rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2003-1331rsp-1209Research ArticleСтатьиArticlesГипергомоцистеинемия -дополнительный фактор риска тромбозов при системной красной волчанке и антифосфолипидном синдромеHyperhomocysteinemia - an additional risk factor of thrombosis in systemic lupus erythematosus and antiphospholipid syndromeShirokovaI. E.ShirokovaI. E.-ReshelnyakT MReshelnyakT M-200315082003414№4 (2003)3943Copyright © Shirokova I.E., Reshelnyak T.M., 20032003Shirokova I.E., Reshelnyak T.M.Shirokova I.E., Reshelnyak T.M.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/1209

Цель. Оценить уровень гомоиистеина (ГЦ) при системной красной волчанке (СКВ) и аитифо- сфолипидном синдроме (АФС), его связь с развитием тромбозов и нарушениями липидного спектра крови. Материал и методы. В исследование включено 32 пациента (12 муж и 20 жен), средний возраст составил 36+12 лет, средняя продолжительность заболевания 13+11лет. 8 пациентов имели СКВ без АФС, 13 - СКВ с АФС и 11 - ПАФС. Все пациенты были разделены на 2 группы в зависимости от уровня ГЦ в крови. В первую группу с уровнем ГЦ более 12 мкг/дл включено 26 чел., во 2-ю - с уровнем ГЦ менее 12 мкг/дл- 6 чел. Уровень ГЦ определялся методом высоко-эффективной жидкостной хроматографии (ВЭЖХ). У всех пациентов исследовался липид- белковый спектр крови. Результаты. Повышенный уровень ГЦ выявлен у 26 из 32 человек: у 16 - с СКВ, из них - 12 пациентов с вторичным АФС, и у 10 - с ПАФС. Средние значения ГЦ в зависимости от наличия АФС статистически не отличались. Однако частота выявления ГГЦ достоверно ассоциировалась с АФС и с тромботическими осложнениями. 20 из 26 (76,9 %) пациентов с ГГЦ имели тромбозы в анамнезе, во 2-ой группе - с нормальными значениями ГЦ - тромбоз в анамнезе был зарегистрирован только у I из 6 (16,7%) пациентов (точный критерий Фишера р=0,02). Не получено зависимости уровня ГЦ от возраста и пола. Изменения липид-белковых показателей крови выявлены у большей части больных. Нарушения липидного спектра в основном проявлялись повышением общего холестерина за счет повышения холестерина атерогенных липо- протеидов - ХС ЛПНП. При этом снижение концентрации ХС ЛПВП (антиатерогенных липо- протеидов) отмечалось только у 22% больных. Показатели липид-белкового спектра крови не зависели от уровня ГЦ. Заключение. ГГЦ отмечается у 84,6% больных с АФС (первичным и вторичным). У пациентов с наличием АФС частота выявления ГГЦ достоверно выше по сравнению с пациентами без АФС. Выявлена ассоциация ГГЦ с тромботическими осложнениями. Наличие ГГЦ вместе с нарушениями липид-белкового спектра крови являются независимым фактором риска тромботических осложнений у пациентов с СКВ и АФС.

Objective. To assess homocystein (HC) level in systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS) and its relation to thrombosis development and blood lipide spectrum disturbances. Material and methods. 32 pts (12 male and 20 female) with mean age 36 12 years and mean disease duration 13 11 years were included. 8 pts had SLE without APS, 13 - SLE with APS and 11 - primary APS (PAPS). All pts were divided into 2 groups depending on blood HC level. 26 pts with HC level more than 12 mcg/d! were included In group 1 and 6 pts with HC level less than 12 mcg/dl - in group 2. HC level was measured with high efficacious liquid chromatography (HELC). Lipid-protein blood spectrum was assessed in all pts. Results. Elevated HC level was revealed in 26 from 32 pts: in 16 with SLE (including 12 pts with APS) and in 10 with PAPS. HC concentration did not depend on APS presence, but frequence of hyperhomocysteinemia (HHC) significantly associated with APS and thrombotic complications. 20 from 26 (76,9%) pts with HHC had thrombosis history. Only I from 6 (16,7%) pts with normal HC level had thrombosis history (exact Fisher test p=0,02). HC level did not depend on age and sex. Changes of blood lipid-protein indices were revealed in most pts. Lipid spectrum disturbances were confined largely to cholesterol elevation due to increase of atherogenic lipoproteins cholesterol. Only 22% of pts showed decrease of antiatherogenic lipoproteins concentration. Bblood lipid-protein spectrum indices did not depend on HC level. Conclusion. HHC is present in 84,6% of pts with APS (primary and secondary). In pts with APS HHC is more frequent than in pts without APS. HHC is associated with thrombotic complications. HHC and lipid-protein spectrum disturbances are independent risk factors of thrombotic complications in pts with SLE and APS.

антифосфсыипидный синдромсистемная красная волчанкатромбозыго- моцистеинantiphospholipid syndromesystemic lupus erythematosushomocysteinReferences<div><p>Алекберова З.С., Попкова Т. В., Насонов Е.Л. с соавт. Липид-белковые системы транспорта холестерина у больных системной красной волчанкой в зависимости от антифосфолипндного синдрома. Тер.архив, 1999, 5, 34-38.</p><p>Баркаган З.С., Момот А.П. Основы диагностики нарушения гемостаза. М., Ныодиамед-АО, 1999, 215.</p><p>Насонова В.А. Системная красная волчанка. М., Медицина, 1972.</p><p>Насонов ЕЛ., Карпов Ю.А., Алекберова З.С. Антифо- сфолипидный синдром: кардиологические аспек- ты.Тер.архив, 1993,11, 5-13.</p><p>Abu-Shakra М., Urowitz М.В., Gladinan D.D. et al. Mortality studies in SLE. Results from a single center. I. Causes of death. J Rheumatol., 1995, 22,1259-1264.</p><p>Alpert M.A. Homocyst(e)ine, atherosclerosis and thrombosis. South Med. J. 1999, 92 (9). 858-865.</p><p>Asherson R.A., Rhamaihta M.A., Ordi-Ros J. et al. The "primary” antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore), 1989, 68, 366374.</p><p>Bruce IN, Burns RJ. High prelevance of myocardial perfusion abnormalities in women with SLE. Arthr. Rheum, 1997, 40 (suppl.9), 219.</p><p>Cattaneo M. Hyperhomocysteinemia, atherosclerosis and thrombosis. Thromb. Haemost., 1999, 81, 65-76.</p><p>DAngello A., Mazzola G., Grippa L. Hyperhomocysteine- mia and venous thromboembolic disease. Haematologica,, 1997, 82, 211-219.</p><p>Exner Т., Sahman N. Trudinger B. Separation of anticar- diolipin antibodies from lupus anticoagulant on phospho- lipidcoated polysterine column. Biochem. Biophys. Res.Commun., 1988, 155, 1001-1007.</p><p>Falconi C.R., Cattaneo M. Prevalence of moderate hyper- homocysteinemia in patients with early- onset venouse and arterial occlusive disease. Ann. Intern. Med., 1995, 123, 747.</p><p>Fijnheer R. Roest М., Haas FJ. et al. Homocysteine, methylenetetrahydrofolate reductase polymorphism, antiphospholipid antibodies, and thromboembolic events in systemic lupus erythematosus: a retrospective cohort study J. Rheumatol., 1998, 25(9), 1737-1742.</p><p>Harker L.A., Ross R., Slichter S.J., Scott C.R. Homocysteine-induced arteriosclerosis. The role of endothelial cell injure and platelet response in its genesis. J. Clin.Invest., 1976, 58, 731-741.</p><p>Hughes G.R.V., Harris E.N., Charavi А.Е. The anlicardi- olipin syndrome. J.Reumatol., 1986, 13, 486-489.</p><p>Jensen R. The new markers of cardiovascular risk. Clin. Haemostasis Rev., 2000, 14, 1-4.</p><p>Petri М., RoubenotT R., Dallal G.E. et al. Plasma homocysteine as a risk factor for atherothroinbotic events in systemic lupus erythematosus. Lancet, 1996. 26, 348(9035), 1120-1124.</p><p>Saez G., Thornalley P.J., Hill H.A. et al. The production of free redicals during the autoxidation of cysteine and their eflecl on isolated rat hepatocytes. Biochim. Biophys., 1982. 719, 24-31,</p><p>Seriolo B., Fasciolo D., Sulli A. Homocysteine and antiphospholipid antibodies in rheumatoid arthritis patients: relationships with thrombotic events. Clin. Exp.Rheumatol., 2001, 19(5), 561-564.</p><p>SeLhub J., Jacques P.F., Wilson P.W. et al. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA., 1993. 270, 2693-2698.</p><p>Starkebaum G., Harlan M. Endothelial cell injure due lo copper-catalysed hydrogen peroxide generation from homocysteine. J.Clin.Invest., 1986, 77, 1370-1376.</p><p>Svenungsson E., Jensen-Urstad K., Heimburger M. et al. Risk factors for cardiovascular disease in systemic lupus erythematosus. J.Circulation, 2001, 16,104(16), 1887-1893,</p><p>Tan E.M., Cohen A.S., Fries J.F. et al. The 1982 revised criteria for classification of systemic lupus erythematosus. Arthr. Rheum., 1982. 136, 347-354.</p><p>Tsai J-С., Perrella M.A., Yoshizumi M. et al. Promolion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. Proc.Natl. Acad. Sci. (USA), 1994, 91, 6369-6373.</p><p>Upchurch G.R., Welch G.N. Homocysteine attenuates endothelial glutatione peroxidase and thereby potentiates peroxide-mediated cell injure. Circulation, 1995, 92, 1228.</p><p>Vianna J.K., Khamasha M.A., Ordi-Ros J., et al. Comparision of the primary and secondary antiphospholipid syndrome: a European multicenter study of 114 patients. Am. J. Med., 1994, 96, 3-9.</p><p>Zmuda J.M., Bausserman L.L., Maceroni D. The effect of supraphysiologic doses of testosteroni on fasting total homocysteine levels in normal men. Atherosclerosis, 1997. 130. 199-202.</p><p>Welch G.N, Upchurch G., Loscalzo J, Hyperhomo- cyst(e)inemia and atherothrombosis. Ann. N. Y. Acad. Sci,1997, 15, 811.48-58.</p></div><br /><div><p>Алекберова З.С., Попкова Т. В., Насонов Е.Л. с соавт. Липид-белковые системы транспорта холестерина у больных системной красной волчанкой в зависимости от антифосфолипндного синдрома. Тер.архив, 1999, 5, 34-38.</p><p>Баркаган З.С., Момот А.П. Основы диагностики нарушения гемостаза. М., Ныодиамед-АО, 1999, 215.</p><p>Насонова В.А. Системная красная волчанка. М., Медицина, 1972.</p><p>Насонов ЕЛ., Карпов Ю.А., Алекберова З.С. Антифо- сфолипидный синдром: кардиологические аспек- ты.Тер.архив, 1993,11, 5-13.</p><p>Abu-Shakra М., Urowitz М.В., Gladinan D.D. et al. Mortality studies in SLE. Results from a single center. I. Causes of death. J Rheumatol., 1995, 22,1259-1264.</p><p>Alpert M.A. Homocyst(e)ine, atherosclerosis and thrombosis. South Med. J. 1999, 92 (9). 858-865.</p><p>Asherson R.A., Rhamaihta M.A., Ordi-Ros J. et al. The "primary” antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore), 1989, 68, 366374.</p><p>Bruce IN, Burns RJ. High prelevance of myocardial perfusion abnormalities in women with SLE. Arthr. Rheum, 1997, 40 (suppl.9), 219.</p><p>Cattaneo M. Hyperhomocysteinemia, atherosclerosis and thrombosis. Thromb. Haemost., 1999, 81, 65-76.</p><p>DAngello A., Mazzola G., Grippa L. Hyperhomocysteine- mia and venous thromboembolic disease. Haematologica,, 1997, 82, 211-219.</p><p>Exner Т., Sahman N. Trudinger B. Separation of anticar- diolipin antibodies from lupus anticoagulant on phospho- lipidcoated polysterine column. Biochem. Biophys. Res.Commun., 1988, 155, 1001-1007.</p><p>Falconi C.R., Cattaneo M. Prevalence of moderate hyper- homocysteinemia in patients with early- onset venouse and arterial occlusive disease. Ann. Intern. Med., 1995, 123, 747.</p><p>Fijnheer R. Roest М., Haas FJ. et al. Homocysteine, methylenetetrahydrofolate reductase polymorphism, antiphospholipid antibodies, and thromboembolic events in systemic lupus erythematosus: a retrospective cohort study J. Rheumatol., 1998, 25(9), 1737-1742.</p><p>Harker L.A., Ross R., Slichter S.J., Scott C.R. Homocysteine-induced arteriosclerosis. The role of endothelial cell injure and platelet response in its genesis. J. Clin.Invest., 1976, 58, 731-741.</p><p>Hughes G.R.V., Harris E.N., Charavi А.Е. The anlicardi- olipin syndrome. J.Reumatol., 1986, 13, 486-489.</p><p>Jensen R. The new markers of cardiovascular risk. Clin. Haemostasis Rev., 2000, 14, 1-4.</p><p>Petri М., RoubenotT R., Dallal G.E. et al. Plasma homocysteine as a risk factor for atherothroinbotic events in systemic lupus erythematosus. Lancet, 1996. 26, 348(9035), 1120-1124.</p><p>Saez G., Thornalley P.J., Hill H.A. et al. The production of free redicals during the autoxidation of cysteine and their eflecl on isolated rat hepatocytes. Biochim. Biophys., 1982. 719, 24-31,</p><p>Seriolo B., Fasciolo D., Sulli A. Homocysteine and antiphospholipid antibodies in rheumatoid arthritis patients: relationships with thrombotic events. Clin. Exp.Rheumatol., 2001, 19(5), 561-564.</p><p>SeLhub J., Jacques P.F., Wilson P.W. et al. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA., 1993. 270, 2693-2698.</p><p>Starkebaum G., Harlan M. Endothelial cell injure due lo copper-catalysed hydrogen peroxide generation from homocysteine. J.Clin.Invest., 1986, 77, 1370-1376.</p><p>Svenungsson E., Jensen-Urstad K., Heimburger M. et al. Risk factors for cardiovascular disease in systemic lupus erythematosus. J.Circulation, 2001, 16,104(16), 1887-1893,</p><p>Tan E.M., Cohen A.S., Fries J.F. et al. The 1982 revised criteria for classification of systemic lupus erythematosus. Arthr. Rheum., 1982. 136, 347-354.</p><p>Tsai J-С., Perrella M.A., Yoshizumi M. et al. Promolion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. Proc.Natl. Acad. Sci. (USA), 1994, 91, 6369-6373.</p><p>Upchurch G.R., Welch G.N. Homocysteine attenuates endothelial glutatione peroxidase and thereby potentiates peroxide-mediated cell injure. Circulation, 1995, 92, 1228.</p><p>Vianna J.K., Khamasha M.A., Ordi-Ros J., et al. Comparision of the primary and secondary antiphospholipid syndrome: a European multicenter study of 114 patients. Am. J. Med., 1994, 96, 3-9.</p><p>Zmuda J.M., Bausserman L.L., Maceroni D. The effect of supraphysiologic doses of testosteroni on fasting total homocysteine levels in normal men. Atherosclerosis, 1997. 130. 199-202.</p><p>Welch G.N, Upchurch G., Loscalzo J, Hyperhomo- cyst(e)inemia and atherothrombosis. Ann. N. Y. Acad. Sci,1997, 15, 811.48-58.</p></div><br />

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