russjcardiolРоссийский кардиологический журналRussian Journal of Cardiology1560-40712618-7620«SILICEA-POLIGRAF» LLC10.15829/1560-4071-2020-4202russjcardiol-4202Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWНовые биологические маркёры диагностики и прогнозирования риска смерти у пациентов с тромбоэмболией лёгочной артерииNovel biological markers for the diagnosis and prediction of mortality risk in patients with pulmonary embolismhttps://orcid.org/0000-0002-2417-6532ПодлипаеваА. А.PodlipaevaA. A.

Врач-терапевт консультативно-реабилитационного отделения, клинический ординатор

anchous1808@yandex.ruhttps://orcid.org/0000-0002-9321-6251МулловаИ. С.MullovaI. S.

Кандидат медицинских наук, ассистент кафедры кардиологии и сердечно-сосудистой хирургии, врач-кардиолог

irinamullova@gmail.comhttps://orcid.org/0000-0003-3301-1577ПавловаТ. В.PavlovaT. V.

Доктор медицинских наук, профессор кафедры кардиологии и сердечно-сосудистой хирургии, врач-гематолог

ptvsam63@mail.ruhttps://orcid.org/0000-0003-2295-676XУшаковаЕ. В.UshakovaE. V.

Кандидат медицинских наук, зав. клинико-диагностической лабораторией

ellenksa@mail.ruhttps://orcid.org/0000-0002-6453-2976ДупляковД. В.DuplyakovD. V.

Доктор медицинских наук, профессор, заместитель главного врача по медицинской части, профессор кафедры кардиологии и сердечно-сосудистой хирургии

duplyakov@yahoo.comФГБОУ ВО Самарский государственный медицинский университет Минздрава России; ГБУЗ Самарский областной клинический кардиологический диспансер им. В.П. ПоляковаРоссияSamara State Medical University; V.P. Polyakov Samara Regional Clinical Cardiology DispensaryRussian FederationГБУЗ Самарский областной клинический кардиологический диспансер им. В.П. ПоляковаРоссияV.P. Polyakov Samara Regional Clinical Cardiology DispensaryRussian Federation202011012021254S4S42024202Copyright © Подлипаева А.А., Муллова И.С., Павлова Т.В., Ушакова Е.В., Дупляков Д.В., 20212021Подлипаева А.А., Муллова И.С., Павлова Т.В., Ушакова Е.В., Дупляков Д.В.Podlipaeva A.A., Mullova I.S., Pavlova T.V., Ushakova E.V., Duplyakov D.V.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/4202

Одна из форм проявления венозных тромбоэмболических осложнений (ВТЭО) — тромбоэмболия лёгочной артерии (ТЭЛА) — занимает третье место в структуре причин смерти среди всех сердечно-сосудистых заболеваний, уступая инфаркту миокарда и инсульту. Именно поэтому особое значение имеет своевременная и максимально ранняя диагностика ВТЭО, что будет способствовать улучшению как краткосрочных, так и долгосрочных прогнозов пациентов.

Учитывая недостаточную специфичность имеющихся лабораторных параметров, таких как D-димер, NT-proBNP, сердечный тропонин I, существует насущная необходимость в поиске новых биомаркеров, способных повысить качество выявления и стратификации ВТЭО, в т.ч. ТЭЛА. Диагностический и прогностический тест для верификации ТЭЛА должен быть точным, безопасным, легкодоступным и недорогим, а также воспроизводимым и неинвазивным. В данном обзоре представлены доступные к настоящему моменту литературные данные по новейшим лабораторным показателям, которые характеризуют дисфункцию правого желудочка, развивающуюся вследствие ТЭЛА, и имеют доказательную базу в отношении стратификации риска смерти у этой категории больных.

Pulmonary embolism (PE) ranks third in the structure of death causes among all cardiovascular diseases after myocardial infarction and stroke. That is why the timely and earliest possible diagnosis of venous thromboembolism is of particular importance, which will help improve both short-term and long-term patient prognosis. Given the low specificity of current laboratory parameters, such as D-dimer, NT-proBNP, cardiac troponin I, there is an urgent need to search for new biomarkers that can improve the quality of detection and stratification of VTE, including PE. A diagnostic and prognostic test for PE must be accurate, safe, easily accessible and inexpensive, as well as reproducible and non-invasive.

This review presents the currently available literature data on the latest laboratory parameters that characterize right ventricular dysfunction due to PE and provide an evidence base for stratification of the death risk in this category of patients.

тромбоэмболия легочной артериитромбоз глубоких венмаркерыисходыпрогнозpulmonary embolismdeep vein thrombosismarkersoutcomesprognosisReferencesWendelboe AM, Raskob GE. Global burden of thrombosis: epidemiologic aspects. Circ Res. 2016;118:1340-7. doi:10.1161/CIRCRESAHA.115.306841.Wendelboe AM, Raskob GE. Global burden of thrombosis: epidemiologic aspects. Circ Res. 2016;118:1340-7. doi:10.1161/CIRCRESAHA.115.306841.Дупляков Д. В., Павлова Т. В., Муллова И. С. и др. Различия в клинической картине и ведении пациентов с подтвержденной и неподтвержденной тромбоэмболией легочной артерии. Российский кардиологический журнал. 2015;3(119):18-24. doi:10.15829/1560-4071-2015-03-18-24.Duplyakov DV, Pavlova TV, Mullova IS, et al. Differences in the clinical picture and management of patients with confirmed and unconfirmed pulmonary embolism. Russian Journal of Cardiology. 2015;3(119):18-24. (In Russ.) doi:10.15829/1560-4071-2015-03-18-24.Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). European Heart Journal. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405.Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). European Heart Journal. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405.Lippi G, Bonfanti L, Saccenti C, Cervellin G. Causes of elevated D-dimer in patients admitted to a large urban emergency department. Eur. J. Intern. Med. 2014;25(1):45-8. doi:10.1016/j.ejim.2013.07.012.Lippi G, Bonfanti L, Saccenti C, Cervellin G. Causes of elevated D-dimer in patients admitted to a large urban emergency department. Eur. J. Intern. Med. 2014;25(1):45-8. doi:10.1016/j.ejim.2013.07.012.Kucher N, Goldhaber SZ. Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism. Circulation. 2003;108:2191-4. doi:10.1161/01.CIR.0000100687.99687.CE.Kucher N, Goldhaber SZ. Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism. Circulation. 2003;108:2191-4. doi:10.1161/01.CIR.0000100687.99687.CE.Pieralli F, Olivotto I, Vanni S, et al. Usefulness of bedside testing for brain natriuretic peptide to identify right ventricular dysfunction and outcome in normotensive patients with acute pulmonary embolism. Am J Cardiol. 2006;97(9):1386-90. doi:10.1016/j.amjcard.2005.11.075.Pieralli F, Olivotto I, Vanni S, et al. Usefulness of bedside testing for brain natriuretic peptide to identify right ventricular dysfunction and outcome in normotensive patients with acute pulmonary embolism. Am J Cardiol. 2006;97(9):1386-90. doi:10.1016/j.amjcard.2005.11.075.Cavallazzi R, Nair A, Vasu T, Marik PE. Natriuretic Peptides in Acute Pulmonary Embolism: A Systematic Review. Intensive Care Med. 2008;34(12):2147-56. doi:10.1007/s00134-008-1214-5.Cavallazzi R, Nair A, Vasu T, Marik PE. Natriuretic Peptides in Acute Pulmonary Embolism: A Systematic Review. Intensive Care Med. 2008;34(12):2147-56. doi:10.1007/s00134-008-1214-5.Bajaj A, Saleeb M, Rathor P, et al. Prognostic Value of Troponins in Acute Nonmassive Pulmonary Embolism: A Meta-Analysis. Heart Lung. 2015;44(4):327-34. doi:10.1016/j.hrtlng.2015.03.007.Bajaj A, Saleeb M, Rathor P, et al. Prognostic Value of Troponins in Acute Nonmassive Pulmonary Embolism: A Meta-Analysis. Heart Lung. 2015;44(4):327-34. doi:10.1016/j.hrtlng.2015.03.007.Poste G. Bring on the biomarkers. Nature. 2011;469(7329):156. doi:10.1038/469156a.Poste G. Bring on the biomarkers. Nature. 2011;469(7329):156. doi:10.1038/469156a.Pradhan NM, Mullin C, Poor HD. Biomarkers and Right Ventricular Dysfunction. Crit Care Clin. 2020;36(1):141-53. doi:10.1016/j.ccc.2019.08.011.Pradhan NM, Mullin C, Poor HD. Biomarkers and Right Ventricular Dysfunction. Crit Care Clin. 2020;36(1):141-53. doi:10.1016/j.ccc.2019.08.011.Kaczynskaya A, Pelsers MM, Bochowicz A, et al. Plasma heart-type fatty acid binding protein is superior to troponin and myoglobin for rapid risk stratification in acute pulmonary embolism. ClinChimActa. 2006;371(1-2):117-23. doi:10.1016/j.cca.2006.02.032.Kaczynskaya A, Pelsers MM, Bochowicz A, et al. Plasma heart-type fatty acid binding protein is superior to troponin and myoglobin for rapid risk stratification in acute pulmonary embolism. ClinChimActa. 2006;371(1-2):117-23. doi:10.1016/j.cca.2006.02.032.Bajaj A, Rathor P, Sehgal V, et al. Risk Stratification in Acute Pulmonary Embolism With Heart-Type Fatty Acid-Binding Protein: A Meta-Analysis. J Crit Care. 2015;30(5):1151. doi:10.1016/j.jcrc.2015.05.026.Bajaj A, Rathor P, Sehgal V, et al. Risk Stratification in Acute Pulmonary Embolism With Heart-Type Fatty Acid-Binding Protein: A Meta-Analysis. J Crit Care. 2015;30(5):1151. doi:10.1016/j.jcrc.2015.05.026.Dellas C, Lobo JL, Rivas A, et al. Risk stratification of acute pulmonary embolism based on clinical parameters, H-FABP and multidetector CT. Int J Cardiol. 2018;265:223-8. doi:10.1016/j.ijcard.2018.04.066.Dellas C, Lobo JL, Rivas A, et al. Risk stratification of acute pulmonary embolism based on clinical parameters, H-FABP and multidetector CT. Int J Cardiol. 2018;265:223-8. doi:10.1016/j.ijcard.2018.04.066.Европейское общество кардиологов. Рекомендации ESC по диагностике и ведению пациентов с острой эмболией системы лёгочной артерии 2014. Российский кардиологический журнал. 2015;(8):67-110. doi:10.15829/1560-4071-2015-08-67-110.European Society of Cardiology. 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism. Russ J Cardiol. 2015;(8):67-110. (In Russ.) doi:10.15829/1560-4071-2015-08-67-110.Wollert KC, Kempf T, Peter T, et al. Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome. Circulation. 2007;115:962-71. doi:10.1161/CIRCULATIONAHA.106.650846.Wollert KC, Kempf T, Peter T, et al. Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome. Circulation. 2007;115:962-71. doi:10.1161/CIRCULATIONAHA.106.650846.Lankeit M, Kempf T, Dellas C, et al. Growth differentiation factor-15 for prognostic assessment of patients with acute pulmonary embolism. Am J RespirCrit Care Med. 2008;177(9):1018-25. doi:10.1164/rccm.200712-1786OC.Lankeit M, Kempf T, Dellas C, et al. Growth differentiation factor-15 for prognostic assessment of patients with acute pulmonary embolism. Am J RespirCrit Care Med. 2008;177(9):1018-25. doi:10.1164/rccm.200712-1786OC.Katan M, Christ-Crain M. The stress hormone copeptin: a new prognostic biomarker in acute illness. Swiss Med Wkly. 2010;140:13101. doi:10.4414/smw.2010.13101.Katan M, Christ-Crain M. The stress hormone copeptin: a new prognostic biomarker in acute illness. Swiss Med Wkly. 2010;140:13101. doi:10.4414/smw.2010.13101.Nickel NP, Lichtinghagen R, Golpon H, et al. Circulating levels of copeptin predict outcome in patients with pulmonary arterial hypertension. Respir Res. 2013;14:130. doi:10.1186/1465-9921-14-130.Nickel NP, Lichtinghagen R, Golpon H, et al. Circulating levels of copeptin predict outcome in patients with pulmonary arterial hypertension. Respir Res. 2013;14:130. doi:10.1186/1465-9921-14-130.Kalkan AK, Ozturk D, Erturk M, et al. The diagnostic value of serum copeptin levels in an acute pulmonary embolism. Cardiology J. 2016;23:42-50. doi:10.5603/CJ.a2015.0077.Kalkan AK, Ozturk D, Erturk M, et al. The diagnostic value of serum copeptin levels in an acute pulmonary embolism. Cardiology J. 2016;23:42-50. doi:10.5603/CJ.a2015.0077.Deveci F, Oner 0, Telo S, et al. Prognostic value of copeptin in patients with acute pulmonary thromboembolism. ClinRespir J. 2019;13:630-6. doi:10.1111/crj.13071.Deveci F, Oner 0, Telo S, et al. Prognostic value of copeptin in patients with acute pulmonary thromboembolism. ClinRespir J. 2019;13:630-6. doi:10.1111/crj.13071.Akgedik R, Karamanli H, Kurt AB, Gunaydin ZY. Usefulness of admission red blood cell distribution width as a predictor of severity of acute pulmonary embolism. Clin Respir J. 2018;12(2):786-94. doi:10.1111/crj.12595.Akgedik R, Karamanli H, Kurt AB, Gunaydin ZY. Usefulness of admission red blood cell distribution width as a predictor of severity of acute pulmonary embolism. Clin Respir J. 2018;12(2):786-94. doi:10.1111/crj.12595.Hammons L, Filopei J, Steiger D, et al. A narrative review of red blood cell distribution width as a marker for pulmonary embolism. J Thromb Thrombolysis. 2019;48;638-47. doi.10.1007/s11239-019-01906-w.Hammons L, Filopei J, Steiger D, et al. A narrative review of red blood cell distribution width as a marker for pulmonary embolism. J Thromb Thrombolysis. 2019;48;638-47. doi.10.1007/s11239-019-01906-w.Bath PM, Butterworth RJ. Platelet size: measurement, physiology and vascular disease. J Cardiovasc Thorac Res. 2020;12(1):56-62. doi:10.34172/jcvtr.2020.09.Bath PM, Butterworth RJ. Platelet size: measurement, physiology and vascular disease. J Cardiovasc Thorac Res. 2020;12(1):56-62. doi:10.34172/jcvtr.2020.09.Gulcan M, Varol E, Etli M, et al. Mean platelet volume is increased in patients with deep vein thrombosis. Clin Appl Thromb Hemost. 2012;18(4):42730. doi:10.1177/1076029611427437.Gulcan M, Varol E, Etli M, et al. Mean platelet volume is increased in patients with deep vein thrombosis. Clin Appl Thromb Hemost. 2012;18(4):42730. doi:10.1177/1076029611427437.Varol E, Icli A, Uysal BA, Ozaydin M. Platelet indices in patients with acute pulmonary embolism. Scand J Clin Lab Invest. 2011;71(2):163-7. doi:10.3109/00365513.2010.547596.Varol E, Icli A, Uysal BA, Ozaydin M. Platelet indices in patients with acute pulmonary embolism. Scand J Clin Lab Invest. 2011;71(2):163-7. doi:10.3109/00365513.2010.547596.Talay F, Ocak T, Alcelik A, et al. A New Diagnostic Marker For Acute Pulmonary Embolism In Emergency Department: Mean Platelet Volume. Afr Health Sci. 2014;14(1):94-9. doi:10.4314/ahs.v14i1.15.Talay F, Ocak T, Alcelik A, et al. A New Diagnostic Marker For Acute Pulmonary Embolism In Emergency Department: Mean Platelet Volume. Afr Health Sci. 2014;14(1):94-9. doi:10.4314/ahs.v14i1.15.Ghaffari S, Parvizian N, Pourafkari L, et al. Prognostic value of platelet indices in patients with acute pulmonary thromboembolism. Blood Coagul Fibrinolysis. 1996;7(2):157-61. doi:10.34172/jcvtr.2020.09.Ghaffari S, Parvizian N, Pourafkari L, et al. Prognostic value of platelet indices in patients with acute pulmonary thromboembolism. Blood Coagul Fibrinolysis. 1996;7(2):157-61. doi:10.34172/jcvtr.2020.09.Artoni A, Abbattista M, Bucciarelli P, et al. Platelet to Lymphocyte Ratio and Neutrophil to Lymphocyte Ratio as Risk Factors for Venous Thrombosis. Clin Appl Thromb Hemost. 2018;24(5):808-14. doi:10.1177/1076029617733039.Artoni A, Abbattista M, Bucciarelli P, et al. Platelet to Lymphocyte Ratio and Neutrophil to Lymphocyte Ratio as Risk Factors for Venous Thrombosis. Clin Appl Thromb Hemost. 2018;24(5):808-14. doi:10.1177/1076029617733039.Calkovska A, Mokra D, Calkovsky V. Lung surfactant alterations in pulmonary thromboembolism. Eur J Med Res. 2009;14 Suppl 4(Suppl 4):38-41. doi:10.1186/2047-783x-14-s4-38.Calkovska A, Mokra D, Calkovsky V. Lung surfactant alterations in pulmonary thromboembolism. Eur J Med Res. 2009;14 Suppl 4(Suppl 4):38-41. doi:10.1186/2047-783x-14-s4-38.Rosenberg OA. Pulmonary surfactant and its use in lung diseases. General resuscitation. 2007;1:66-77. (In Russ.) Розенберг О. А. Легочный сурфактант и его применение при заболеваниях легких. Общая реаниматология. 2007;1:66-77.Rosenberg OA. Pulmonary surfactant and its use in lung diseases. General resuscitation. 2007;1:66-77. (In Russ.) Розенберг О. А. Легочный сурфактант и его применение при заболеваниях легких. Общая реаниматология. 2007;1:66-77.Pastva AM, Wright JR, Williams KL. Immunomodulatory roles of surfactant proteins A and D: implications in lung disease. Proc Am Thorac Soc. 2007;4(3):252-7. doi:10.1513/pats.200701-018AW.Pastva AM, Wright JR, Williams KL. Immunomodulatory roles of surfactant proteins A and D: implications in lung disease. Proc Am Thorac Soc. 2007;4(3):252-7. doi:10.1513/pats.200701-018AW.Liu CP, Zhang YJ, Lu WX, et al. The change of pulmonary surfactant associated protein A in acute pulmonary embolism. ZhonghuaJie He He Hu Xi ZaZhi. 2005;28(9):600-3.Liu CP, Zhang YJ, Lu WX, et al. The change of pulmonary surfactant associated protein A in acute pulmonary embolism. ZhonghuaJie He He Hu Xi ZaZhi. 2005;28(9):600-3.Kati C, Alacam H, Duran L, et al. The effectiveness of the serum surfactant protein D (Sp-D) level to indicate lung injury in pulmonary embolism. Clin Lab. 2014;60(9):1457-64. doi:10.7754/Clin.Lab.2013.131009.Kati C, Alacam H, Duran L, et al. The effectiveness of the serum surfactant protein D (Sp-D) level to indicate lung injury in pulmonary embolism. Clin Lab. 2014;60(9):1457-64. doi:10.7754/Clin.Lab.2013.131009.Mutlu H, Kokulu K, Sert ET, Caglar A. Lipocalin-type prostaglandin D synthase levels are associated with the severity of pulmonary embolism. Heart Vessels. 2020. doi:10.1007/s00380-020-01568-2.Mutlu H, Kokulu K, Sert ET, Caglar A. Lipocalin-type prostaglandin D synthase levels are associated with the severity of pulmonary embolism. Heart Vessels. 2020. doi:10.1007/s00380-020-01568-2.Sun Y, Zhang X, Gao H, et al. Expression of microRNA-514a-5p and its biological function in experimental pulmonary thromboembolism. Am J Transl Res. 2019;11(9):5514-30.Sun Y, Zhang X, Gao H, et al. Expression of microRNA-514a-5p and its biological function in experimental pulmonary thromboembolism. Am J Transl Res. 2019;11(9):5514-30.Xiang Q, Zhang HX, Wang Z, et al. The predictive value of circulating microRNAs for venous thromboembolism diagnosis: A systematic review and diagnostic meta-analysis. Thromb Res. 2019;181:127-34. doi:10.1016/j.thromres.2019.07.024.Xiang Q, Zhang HX, Wang Z, et al. The predictive value of circulating microRNAs for venous thromboembolism diagnosis: A systematic review and diagnostic meta-analysis. Thromb Res. 2019;181:127-34. doi:10.1016/j.thromres.2019.07.024.Kessler T, Erdmann J, Vilne B, et al. Serum microRNA-1233 Is a Specific Biomarker for Diagnosing Acute Pulmonary Embolism. J Transl Med. 2016;14(1):120. doi:10.1186/s12967-016-0886-9.Kessler T, Erdmann J, Vilne B, et al. Serum microRNA-1233 Is a Specific Biomarker for Diagnosing Acute Pulmonary Embolism. J Transl Med. 2016;14(1):120. doi:10.1186/s12967-016-0886-9.Liu T, Kang J, Liu F. Plasma Levels of microRNA-221 (miR-221) Are Increased in Pa -tients With Acute Pulmonary Embolism. Med SciMonit. 2018;24:8621-26. doi:10.12659/MSM.910893.Liu T, Kang J, Liu F. Plasma Levels of microRNA-221 (miR-221) Are Increased in Pa -tients With Acute Pulmonary Embolism. Med SciMonit. 2018;24:8621-26. doi:10.12659/MSM.910893.Griffin JH, Fernandez JA, Deguchi H. Plasma lipoproteins, hemostasis and thrombosis. Thromb Haemost. 2001;86(1):386-94. doi:10.1055/s-0037-1616236.Griffin JH, Fernandez JA, Deguchi H. Plasma lipoproteins, hemostasis and thrombosis. Thromb Haemost. 2001;86(1):386-94. doi:10.1055/s-0037-1616236.Orsi FA, Lijfering WM, Van der Laarse A, et al. Association of apolipoproteins C-I, C-II, C-III and E with coagulation markers and venous thromboembolism risk. Clin Epidemiol. 2019;11:625-33.Orsi FA, Lijfering WM, Van der Laarse A, et al. Association of apolipoproteins C-I, C-II, C-III and E with coagulation markers and venous thromboembolism risk. Clin Epidemiol. 2019;11:625-33.Van Schouwenburg IM, Mahmoodi BK, Gansevoort RT, et al. Lipid levels do not influence the risk of venous thromboembolism. Results of a population-based cohort study. Thromb Haemost. 2012;108(5):923-9. doi:10.1160/TH12-06-0426.Van Schouwenburg IM, Mahmoodi BK, Gansevoort RT, et al. Lipid levels do not influence the risk of venous thromboembolism. Results of a population-based cohort study. Thromb Haemost. 2012;108(5):923-9. doi:10.1160/TH12-06-0426.

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