ulceration by injection sclerotherapy and compression hosiery: A 5-Year study // Phlebology 1992. Vol. 7(1). P.23–26.
26. Kiev J., Noyes L.D., Rice J.C., Kerstein M.D. Patient compliance with fitted compression hosiery monitored by photoplethysmography. Arch Phys Med Rehabil. 1990. Vol. 71(6). P. 376–379.
27. Finlayson K., Edwards H., Courtney M. The impact of psychosocial factors on adherence to compression therapy to prevent recurrence of venous leg ulcers // J Clin Nurs. 2010. Vol. 19(9–10). P.1289–1297.
28. Jull A.B., Mitchell N., Arroll J. et al. Factors influencing concordance with compression stockings after venous leg ulcer healing // J Wound Care. 2004. Vol. 13(3). P.90–92.
29. Ito T., Kukino R., Takahara M. et al. The wound/burn guidelines — 5: Guidelines for the management oflower leg ulcers/varicose veins // Japanese Journal of Dermatology. 2011.Vol. 121(12). P.2431–2448.
30. Майнсков А.В., Киселева Т.Л., Колхир В.К. и др. Лекарственные средства растительного происхождения в терапии хронической венозной недостаточности. М.: МОКБ Марс, 1999. 42 с. [Majnskov A.V., Kiseleva T.L., Kolhir V.K. i dr. Lekarstvennye sredstva rastitel’nogo proishozhdenija v terapii hronicheskoj venoznoj nedostatochnosti. M.: MOKB Mars, 1999. 42 s. (in Russian)].
31. Богачев В.Б., Голованова О.В., Кузнецов А.Н., Ершов П.В. Особенности лечения начальных форм хронических заболеваний вен. Российский научно-практический тематический журнал: Стационарзамещающие технологии // Амбулаторная хирургия. 2014. 3–4. С.15–20 [Bogachev V.B., Golovanova O.V., Kuznecov A.N., Ershov P.V. Osobennosti lechenija nachal’nyh form hronicheskih zabolevanij ven. Rossijskij nauchno-prakticheskij tematicheskij zhurnal: Stacionarzameshhajushhie tehnologii // Ambulatornaja hirurgija. 2014. 3–4. S.15–20 (in Russian)].
32. Pittler M.H., Ernst E. Horse chestnut seed extract for chronic venous insufficiency // Cochrane Databse of Systematic Reviews. 2012. Issue 11. Art. No: CD003230.
33. Suter A., Bommer S, Rechner J. Treatment of patients with venous insufficiency with fresh plant horse chestnut seed extract: a review of 5 clinical studies // Adv ther. 2006. Vol. 23(1). P.179–190.
34. Siebert U., Brach M, Sroczynski G, Berla K. Efficacy, routine effectiveness, and safety of horsechestnut seed extract in the treatment of chronic venous insufficiency. A meta-analysis of randomized controlled trials and large observational studies // Int Angiol. 2002. Vol. 21(4). P.305–315.
35. Joseph J. Naoum, Glenn C. Hunter. Pathogenesis of Varicose Veins and Implications for Clinical Management // Vascular. 2007. Vol. 15(5). P.242–249.
36. Sirtori CR. Aescin: pharmacology, pharmacokinetics and therapeutic profile // Pharmacol Res. 2001. Vol. 44. P.183–193.
37. Perrin M., Ramelet A-A. Pharmacological Treatment of Primary Chronic Venous Disease: Rationale, Results and Unanswered Questions // Eur J Vasc Endovasc Surg. 2011. Vol. 41. P. 117–125.
38. Diehm C., Trampisch H.J., Lange S., Schmidt C. Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency // Lancet. 1996. Feb 3. Vol. 347(8997). P. 292–294.
This work is licensed under a Creative Commons «Attribution» 4.0 License.
Previous article
Next article
