cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLC10.15829/1728-8800-2020-2573cardiovascular-2573Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEW ARTICLESВалидные кардиоспецифические биохимические маркеры. Часть IValid cardiac biomarkers. Part Ihttps://orcid.org/0000-0001-8665-9129МетельскаяВ. А.MetelskayaV. A.

Виктория Алексеевна Метельская - доктор биологических наук, профессор, главный научный сотрудник, руководитель Отдела изучения биохимических маркеров риска хроничесских неинфекционных заболеваний 

Москва

VMETELSKAYA@GNICPM.RUhttps://orcid.org/0000-0002-6108-3538ГумановаН. Г.GumanovaN. G.

Надежда Георгиевна Гуманова - кандидат биологических наук, ведущий научный сотрудник отдела изучения биохимических маркеров риска хроничесских неинфекционных заболеваний 

Москва

ngumanova@gnicpm.ruФГБУ "Национальный медицинский исследовательский центр терапии и профилактической медицины" Минздрава РоссииNational Medical Center for Therapy and Preventive Medicine20201307202019425732573Copyright © Метельская В.А., Гуманова Н.Г., 20202020Метельская В.А., Гуманова Н.Г.Metelskaya V.A., Gumanova N.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/2573

Биомаркеры находят широкое применение в диагностике заболеваний, оценке их выраженности и определении прогноза по исходам, а также используются при выборе оптимальной терапии, мониторинге ее эффективности и безопасности. Настоящий обзор посвящен описанию кардиоспецифических биомаркеров, одобренных FDA (Food and Drug Administration), США, что гарантирует целесообразность их применения. Перечень анализируемых маркеров не является исчерпывающим ни с точки зрения списка валидных маркеров, одобренных FDA, ни с точки зрения их охвата в Рекомендациях по лечению различных сердечно-сосудистых заболеваний. Помимо изложения общих понятий о биомаркерах, определений и классификации в настоящей (первой) части обзора приведены данные о диагностических и прогностических биомаркерах сердечно-сосудистых заболеваний, связанных с атеросклерозом.

Biomarkers are widely used for the diagnosing of diseases, evaluation of their severity, prediction of outcomes, and for monitoring the effectiveness and safety of targeted therapy. This review describes specific cardiac biomarkers approved by FDA (Food and Drug AdministrationбUSA). The list of described biomarkers is not exhaustive. In addition to the general concepts of biomarkers, definitions and classification, this Part I of the review contains data on diagnostic and prognostic biomarkers of cardiovascular diseases associated with atherosclerosis.

циркулирующие биомаркерылабораторная диагностикаFDAсердечно-сосудистые заболеванияатеросклерозишемическая болезнь сердцаcirculating biomarkerslaboratory diagnosticsFDAcardiovascular diseasesatherosclerosiscoronary artery diseaseReferencesVasan RS. Biomarkers of Cardiovascular Disease. Molecular Basis and Practical Considerations. Circulation. 2006;113(19):2335-62. doi: 10.1161/CIRCULATIONAHA.104.482570Vasan RS. Biomarkers of Cardiovascular Disease. Molecular Basis and Practical Considerations. Circulation. 2006;113(19):2335-62. doi:10.1161/CIRCULATIONAHA.104.482570Аничков Д.А., Шостак Н.А. Новые маркеры сердечно-сосудистого риска: от исследований к клиническим рекомендациям. Клиницист. 2014;8(1):4-8. doi:10.17650/1818-8338-2014-1-4-8Anichkov DA, Shostak NA. New markers for cardiovascular risk: from studies to clinical guidelines. The Clinician. 2014;8(1):4-8. (In Russ.). doi:10.17650/1818-8338-2014-1-4-8Гуманова Н.Г. Аналитический комплекс биохимических маркеров для доклинической диагностики и профилактики сердечно-сосудистых заболеваний. Кардиоваскулярная терапия и профилактика. 2019;18(5):117-27. doi: 10.15829/1728-8800-2019-5-117-127Gumanova NG. Analytical complex of biochemical markers for preclinical diagnosis and prevention of cardiovascular diseases. Cardiovascular Therapy and Prevention. 2019;18(5):117-27). (In Russ.). doi:10.15829/1728-8800-2019-5-117-127Дон Е.С., Тарасов А.В., Эпштейн О.И., Тарасов С.А. Биомаркеры в медицине: поиск, выбор, изучение и валидация. Клин лабор диагн. 2017;62(1):52-9. doi:10.18821/0869-2084-2017-62-1-52-59Don ES, Tarasov AV, Epshtein OI, Tarasov SA. The biomarkers in medicine: search, choice, study and validation. Klinicheskaya Laboratornaya Diagnostika 2017;62(1):52-9. (In Russ.) doi:10.18821/0869-2084-2017-62-1-52-59Магрук М.А., Мосикян А., Бабенко А.Ю. Биомаркеры, ассоциированные с атерогенезом: актуальный статус и перспективные направления. Российский кардиологический журнал. 2019;24(12):148-52. doi:10.15829/1560-4071-2019-12-148-152Magruk MA, Mosikyan AA, Babenko AYu. Biomarkers associated with atherogenesis: current status and promising areas. Russian Journal of Cardiology. 2019;24(12):148-52. (In Russ.) Магрук М.А., Мосикян А., Бабенко А.Ю. Биомаркеры, ассоциированные с атерогенезом: актуальный статус и перспективные направления. Российский кардиологический журнал. 2019;24(12):148-52. doi:10.15829/1560-4071-2019-12-148-152Biomarkers Definitions Working Group. Biomarkers and surrogate end points: preferred definitions and conceptual frame work. Clin Pharmacol Ther 2001;69:89-95. doi: 10.1067/mcp.2001.113989Biomarkers Definitions Working Group. Biomarkers and surrogate end points: preferred definitions and conceptual frame work. Clin Pharmacol Ther 2001;69:89-95. doi: 10.1067/mcp.2001.113989Biomarkers, Endpoints, and other Tools Resource (BEST) https://www. ncbi.nlm.nih.gov/books/NBK326791Biomarkers, Endpoints, and other Tools Resource (BEST) https://www.ncbi.nlm.nih.gov/books/NBK326791CDER Biomarker Qualification Program. https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/cder-biomarker-qualification-programCDER Biomarker Qualification Program. https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/cder-biomarker-qualification-programHeinonen TM, Aamer M, Marshall C, et al. Cardiovascular biomarkers and surrogate end points: key initiatives and clinical trial challenges. Expert Rev Cardiovasc Ther. 2012; 10(8):989-94. doi: 10.1586/erc.12.84Heinonen TM, Aamer M, Marshall C, et al. Cardiovascular biomarkers and surrogate end points: key initiatives and clinical trial challenges. Expert Rev Cardiovasc Ther. 2012; 10(8):989-94. doi: 10.1586/erc.12.84Hlatky MA, Greenland P, Arnett DK, et al. Criteria for evaluation of novel markers of cardiovascular risk. A Scientific Statement from the AHA. Circulation. 2009;119:2408-16. doi.org/10.1161/CIRCULATIONAHA.109.192278Hlatky MA, Greenland P, Arnett DK, et al. Criteria for evaluation of novel markers of cardiovascular risk. A Scientific Statement from the AHA. Circulation. 2009;119:2408-16. doi:10.1161/CIRCULATIONAHA.109.192278Wang TJ. Assessing the Role of Circulating, Genetic, and Imaging Biomarkers in Cardiovascular Risk Prediction. Circulation. 2011;123:551-65. doi: 10.1161/CIRCULATIONAHA.109.912568.Wang TJ. Assessing the Role of Circulating, Genetic, and Imaging Biomarkers in Cardiovascular Risk Prediction. Circulation. 2011;123:551-65. doi: 10.1161/CIRCULATIONAHA.109.912568.Pencina MJ, D'Agostino RB, D'Agostino RB Jr, et al. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27(2):157-72. doi: 10.1002/sim.2929.Pencina MJ, D'Agostino RB, D'Agostino RB Jr, et al. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27(2):157-72. doi: 10.1002/sim.2929.Cook NR. Use and Misuse of the Receiver Operating Characteristic Curve in Risk Prediction. Circulation. 2007;115:928-35. doi: 10.1161/CIRCULATIONAHA.106.672402Cook NR. Use and Misuse of the Receiver Operating Characteristic Curve in Risk Prediction. Circulation. 2007;115:928-35. doi: 10.1161/CIRCULATIONAHA.106.672402Liu J, Hong Y, D’Agostino RB Sr, et al. Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-provincial Cohort Study. JAMA. 2004;291:2591-9. doi: 10.1001/jama.291.21.2591.Liu J, Hong Y, D’Agostino RB Sr, et al. Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-provincial Cohort Study. JAMA. 2004;291:2591-9. doi: 10.1001/jama.291.21.2591.Moons KG, de Groot JA, Linnet K, et al. Quantifying the added value of a diagnostic test or marker. Clin Chem. 2012; 58:1408-17. doi: 10.1373/clinchem.2012.182550.Moons KG, de Groot JA, Linnet K, et al. Quantifying the added value of a diagnostic test or marker. Clin Chem. 2012; 58:1408-17. doi: 10.1373/clinchem.2012.182550.Niiranen TJ, Vasan RS. Epidemiology of cardiovascular disease: recent novel outlooks on risk factors and clinical approaches. Expert Rev Cardiovasc Ther. 2016; 14 (7): 855-69. doi: 10.1080/14779072.2016.1176528Niiranen TJ, Vasan RS. Epidemiology of cardiovascular disease: recent novel outlooks on risk factors and clinical approaches. Expert Rev Cardiovasc Ther. 2016; 14 (7): 855-69. doi: 10.1080/14779072.2016.1176528Danese E, Montagnana M. An historical approach to the diagnostic biomarkers of acute coronary syndrome. Transl Med. 2016;4(10):194. doi: 10.21037/atm.2016.05.19Danese E, Montagnana M. An historical approach to the diagnostic biomarkers of acute coronary syndrome. Transl Med. 2016;4(10):194. doi: 10.21037/atm.2016.05.19Penttilä I, Penttilä K, Rantanen T. Laboratory diagnosis of patients with acute chest pain. Clin Chem Lab Med. 2000;38:187-97. doi: 10.1515/CCLM.2000.027Penttilä I, Penttilä K, Rantanen T. Laboratory diagnosis of patients with acute chest pain. Clin Chem Lab Med. 2000;38:187-97. doi: 10.1515/CCLM.2000.027Jialal I, Sokoll LJ. Am J Clin Pathol. Clinical Utility of Lactate Dehydrogenase in Determining the Severity of Hemolysis in Sickle Cell Anemia. 2015;143(2):158-9. doi: 10.1309/AJCTP0FC8QFYDFA.Jialal I, Sokoll LJ. Am J Clin Pathol. Clinical Utility of Lactate Dehydrogenase in Determining the Severity of Hemolysis in Sickle Cell Anemia. 2015;143(2):158-9. doi: 10.1309/AJCTP0FC8QFYDFA.Lewandrowski KB. Cardiac markers of myocardial necrosis: a history and discussion of milestones and emerging new trends. Clin Lab Med. 2014;34(1):31-41,xi. doi: 10.1016/j.cll.2013.11.001.Lewandrowski KB. Cardiac markers of myocardial necrosis: a history and discussion of milestones and emerging new trends. Clin Lab Med. 2014;34(1):31-41,xi. doi: 10.1016/j.cll.2013.11.001.Pöyhönen P, Kylmälä M, Vesterinen P, et al. Peak CK-MB has a strong association with chronic scar size and wall motion abnormalities after revascularized non-transmural myocardial infarction - a prospective CMR study. BMC Cardiovasc Disord. 2018; 8:18(1):27. doi: 10.1186/s12872-018-0767-7Pöyhönen P, Kylmälä M, Vesterinen P, et al. Peak CK-MB has a strong association with chronic scar size and wall motion abnormalities after revascularized non-transmural myocardial infarction - a prospective CMR study. BMC Cardiovasc Disord. 2018; 8:18(1):27. doi: 10.1186/s12872-018-0767-7Hendgen-Cotta U, Kelm M, Rassaf T. Myoglobin functions in the heart. Free Radic Biol Med. 2014;73:252-9. doi: 10.1016/j.freeradbiomed.2014.05.005.Hendgen-Cotta U, Kelm M, Rassaf T. Myoglobin functions in the heart. Free Radic Biol Med. 2014;73:252-9. doi: 10.1016/j.freeradbiomed.2014.05.005.Recognized Consensus Standards https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/detail.cfm?standard_identification_no=11555Recognized Consensus Standards https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/detail.cfm?standard_identification_no=11555Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomized trials. Lancet. 2010;376:1670-81. doi: 10.1016/S0140-6736(10)61350-5Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomized trials. Lancet. 2010;376:1670-81. doi: 10.1016/S0140-6736(10)61350-5Holmes MV, Asselbergs FW, Palmer TM, et al. Mendelian randomization of blood lipids for coronary heart disease. Eur Heart J. 2015;36(9):539-50. doi: 10.1093/eurheartj/eht571Holmes MV, Asselbergs FW, Palmer TM, et al. Mendelian randomization of blood lipids for coronary heart disease. Eur Heart J. 2015;36(9):539-50. doi: 10.1093/eurheartj/eht571Frikke-Schmidt R. HDL cholesterol and apolipoprotein A-I concentrations and risk of atherosclerotic cardiovascular disease: Human genetics to unravel causality. Atherosclerosis.2020;299:53-5. https://doi.org/10.1016/j.atherosclerosis.2020.02.002Frikke-Schmidt R. HDL cholesterol and apolipoprotein A-I concentrations and risk of atherosclerotic cardiovascular disease: Human genetics to unravel causality. Atherosclerosis.2020;299:53-5. https://doi.org/10.1016/j.atherosclerosis.2020.02.002Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384:626-35. doi: 10.1016/S0140-6736(14)61177-6Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384:626-35. doi: 10.1016/S0140-6736(14)61177-6Anderson NL. The clinical plasma proteome: a survey of clinical assays for proteins in plasma and serum. Clin Chem. 2010;56(2):177-85. doi: 10.1373/clinchem.2009.126706Anderson NL. The clinical plasma proteome: a survey of clinical assays for proteins in plasma and serum. Clin Chem. 2010;56(2):177-85. doi: 10.1373/clinchem.2009.126706The Emerging Risk Factors Collaboration. Major lipids, apolipoproteins and risk of vascular disease. JAMA. 2009; 302(18):1993-2000 doi: 10.1001/jama.2009.1619The Emerging Risk Factors Collaboration. Major lipids, apolipoproteins and risk of vascular disease. JAMA. 2009; 302(18):1993-2000 doi: 10.1001/jama.2009.1619Eckel RH, Cornier M. Update on the NCEP ATP-III emerging cardiometabolic risk factors. BMC Med. 2014;12:115. https://doi.org/10.1186/1741-7015-12-115Eckel RH, Cornier M. Update on the NCEP ATP-III emerging cardiometabolic risk factors. BMC Med. 2014;12:115. https://doi.org/10.1186/1741-7015-12-115Di Angelantonio E, Gao P, Pennells L, et al. Lipid-related markers and cardiovascular disease prediction. JAMA. 2012;307:2499-2506. doi: 10.1001/jama.2012.6571Di Angelantonio E, Gao P, Pennells L, et al. Lipid-related markers and cardiovascular disease prediction. JAMA. 2012;307:2499-2506. doi: 10.1001/jama.2012.6571Ежов М.В., Сергиенко И.В., Аронов Д.М. и др. Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации VI пересмотр. Атеросклероз и дислипидемии. 2017;3:5-22. doi:10.15829/1560-4071-2019-9-44-51Ezhov M V, Sergienko I V, Aronov DM, et al. Diagnostics and correction of lipid metabolism disorders in order to prevent and treat atherosclerosis. Russian recommendations VI revision. Atherosclerosis and Dyslipidemias. 2017;3:5-22. (In Russ.). doi:10.15829/1560-4071-2019-9-44-51Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias: Lipid Modification to Reduce Cardiovascular Risk. Eur Heart J. 2020;41(1):111-88. doi: 10.1093/eurheartj/ehz455.Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias: Lipid Modification to Reduce Cardiovascular Risk. Eur Heart J. 2020;41(1):111-88. doi: 10.1093/eurheartj/ehz455.Boffa MB, Marcovina SM, Koschinsky ML. Lipoprotein(a) as a risk factor for atherosclerosis and thrombosis: mechanistic insights from animal models. Clin Biochem. 2004;37(5):333-43. doi: 10.1016/j.clinbiochem.2003.12.007Boffa MB, Marcovina SM, Koschinsky ML. Lipoprotein(a) as a risk factor for atherosclerosis and thrombosis: mechanistic insights from animal models. Clin Biochem. 2004;37(5):333-43. doi: 10.1016/j.clinbiochem.2003.12.007Stefanutti C, Morozzi C. HyperLp(a)lipoproteinaemia: unmet need of diagnosis and treatment? Blood Transfus 2016;14:408-12. doi: 10.2450/2016.0027-16Stefanutti C, Morozzi C. HyperLp(a)lipoproteinaemia: unmet need of diagnosis and treatment? Blood Transfus 2016;14:408-12. doi: 10.2450/2016.0027-16Bennet A, Di Angelantonio E, Erqou S, et al. Lipoprotein(a) levels and risk of future coronary heart disease: large-scale prospective data. Arch Intern Med. 2008;168(6):598-608. doi: 10.1001/archinte.168.6.598Bennet A, Di Angelantonio E, Erqou S, et al. Lipoprotein(a) levels and risk of future coronary heart disease: large-scale prospective data. Arch Intern Med. 2008;168(6):598-608. doi: 10.1001/archinte.168.6.598Nordestgaard BG, Chapman MJ, Ray K, et al. EAS Consensus Panel. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31:2844-53. doi:10.1093/eurheartj/ehq386Nordestgaard BG, Chapman MJ, Ray K, et al. EAS Consensus Panel. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31:2844-53. doi: 10.1093/eurheartj/ehq386Erqou S, Kaptoge S, Perry PL, et al. Lipoprotein(a) Concentration and the Risk of Coronary Heart Disease, Stroke, and Nonvascular Mortality. JAMA. 2009;302(4):412-23. doi:10.1001/jama.2009.1063Erqou S, Kaptoge S, Perry PL, et al. Lipoprotein(a) Concentration and the Risk of Coronary Heart Disease, Stroke, and Nonvascular Mortality. JAMA. 2009;302(4):412-23. doi:10.1001/jama.2009.1063Tsimikas S, Stroes ES. The dedicated «Lp(a) clinic»: a concept whose time has arrived? Atherosclerosis. 2020;300:1-9. doi: 10.1016/j.atherosclerosis.2020.03.003Tsimikas S, Stroes ES. The dedicated «Lp(a) clinic»: a concept whose time has arrived? Atherosclerosis. 2020;300:1-9. doi: 10.1016/j.atherosclerosis.2020.03.003O'Riordan M. FDA Approves Lp-PLA2 Test for Patients without Existing Coronary Disease. https://www.medscape.com/viewarticle/836640O'Riordan M. FDA Approves Lp-PLA2 Test for Patients without Existing Coronary Disease. https://www.medscape.com/viewarticle/836640Stefano A, Liliana M, Federica T, et al. Lp-PLA2, a new biomarker of vascular disorders in metabolic diseases Int J Immunopathol Pharmacol. 2019;33:2058738419827154. doi: 10.1177/2058738419827154Stefano A, Liliana M, Federica T, et al. Lp-PLA2, a new biomarker of vascular disorders in metabolic diseases Int J Immunopathol Pharmacol. 2019;33:2058738419827154. doi: 10.1177/2058738419827154Stafforini DM. Plasma PAF-AH (PLA2G7): Biochemical properties, association with LDLs and HDLs, and regulation of expression. The Enzymes. 2015;38:71-93. doi: 10.1016/bs.enz.2015.09.004.Stafforini DM. Plasma PAF-AH (PLA2G7): Biochemical properties, association with LDLs and HDLs, and regulation of expression. The Enzymes. 2015;38:71-93. doi: 10.1016/bs.enz.2015.09.004.Thompson A, Gao P, Orfei L, et al. Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet. 2010;375(9725):1536-44. doi: 10.1016/S0140-6736(10)60319-4Thompson A, Gao P, Orfei L, et al. Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet. 2010;375(9725):1536-44. doi: 10.1016/S0140-6736(10)60319-4Packard CJ, O'Reilly DS, Caslake MJ, et al. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med. 2000;19:343(16):1148-55. doi: 10.1056/NEJM200010193431603Packard CJ, O'Reilly DS, Caslake MJ, et al. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med. 2000;19:343(16):1148-55. doi: 10.1056/NEJM200010193431603Li D, Zhao L, Yu J, et al. Lipoprotein-associated phospholipase A2 in coronary heart disease: Review and meta-analysis Clin Chim Acta. 2017;465:22-9. doi: 10.1016/j.cca.2016.12.006Li D, Zhao L, Yu J, et al. Lipoprotein-associated phospholipase A2 in coronary heart disease: Review and meta-analysis Clin Chim Acta. 2017;465:22-9. doi: 10.1016/j.cca.2016.12.006Wallentin L, Held C, Armstrong PW, et al. Lipoprotein-Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease. J Am Heart Assoc. 2016;5(6):e003407 doi:10.1161/JAHA.116.003407.Wallentin L, Held C, Armstrong PW, et al. Lipoprotein-Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease. J Am Heart Assoc. 2016;5(6):e003407 doi: 10.1161/JAHA.116.003407.Kaptoge S, Di Angelantonio E, Lowe G, et al. Emerging Risk Factors Collaboration C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375(9709):132-40. doi: 10.1016/S0140-6736(09)61717-7Kaptoge S, Di Angelantonio E, Lowe G, et al. Emerging Risk Factors Collaboration C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375(9709):132-40. doi: 10.1016/S0140-6736(09)61717-7Rudolf J, Lewandrowski KB. Cholesterol, lipoproteins, high-sensitivity С-reactive protein, and other risk factors for atherosclerosis Clin Lab Med. 2014;34:113-27. doi: 10.1016/j.cll.2013.11.003Rudolf J, Lewandrowski KB. Cholesterol, lipoproteins, high-sensitivity С-reactive protein, and other risk factors for atherosclerosis Clin Lab Med. 2014;34:113-27. doi: 10.1016/j.cll.2013.11.003Review Criteria for Assessment of C Reactive Protein (CRP), High Sensitivity C-Reactive Protein (hsCRP) and Cardiac C-Reactive Protein (cCRP) Assay. 2005. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/review-criteria-assessment-c-reactive-protein-crp-high-sensitivity-c-reactive-protein-hscrp-and-0Review Criteria for Assessment of C Reactive Protein (CRP), High Sensitivity C-Reactive Protein (hsCRP) and Cardiac C-Reactive Protein (cCRP) Assay. 2005. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/review-criteria-assessment-c-reactive-protein-crp-high-sensitivity-c-reactive-protein-hscrp-and-0Rifai N, Ballantyne C, Cushman M, et al. Point: High-Sensitivity C-Reactive Proteinand Cardiac C-Reactive Protein Assays: Is There a Need to Differentiate? Clinical Chemistry. 2006;52(7):1254-6. doi:10.1373/clinchem.2006.070904.Paxton A. 2006. http://www.captodayonline.com/Archives/feature_stories/0806hsCRP.htmlYousuf O, Mohanty BD, Martin SS, et al. High-sensitivity C-reactive protein and cardiovascular disease. J Am Coll Cardiol, 2013; 62:397-408. doi: 10.1016/j.jacc.2013.05.016Yousuf O, Mohanty BD, Martin SS, et al. High-sensitivity C-reactive protein and cardiovascular disease. J Am Coll Cardiol, 2013; 62:397-408. doi: 10.1016/j.jacc.2013.05.016Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003; 28;107(3):499-511. doi: 10.1161/01.cir.0000052939.59093.45Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003; 28;107(3):499-511. doi: 10.1161/01.cir.0000052939.59093.45Executive Summary for Plasma Fibrinogen. https://www.fda.gov/media/92567/Executive Summary for Plasma Fibrinogen. https://www.fda.gov/media/92567/Forsyth CB, Solovjov DA, Ugarova TP, Plow EF. Integrin αMβ2-Mediated Cell Migration to Fibrinogen and Its Recognition Peptides. J Exp Med. 2001;193(10):1123-34. doi: 10.1084/jem.193.10.1123Forsyth CB, Solovjov DA, Ugarova TP, Plow EF. Integrin αMβ2-Mediated Cell Migration to Fibrinogen and Its Recognition Peptides. J Exp Med. 2001;193(10):1123-34. doi: 10.1084/jem.193.10.1123Tousoulis D, Papageorgio N. Fibrinogen and cardiovascular disease: Genetics and biomarkers. Blood Rev. 2011;25(6) 239-45. https://doi.org/10.1016/j.blre.2011.05.001Tousoulis D, Papageorgio N. Fibrinogen and cardiovascular disease: Genetics and biomarkers. Blood Rev. 2011;25(6) 239-45. https://doi.org/10.1016/j.blre.2011.05.001Rizzo M, Corrado E, Coppola G, et al. Markers of inflammation are strong predictors of subclinical and clinical atherosclerosis in women with hypertension. Coron Artery Dis. 2009; 20:15-20. doi: 10.1097/MCA.0b013e3283109065Rizzo M, Corrado E, Coppola G, et al. Markers of inflammation are strong predictors of subclinical and clinical atherosclerosis in women with hypertension. Coron Artery Dis. 2009; 20:15-20. doi: 10.1097/MCA.0b013e3283109065Danesh J, Lewington S, Thompson SG, et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA. 2005;294:1799-1809. doi: 10.1001/jama.294.14.1799Danesh J, Lewington S, Thompson SG, et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA. 2005;294:1799-1809. doi: 10.1001/jama.294.14.1799Rønnow SR, Sand JMB, Langholm LL. Type IV collagen turnover is predictive of mortality in COPD: a comparison to fibrinogen in a prospective analysis of the ECLIPSE cohort. Respir Res. 2019; 20:63. doi: 10.1186/s12931-019-1026-xRønnow SR, Sand JMB, Langholm LL. Type IV collagen turnover is predictive of mortality in COPD: a comparison to fibrinogen in a prospective analysis of the ECLIPSE cohort. Respir Res. 2019; 20:63. doi: 10.1186/s12931-019-1026-xMiller BE, Tal-Singer R, Rennard SI, et al. Plasma Fibrinogen Qualification as a Drug Development Tool in Chronic Obstructive Pulmonary Disease. Perspective of the Chronic Obstructive Pulmonary Disease Biomarker Qualification Consortium. Am J Respir Crit Care Med. 2016;193(6):607-13. doi: 10.1164/rccm.201509-1722PPMiller BE, Tal-Singer R, Rennard SI, et al. Plasma Fibrinogen Qualification as a Drug Development Tool in Chronic Obstructive Pulmonary Disease. Perspective of the Chronic Obstructive Pulmonary Disease Biomarker Qualification Consortium. Am J Respir Crit Care Med. 2016;193(6):607-13. doi: 10.1164/rccm.201509-1722PPDanesh J, Collins R, Appleby P, et al. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: metaanalyses of prospective studies. JAMA. 1998;279:1477-82. doi: 10.1155/2020/8743548Danesh J, Collins R, Appleby P, et al. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: metaanalyses of prospective studies. JAMA. 1998;279:1477-82. doi: 10.1155/2020/8743548Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature. Ann Intern Med. 1993;118:956-63. doi:10.7326/0003-4819-118-12-199306150-00008Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature. Ann Intern Med. 1993;118:956-63. doi:10.7326/0003-4819-118-12-199306150-00008Moncada S, Palmer RMJ, Higgs A. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev.1991;43:109-42.Moncada S, Palmer RMJ, Higgs A. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev.1991;43:109-42.Метельская В.А., Гуманова Н.Г. Скрининг-метод определения уровня метаболитов оксида азота в сыворотке крови человека. Клин. лаб. диагн., 2005; №6:15-8.Metelskaya VA, Gumanova NG. Screening-method for nitric oxide metabolites determination in human serum. Clin Lab Diagn. 2005;6:15-18. (In Russ.)Гуманова Н.Г., Климушина М.В., Метельская В.А. Оптимизация метода одноэтапного определения циркулирующих нитрит- и нитрат-ионов (NOx) как фактора риска сердечно-сосудистой смерти. Бюлл. Эксперим. Биол. Мед. 2018;165(2):284-7). doi:10.1007/s10517-018-4149-zGumanova NG, Klimushina MV, Metel'skaya VA. Optimization of Single-Step Assay for Circulating Nitrite and Nitrate Ions (NOx) as Risk Factors of Cardiovascular Mortality. VA. Bull Exp Biol Med. 2018;165(2):284-7. (In Russ.). doi:10.1007/s10517-018-4149-zGumanova NG, Deev AD, Zhang W, et al. Serum nitrite and nitrate levels, NOx, can predict cardiovascular mortality in the elderly in a 3-year follow-up study. Biofactors. 2017;2;43(1):82-9. doi: 10.1002/biof.1321Gumanova NG, Deev AD, Zhang W, et al. Serum nitrite and nitrate levels, NOx, can predict cardiovascular mortality in the elderly in a 3-year follow-up study. Biofactors. 2017;2;43(1):82-9. doi: 10.1002/biof.1321Gumanova NG, Deev AD, Kots AY, et al. Elevated levels of serum nitrite and nitrate, NOx, are associated with increased total and cardiovascular mortality in an 8-year follow-up study. Eur J Clin Invest. 2019;49(3):e13061. doi: 10.1111/eci.13061Gumanova NG, Deev AD, Kots AY, et al. Elevated levels of serum nitrite and nitrate, NOx, are associated with increased total and cardiovascular mortality in an 8-year follow-up study. Eur J Clin Invest. 2019;49(3):e13061. doi: 10.1111/eci.13061Maas R, Xanthakis V, Göen T, et al. Plasma Nitrate and Incidence of Cardiovascular Disease and All-Cause Mortality in the Community: The Framingham Offspring Study. J Am Heart Assoc. 2017;18:6(11):e006224. doi: 10.1161/JAHA.117.004222Maas R, Xanthakis V, Göen T, et al. Plasma Nitrate and Incidence of Cardiovascular Disease and All-Cause Mortality in the Community: The Framingham Offspring Study. J Am Heart Assoc. 2017;18:6(11):e006224. doi: 10.1161/JAHA.117.004222Gumanova NG, Klimushina MV, Smetnev SA, et al. Levels of nitric oxide metabolites, adiponectin and endothelin are associated with SNPs of the adiponectin and endothelin genes. Biomed Rep. 2019;11(4):154-64. doi: 10.3892/br.2019.1238Gumanova NG, Klimushina MV, Smetnev SA, et al. Levels of nitric oxide metabolites, adiponectin and endothelin are associated with SNPs of the adiponectin and endothelin genes. Biomed Rep. 2019;11(4):154-64. doi: 10.3892/br.2019.1238Hayashi T, Nomura H, Osawa M, et al. Nitric oxide metabolites are associated with survival in older patients. J Am Geriatr Soc. 2007;55(9):1398-403. doi: 10.1111/j.1532-5415.2007.01296.x.Hayashi T, Nomura H, Osawa M, et al. Nitric oxide metabolites are associated with survival in older patients. J Am Geriatr Soc. 2007;55(9):1398-403. doi: 10.1111/j.1532-5415.2007.01296.x.Gumanova NG, Deev AD, Klimushina MV, et al., Serum nitrate and nitrite are associated with the prevalence of various chronic diseases except cancer. Int Angiol. 2017;36(2):160-6. doi: 10.23736/S0392-9590.16.03674-9Gumanova NG, Deev AD, Klimushina MV, et al., Serum nitrate and nitrite are associated with the prevalence of various chronic diseases except cancer. Int Angiol. 2017;36(2):160-6. doi: 10.23736/S0392-9590.16.03674-9Zethelius B, Berglund L, Sundstrom J, et al. Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Engl J Med 2008;358:2107-16. doi: 10.1056/NEJMoa0707064Zethelius B, Berglund L, Sundstrom J, et al. Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Engl J Med 2008;358:2107-16. doi: 10.1056/NEJMoa0707064Koenig W. Integrating biomarkers: the new frontier? Scand J Clin Lab Invest Suppl. 2010;242:117-23. doi: 10.3109/00365513.2010.493427Koenig W. Integrating biomarkers: the new frontier? Scand J Clin Lab Invest Suppl. 2010;242:117-23. doi: 10.3109/00365513.2010.493427Wang TJ. Multiple biomarkers for predicting cardiovascular events: lessons learned. J Am Coll Cardiol 2010;55:2092-5. doi: 10.1016/j.jacc.2010.02.019Wang TJ. Multiple biomarkers for predicting cardiovascular events: lessons learned. J Am Coll Cardiol 2010;55:2092-5. doi: 10.1016/j.jacc.2010.02.019Гаврилова Н.Е., Метельская В.А., Перова Н.В. и др. Выбор метода количественной оценки поражения коронарных артерий на основе сравнительного анализа ангиографических шкал. Российский кардиологический журнал 2014;6:24-9. doi: 10.15829/1560-4071-2014-6-24-29Gavrilova NE, Metelskaya VA, Perova NV, et al. Selection for the quantitative evaluation method of coronary arteries based upon comparative analysis of angiographic scales. Russian Journal of Cardiology. 2014;6:24-9. (In Russ.). doi: 10.15829/1560-4071-2014-6-24-29Gumanova NG, Gavrilova NE, Chernushevich OI, et al. Ratios of leptin to insulin and adiponectin to endothelin are sex-dependently associated with extent of coronary atherosclerosis. Biomarkers. 2017;22(3-4):239-45. doi: 10.1080/1354750X.2016.1201539Gumanova NG, Gavrilova NE, Chernushevich OI, et al. Ratios of leptin to insulin and adiponectin to endothelin are sex-dependently associated with extent of coronary atherosclerosis. Biomarkers. 2017;22(3-4):239-45. doi: 10.1080/1354750X.2016.1201539Гуманова Н.Г., Климушина М.В., Гаврилова Н.Е., Метельская В.А. Комбинированные маркеры начальной стадии атеросклероза коронарных артерий. Биомедицинская химия. 2017;63(3):272-7. doi: 10.18097/PBMC20176303272Gumanova NG, Klimushina MV, Gavrilova NE, Metelskaya VA. Combined markers of initial stages of coronary atherosclerosis. Biomeditsinskaya khimiya. 2017:63;3:272-7. (In Russ.). doi: 10.18097/PBMC20176303272Метельская В.А. Атеросклероз: мультимаркерные диагностические панели. Российский кардиологический журнал. 2018;8:65-73. doi:10.15829/1560-4071-2018-8-65-73Metelskaya VA. Multimarker diagnostic panels for atherosclerosis. Russian Journal of Cardiology. 2018;8:65-73. (In Russ.). doi: 10.15829/1560-4071-2018-8-65-73

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