russjcardiolРоссийский кардиологический журналRussian Journal of Cardiology1560-40712618-7620«SILICEA-POLIGRAF» LLC10.15829/1560-4071-2018-9-17-22russjcardiol-2865Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESМаркеры воспаления у больных хронической ишемической болезнью сердца со стенозом аортального клапанаInflammation markers in coronary heart disease patients with aortic valve stenosishttps://orcid.org/0000-0001-8909-8662АфанасьеваО. И.AfansievaO. I.

Доктор биологических наук, ведущий научный сотрудник лаборатории проблем атеросклероза института экспериментальной кардиологии.

Москва

Moscow

Razova1@yandex.ruhttps://orcid.org/0000-0002-3617-9343ТмоянН. А.TmojanN. A.

Аспирант отдела атеросклероза института клинической кардиологии

Moscow

ntmoyan@gmail.comhttps://orcid.org/0000-0002-0682-8699КлесареваЕ. А.KlesarevaE. A.

Кандидат технических наук, научный сотрудник лаборатории проблем атеросклероза института экспериментальной кардиологии.

Москва

Moscow

hea@mail.ruhttps://orcid.org/0000-0002-1132-2529РазоваО. А.RazovaO. A.

Научный сотрудник лаборатории проблем атеросклероза института экспериментальной кардиологии.

Москва

Moscow

razova1@yandex.ruhttps://orcid.org/0000-0002-5725-3805АфанасьеваМ. И.AfanasievaM. A.

Научный сотрудник лаборатории проблем атеросклероза института экспериментальной кардиологии.

Москва

Moscow

miafanasieva.cardio@yandex.ruБурдейнаяА. Л.BurdeynayaА. L.

Аспирант отдела атеросклероза института клинической кардиологии.

Москва

Moscow

burdeynaya.md@gmail.comСаидоваМ. А.SaidovaM. A.

Профессор, доктор медицинских наук, руководитель отдела, зав. отделением института клинической кардиологии.

Москва

Moscow

saidova@cardio.ruhttps://orcid.org/0000-0002-1518-6552ЕжовМ. В.EzhovM. V.

Доктор медицинских наук, ведущий научный сотрудник отдела атеросклероза института клинической кардиологии.

Москва

Moscow

marat_ezhov@mail.ruhttps://orcid.org/0000-0001-5944-6427ПокровскийС. Н.PokrovskyS. N.

Профессор, доктор биологических наук, и. о. руководителя лаборатории проблем атеросклероза института экспериментальной кардиологии.

Москва

Moscow

dr.pokrovsky@mail.ruФГБУ Национальный медицинский исследовательский центр кардиологии Минздрава РоссииРоссияNational Medical Research Center of Cardiology of the Ministry of HealthRussian Federation201823092018091722Copyright © Афанасьева О.И., Тмоян Н.А., Клесарева Е.А., Разова О.А., Афанасьева М.И., Бурдейная А.Л., Саидова М.А., Ежов М.В., Покровский С.Н., 20182018Афанасьева О.И., Тмоян Н.А., Клесарева Е.А., Разова О.А., Афанасьева М.И., Бурдейная А.Л., Саидова М.А., Ежов М.В., Покровский С.Н.Afansieva O.I., Tmojan N.A., Klesareva E.A., Razova O.A., Afanasieva M.A., Burdeynaya А.L., Saidova M.A., Ezhov M.V., Pokrovsky S.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://russjcardiol.elpub.ru/jour/article/view/2865

Повышенный уровень липопротеида(a) (Лп(a)) является независимым фактором риска развития ишемической болезни сердца (ИБС), а также моногенным предиктором (отмечено увеличение риска развития) стеноза аортального клапана (АоС) при увеличении уровня Лп(а) в популяции. Лизофосфатидная кислота, вырабатываемая ферментом с активностью фосфолипазы D — аутотаксином (autotaxin) ((АТХ))  — является медиатором воспаления. Участие факторов гуморального иммунитета в процессах воспаления в коронарных артериях и аортальном клапане могут отражаться наличием циркулирующих аутоантител (аутоАт) и сдвигами в клеточных показателях иммунитета.

Цель

Цель. Изучить связь между Лп(а), ATX и иммунными показателями с наличием АоС у больных хронической ИБС.

Материал и методы

Материал и методы. В одномоментное исследование было включено 210 пациентов с хронической ИБС. Больные были разделены на две группы в зависимости от наличия (основная группа, n=47) или отсутствия (контрольная группа, n=163) дегенеративного АоС по данным эхокардиографии. Больные получали терапию стандартную по поводу ИБС. Всем пациентам проводили общий анализ крови, определение концентрации липидов, Лп(а), ATX, C-реактивного белка, аутоантител к апоВ-100 содержащим липопротеидам и их Cu2+окисленным модификациям. Фенотипы апобелка(а) (апо(а)) были определены для 168 больных.

Результаты

Результаты. Больные ИБС с наличием дегенеративного АоС были несколько старше (74,2±7,8 против 67,6±9,4 лет, p=0,0007), но не различались по клиническим и основным биохимическим характеристикам, уровню Лп(а) и высокочувствительному С-реактивному белку (вчСРБ). Концентрация АТХ в плазме была достоверно выше (554±95 и 497±105 нг/мл, p=0,001), тогда как уровень IgM аутоантител против окисленного липопротеида(а) (окЛп(а)  — достоверно ниже (10,8 [7,9;15,1] и 13,4 [11,4;16,7] отн.лаб.ед., p<0,001) в основной, чем в контрольной группе. Нейтрофильно-лимфоцитарный индекс также значимо различался у больных с АоС и без (2,04 [1,56;3,14] и 1,72 [1,39;2,14]). По результатам логистического анализа возраст, уровень АТХ, титр аутоАт к окЛп(а) и нейтрофильно-лимфоцитарный индекс были достоверными независимыми предикторами наличия дегенеративного АоС.

Заключение

Заключение. У  пациентов с  хроническим течением ИБС, находящихся на  терапии статинами, уровень АТХ, аутоАт IgM против окисленных Лп(а) и соотношения нейтрофилов к лимфоцитам, но не концентрация Лп(а) и низкомолекулярный фенотип апо(а), были связаны с наличием АоС.

Raised level of lipoproteide (a) (Lpa) is an independent risk factor of coronary heart disease (CHD) and is also a monogenic predictor (there is growth of prevalence) of aortic stenosis (AS) with the increase of Lpa in population. Lysophosphatide acid, secreted by an enzyme with phospholipase D activity — autotaxin (ATX) is an inflammatory mediator. Humoral immunity involvement in inflammatory processes in coronary arteries and aortic valve might present with the presence of circulating autoantibodies and shifts in the values of cellular immunity.

Aim

Aim. To assess the relation of Lpa, ATX and immunity with the presence of AS in chronic CHD patients.

Material and methods

Material and methods. To a single moment study, 210 patients were included, with chronic CHD. Patients were selected to two groups by the presence (main group, n=47) or absence (controls, n=163) of degenerative AS by echocardiography. Patients were taking standard CHD therapy. All patients underwent clinical blood count, lipids concentration and Lpa. ATX, C-reactive protein, autoantibodies to ApoB-100 lipoproteides and their Cu2+-oxidated modifications. Phenotypes of apoprotein (a) were assessed in 168 patients.

Results

Results. CHD patients with degenerative AS were older (74,2±7,8 versus 67,6±9,4 y., p=0,0007), but did not differ by the clinical and biochemical characteristics, level of Lpa and high sensitive С-reactive protein (hsCRP). Concentration of АТХ in plasma was significantly higher (554±95 and 497±105 ng/mL, p=0,001), but the level of IgM autoantibodies against the oxidated lipoproteid (а) (oxLpa) — significantly lower (10,8 [7,9;15,1] and 13,4 [11,4;16,7] relative units, p<0,001) in the main group comparing to control. Neutrophilic-lymphocytal index also differed significantly in the AS group and non-AS (2,04 [1,56;3,14] and 1,72 [1,39;2,14]). By the results of logistic analysis, the age, level of ATX, titer of autoantibodies to oxLpa and neutrophilic-limphocytal index were significant independent predictors of the degenerative AS.

Conclusion

Conclusion. In the patients with chronic CHD, undergoing statin therapy, the levels of ATX, autoantiboides IgM against the oxLpa and relation of neutrophils to lymphocytes, but not the concentration of Lpa and low molecular phenotype of apo(a), were related to AS presence.

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