arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2015-21-2-168-180arthyper-210Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯORIGINAL ARTICLEОценка функционального состояния эндотелия у больных ревматологическими заболеваниямиEndothelial function in patients with rheumatologic diseasesМаслянскийА. Л.MaslyanskiyA. L.

кандидат медицинских наук, старший научный сотрудник научно-исследовательской лаборатории ревматологии ФГБУ «СЗФМИЦ» Минздрава России; 

MD, PhD, Senior Researcher, Research Department for Rheumatology, Federal North-West Medical Research Centre; 

esc_4@mail.ruЗвартауН. Э.ZvartauN. E.

кандидат медицинских наук, старший научный сотрудник научно-исследовательской лаборатории патогенеза и лечения артериальной гипертензии ФГБУ «СЗФМИЦ» Минздрава России; 

MD, PhD, Senior Researcher, Department of Hypertension Pathogenesis and Management, Research Department for Hypertension, Federal North-West Medical Research Centre;

КолесоваЕ. П.KolesovaE. P.

научный сотрудник научноисследовательской лаборатории эпидемиологии артериальной гипертензии ФГБУ «СЗФМИЦ» Минздрава России; 

MD, Researcher, Laboratory of Epidemiology of Hypertension, Research Department for Hypertension, Federal NorthWest Medical Research Centre

БезкишкийЭ. Н.BezkishkyE. N.

ведущий научный сотрудник ЗАО «Северо-Западный Центр доказательной медицины»; 

MD, Senior Researcher, North-Western Centre of Evidence-Based Medicine;

ШевчукИ. А.ShevchukI. A.

ведущий научный сотрудник ЗАО «Северо-Западный Центр доказательной медицины»;

MD, Senior Researcher, North-Western Centre of Evidence-Based Medicine;

ВасильеваЕ. Ю.VasilievaE. Yu.

заведующая центральной клиникодиагностической лабораторией ФГБУ «СЗФМИЦ» Минздрава России; 

Head, Clinical and Diagnostic Laboratory, Federal North-West Medical Research Centre;

МазуровВ. И.MazurovV. I.

доктор медицинских наук, профессор, академик РАН, заслуженный деятель науки Российской Федерации, главный ученый секретарь Президиума Северо-Западного отделения РАН, заведующий научно-исследовательской лабораторией ревматологии ФГБУ «СЗФМИЦ» Минздрава России;

MD, PhD, DMSc, Professor, Academician of Russian Academy of Sciences, Honoured Scientists of Russian Federation, Principal Academic Secretary of the Presidium of North-West Department of Russian Academy of Sciences, Head, Research Laboratory of Rheumatology, Federal North-West Medical Research Centre; 

КонрадиА. О.KonradiA. O.

доктор медицинских наук, профессор, заместитель генерального директора по научной работе ФГБУ «СЗФМИЦ» Минздрава России, руководитель научно-исследовательского отдела артериальной гипертензии ФГБУ «СЗФМИЦ» Минздрава России. 

MD, PhD, MDSc, Professor, Deputy Director General, Head, Research Department for Hypertension, Federal North-West Medical Research Centre

Федеральное государственное бюджетное учреждение «Северо-Западный федеральный медицинский исследовательский центр» Министерства здравоохранения Российской Федерации, Санкт-Петербург, РоссияРоссияFederal North-West Medical Research Centre, St Petersburg, RussiaRussian Federation201516072015212168180Copyright © Маслянский А.Л., Звартау Н.Э., Колесова Е.П., Безкишкий Э.Н., Шевчук И.А., Васильева Е.Ю., Мазуров В.И., Конради А.О., 20152015Маслянский А.Л., Звартау Н.Э., Колесова Е.П., Безкишкий Э.Н., Шевчук И.А., Васильева Е.Ю., Мазуров В.И., Конради А.О.Maslyanskiy A.L., Zvartau N.E., Kolesova E.P., Bezkishky E.N., Shevchuk I.A., Vasilieva E.Y., Mazurov V.I., Konradi A.O.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/210

Актуальность. Известно, что одной из лидирующих причин смертности у пациентов с ревматологической патологией являются сердечно-сосудистые заболевания и их осложнения. В связи с высокой актуальностью этой проблемы ученые различных стран в последние десятилетия изучают причины возникновения и быстрого прогрессирования сердечно-сосудистых заболеваний среди ревматологических пациентов. Одним из самых распространенных процессов, протекающих у данной когорты, является атеросклероз. Исследования последних лет показали, что традиционные факторы риска развития сердечно-сосудистых заболеваний играют далеко не ведущую роль в столь агрессивном характере атеросклеротического процесса. В связи с этим интересен поиск других факторов. Особого внимания заслуживает воспаление, которое характерно как для ревматологических заболеваний, так и для развития атеросклеротического поражения. Поэтому интерес представляет изучение ассоциации маркеров воспаления с изменением эндотелиальной функции как одного из ранних предикторов атеросклеротического процесса у больных ревматологическими заболеваниями. Цель исследования — изучить функциональное состояние эндотелия с использованием различных маркеров у больных системной красной волчанкой (СКВ), системной склеродермией (ССД), анкилозирующим спондилоартритом (АС) и ревматоидным артритом (РА) в зависимости от типа ревматологического заболевания. Материалы и методы. В исследование было включено 213 больных РЗ, 63 пациента без ревматологической патологии с наличием более чем 2 факторов риска сердечно-сосудистых заболеваний и 10 здоровых добровольцев. У всех пациентов определялись маркеры эндотелиальной дисфункции [гомоцистеин, асимметричный диметиларгинин (АДМА), эндотелин 1–21; молекула адгезии сосудистого эндотелия 1-го типа — vascular cell adhesion molecule 1, 1sVCAM-1; молекула межклеточной адгезии 1-го типа — intercellular adhesion molecule 1, sICAM-1] и индекс реактивной гиперемии (EndoPat 2000, Itamar Medical). Результаты. Профиль маркеров ЭД отличается при различных ревматологических заболеваниях, однако наиболее информативным показателем является уровень АДМА, особенно при подтипах, важным аспектом патогенеза которых является наличие аутоантител (СКВ, РА, ССД). 

Background. Сardiovascular diseases and their complications occupy one of the leading positions among causes of death in patients with rheumatologic diseases (RD), though the precise underlying mechanisms explaining fast progression of cardiovascular diseases are unknown. Early onset and high progression rate of atherosclerosis are the most common features, which cannot be fully explained by traditional cardiovascular risk factors. Inflammation, which is present in all RD and is involved in the pathogenesis of atherosclerosis, may contribute to the development of cardiovascular complications. Evaluation of the association between inflammation and endothelial dysfunction (an early predictor of atherosclerosis) may facilitate the understanding this mechanism. The objective of our study was to assess endothelial function in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), ankylosing spondylitis (AS) and rheumatoid arthritis (RA) and to evaluate the significance of various markers of endothelial dysfunction (ED), depending on the type of RD. Design and methods. The study enrolled 213 patients with various RD, 63 patients with ≥ 2 cardiovascular risk factors without RD and 10 healthy volunteers. Markers of endothelial dysfunction — homocysteine, asymmetric dimethylarginine (ADMA), endothelin 1–21, vascular cell adhesion molecule 1, 1sVCAM-1; intercellular adhesion molecule 1, sICAM-1 — and reactive hyperemia index (EndoPat 2000, Itamar Medical) were assessed in all patients. Results. The profile of ED markers differs in various RD, however, the most universal indicator is the ADMA level, especially in autoimmune RD with circulating autoantibodies (SLE, RA, SSc). 

дисфункция эндотелияревматологические заболеванияиндекс реактивной гиперемииасимметричный диметиларгининАДМАэндотелин 1–21адгезионные молекулыsICAM-1sVCAM-1гомоцистеинendothelial dysfunctionrheumatic diseasesreactive hyperemia indexasymmetric dimethylarginineADMAendothelin 1–21adhesion moleculessICAM-1sVCAM-1homocysteineReferencesRoifman I, Beck PL, Anderson TJ, Eisenberg MJ, Genest J. Chronic inflammatory diseases and cardiovascular risk: a systematic review. Can J Cardiol. 2011;27(2):174–182.Roifman I, Beck PL, Anderson TJ, Eisenberg MJ, Genest J. Chronic inflammatory diseases and cardiovascular risk: a systematic review. Can J Cardiol. 2011;27(2):174–182.Shoenfeld Y, Gerli R, Doria A, Matsuura E, Cerinic MM, Ronda N et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation. 2005;112(21):3337–3347.Shoenfeld Y, Gerli R, Doria A, Matsuura E, Cerinic MM, Ronda N et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation. 2005;112(21):3337–3347.Doria A, Pauletto P. The heart in systemic autoimmune diseases. Amsterdam, London. Elsevier; 2004. 260 р.Doria A, Pauletto P. The heart in systemic autoimmune diseases. Amsterdam, London. Elsevier; 2004. 260 р.Svenungsson E, Jensen-Urstad K, Heimburger M, Silveira A, Hamsten A, de Faire U et al. Risk factors for cardiovascular disease in systemic lupus erythematosus. Circulation. 2001;104 (16):1887–1893.Svenungsson E, Jensen-Urstad K, Heimburger M, Silveira A, Hamsten A, de Faire U et al. Risk factors for cardiovascular disease in systemic lupus erythematosus. Circulation. 2001;104 (16):1887–1893.Frostegard J. Rheumatic diseases: insights into inflammation and atherosclerosis. Arterioscler Thromb Vasc Biol. 2010;30 (5):892–893.Frostegard J. Rheumatic diseases: insights into inflammation and atherosclerosis. Arterioscler Thromb Vasc Biol. 2010;30 (5):892–893.Szekanecz Z, Koch AE. Vascular involvement in rheumatic diseases: vascular rheumatology. Arthritis Res Ther. 2008;10 (5):224.Szekanecz Z, Koch AE. Vascular involvement in rheumatic diseases: vascular rheumatology. Arthritis Res Ther. 2008;10 (5):224.Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980;23(5):581–590.Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980;23(5):581–590.Bijlsma JWJ. EULAR compendium on rheumatic diseases. London: Br Med J Publishing; 2009.Bijlsma JWJ. EULAR compendium on rheumatic diseases. London: Br Med J Publishing; 2009.Hudson M, Steele R, Baron M. Update on indices of disease activity in systemic sclerosis. Semin Arthritis Rheum. 2007;37 (2):93–98.Hudson M, Steele R, Baron M. Update on indices of disease activity in systemic sclerosis. Semin Arthritis Rheum. 2007;37 (2):93–98.Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25(6):1105–1187.Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25(6):1105–1187.Bonetti PO, Pumper GM, Higano ST, Holmes DRJr, Kuvin JT, Lerman A et al. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol. 2004;44(11):2137–2141.Bonetti PO, Pumper GM, Higano ST, Holmes DRJr, Kuvin JT, Lerman A et al. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol. 2004;44(11):2137–2141.Dunn OJ. Multiple contrasts using rank sums. Technometrics. 1964;5:241–252.Dunn OJ. Multiple contrasts using rank sums. Technometrics. 1964;5:241–252.Bodnar N, Kerekes G, Seres I, Paragh G, Kappelmayer J, Nemethne ZG et al. Assessment of subclinical vascular disease associated with ankylosing spondylitis. J Rheumatol. 2011;38 (4):723–729.Bodnar N, Kerekes G, Seres I, Paragh G, Kappelmayer J, Nemethne ZG et al. Assessment of subclinical vascular disease associated with ankylosing spondylitis. J Rheumatol. 2011;38 (4):723–729.Sari I, Okan T, Akar S, Cece H, Altay C, Secil M et al. Impaired endothelial function in patients with ankylosing spondylitis. Rheumatology (Oxford). 2006;45(3):283–286.Sari I, Okan T, Akar S, Cece H, Altay C, Secil M et al. Impaired endothelial function in patients with ankylosing spondylitis. Rheumatology (Oxford). 2006;45(3):283–286.Erre GL, Sanna P, Zinellu A, Ponchietti A, Fenu P, Sotgia S et al. Plasma asymmetric dimethylarginine (ADMA) levels and atherosclerotic disease in ankylosing spondylitis: a cross-sectional study. Clin Rheumatol. 2011;30(1):21–27.Erre GL, Sanna P, Zinellu A, Ponchietti A, Fenu P, Sotgia S et al. Plasma asymmetric dimethylarginine (ADMA) levels and atherosclerotic disease in ankylosing spondylitis: a cross-sectional study. Clin Rheumatol. 2011;30(1):21–27.Turiel M, Atzeni F, Tomasoni L, de Portu S, Delfino L, Bodini BD et al. Non-invasive assessment of coronary flow reserve and ADMA levels: a case-control study of early rheumatoid arthritis patients. Rheumatology (Oxford). 2009;48(7):834–839.Turiel M, Atzeni F, Tomasoni L, de Portu S, Delfino L, Bodini BD et al. Non-invasive assessment of coronary flow reserve and ADMA levels: a case-control study of early rheumatoid arthritis patients. Rheumatology (Oxford). 2009;48(7):834–839.Bultink IE, Teerlink T, Heijst JA, Dijkmans B, Voskuyl A. Raised plasma levels of asymmetric dimethylarginine are associated with cardiovascular events, disease activity, and organ damage in patients with systemic lupus erythematosus. Ann Rheum Dis.2005;64(9):1362–1365.Bultink IE, Teerlink T, Heijst JA, Dijkmans B, Voskuyl A. Raised plasma levels of asymmetric dimethylarginine are associated with cardiovascular events, disease activity, and organ damage in patients with systemic lupus erythematosus. Ann Rheum Dis.2005;64(9):1362–1365.Kemeny-Beke A, Gesztelyi R, Bodnar N, Zsuga J, Kerekes G, Zsuga M et al. Increased production of asymmetric dimethylarginine (ADMA) in ankylosing spondylitis: association with other clinical and laboratory parameters. Joint Bone Spine. 2011;78(2):184–187.Kemeny-Beke A, Gesztelyi R, Bodnar N, Zsuga J, Kerekes G, Zsuga M et al. Increased production of asymmetric dimethylarginine (ADMA) in ankylosing spondylitis: association with other clinical and laboratory parameters. Joint Bone Spine. 2011;78(2):184–187.Sobczak A, Goniewicz ML, Szoltysek-Boldys I. ADMA and SDMA levels in healthy men exposed to tobacco smoke. Atherosclerosis. 2009;205(2):357–359.Sobczak A, Goniewicz ML, Szoltysek-Boldys I. ADMA and SDMA levels in healthy men exposed to tobacco smoke. Atherosclerosis. 2009;205(2):357–359.Siervo M, Bluck LJ. In vivo nitric oxide synthesis, insulin sensitivity, and asymmetric dimethylarginine in obese subjects without and with metabolic syndrome. Metabolism. 2012;61 (5):680–688.Siervo M, Bluck LJ. In vivo nitric oxide synthesis, insulin sensitivity, and asymmetric dimethylarginine in obese subjects without and with metabolic syndrome. Metabolism. 2012;61 (5):680–688.Kaprove RE, Little AH, Graham DC, Rosen P. Ankylosing spondylitis: survival in men with and without radiotherapy. Arthritis Rheum. 1980;23(1):57–61.Kaprove RE, Little AH, Graham DC, Rosen P. Ankylosing spondylitis: survival in men with and without radiotherapy. Arthritis Rheum. 1980;23(1):57–61.Lehtinen K. Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis. Ann Rheum Dis. 1993;52(3):174–176.Lehtinen K. Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis. Ann Rheum Dis. 1993;52(3):174–176.Surdacki A, Martens-Lobenhoffer J, Wloch A, Gluszko P, Rakowski T, Dubiel E et al. Plasma asymmetric dimethylarginine is related to anticitrullinated protein antibodies in rheumatoid arthritis of short duration. Metabolism. 2009;58(3):316–318.Surdacki A, Martens-Lobenhoffer J, Wloch A, Gluszko P, Rakowski T, Dubiel E et al. Plasma asymmetric dimethylarginine is related to anticitrullinated protein antibodies in rheumatoid arthritis of short duration. Metabolism. 2009;58(3):316–318.Dimitroulas T, Sandoo A, Veldhuijzen van Zanten JJ, Smith J, Hodson J, Metsios G, et al. Predictors of asymmetric dimethylarginine levels in patients with rheumatoid arthritis: the role of insulin resistance. Scand J Rheumatol. 2013;42(3):176–181.Dimitroulas T, Sandoo A, Veldhuijzen van Zanten JJ, Smith J, Hodson J, Metsios G, et al. Predictors of asymmetric dimethylarginine levels in patients with rheumatoid arthritis: the role of insulin resistance. Scand J Rheumatol. 2013;42(3):176–181.Kwasny-Krochin B, Gluszko P, Undas A. Plasma asymmetric dimethylarginine in active rheumatoid arthritis: links with oxidative stress and inflammation. Pol Arch Med Wewn. 2012;122(6):270–276.Kwasny-Krochin B, Gluszko P, Undas A. Plasma asymmetric dimethylarginine in active rheumatoid arthritis: links with oxidative stress and inflammation. Pol Arch Med Wewn. 2012;122(6):270–276.Klimek E, Skalska A, Kwasny-Krochin B, Surdacki A, Sulicka J, Korkosz M et al. Differential associations of inflammatory and endothelial biomarkers with disease activity in rheumatoid arthritis of short duration. Mediators Inflamm. 2014;2014:681–635.Klimek E, Skalska A, Kwasny-Krochin B, Surdacki A, Sulicka J, Korkosz M et al. Differential associations of inflammatory and endothelial biomarkers with disease activity in rheumatoid arthritis of short duration. Mediators Inflamm. 2014;2014:681–635.Blaise S, Maas R, Trocme C, Kom G, Roustit M, Carpentier P et al. Correlation of biomarkers of endothelium dysfunction and matrix remodeling in patients with systemic sclerosis. J Rheumatol. 2009;36(5):984–988.Blaise S, Maas R, Trocme C, Kom G, Roustit M, Carpentier P et al. Correlation of biomarkers of endothelium dysfunction and matrix remodeling in patients with systemic sclerosis. J Rheumatol. 2009;36(5):984–988.Korkosz M, Gasowski J, Surdacki A, Leszczyński P, Katarzyna Pawlak-Bus, Sławomir Jeka et al. Disparate effects of anti-TNF-alpha therapies on measures of disease activity and mediators of endothelial damage in ankylosing spondylitis. Pharmacol Rep. 2013;65(4):891–897.Korkosz M, Gasowski J, Surdacki A, Leszczyński P, Katarzyna Pawlak-Bus, Sławomir Jeka et al. Disparate effects of anti-TNF-alpha therapies on measures of disease activity and mediators of endothelial damage in ankylosing spondylitis. Pharmacol Rep. 2013;65(4):891–897.Cobanoglu AK, Gungor O, Kircelli F, Altunel E, Asci G, Ozbek S et al. Role of asymmetric dimethylarginine in the progression of carotid atherosclerosis in renal transplant patients. Int Urol Nephrol. 2013;45(5):1463–1469.Cobanoglu AK, Gungor O, Kircelli F, Altunel E, Asci G, Ozbek S et al. Role of asymmetric dimethylarginine in the progression of carotid atherosclerosis in renal transplant patients. Int Urol Nephrol. 2013;45(5):1463–1469.Kuryliszyn-Moskal A, Klimiuk PA, Sierakowski S. Serum soluble adhesion molecules sICAM-1, sVCAM-1, sE-selectin in patients with systemic rheumatoid arthritis. Pol Merkur Lekarski. 2004;17 (100):353–356.Kuryliszyn-Moskal A, Klimiuk PA, Sierakowski S. Serum soluble adhesion molecules sICAM-1, sVCAM-1, sE-selectin in patients with systemic rheumatoid arthritis. Pol Merkur Lekarski. 2004;17 (100):353–356.Kuryliszyn-Moskal A, Klimiuk PA, Sierakowski S, Ciolkiewicz M. A study on vascular endothelial growth factor and endothelin-1 in patients with extra-articular involvement of rheumatoid arthritis. Clin Rheumatol. 2006;25(3):314–319.Kuryliszyn-Moskal A, Klimiuk PA, Sierakowski S, Ciolkiewicz M. A study on vascular endothelial growth factor and endothelin-1 in patients with extra-articular involvement of rheumatoid arthritis. Clin Rheumatol. 2006;25(3):314–319.Constans J, Conri C. Circulating markers of endothelial function in cardiovascular disease. Clin Chim Acta. 2006;368 (1–2):33–47.Constans J, Conri C. Circulating markers of endothelial function in cardiovascular disease. Clin Chim Acta. 2006;368 (1–2):33–47.Gustafsson JT, Simard JF, Gunnarsson I, Pettersson S, Moller S, Fei GZ et al. Risk factors for cardiovascular mortality in patients with systemic lupus erythematosus, a prospective cohort study. Arthritis Res Ther. 2012;14(2): R46.Gustafsson JT, Simard JF, Gunnarsson I, Pettersson S, Moller S, Fei GZ et al. Risk factors for cardiovascular mortality in patients with systemic lupus erythematosus, a prospective cohort study. Arthritis Res Ther. 2012;14(2): R46.Pizarro S, Monarrez Espino J, Ruiz A, Jara LJ, Nava A, Riebeling-Navarro C. Soluble vascular cell adhesion molecule-1 indicates SLE disease activity and specific organ involvement. Rev Alerg Mex. 2007;54(6):189–195.Pizarro S, Monarrez Espino J, Ruiz A, Jara LJ, Nava A, Riebeling-Navarro C. Soluble vascular cell adhesion molecule-1 indicates SLE disease activity and specific organ involvement. Rev Alerg Mex. 2007;54(6):189–195.Wei JC, Jan MS, Yu CT, Huang YC, Yang CC, Tsou HK et al. Plasma homocysteine status in patients with ankylosing spondylitis. Clin Rheumatol. 2007;26(5):739–742.Wei JC, Jan MS, Yu CT, Huang YC, Yang CC, Tsou HK et al. Plasma homocysteine status in patients with ankylosing spondylitis. Clin Rheumatol. 2007;26(5):739–742.Caramaschi P, Martinelli N, Biasi D, Carletto A, Faccini G, Volpe A et al. Homocysteine plasma concentration is related to severity of lung impairment in scleroderma. J Rheumatol. 2003;30 (2):298–304.Caramaschi P, Martinelli N, Biasi D, Carletto A, Faccini G, Volpe A et al. Homocysteine plasma concentration is related to severity of lung impairment in scleroderma. J Rheumatol. 2003;30 (2):298–304.

The authors declare that there are no conflicts of interest present.