uzspbgmuУчёные записки Первого Санкт-Петербургского государственного медицинского университета имени академика И. П. ПавловаThe Scientific Notes of the Pavlov University1607-41812541-8807Academician I.P. Pavlov First St. Petersburg State Medical University10.24884/1607-4181-2019-26-3-31-42uzspbgmu-613Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESВлияние сердечно-сосудистых заболеваний на течение рассеянного склероза (обзор литературы)The effect of cardiovascular diseases on the course of multiple sclerosis (review of literature)https://orcid.org/0000-0001-9043-9823НеофидовН. А.NeofidovN. A.

Неофидов Николай Александрович, врач-невролог Городского центра рассеянного склероза и других аутоиммунных заболеваний (ГБУЗ ГКБ №31); аспирант кафедры неврологии ПСПбГМУ им. акад. И.П. Павлова

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8.

6-8, L. Tolstoy str., Saint Petersburg, 197022. 

neofidoff@yandex.ruhttps://orcid.org/0000-0002-6715-8203ТотолянН. А.TotolyanN. A.

Тотолян Наталья Агафоновна, д.м.н., профессор кафедры неврологии 

Санкт-Петербург

Saint Petersburg

ntotolyan@mail.ruhttps://orcid.org/0000-0001-7439-2690ШумилинаМ. В.ShumilinaM. V.

Шумилина Мария Васильевна, к.м.н.

Санкт-Петербург

Saint Petersburg

m.shumilina@centrems.comhttps://orcid.org/0000-0002-5884-3110СкоромецА. А.SkorometsA. A.

Скоромец Александр Анисимович, заведующий кафедрой, д.м.н., проф. кафедры неврологии 

Санкт-Петербург

Saint Petersburg

askoromets@gmail.comhttps://orcid.org/0000-0002-8006-237XЕвдошенкоЕ. П.EvdoshenkoE. P.

Евдошенко Евгений Петрович, руководитель Городского центра рассеянного склероза и других аутоиммунных заболеваний СПб (ГБУЗ ГКБ №31), к.м.н.

Санкт-Петербург

Saint Petersburg

e.evdoshenko@centrems.comСанкт-Петербургское государственное учреждение здравоохранения «Городская клиническая больница № 31», Городской центр рассеянного склероза и других аутоиммунных заболеваний; Федеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияCity Clinical Hospital № 31, City Center for Multiple Sclerosis and Other Autoimmune Diseases; Pavlov UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияPavlov UniversityRussian Federation2019041020192633142Copyright © Неофидов Н.А., Тотолян Н.А., Шумилина М.В., Скоромец А.А., Евдошенко Е.П., 20202020Неофидов Н.А., Тотолян Н.А., Шумилина М.В., Скоромец А.А., Евдошенко Е.П.Neofidov N.A., Totolyan N.A., Shumilina M.V., Skoromets A.A., Evdoshenko E.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sci-notes.ru/jour/article/view/613

Коморбидность является одним из факторов, определяющих течение рассеянного склероза. Кардиоваскулярная патология является одной из самых распространенных в популяции в целом, особенно в возрастных группах старше 50 лет. В нескольких исследованиях показано, что артериальная гипертензия и дислипидемия оказывают влияние на течение, скорость прогрессирования и нейровизуализационные характеристики пациентов с рассеянным склерозом. Важным вопросом является влияние препаратов, изменяющих течение рассеянного склероза, на течение сопутствующих заболеваний у пациентов с рассеянным склерозом и влияние сопутствующих заболеваний на эффективность и безопасность препаратов, изменяющих течение рассеянного склероза. Противоречивым остается вопрос о применении статинов при рассеянном склерозе. В настоящем обзоре приведены данные о сосудистой коморбидности при рассеянном склерозе, включающие в себя распространенность факторов риска сердечно-сосудистой патологии и сопутствующих сосудистых заболеваний в популяции пациентов с рассеянным склерозом. Также проанализированы данные о влиянии сердечно-сосудистой патологии на течение и терапию рассеянного склероза.

Comorbidity is one of the factors determining the course of multiple sclerosis. Cardiovascular pathology is one of the most common in the population as a whole, especially in age groups over 50. Several studies showed that arterial hypotension and dyslipidemia affected the course, progression rate, and neuroimaging characteristics of patients with multiple sclerosis. An important issue is the effect of disease modifying therapy on the course of concomitant diseases in patients with multiple sclerosis and the effect of concomitant diseases on the effectiveness and safety of disease modifying therapy. The question of the use of statins in multiple sclerosis remains controversial. This review presents data on vascular comorbidity in multiple sclerosis, including the prevalence of risk factors for cardiovascular pathology and concomitant vascular diseases in the population of patients with multiple sclerosis. Data on the effect of cardiovascular pathology on the course and treatment of multiple sclerosis were also analyzed.

рассеянный склерозкоморбидностьсосудистая коморбидностьартериальная гипертензияинсультхроническая сердечная недостаточностьишемическая болезнь сердцаинфаркт миокардадислипидемияожирениеmultiple sclerosiscomorbidityvascular comorbidityhypertensionstrokechronic heart failureischemic heart diseasemyocardial infarctiondyslipidemiaobesityReferencesProgressive multiple sclerosis: from pathogenic mechanisms to treatment / J. Correale, M. I. Gaitan, M. C. Ysrraelit, M. P. Fiol // Brain. – 2017. – Vol. 140, № 3. – Р. 527–546. Doi: 10.1093/brain/aww258.Correale J., Gaitan M. I., Ysrraelit M. C., Fiol M. P. Progressive multiple sclerosis: from pathogenic mechanisms to treatment. Brain. 2017 Mar 1;140(3):527–546. Doi: 10.1093/brain/aww258.Langer-Gould A., Popat R. A., Huang S. M. et al. Clinical and Demographic Predictors of Long-term Disability in Patients With Relapsing-Remitting Multiple Sclerosis // Arch. Neurol. – 2006. – Vol. 63, № 12. – Р. 1686–1691.Langer-Gould A., Popat R. A., Huang S. M., Cobb K., Fontoura P., Gould M. K., Nelson L. M. Clinical and Demographic Predictors of Long-term Disability in Patients With Relapsing-Remitting Multiple Sclerosis. Arch Neurol. 2006 Dec;63(12):1686–1691.Weinshenker B. G., Bass B., Rice G. P. еt al. The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability // Brain. – 1989. – Vol. 112, Pt 1. – P. 133–146.Weinshenker B. G., Bass B., Rice G. P., Noseworthy J., Carriere W., Baskerville J. et al. The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability. Brain. 1989;112(Pt 1):133–146.Marrie R. A., Rudick R., Horwitz R. et al. Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis // Neurology. – 2010. – Vol. 74, № 13. – P. 1041–1047. Doi: 10.1212/WNL.0b013e3181d6b125.Marrie R. A., Rudick R., Horwitz R., Cutter G., Tyry T., Campagnolo D., Vollmer T. Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology. 2010 Mar 30;74(13):1041–1047. Doi: 10.1212/WNL.0b013e3181d6b125.Multiple sclerosis as a vascular disease / A. Minagar, W. Jy, J. J. Jimenez, J. S. Alexander // Neurol. Res. – 2006. – Vol. 28, № 3. – P. 230–235.Minagar A., Jy W., Jimenez J. J., Alexander J. S. Multiple sclerosis as a vascular disease. Neurol Res. 2006 Apr; 28(3):230–235.Sternberg Z., Leung C., Sternberg D. et al. The prevalence of the classical and non-classical cardiovascular risk factors in multiple sclerosis patients // CNS Neurol. Disord. Drug Targets. – 2013. – Vol. 12, № 1. – Р. 104–111.Sternberg Z., Leung C., Sternberg D., Li F., Karmon Y., Chadha K., Levy E. The prevalence of the classical and nonclassical cardiovascular risk factors in multiple sclerosis patients. CNS Neurol Disord Drug Targets. 2013 Feb 1; 12(1):104–111.Palavra F., Marado D., Mascarenhas-Melo F. et al. New markers of early cardiovascular risk in multiple sclerosis patients: oxidized-LDL correlates with clinical staging // Dis. Markers. – 2013. – Vol. 34, № 5. – Р. 341–348. Doi: 10.3233/DMA-130979.Palavra F., Marado D., Mascarenhas-Melo F., Sereno J., Teixeira-Lemos E., Nunes C. C., Gonçalves G., Teixeira F., Reis F. New markers of early cardiovascular risk in multiple sclerosis patients: oxidized-LDL correlates with clinical staging. Dis Markers. 2013;34(5):341–348. Doi: 10.3233/DMA-130979.Tettey P., Simpson S. Jr., Taylor B. et al. An adverse lipid profile is associated with disability and progression in disability, in people with MS // Mult. Scler. – 2014. – Vol. 20, № 13. – Р. 1737–1744. Doi: 10.1177/1352458514533162. Epub 2014 May 14.Tettey P., Simpson S. Jr., Taylor B., Blizzard L., Pon sonby A. L., Dwyer T., Kostner K., Mei I. van der. An adverse lipid profile is associated with disability and progression in disability, in people with MS. Mult Scler. 2014 Nov;20(13):1737–1744. Doi: 10.1177/1352458514533162. Epub 2014 May 14.Weinstock-Guttman B., Zivadinov R., Mahfooz N. et al. Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis // J. Neuroinflammation. – 2011. – Vol. 8. – Р. 127. Doi: 10.1186/1742-2094-8-127.Weinstock-Guttman B., Zivadinov R., Mahfooz N., Carl E., Drake A., Schneider J., Teter B., Hussein S., Mehta B., Weiskopf M., Durfee J., Bergsland N., Ramanathan M. Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis. J Neuroinflammation. 2011 Oct 4;8:127. Doi: 10.1186/1742-2094-8-127.Conway D. S., Thompson N. R., Cohen J. A. Influ ence of hypertension, diabetes, hyperlipidemia, and obstruc tive lung disease on multiple sclerosis disease course // Mult. Scler. – 2017. – Vol. 23, № 2. – Р. 277–285. Doi: 10.1177/1352458516650512. Epub 2016 Jul 11.Conway D. S., Thompson N. R., Cohen J. A. Influence of hypertension, diabetes, hyperlipidemia, and obstructive lung disease on multiple sclerosis disease course. Mult Scler. 2017 Feb;23(2):277–285. Doi: 10.1177/1352458516650512. Epub 2016 Jul 11.Roshanisefat H., Bahmanyar S., Hillert J. et al. Multiple sclerosis clinical course and cardiovascular disease risk – Swedish cohort study // Eur. J. Neurol. – 2014. – Vol. 21, № 11. – Р. 1353–e88. Doi: 10.1111/ene.12518. Epub 2014 Jul 17.Roshanisefat H., Bahmanyar S., Hillert J., Olsson T., Montgomery S. Multiple sclerosis clinical course and cardiovascular disease risk – Swedish cohort study. Eur J Neurol. 2014 Nov;21(11):1353–e88. Doi: 10.1111/ene.12518. Epub 2014 Jul 17.Jadidi E., Mohammadi M., Moradi T. High risk of cardiovascular diseases after diagnosis of multiple sclerosis // Mult. Scler. – 2013. – Vol. 19, № 10. – Р. 1336–1340. Doi: 10.1177/1352458513475833. Epub 2013 Jan 30.Jadidi E., Mohammadi M., Moradi T. High risk of cardiovascular diseases after diagnosis of multiple scle rosis. Mult Scler. 2013 Sep;19(10):1336–1340. Doi: 10.1177/1352458513475833. Epub 2013 Jan 30.Increased risk of ischaemic stroke among patients with multiple sclerosis / C. H. Tseng, W. S. Huang, C. L. Lin, Y. J. Chang // Eur. J. Neurol. – 2015. – Vol. 22, № 3. – Р. 500–506. Doi: 10.1111/ene.12598. Epub 2014 Nov 29.Tseng C. H., Huang W. S., Lin C. L., Chang Y. J. Incre ased risk of ischaemic stroke among patients with multiple sclerosis. Eur J Neurol. 2015 Mar;22(3):500–506. Doi: 10.1111/ene.12598. Epub 2014 Nov 29.Christiansen C. F., Christensen S., Farkas D. K. et al. Risk of arterial cardiovascular diseases in patients with multiple sclerosis: a population-based cohort study // Neuroepidemiology. – 2010. – Vol. 35, № 4. – Р. 267–274. Doi: 10.1159/000320245. Epub 2010 Sep 24.Christiansen C. F., Christensen S., Farkas D. K., Miret M., Sorensen H. T., Pedersen L. Risk of arterial cardiovascular diseases in patients with multiple sclerosis: a population-based cohort study. Neuroepidemiology. 2010;35(4):267–274. Doi: 10.1159/000320245. Epub 2010 Sep 24.Allen N. B., Lichtman J. H., Cohen H. W. et al. Vascular disease among hospitalized multiple sclerosis patients // Neuroepidemiology. – 2008. – Vol. 30, № 4. – Р. 234–238. Doi: 10.1159/000128103. Epub 2008 Apr 25.Allen N. B., Lichtman J. H., Cohen H. W., Fang J., Brass L. M., Alderman M. H. Vascular disease among hospitalized multiple sclerosis patients. Neuroepidemiology. 2008;30(4):234–238. Doi: 10.1159/000128103. Epub 2008 Apr 25.Chataway J., Schuerer N., Alsanousi A. et al. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial // Lancet. – 2014. – Vol. 383, № 9936. – Р. 2213–2221. Doi: 10.1016/S0140-6736(13)62242-4. Epub 2014 Mar 19.Chataway J., Schuerer N., Alsanousi A., Chan D., Mac Manus D., Hunter K., Anderson V., Bangham C. R., Clegg S., Nielsen C., Fox N. C., Wilkie D., Nicholas J. M., Calder V. L., Greenwood J., Frost C., Nicholas R. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet. 2014 Jun 28;383(9936):2213–2221. Doi: 10.1016/S0140-6736(13)62242-4. Epub 2014 Mar 19.Lanzillo R., Orefice G., Quarantelli M. et al. Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy // Mult. Scler. – 2010. – Vol. 16, № 4. – Р. 450–454. Doi: 10.1177/1352458509358909. Epub 2010 Feb 11.Lanzillo R., Orefice G., Quarantelli M., Rinaldi C., Prinster A., Ventrella G., Spitaleri D., Lus G., Vacca G., Carotenuto B., Salvatore E., Brunetti A., Tedeschi G., Brescia Morra V. Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy. Mult Scler. 2010 Apr;16(4):450–454. Doi: 10.1177/1352458509358909. Epub 2010 Feb 11.Togha M., Karvigh S. A., Nabavi M. et al. Simvastatin treatment in patients with relapsing-remitting multiple sclerosis receiving interferon beta 1a: a double-blind randomized controlled trial // Mult. Scler. – 2010. – Vol. 16, № 7. – Р. 848–854. Doi: 10.1177/1352458510369147. Epub 2010 May 20.Togha M., Karvigh S. A., Nabavi M., Moghadam N. B., Harirchian M. H., Sahraian M. A., Enzevaei A., Nourian A., Ghanaati H., Firouznia K., Jannati A., Shekiba M. Simvastatin treatment in patients with relapsing-remitting multiple sclerosis receiving interferon beta 1a: a double-blind randomized controlled trial. Mult Scler. 2010 Jul;16(7):848–854. Doi: 10.1177/1352458510369147. Epub 2010 May 20.Kang J. H., Chen Y. H., Lin H. C. Comorbidities amongst patients with multiple sclerosis: a population-based controlled study // Eur. J. Neurol. – 2010. – Vol. 17, № 9. – Р. 1215–1219. Doi: 10.1111/j.1468-1331.2010.02971.x. Epub 2010 Feb 23.Kang J. H., Chen Y. H., Lin H. C. Comorbidities amongst patients with multiple sclerosis: a population-based controlled study. Eur J Neurol. 2010 Sep;17(9):1215–1219. Doi: 10.1111/j.1468-1331.2010.02971.x. Epub 2010 Feb 23.Kamm C. P., El-Koussy M., Humpert S. et al. Atorvastatin added to interferon β for relapsing multiple sclerosis: a randomized controlled trial // J. Neurol. – 2012. – Vol. 259, № 11. – Р. 2401–2413. Doi: 10.1007/s00415-012-6513-7. Epub 2012 May 9.Kamm C. P., El-Koussy M., Humpert S., Findling O., von Bredow F., Burren Y., Schwegler G., Schött D., Donati F., Müller M., Goebels N., Müller F, Slotboom J., Tettenborn B., Kappos L., Naegelin Y., Mattle H. P. Atorvastatin added to interferon β for relapsing multiple sclerosis: a randomized controlled trial. J Neurol. 2012 Nov;259(11):2401–2413. Doi: 10.1007/s00415-012-6513-7. Epub 2012 May 9.Birnbaum G., Cree B., Altafullah I. et al. Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis // Neurology. – 2008. – Vol. 71, № 18. – Р. 1390–1395. Doi: 10.1212/01.wnl.0000319698.40024.1c. Epub 2008 Jun 4.Birnbaum G., Cree B., Altafullah I., Zinser M., Reder A. T. Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis. Neurology. 2008 Oct 28;71(18):1390–1395. Doi: 10.1212/01.wnl.0000319698.40024.1c. Epub 2008 Jun 4.Marrie R., Horwitz R., Cutter G. et al. Comorbidity, socioeconomic status and multiple sclerosis // Mult. Scler. – 2008. – Vol. 14, № 8. – Р. 1091–1098. Doi: 10.1177/1352458508092263.Marrie R., Horwitz R., Cutter G., Tyry T., Campagnolo D., Vollmer T. Comorbidity, socioeconomic status and multiple sclerosis. Mult Scler. 2008 Sep;14(8):1091–1098. Doi: 10.1177/1352458508092263.Marrie R. A., Patten S. B., Tremlett H. et al. Sex differences in comorbidity at diagnosis of multiple sclerosis: A population-based study // Neurology. – 2016. – Vol. 86, № 14. – Р. 1279–1286. Doi: 10.1212/WNL.0000000000002481. Epub 2016 Mar 9.Marrie R. A., Patten S. B., Tremlett H., Wolfson C., Warren S., Svenson L. W., Jette N., Fisk J.; CIHR Team in the Epidemiology and Impact of Comorbidity on Multiple Sclerosis. Sex differences in comorbidity at diagnosis of multiple sclerosis: A population-based study. Neurology. 2016 Apr 5;86(14):1279–1286. Doi: 10.1212/WNL.0000000000002481. Epub 2016 Mar 9.Simpson R. J., McLean G., Guthrie B. et al. Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis // BMC Neurol. – 2014. – Vol. 14. – Р. 128. Doi: 10.1186/1471-2377-14-128.Simpson R. J., McLean G., Guthrie B., Mair F., Mercer S. W. Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis. BMC Neurol. 2014 Jun 13;14:128. Doi: 10.1186/1471-2377-14-128.Kang J. H., Chen Y. H., Lin H. C. Comorbidities amongst patients with multiple sclerosis: a population-based controlled study // Eur. J. Neurol. – 2010. – Vol. 17, № 9. – Р. 1215–1219. Doi: 10.1111/j.1468-1331.2010.02971.x.Kang J. H., Chen Y. H., Lin H. C. Comorbidities amongst patients with multiple sclerosis: a population-based controlled study. Eur J Neurol. 2010 Sep;17(9):1215–1219. Doi: 10.1111/j.1468-1331.2010.02971.x. Epub 2010 Feb 23.Tettey P., Siejka D., Simpson S. Jr. et al. Frequency of Comorbidities and Their Association with Clinical Disability and Relapse in Multiple Sclerosis // Neuroepidemiology. – 2016. – Vol. 46, № 2. – Р. 106–113. Doi: 10.1159/000442203.Tettey P., Siejka D., Simpson S. Jr., Taylor B., Blizzard L., Ponsonby A. L., Dwyer T., van der Mei I. Frequency of Comorbidities and Their Association with Clinical Disability and Relapse in Multiple Sclerosis. Neuroepidemiology. 2016;46(2):106–113. Doi: 10.1159/000442203. Epub 2016 Jan 20.Marrie R. A., Fisk J., Tremlett H. et al. Differing trends in the incidence of vascular comorbidity in MS and the general population // Neurol. Clin. Pract. – 2016. – Vol. 6, № 2. – Р. 120–128. Doi: 10.1212/CPJ.0000000000000230.Marrie R. A., Fisk J., Tremlett H., Wolfson C, Warren S., Blanchard J., Patten S. B.; CIHR Team in the Epidemiology and Impact of Comorbidity on Multiple Sclerosis. Differing trends in the incidence of vascular comorbidity in MS and the general population. Neurol Clin Pract. 2016 Apr; 6(2):120–128. Doi: 10.1212/CPJ.0000000000000230.Marrie R. A., Cutter G., Tyry T. Substantial adverse association of visual and vascular comorbidities on visual disability in multiple sclerosis // Mult. Scler. – 2011. – Vol. 17. – Р. 1464–1471.Marrie R. A., Cutter G., Tyry T. Substantial adverse asso ciation of visual and vascular comorbidities on visual disability in multiple sclerosis. Mult Scler. 2011;17:1464–1471.Neofidov N., Totolyan N., Shumilina M. et al. Arterial hypertension in patients with multiple sclerosis as a significant risk factor of disability progression // ECTRIMS Online Library. – 2018. – Oct 10. – Р. 228257.Neofidov N., Totolyan N., Shumilina M., Skoromets A., Evdoshenko E. Arterial hypertension in patients with multiple sclerosis as a significant risk factor of disability progression. ECTRIMS Online Library. 2018 Oct 10;228257.Chronic diseases in male veterans with multiple sclerosis / S. L. Lavela, T. R. Prohaska, S. Furner, F. M. Weaver // Prev Chronic Dis. – 2012. – Vol. 9. – P. E55.Lavela S. L., Prohaska T. R., Furner S., Weaver F. M. Chronic diseases in male veterans with multiple sclerosis. Prev Chronic Dis. 2012;9:E55. Epub 2012 Feb 9.Krökki O., Bloigu R., Ansakorpi H. et al. Neurological comorbidity and survival in multiple sclerosis // Mult. Scler. Relat. Disord. – 2014. – Vol. 3, № 1. – Р. 72–77. Doi: 10.1016/j.msard.2013.06.006. Epub 2013 Jul 18.Krökki O., Bloigu R., Ansakorpi H., Reunanen M., Remes A. M. Neurological comorbidity and survival in multiple sclerosis. Mult Scler Relat Disord. 2014 Jan;3(1):72–77. Doi: 10.1016/j.msard.2013.06.006. Epub 2013 Jul 18.Marrie R. A., Yu B. N., Leung S. et al. Rising prevalence of vascular comorbidities in multiple sclerosis: validation of administrative definitions for diabetes, hypertension, and hyperlipidemia // Mult. Scler. – 2012. – Vol. 18, № 9. – Р. 1310–1319. Epub 2012 Feb 10.Marrie R. A., Yu B. N., Leung S., Elliott L., Caetano P., Warren S., Wolfson C., Patten S. B., Svenson L. W., Tremlett H., Fisk J., Blanchard J. F.; CIHR Team in Epidemiology and Impact of Comorbidity on Multiple Sclerosis. Rising preva lence of vascular comorbidities in multiple sclerosis: validation of administrative definitions for diabetes, hypertension, and hyperlipidemia. Mult Scler. 2012 Sep;18(9):1310–1319. Epub 2012 Feb 10.Chan D., Binks S., Nicholas J. M. et al. Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial // Lancet Neurol. – 2017. – Vol. 16, № 8. – Р. 591–600. Doi: 10.1016/S1474-4422(17)30113-8. Epub 2017 Jun 7.Chan D., Binks S., Nicholas J. M., Frost C., Cardoso M. J., Ourselin S., Wilkie D., Nicholas R., Chataway J. Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial. Lancet Neurol. 2017 Aug;16(8):591–600. Doi: 10.1016/S1474-4422(17)30113-8. Epub 2017 Jun 7.Weinstock-Guttman B., Zivadinov R., Horakova D. et al. Lipid profiles are associated with lesion formation over 24 months in interferon-β treated patients following the first demyelinating event // J. Neurol. Neurosurg. Psychiatry. – 2013. – Vol. 84, № 11. – Р. 1186–1191. Doi: 10.1136/jnnp-2012-304740. Epub 2013 Apr 17.Weinstock-Guttman B., Zivadinov R., Horakova D., Havrdova E., Qu J., Shyh G., Lakota E., O’Connor K., Badgett D., Tamaño-Blanco M., Tyblova M., Hussein S., Bergsland N., Willis L., Krasensky J., Vaneckova M., Seidl Z., Ramanathan M. Lipid profiles are associated with lesion formation over 24 months in interferon-β treated patients following the first demyelinating event. J Neurol Neurosurg Psychiatry. 2013 Nov;84(11):1186–1191. Doi: 10.1136/jnnp-2012-304740. Epub 2013 Apr 17.Giubilei F., Antonini G., Di Legge S. et al. Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis // Acta Neurol. Scand. – 2002. – Vol. 106, № 2. – Р. 109–112.Giubilei F., Antonini G., Di Legge S., Sormani M. P., Pantano P., Antonini R., Sepe-Monti M., Caramia F., Pozzilli C. Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis. Acta Neurol Scand. 2002 Aug;106(2):109–112.Sorensen P. S., Lycke J., Erälinna J. P. et al. Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial // Lancet Neurol. – 2011. – Vol. 10, № 8. – Р. 691–701. Doi: 10.1016/S1474-4422(11)70144-2.Sorensen P. S., Lycke J., Erälinna J. P., Edland A., Wu X., Frederiksen J. L., Oturai A., Malmeström C., Stenager E., Sellebjerg F., Sondergaard H. B.; SIMCOMBIN study investigators. Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. Lancet Neurol. 2011 Aug;10(8):691–701. Doi: 10.1016/S1474-4422(11)70144-2.Marrie R., Horwitz R., Cutter G. et al. High frequency of adverse health behaviors in multiple sclerosis // Mult. Scler. – 2009. – Vol. 15. – Р. 105–113.Marrie R., Horwitz R., Cutter G., Tyry T., Campagnolo D., Vollmer T. High frequency of adverse health behaviors in multiple sclerosis. Mult Scler. 2009;15:105–113.Slawta J. N., Wilcox A. R., McCubbin J. A. et al. Health behaviors, body composition, and coronary heart disease risk in women with multiple sclerosis // Arch. Phys. Med. Rehabil. – 2003. – Vol. 84. – Р. 1823–1830.Slawta J. N., Wilcox A. R., McCubbin J. A., Nalle D. J., Fox S. D., Anderson G. Health behaviors, body composition, and coronary heart disease risk in women with multiple sclerosis. Arch Phys Med Rehabil. 2003;84:1823–1830.Weight status in persons with multiple sclerosis: implications for mobility outcomes / L. A. Pilutti, D. Dlugonski, J. H. Pula, R. W. Motl // J. Obes. – 2012. – Vol. 2012. – P. 868256.Pilutti L. A., Dlugonski D., Pula J. H., Motl R. W. Weight status in persons with multiple sclerosis: implications for mobility outcomes. J Obes. 2012;2012:868256.Marrie R. A., Horwitz R. I., Cutter G. et al. Association between comorbidity and clinical characteristics of MS // Acta Neurol Scand. – 2011. – Vol. 124. – P. 135–141.Marrie R. A., Horwitz R. I., Cutter G., Tyry T., Vollmer T. Association between comorbidity and clinical characteristics of MS. Acta Neurol Scand. 2011;124:135–141.Khurana S. R., Bamer A. M., Turner A. P. et al. The pre valence of overweight and obesity in veterans with multiple sclerosis // Am. J. Phys. Med. Rehabil. – 2009. – Vol. 88, № 2. – Р. 83–91.Khurana S. R., Bamer A. M., Turner A. P., Wadhwani R. V., Bowen J. D., Leipertz S. L. et al. The prevalence of overweight and obesity in veterans with multiple sclerosis. Am J Phys Med Rehabil. 2009;88(2):83–91.Sioka C., Fotopoulos A., Georgiou A. et al. Body composition in ambulatory patients with multiple sclerosis // J. Clin. Densitom. – 2011. – Vol. 14, № 4. – Р. 465–470.Sioka C., Fotopoulos A., Georgiou A., Papakonstantinou S., Pelidou S.-H., Kyritsis A. P. et al. Body composition in ambulatory patients with multiple sclerosis. J Clin Densitom. 2011;14(4):465–470.Mähler A., Steiniger J., Bock M. et al. Is metabolic flexibility altered in multiple sclerosis patients? – PLoS ONE. – 2012. – Vol. 7, № 8. – Р. e43675.Mähler A., Steiniger J., Bock M., Brandt A. U., Haas V., Boschmann M. et al. Is metabolic flexibility altered in multiple sclerosis patients? PLoS ONE. 2012;7(8):e43675.Çomoğlu S., Yardimci S., Okçu Z. Body fat distribution and plasma lipid profiles of patients with multiple sclerosis // Turk. J. Med. Sci. – 2004. – Vol. 34. – P. 43–48.Çomoğlu S., Yardimci S., Okçu Z. Body fat distribution and plasma lipid profiles of patients with multiple sclerosis. Turk J Med Sci. 2004;34:43–48.Allen N. B., Lichtman J. H., Cohen H. W. et al. Vascular disease among hospitalized multiple sclerosis patients // Neuroepidemiology. – 2008. – Vol. 30. – P. 234–238.Allen N. B., Lichtman J. H., Cohen H. W., Fang J., Brass L. M., Alderman M. H. Vascular disease among hospitalized multiple sclerosis patients. Neuroepidemiology. 2008;30:234–238.Pilutti L. A., McAuley E., Motl R. W. Weight status and disability in multiple sclerosis: an examination of bi-directional associations over a 24-month period // Mult. Scler. Relat. Disord. – 2012. – Vol. 1, № 3. – Р. 139–144.Pilutti L. A., McAuley E., Motl R. W. Weight status and disability in multiple sclerosis: an examination of bi-directional associations over a 24-month period. Mult Scler Relat Disord. 2012;1(3):139–144.Kalron A. Relationship of Obesity With Gait and Balance in People With Multiple Sclerosis // Am. J. Phys. Med. Rehabil. – 2017. – Vol. 96, № 3. – P. 140–145. Doi: 10.1097/PHM.0000000000000552.Kalron A. Relationship of Obesity With Gait and Balance in People With Multiple Sclerosis. Am J Phys Med Rehabil. 2017 Mar;96(3):140–145. Doi: 10.1097/PHM.0000000000000552.Parks N. E. NEDA treatment target? No evident disease activity as an actionable outcome in practice // J. Neurol. Sci. – 2017. – Vol. 383. – P. 31–34.Parks N. E. NEDA treatment target? No evident disease activity as an actionable outcome in practice. J Neurol Sci. 2017;383:31–34.Kvistad S. S., Myhr K. M., Holmøy T. et al. Body mass index influence interferon-beta treatment response in multiple sclerosis // J. Neuroimmunol. – 2015. – Vol. 288. – P. 92–97. Doi: 10.1016/j.jneuroim.2015.09.008.Kvistad S. S., Myhr K. M., Holmøy T., Šaltytė Benth J., Wergeland S., Beiske A. G., Bjerve K. S., Hovdal H., Lilleås F., Midgard R., Pedersen T., Bakke S. J., Michelsen A. E., Aukrust P., Ueland T., Sagen J. V., Torkildsen О. Body mass index influence interferon-beta treatment response in multiple sclerosis. J Neuroimmunol. 2015 Nov 15;288:92–97. Doi: 10.1016/j.jneuroim.2015.09.008. Epub 2015 Sep 26.Nielsen N. M., Westergaard T., Frisch М. Type 1 diabetes and multiple sclerosis: A Danish population-based cohort study // Arch. Neurol. – 2006. – Vol. 63, № 7. – Р. 1001–1004.Nielsen N. M., Westergaard T., Frisch М. Type 1 diabetes and multiple sclerosis: A Danish population-based cohort study. Arch Neurol. 2006 Jul;63(7):1001–1004.Barcellos L. F., Kamdar B. B., Ramsay P. P. et al. Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis: a descriptive study // Lancet Neurol. – 2006. – Vol. 5, № 11. – Р. 924–931.Barcellos L. F., Kamdar B. B., Ramsay P. P., DeLoa C., Lincoln R. R., Caillier S., Schmidt S., Haines J. L., Pericak-Vance M. A., Oksenberg J. R., Hauser S. L. Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis: a descriptive study. Lancet Neurol. 2006 Nov;5(11):924–931.Laroni A., Calabrese M., Perini P. et al. Multiple sclero sis and autoimmune diseases: epidemiology and HLADR association in North-east Italy // J. Neurol. – 2006. – Vol. 253, № 5. – Р. 636–639.Laroni A., Calabrese M., Perini P., Albergoni M. P., Ranzato F., Tiberio M., Battistin L., Gallo P. Multiple sclerosis and autoimmune diseases: epidemiology and HLA-DR association in North-east Italy. J Neurol. 2006 May;253(5):636–639. Epub 2006 Mar 6.Nuyen J., Schellevis F. G., Satariano W. A. et al. Comorbidity was associated with neurologic and psychiatric diseases: a general practice-based controlled study // J. Clin. Epidemiol. – 2006. – Vol. 59, № 12. – Р. 1274–1284. Epub 2006 May 30.Nuyen J., Schellevis F. G., Satariano W. A., Spreeuwenberg P. M., Birkner M. D., van den Bos G. A., Groenewegen P. P. Comorbidity was associated with neurologic and psychiatric diseases: a general practice-based controlled study. J Clin Epidemiol. 2006 Dec;59(12):1274–1284. Epub 2006 May 30.Edwards L. J., Constantinescu C. S. A prospective study of conditions associated with multiple sclerosis in a cohort of 658 consecutive outpatients attending a multiple sclerosis clinic // Mult. Scler. – 2004. – Vol. 10, № 5. – Р. 575–581.Edwards L. J., Constantinescu C. S. A prospective study of conditions associated with multiple sclerosis in a cohort of 658 consecutive outpatients attending a multiple sclerosis clinic. Mult Scler. 2004 Oct;10(5):575–581.Prevalence of overweight, obesity and metabolic syndrome components in multiple sclerosis patients with significant disability / O. Pinhas-Hamiel, M. Livne, G. Harari, A. Achiron // Eur. J. Neurol. – 2015. – Vol. 22, № 9. – P. 1275–1279. Doi: 10.1111/ene.12738.Pinhas-Hamiel O., Livne M., Harari G., Achiron A. Prevalence of overweight, obesity and metabolic syndrome components in multiple sclerosis patients with significant disability. Eur J Neurol. 2015 Sep;22(9):1275–1279. Doi: 10.1111/ene.12738. Epub 2015 May 14.Fromont A., Binquet C., Rollot F. et al. Comorbidities at multiple sclerosis diagnosis // J. Neurol. – 2013. – Vol. 260, № 10. – Р. 2629–2637. Doi: 10.1007/s00415-013-7041-9.Fromont A., Binquet C., Rollot F., Despalins R., Weill A., Clerc L., Bonithon-Kopp C., Moreau T. Comorbidities at multiple sclerosis diagnosis. J Neurol. 2013 Oct;260(10):2629– 2637. Doi: 10.1007/s00415-013-7041-9. Epub 2013 Aug 2.Oliveira S. R., Simão A. N., Kallaur A. P. et al. Disability in patients with multiple sclerosis: influence of insulin resistance, adiposity, and oxidative stress // Nutrition. – 2014. – Vol. 30, № 3. – Р. 268–273. Doi: 10.1016/j.nut.2013.08.001.Oliveira S. R., Simão A. N., Kallaur A. P., de Almeida E. R., Morimoto H. K., Lopes J., Dichi I., Kaimen-Maciel D. R., Reiche E. M. Disability in patients with multiple sclerosis: influence of insulin resistance, adiposity, and oxidative stress. Nutrition. 2014 Mar;30(3):268–273. Doi: 10.1016/j.nut.2013.08.001.Autoimmune diseases prior to the diagnosis of multiple sclerosis: a population-based case-control study / A. LangerGould, K. B. Albers, S. K. Van Den Eeden, L. M. Nelson // Send to Mult. Scler. – 2010. – Vol. 16, № 7. – Р. 855–861. Doi: 10.1177/1352458510369146.Langer-Gould A., Albers K. B., Van Den Eeden S. K., Nelson L. M. Autoimmune diseases prior to the diagnosis of multiple sclerosis: a population-based case-control study. Send to Mult Scler. 2010 Jul;16(7):855–861. Doi: 10.1177/1352458510369146. Epub 2010 May 12.Cheng X., Yu X., Ding Y. J. et al. The Th17/Treg imbalance in patients with acute coronary syndrome // Clin. Immunol. – 2008. – Vol. 127. – P. 89–97.Cheng X., Yu X., Ding Y. J. et al. The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol 2008;127:89–97.Ramsaransing G. S., Fokkema M. R., Teelken A. et al. Plasma homocysteine levels in multiple sclerosis // J. Neurol. Neurosurg. Psychiatry. – 2006. – Vol. 77. – P. 189–192.Ramsaransing G. S., Fokkema M. R., Teelken A. et al. Plasma homocysteine levels in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2006;77:189–192.Aksungar F. B., Topkaya A. E., Yildiz Z. et al. Coagulation status and biochemical and inflammatory markers in multiple sclerosis // J. Clin. Neurosci. – 2008. – Vol. 15. – P. 393–397.Aksungar F. B., Topkaya A. E., Yildiz Z. et al. Coagulation status and biochemical and inflammatory markers in multiple sclerosis. J Clin Neurosci. 2008;15:393–397.Horstman L. L, Jy W., Ahn Y. S et al. Role of platelets in neuroinflammation: a wide-angle perspective // J. Neuroinflammation. – 2010. – Vol. 7. – P. 10. Published online 2010 Feb 3. Doi: 10.1186/1742-2094-7-10.Horstman L. L, Jy W., Ahn Y. S, Zivadinov R., Maghzi A. H, Etemadifar M., Steven Alexander J., Minagar A. Role of platelets in neuroinflammation: a wide-angle perspective. J Neuroinflammation. 2010;7:10. Published online 2010 Feb 3. Doi: 10.1186/1742-2094-7-10.Minagar A., Jy W., Jimenez J. J. et al. Elevated plasma endothelial microparticles in multiple sclerosis // Neurology. – 2001. – Vol. 56. – P. 1319–1324.Minagar A., Jy W., Jimenez J. J. et al. Elevated plasma endothelial microparticles in multiple sclerosis. Neurology. 2001;56:1319–1324.Acevedo A. R., Nava C., Arriada N. et al. Cardiovascular dysfunction in multiple sclerosis // Acta Neurol. Scand. – 2000. – Vol. 101. – P. 85–88.Acevedo A. R., Nava C., Arriada N. et al. Cardiovascular dysfunction in multiple sclerosis. Acta Neurol Scand. 2000;101:85–88.Konukoglu D., Uzun H. Endothelial Dysfunction and Hypertension // Adv. Exp. Med. Biol. –2017. – Vol. 956. – P. 511–540. Doi: 10.1007/5584_2016_90.Konukoglu D., Uzun H. Endothelial Dysfunction and Hypertension. Adv Exp Med Biol. 2017;956:511–540. Doi: 10.1007/5584_2016_90.Vascular aspects of multiple sclerosis / M. D’haeseleer, M. Cambron, L. Vanopdenbosch, J. De Keyser // Lancet Neurol. – 2011. – Vol. 10. – P. 657–666.D’haeseleer M., Cambron M., Vanopdenbosch L., De Keyser J. Vascular aspects of multiple sclerosis. Lancet Neurol. 2011;10:657–666.Alexander J. S., Zivadinov R., Maghzi A.-H. et al. Multiple sclerosis and cerebral endothelial dysfunction: Mechanisms // Pathophysiology. – 2011. – Vol. 18. – Р. 3–12.Alexander J. S., Zivadinov R., Maghzi A.-H., Ganta V. C., Harris M. K., Minagar A. Multiple sclerosis and cerebral endothelial dysfunction: Mechanisms. Pathophysiology. 2011;18:3–12.Спирина Н. Н., Спирин Н. Н., Фадеева О. А. и др. Рассеянный склероз и эндотелиальная дисфункция (обзор) // Журн. неврологии и психиатрии им. С. С. Корсакова. Спецвыпуск. – 2013. – Т. 113, № 10. – С. 32–42.Spirina N. N., Spirin N. N., Fadeeva O. A., Shipova E. G., Boiko A. N. Rasseyannyi skleroz i endotelial’naya disfunktsiya (obzor). Zhurnal nevrologii i psikhiatrii im. S. S. Korsakova. Spetsvypuski. 2013;113(10):32–42. (In Russ.).Progressive multiple sclerosis: from pathogenic mechanisms to treatment / J. Correale, M. I. Gaita ́n, M. C. Ysrraelit, M. P. Fiol // Brain. – 2017. – Vol. 140, № 3. – Р. 527–546. Doi: 10.1093/brain/aww258.Correale J., Gaita ́n M. I., Ysrraelit M. C., Fiol M. P. Progressive multiple sclerosis: from pathogenic mechanisms to treatment. Brain. 2017 Mar 1;140(3):527–546. Doi: 10.1093/brain/aww258.Negroìo L., Farez M. F., Correale J. Immunologic effects of meformin and pioglitazone treatment on metabolic syndrome and mulVple sclerosis // JAMA Neurol. – 2016. – Vol. 73. – P. 520–528.Negroìo L., Farez M. F., Correale J. Immunologic effects of meformin and pioglitazone treatment on metabolic syndrome and mulVple sclerosis. JAMA Neurol. 2016;73:520–528.

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