DOI: https://doi.org/10.30841/2307-5112.2.2019.175140

Effectiveness of Cardiometabolic Therapy in the Treatment of Acute Coronary Syndrome without ST-segment Elevation in Perimenopausal Women

Т. М. Соломенчук, В. В. Процько, О. В. Восух, Х. М. Хамуляк

Abstract


Acute forms of coronary heart disease (CHD) are one of the most pressing problems in the structure of morbidity and mortality, especially among perimenopausal women. Of particular interest are approaches to the medical correction of acute myocardial ischemia that occurs on the background of non-obstructive lesions or intact coronary arteries.

The objective: to study the effectiveness of a fixed combination of meldonium with γ-butyrobetaine (γ-BB) as part of the optimal pharmacotherapy of GKSbelST.

Materials and methods. 81 women with percutaneous and postmenopausal GKSbelST at the age of 39–69 years (mean age – 50.26 ± 1.24 years) were examined. Patients were evaluated major circadian blood pressure monitoring parameters (MMAD) was determined levels of female sex hormones (estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH)), circulating endothelial dysfunction markers (endothelial NO-synthase (eNOS), endothelin-1 (ET-1)), indicators of systemic inflammation (PSA) and POL (malonic dialdehyde (MDA), ceruloplasmin (CP)), the main indicators of lipid, carbohydrate and purine metabolism at the beginning of the study on the first day of hospitalization and after 2 weeks hospital treatment. Patients were divided into two groups. The 1-st group (n = 29) included women (average age – 51.26 ± 1.82 years), to whom a fixed combination of γ-BB dihydrate (60 mg) and meldonium dihydrate (180 mg) was added to the standard OMT (Kapikor, “Olainfarm”, Latvia) 2 capsules 2 times a day; in the 2nd group (n = 52) – women with GKSbelST women (average age – 49.64 ± 1.12 years), who received only the standard OMT complex.

Results. On the first day of hospitalization of patients with GKSbelST, there was a decrease in eNOS and an increase in ET-1, MDA, CB, and SRP compared to practically healthy individuals, with ABPM, an increase in BP variability (VAD), an increase in BP (HV AD), time index (YV ) at night and insufficient nightly decrease in blood pressure. Compared with women of the 2nd group, two-week treatment of patients of the 1st group significantly accelerates the restoration of endothelial function. The content of eNOS increased in the 1st group by 22.13% (from 191.76 ± 7.67 to 234.82 ± 17.26 pg / ml; p <0.05) against a decrease of –4.92% in 2 th group (from 212.31 ± 10.45 to 201.86 ± 8.39 pg/ml; p> 0.05), levels of E T-1 decreased (by 23.45% in the 1st group (from 15 , 31 ± 0.60 to 11.71 ± 0.68 pg / ml; p <0.05) versus 11.69% in the 2nd group (from 13.62 ± 1.23 to 12.02 ± 0, 69 pg / ml; p<0.05); PSA - by 32.73% (from 5.53 ± 0.73 to 3.72 ± 0.82 mg/l; p<0.05) versus 13.11 % in the 2nd group (from 5.72 ± 0.37 to 4.97 ±0.94 mg / l; p <0.05); MDA – by 10.22% (from 0.65 ± 0.01 to 0.58 ± 0.01; p <0.05) in the 1st group versus 7.36% (from 0.67 ± 0.02 to 0.62 ± 0.01 nmol / mg; p <0, 05) in group 2. Analysis of indicators characterizing the metabolic status of patients with GKSbelST in dynamics observations, that is, lipid, carbohydrate and purine metabolism, liver and kidney function, suggests that the levels of most of them did not significantly change in the treatment process in patients of the two groups of women. At the same time, patients of the 1st group had a more pronounced positive trend of changes in the levels of some indicators, in particular – a decrease in the content of atherogenic lipid fractions and an increase in the glomerular filtration rate (GFR). In group 1, there was a significant decrease in pressure load, an increase in daily index and a fast positive clinical dynamics (2.5 times less risk of recurrences of anginal seizures and arrhythmias), hospitalization due to GKSbelST is less than 1.5 days. Also found a significant increase of 20.8% in the concentration of estradiol in the blood of female patients with GKSbelST of the 1st group (from 26.04 ± 4.69 to 32.89 ± 6.21 pg/ml; p<0.05), while in patients of the 2nd group, on the contrary, negative dynamics of this indicator was revealed (–15.2%), although without a significant difference compared with its initial levels at the beginning of the observation (from 24.26 ± 5.27 to 20.56 ± 4.32 pg / ml; p> 0.05).

Conclusion. Adding to the GKSbelST treatment in women of a fixed combination of meldonium with γ-BB significantly speeds up the restoration of endothelial function and contributes to a decrease in peripheral resistance, balances vascular tone, stabilizes systemic and regional blood flow, which is manifested by the rapid positive dynamics of pressure loads, improved clinical course of NS and reduced hospitalization. Women who took the meldonium with γ-BB combination, in addition to the standard OMT, recorded significant positive changes in the content of female sex hormones in the blood, in particular estradiol (by 20.8%), which may be a consequence of the beneficial effect of meldonium with γ-BB on the microcirculation ovary.

Keywords


acute coronary syndrome; women; perimenopause; endothelial dysfunction; Kapikor

References


Acute Myocardial Infarction in Women: A Scientific Statement from the American Heart Association / L.Mehta, T.Beckie, H.DeVon et al. // Circulation. 2016. V.133. P. 916-947. doi: 10.1161/CIR.0000000000000351.

Sex differences in reperfusion in young patients with ST-segment-elevation myocardial infarction: results from the VIRGO study / G. D’Onofrio, B. Safdar, J.H. Lichtman et al. // Circulation. 2015. V.131. P.1324–1332.

Sex differences in cardiovascular disease – Impact on care and outcomes / K.H. Humphriesa, M. Izadnegahdar, T. Sedlaka et al. // Frontiers in Neuroendocrinology. 2017. V.46. P.46–70.

Stern S., Bayes de Luna A. Coronary artery spasm: a 2009 update // Circulation. 2009. V.119. P.2531–2534. doi:10.1161/Circulation AHA.108.843474.

Lanza G.A., Careri G., Crea F. Mechanisms of coronary artery spasm // Circulation. 2011. V.124. P.1774–1782. doi: 10.1161/CIRCULATIONAHA.111.037283.

Патогенез, клиника и диагностика коронарного синдрома Х / Я.К. Рустамова, М.Н. Алехин, Б.А. Сидоренко, В.А. Азизов // Кардиология. 2008. №11. С.74–78.

Coronary sinus filling time: a novel method to assess microcirculatory function in patients with angina and normal coronaries / V. Haridasan, D. Nandan, D. Raju et al. // Indian Heart J. 2013. V. 65. P. 142-146. doi: 10.1016/j.ihj.2013.02.002. Epub 2013 Feb 21.

Prognostic significance of coronary sinus filling time in patients with angina and normal coronaries at one year follow up / P. Kadermuneer, G.V. Vinod, V. Haridasan et al. // Indian Heart J. 2015. V. 67. P. 245–249. Published online 2015 Jun 15. doi: 10.1016/j.ihj.2015.03.008

Соломенчук Т.М., Слаба Н.А. Оцінка добового профілю артеріального тиску у пацієнтів з артеріальною гіпертензією на фоні застосування комбінованої антигіпертензивної терапії // Здоров’я України. 2013. № 6. С.34-35.

Тривожно-депресивні розлади і контроль артеріальної гіпертензії: можливості фітотерапії / Соломенчук Т.М., Слаба Н.А., Климкович О.Ю. та ін. // Ліки України. 2014. №7-8. С.91-96.

Grossman E. Ambulatory Blood Pressure Monitoring in the Diagnosis and Management of Hypertension // Diabetes Care. 2013. V. 36, Suppl 2. P.S307–S311.

Ruehlmann D.O., Mann G.E. Rapid nongenomic vasodilator actions of oestrogens and sex steroids // Curr Med Chem. 2000. V.7. P.533–541. [PubMed: 10702623].

Estradiol-treated mesenchymal stem cells improve myocardial recovery after ischemia / G.S. Erwin, P.R. Crisostomo, Y. Wang et al. // J Surg Res. 2009. V.152. P.319–324. [PubMed: 18511080].

Estradiol stimulates capillary formation by human endothelial progenitor cells: role of estrogen receptor-alpha/beta, heme oxygenase 1, and tyrosine kinase / I. Baruscotti, F. Barchiesi, E.K. Jackson et al. // Hypertension. 2010. V.56. P.397–404. [PubMed: 20644008].

Selective estrogen receptor-alpha agonist provides widespread heart and vascular protection with enhanced endothelial progenitor cell mobilization in the absence of uterotrophic action / C. Bolego, G. Rossoni, G.P. Fadini et al. // FASEB J. 2010. V.24. P.2262–2272.

Гелис Л.Г. Основные аспекты патогенеза, диагностики и лечения острого коронарного синдрома без стойкого подъема сегмента ST на ЭКГ // Медицинские новости. 2003. №9. С. 27-32.

Беловол А.Н., Князькова И.И. Терапевтический потенциал мельдония при остром коронарном синдроме // Ліки України. 2012. №1. С. 48-53.

Зупанец И.А., Шебеко С.К., Отришко И.А. Значение элементов синергической политропности в механизме реализации фармакологического потенциала препарата Капикор // Therapia. 2015. № 5. С. 48-50.

Корж А.Н., Краснокутский С.В., Васькив Н.Н. Возможности медикаментозной коррекции дисфункции эндотелия у больных хронической ишемической болезнью сердца // Серце і судини. 2015. № 2. С.50-55.

Dzerve V. MILSS I Study Group. A Dose-Dependent Improvement in Exercise Tolerance in Patients With Stable Angina Treated With Mildronate: A Clinical Trial «MILSS I» // Medicina (Kaunas). 2011. V.47, N 10. P.544–551.

Посненкова О.М., Киселев А.Р., Шварц В.А. Влияние терапии препаратом Кардионат на качество жизни у больных острым инфарктом миокарда с подъемом сегмента ST в раннем постинфарктном периоде // Concilium medicum. 2010. № 5. С.94-98.

Гордеев И.Г., Лучинкина Е.Е., Хегай С.В. Коррекция дисфункции миокарда у больных стабильной стенокардией, подвергшихся коронарной реваскуляризации, на фоне приема цитопротектора милдроната // Рос. кардиологический журн. 2009. №2. С.54–58.

Сьяксте Н.И., Дзинтаре М.Я., Калвиньш И.Я. Роль индукции NO в механизме действия цитопротектора Капикора – оригинального регулятора эндотелиальной функции // Медичні перспективи. 2012. Т. 17, № 2. С.4-13.

Титов В.Н. Анатомические и функциональные основы эндотелий-зависимой вазодилатации, оксид азота и эндотелин // Российский кардиологический журнал. 2008. № 1. С. 71- 85.

ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology /M. Roffi, C. Patrono, J.P. Collet et al// Europ.Heart J. 2015. V. 37. P.267–315.

Уніфікований клінічний протокол екстреної, первинної, вторинної (спеціалізованої), третинної (високоспеціалізованої) медичної допомоги та медичної реабілітації: гострий коронарний синдром без елевації сегмента ST: Наказ МОЗ України від 03.03.2016 р. № 164. Київ, 2016. 78 с.

Менопауза: міждисциплінарні аспекти: навчальний посібник / Заремба Є.Х., Гжегоцький М.Р., Шатинська–Мицик І.С. та ін.; ЛНМУ. Львів, 2012. 121с.

Estradiol assays: applications and guidelines for the provision of clinical biochemistry service / W.A. Ratcliff, G.D. Carter et al. // Ann. Clin. Biochem. 1988. V. 25. P. 466-483.

Enzymatic Determination of Total serum Cholesterol / C.C. Allain, L.S. Poon, C.S.G. Chan et al. // Clin. Chem. 1974. V. 20. P. 470.

Колб В.Г., Камышников В.С. Справочник по клинической химии. Минск, 1982. 367 с.

Glycosylated hemoglobins: increased glycosylation of hemoglobin A in diabetic patients / K.H. Gabbay, J.M. Sosenko, G.A. Banuchi et al. // Diabetes. 1979. V. 28. P. 337-340.

Горячковський А.М. Клиническая биохимия. Одеса, 1998. С. 335-336; 367; 370-372.

Cockcroft D.W. Gault, M.H Prediction of Creatinine Clearance from Serum Creatinine // Nephron. 1976. V.16. P.31–41.

Системное воспаление у пациентов с ишемической болезнью сердца: взаимосвязь с клиническим течением и наличием факторов риска / М.И. Лутай, И.П. Голикова, С.И. Деяк, В.А. Слободской // Укр. медичний часопис. 2003. №2. С. 80-83.

Коробейникова Э.Н. Модификация определения продуктов перекисного окисления липидов в реакции с тиобарбитуровой кислотой // Лаб. дело. 1989. №7. С. 8.

Willerson J.T., Kereiakes D.J. Endothelial dysfunction // Circulation. 2003. V.108. P. 2060–2061.

Значення добового моніторування артеріального тиску у практиці сімейного лікаря: методичні рекомендації / Укл.: Гечко М.М., Чубірко К.І., Чопей І.В. та ін. Ужгород, 2014. 24 с.

Краснов Л.А., Олейник В.П. Суточное мониторирование артериального давления. Технические средства электронной и компьютерной диагностики в медицине: учебное пособие / Национальный аэрокосмический ун-т им. Н.Е. Жуковского «Харьковский авиационный институт». Харьков, 2014. 56 с.

Рогоза А.Н., Агальцов М.В., Сергеева М.В. Суточное мониторирование артериального давления: варианты врачебных заключений и комментарии. Нижний Новгород: ДЕКОМ, 2005. 64 с.

Біостатистика / В.Ф. Москаленко, О.П. Гульчій, М.В. Голубчиков та ін. К.: Книга плюс, 2009. 184 с.




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