medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2017-12-162-168medsovet-2049Research ArticleПрактикаPracticeПЕРСОНАЛИЗИРОВАННАЯ МЕДИЦИНА В КАРДИОЛОГИИ: СОСТОЯНИЕ ПРОБЛЕМЫ И ПЕРСПЕКТИВЫPERSONALIZED MEDICINE IN CARDIOLOGY: STATE, PROBLEMS AND PROSPECTSКолпачковаЕ. В.KolpachkovaE. V.

к.м.н.

СоколоваА. А.SokolovaA. A.

к.м.н.

PhD in medicine

НапалковД. А.NapalkovD. A.

д.м.н., профессор 

MD, Prof.

Первый Московский государственный медицинский университет им. И.М. Сеченова Минздрава РоссииРоссияSechenov First Moscow State University of the Ministry of HealthRussian Federation201704112017012162168Copyright © Колпачкова Е.В., Соколова А.А., Напалков Д.А., 20172017Колпачкова Е.В., Соколова А.А., Напалков Д.А.Kolpachkova E.V., Sokolova A.A., Napalkov D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/2049

Персонализированная медицина появилась около трех десятилетий назад. Уже тогда она заинтересовала многих ученых, исследователей, врачей. Однако только после полного открытия генома человека в 2001 г. персонализированная медицина стала давать возможность для некоторых патологий (онкология, ревматология, кардиология) подобрать максимально эффективное лечение с минимальными нежелательными лекарственными реакциями для конкретного больного. Возможность владеть генетической информацией дает шанс заподозрить, предсказать, спрогнозировать наступление заболевания. Персонализированная медицина способна в некоторых случаях точно сказать, будет ли препарат работать в отношении данного пациента, приближая нас к тому, чтобы «лечить не болезнь, а больного». Но врачи и по сей день для определения факторов риска ориентируются на индивидуальные особенности пациента, такие как возраст, пол, масса тела, сопутствующие заболевания, и, исходя из этого, назначают препараты, корректируют дозу, при неэффективности меняют схему лечения. Видимо, они не верят в персонализированную медицину, боятся ее и не хотят себя с ней связывать, потому что, как многим кажется, на основании своего опыта и знаний они вполне могут решить, какой препарат, какую дозу назначить пациенту. Также еще есть ряд причин, связанных с конфиденциальностью, безопасностью, проблемой подготовки кадров, которые в ближайшее время необходимо решить.

 

 

 

 

Personalized medicine appeared about three decades ago. Even then many scientists, researchers, doctors were interested into it. However, only after the full opening of the human genome in 2001, personalized medicine could to give the opportunity for some pathologies (oncology, rheumatology, cardiology) to choose the most effective treatment with minimal adverse drug reactions for a specific patient. The opportunity to own genetic information gives the chance to suspect, to predict, to expect the onset of the disease. Personalized medicine is able in some cases to say exactly whether the drug can work for the patient, moving us to «treat not a disease, but the patient.» But doctors to this day when determining risk factors focus on individual characteristics of the patient, such as age, gender, body weight, co-morbidities, and based on that prescribe medications, correct dose and in case of ineffectiveness change the treatment regimen. Apparently they don’t believe in personalized medicine, afraid of it and I don’t want to associate with it, because as many think on the basis of their experience and knowledge they can decide which drug and what dose to prescribe. Also, there are a number of reasons related to privacy, security, problem of training, which will soon need to be addressed.

персонализированная медицинафармакогенетикабиомаркерыгенетическая информациягенетическое тестированиеpersonalized medicinepharmacogenomicsbiomarkersgenetic information and genetic testingReferencesКлиническая фармакогенетика / Д.А.Сычев, И.В.Игнатьев, Г.В.Раменская, В.Г. Кукес (Под ред. В.Г. Кукеса, Н.П. Бочкова). М.: ГЭОТАР-МЕДИА, 2007. 248 с.Клиническая фармакогенетика / Д.А.Сычев, И.В.Игнатьев, Г.В.Раменская, В.Г. Кукес (Под ред. В.Г. Кукеса, Н.П. Бочкова). М.: ГЭОТАР-МЕДИА, 2007. 248 с.Linder MW, and Valdes R: Fundamentals of pharmaco genetics. Washington, DC: AACC Press, 2006.Linder MW, and Valdes R: Fundamentals of pharmaco genetics. Washington, DC: AACC Press, 2006.Khoury MJ: Genetics and genomics in practice: the continuum from genetic disease to genetic information in health and disease. Genet Med. 2003; 5: pp. 261-268.Khoury MJ: Genetics and genomics in practice: the continuum from genetic disease to genetic information in health and disease. Genet Med. 2003; 5: pp. 261-268.McCarthy JJ, McLeod HL, and Ginsburg GS: Genomic medicine: a decade of successes, challenges, and opportunities. Sci. Transl. Med. 2013 Jun 12; 5: pp. 189sr4McCarthy JJ, McLeod HL, and Ginsburg GS: Genomic medicine: a decade of successes, challenges, and opportunities. Sci. Transl. Med. 2013 Jun 12; 5: pp. 189sr4Roden DM, Tyndale RF: Genomic medicine, precision medicine, personalized medicine what’s in a name? Clin Pharmacol Ther. 2013, 94:169-172.Roden DM, Tyndale RF: Genomic medicine, precision medicine, personalized medicine what’s in a name? Clin Pharmacol Ther. 2013, 94:169-172.Innocenti F. Pharmacogenomics: Methods and Protocols (Methods in Molecular Biology) // Humana Press, 2005, 224 p.Innocenti F. Pharmacogenomics: Methods and Protocols (Methods in Molecular Biology) // Humana Press, 2005, 224 p.Pharmacogenomics / Edited by Rothstein M.A. – New Jersey: Willyliss, 2003. – P. 368.Pharmacogenomics / Edited by Rothstein M.A. – New Jersey: Willyliss, 2003. – P. 368.Shapiro SD. Merging personalized medicine and biology of aging in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011; 184: 864–866.Shapiro SD. Merging personalized medicine and biology of aging in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011; 184: 864–866.Nikus K, Birnbaum Y, Eskola M, Sclarovsky S, Zhong-Qun Z, Pahlm O. Updated electrocardio-graphic classification of acute coronary syndromes. Current Cardiology Reviews. 2014; 10(3): 229–236.Nikus K, Birnbaum Y, Eskola M, Sclarovsky S, Zhong-Qun Z, Pahlm O. Updated electrocardio-graphic classification of acute coronary syndromes. Current Cardiology Reviews. 2014; 10(3): 229–236.Mozaffarian D, Shi P, Morris J S, et al. Mercury exposure and risk of hypertension in US men and women in 2 prospective cohorts. Hypertension. 2012; 60(3):645–652.Mozaffarian D, Shi P, Morris J S, et al. Mercury exposure and risk of hypertension in US men and women in 2 prospective cohorts. Hypertension. 2012; 60(3):645–652.Yayan J. Emerging families of biomarkers for coronary artery disease: inflammatory mediators. Vascular Health and Risk Management. 2013; 9(1):435–456.Yayan J. Emerging families of biomarkers for coronary artery disease: inflammatory mediators. Vascular Health and Risk Management. 2013; 9(1):435–456.Kew S, Hamilton JK, Ye C, Hanley AJ, Zinman B, Retnakaran R. Vitamin D status and cardiometabolic assessment in infancy. Pediatric Research. 2013; 74(2):217–222.Kew S, Hamilton JK, Ye C, Hanley AJ, Zinman B, Retnakaran R. Vitamin D status and cardiometabolic assessment in infancy. Pediatric Research. 2013; 74(2):217–222.Mihl C, Loeffen D, Versteylen MO, et al. Auto mated quantification of epicardial adipose tissue (EAT) in coronary CT angiography; comparison with manual assessment and correlation with coronary artery disease. Journal of Cardiovascular Computed Tomography. 2014; 8(3):215–221.Mihl C, Loeffen D, Versteylen MO, et al. Auto mated quantification of epicardial adipose tissue (EAT) in coronary CT angiography; comparison with manual assessment and correlation with coronary artery disease. Journal of Cardiovascular Computed Tomography. 2014; 8(3):215–221.Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, Ingelsson E, Saleheen D, Erdmann J, Goldstein BA, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013; 45:25–33.Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, Ingelsson E, Saleheen D, Erdmann J, Goldstein BA, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013; 45:25–33.Freedman ML, Monteiro AN, Gayther SA, Coetzee GA, Risch A, Plass C, Casey G, De Biasi M, Carlson C, Duggan D, et al. Principles for the post-GWAS functional characterization of cancer risk loci. Nat Genet. 2011; 43:513–518.Freedman ML, Monteiro AN, Gayther SA, Coetzee GA, Risch A, Plass C, Casey G, De Biasi M, Carlson C, Duggan D, et al. Principles for the post-GWAS functional characterization of cancer risk loci. Nat Genet. 2011; 43:513–518.Ermann J, Glimcher LH. After GWAS: mice to the rescue? Curr Opin Immunol. 2012; 24:564–570.Ermann J, Glimcher LH. After GWAS: mice to the rescue? Curr Opin Immunol. 2012; 24:564–570.Wang L, Fan C, Topol SE, Topol EJ, Wang Q. Mutation of MEF2A in an inherited disorder with features of coronary artery disease. Science. 2003; 302:1578–1581.Wang L, Fan C, Topol SE, Topol EJ, Wang Q. Mutation of MEF2A in an inherited disorder with features of coronary artery disease. Science. 2003; 302:1578–1581.Boycott KM, Vanstone MR, Bulman DE, MacKenzie AE. Rare-disease genetics in the era of next-generation sequencing: discovery to translation. Nat Rev Genet. 2013; 14:681–691.Boycott KM, Vanstone MR, Bulman DE, MacKenzie AE. Rare-disease genetics in the era of next-generation sequencing: discovery to translation. Nat Rev Genet. 2013; 14:681–691.Inanloorahatloo K, Zand Parsa AF, Huse K, Rasooli P, Davaran S, Platzer M, Fan JB, Amini S, Steemers F, Elahi E. Mutation in CYP27A1 identified in family with coronary artery disease. Eur J Med Genet. 2013; 56:655–660.Inanloorahatloo K, Zand Parsa AF, Huse K, Rasooli P, Davaran S, Platzer M, Fan JB, Amini S, Steemers F, Elahi E. Mutation in CYP27A1 identified in family with coronary artery disease. Eur J Med Genet. 2013; 56:655–660.InanlooRahatloo K, Parsa AF, Huse K, Rasooli P, Davaran S, Platzer M, Kramer M, Fan JB, Turk C, Amini S, et al. Mutation in ST6GALNAC5 identified in family with coronary artery disease. Sci Rep. 2014; 4:3595.InanlooRahatloo K, Parsa AF, Huse K, Rasooli P, Davaran S, Platzer M, Kramer M, Fan JB, Turk C, Amini S, et al. Mutation in ST6GALNAC5 identified in family with coronary artery disease. Sci Rep. 2014; 4:3595.Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995; 80:795–803.Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995; 80:795–803.Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995; 80:805–811.Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995; 80:805–811.Priori SG, Napolitano C, Schwartz PJ. Low pene-trance in the long-QT syndrome: clinical impact. Circulation. 1999; 99:529–533.Priori SG, Napolitano C, Schwartz PJ. Low pene-trance in the long-QT syndrome: clinical impact. Circulation. 1999; 99:529–533.Schwartz PJ, Ackerman MJ, George AL, Jr, Wilde AAM. Impact of Genetics on the Clinical Management of Channelopathies. Journal of the American College of Cardiology. 2013; 62:169–180.Schwartz PJ, Ackerman MJ, George AL, Jr, Wilde AAM. Impact of Genetics on the Clinical Management of Channelopathies. Journal of the American College of Cardiology. 2013; 62:169–180.Crotti L, Johnson CN, Graf E, De Ferrari GM, Cuneo BF, Ovadia M, Papagiannis J, Feldkamp MD, Rathi SG, Kunic JD, et al. Calmodulin Mutations Associated With Recurrent Cardiac Arrest in Infants. Circulation. 2013; 127:1009– 1017. The technique of exome sequencing was used here to identify de novo mutations in the gene encoding calmodulin as a cause of severe long QT syndrome in infants. Mutations in calmodulin had never been previously described, and prior to development of high throughput resequencing technology, it was not possible to determine the cause of a congenital disease in a single affected child.Crotti L, Johnson CN, Graf E, De Ferrari GM, Cuneo BF, Ovadia M, Papagiannis J, Feldkamp MD, Rathi SG, Kunic JD, et al. Calmodulin Mutations Associated With Recurrent Cardiac Arrest in Infants. Circulation. 2013; 127:1009– 1017. The technique of exome sequencing was used here to identify de novo mutations in the gene encoding calmodulin as a cause of severe long QT syndrome in infants. Mutations in calmodulin had never been previously described, and prior to development of high throughput resequencing technology, it was not possible to determine the cause of a congenital disease in a single affected child.Haldeman GA, Croft JB, Giles WH, et al. Hospitalization of Patients with HF: National Hospital Discharge Survey, 1985 to 1995. Am Heart J. 1999; 137:352-60.Haldeman GA, Croft JB, Giles WH, et al. Hospitalization of Patients with HF: National Hospital Discharge Survey, 1985 to 1995. Am Heart J. 1999; 137:352-60.Roger VL, Go AS, Lloyd- Jones DM, et al. Heart Disease and stroke statistics: 2011 update: a report from American Heart Association. Circulation. 2011; 123:e18-e209.Roger VL, Go AS, Lloyd- Jones DM, et al. Heart Disease and stroke statistics: 2011 update: a report from American Heart Association. Circulation. 2011; 123:e18-e209.Jortani SA, Prabhu SD, Valdes R Jr. Strategies for developing biomarkers of HF. Clin Chem. 2004;50:265-78.Jortani SA, Prabhu SD, Valdes R Jr. Strategies for developing biomarkers of HF. Clin Chem. 2004;50:265-78.Masson S, Latini R, Anand IS, et al. Direct comparison of B-Type Natriuretic Peptide (BNP) and Amino-Terminal proBNP in a Large Population of Patients with Chronic and Symptomatic Heart Failure: The Valsartan Heart Failure (Val-HeFT) Data. Clin Chem. 2006; 52:1528-38.Masson S, Latini R, Anand IS, et al. Direct comparison of B-Type Natriuretic Peptide (BNP) and Amino-Terminal proBNP in a Large Population of Patients with Chronic and Symptomatic Heart Failure: The Valsartan Heart Failure (Val-HeFT) Data. Clin Chem. 2006; 52:1528-38.Doust JA, Pietrzak E, Dobson A, et al. How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review. BMJ. 2005; 330:625.Doust JA, Pietrzak E, Dobson A, et al. How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review. BMJ. 2005; 330:625.Nishiyama K, Tsutamoto T, Yamaji M, et al. Biological Variation of Brain Natriuretic Peptide and Cardiac Events in Stable Outpatients with Nonischemic Chronic Heart Failure. Circ J. 2011; 75:341-7.Nishiyama K, Tsutamoto T, Yamaji M, et al. Biological Variation of Brain Natriuretic Peptide and Cardiac Events in Stable Outpatients with Nonischemic Chronic Heart Failure. Circ J. 2011; 75:341-7.Maisel A, Mueller C, Nowak R, et al. Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea:results from the BACH (Biomarkers in Acute HF) trial. J Am Coll Cardiol. 2010; 55:2062-76.Maisel A, Mueller C, Nowak R, et al. Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea:results from the BACH (Biomarkers in Acute HF) trial. J Am Coll Cardiol. 2010; 55:2062-76.Peacock WF, Nowak R, Christenson R, et al. Short-term Mortality Risk in ED Acute HF. Acad Emerg Med. 2011; 18:947-58.Peacock WF, Nowak R, Christenson R, et al. Short-term Mortality Risk in ED Acute HF. Acad Emerg Med. 2011; 18:947-58.Klip IT, Voors AA, Anker SD, et al. Prognostic value of mid-regional pro-adrenomedullin in patients with HF after an acute myocardial infarction. Heart. 2011; 97:892-8.Klip IT, Voors AA, Anker SD, et al. Prognostic value of mid-regional pro-adrenomedullin in patients with HF after an acute myocardial infarction. Heart. 2011; 97:892-8.Levine B, Kalman J, Mayer L, et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990; 323:236-41.Levine B, Kalman J, Mayer L, et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990; 323:236-41.Kleinbongard P, Schulz R, Heusch G. TNF-α in myocardial ischemia/reperfusion, remodeling and heart failure. Heart Fail Rev. 2011; 16:49-69.Kleinbongard P, Schulz R, Heusch G. TNF-α in myocardial ischemia/reperfusion, remodeling and heart failure. Heart Fail Rev. 2011; 16:49-69.Deswal A, Petersen NJ, Feldman AM, et al. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation. 2001; 103:2055-9.Deswal A, Petersen NJ, Feldman AM, et al. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation. 2001; 103:2055-9.Chrysohoou C, Pitsavos C, Barbetseas J, et al. Chronic systemic inflammation accompanies impaired ventricular diastolic function, detected by Doppler imaging, in patients with newly diagnosed systolic heart failure (Hellenic Heart Failure Study). Heart Vessels. 2009; 24:22-6.Chrysohoou C, Pitsavos C, Barbetseas J, et al. Chronic systemic inflammation accompanies impaired ventricular diastolic function, detected by Doppler imaging, in patients with newly diagnosed systolic heart failure (Hellenic Heart Failure Study). Heart Vessels. 2009; 24:22-6.Valgimigli M, Ceconi C, Malagutti P, et al. Tumor necrosis factor-alpha receptor 1 is a major predictor of mortality and new-onset heart failure in patients with acute myocardial infarction: the Cytokine-Activation and Long-Term Prognosis in Myocardial Infarction (C-ALPHA) study. Circulation. 2005; 111:863-70.Valgimigli M, Ceconi C, Malagutti P, et al. Tumor necrosis factor-alpha receptor 1 is a major predictor of mortality and new-onset heart failure in patients with acute myocardial infarction: the Cytokine-Activation and Long-Term Prognosis in Myocardial Infarction (C-ALPHA) study. Circulation. 2005; 111:863-70.Berton G, Cordiano R, Palmieri R, et al. C-reactive protein in acute myocardial infarction: association with heart failure. Am Heart J. 2003; 145:1094-101.Berton G, Cordiano R, Palmieri R, et al. C-reactive protein in acute myocardial infarction: association with heart failure. Am Heart J. 2003; 145:1094-101.Yin WH, Chen JW, Jen HL, et al. Independent prognostic value of elevated high-sensitivity C-reactive protein in chronic heart failure. Am Heart J. 2004; 147:931-8.Yin WH, Chen JW, Jen HL, et al. Independent prognostic value of elevated high-sensitivity C-reactive protein in chronic heart failure. Am Heart J. 2004; 147:931-8.Chirinos JA, Zambrano JP, Chakko S, et al. Usefulness of C-reactive protein as an independent predictor of death in patients with ischemic cardiomyopathy. Am J Cardiol. 2005; 95:88-90.Chirinos JA, Zambrano JP, Chakko S, et al. Usefulness of C-reactive protein as an independent predictor of death in patients with ischemic cardiomyopathy. Am J Cardiol. 2005; 95:88-90.Cesari M, Penninx BW, Newman AB, et al. Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation. 2003; 108:2317-22.Cesari M, Penninx BW, Newman AB, et al. Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation. 2003; 108:2317-22.Boekholdt SM, Hack CE, Sandhu MS, et al. C-reactive protein levels and coronary artery disease incidence and mortality in apparently healthy men and women: the EPIC-Norfolk prospective population study 1993-2003. Atherosclerosis. 2006; 187:415-22.Boekholdt SM, Hack CE, Sandhu MS, et al. C-reactive protein levels and coronary artery disease incidence and mortality in apparently healthy men and women: the EPIC-Norfolk prospective population study 1993-2003. Atherosclerosis. 2006; 187:415-22.Engström G, Melander O, Hedblad B. Carotid intima-media thickness, systemic inflammation, and incidence of heart failure hospitalizations. Arterioscler Thromb Vasc Biol. 2009; 29:1691-5.Engström G, Melander O, Hedblad B. Carotid intima-media thickness, systemic inflammation, and incidence of heart failure hospitalizations. Arterioscler Thromb Vasc Biol. 2009; 29:1691-5.Oikonomou E, Tousoulis D, Siasos G, et al. The role of inflammation in heart failure: new therapeutic approaches. Hellenic J Cardiol. 2011; 52:30-40.Oikonomou E, Tousoulis D, Siasos G, et al. The role of inflammation in heart failure: new therapeutic approaches. Hellenic J Cardiol. 2011; 52:30-40.Desai AS, Lewis EF, Li R, Solomon SD, Assmann SF, Boineau R, Clausell N, Diaz R, Fleg JL, Gordeev I, McKinlay S, O’Meara E, Shaburishvili T, Pitt B, Pfeffer MA. Rationale and design of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial: a randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction. Am Heart J. 2011; 162:966–972.Desai AS, Lewis EF, Li R, Solomon SD, Assmann SF, Boineau R, Clausell N, Diaz R, Fleg JL, Gordeev I, McKinlay S, O’Meara E, Shaburishvili T, Pitt B, Pfeffer MA. Rationale and design of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial: a randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction. Am Heart J. 2011; 162:966–972.Meta-analysis Global Group in Chronic Heart Failure (MAGGIC). The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis. Eur Heart J. 2012; 33: 1750–1757.Meta-analysis Global Group in Chronic Heart Failure (MAGGIC). The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis. Eur Heart J. 2012; 33: 1750–1757.Беленков Ю.Н. Мозговой натрийуретический пептид – современный биомаркер хронической сердечной недостаточности /Ю. Н. Беленков, Е. Н. Привалова, И. С. Чекнева // Кардиология. –2008. – № 6. – С. 62–69.Беленков Ю.Н. Мозговой натрийуретический пептид – современный биомаркер хронической сердечной недостаточности /Ю. Н. Беленков, Е. Н. Привалова, И. С. Чекнева // Кардиология. –2008. – № 6. – С. 62–69.Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301–1307.Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301–1307.Packard CJ, O’Reilly DS, Caslake MJ, McMahon AD, Ford I, Cooney J, Macphee CH, Suckling KE, Krishna M, Wilkinson FE, Rumley A, Lowe GD. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med. 2000; 343:1148–1155.Packard CJ, O’Reilly DS, Caslake MJ, McMahon AD, Ford I, Cooney J, Macphee CH, Suckling KE, Krishna M, Wilkinson FE, Rumley A, Lowe GD. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med. 2000; 343:1148–1155.Ford I for The WOSCOPS Study Group. Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study. West of Scotland Coronary Prevention Study. Am J Cardiol. 1995; 76:485–491.Ford I for The WOSCOPS Study Group. Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study. West of Scotland Coronary Prevention Study. Am J Cardiol. 1995; 76:485–491.Ford I, Murray H, Packard CJ, Shepherd J, Macfarlane PW, Cobbe SM. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med. 2007; 357:1477–1486.Ford I, Murray H, Packard CJ, Shepherd J, Macfarlane PW, Cobbe SM. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med. 2007; 357:1477–1486.Ford I, Shepherd J, Cobbe SM, Lorimer AR, McKillop J, Packard C, Macfarlane P, Isles C. A coronary primary prevention study of Scottish men aged 45–64 years: trial design. J Clin Epidemiol. 1992; 45:849–860.Ford I, Shepherd J, Cobbe SM, Lorimer AR, McKillop J, Packard C, Macfarlane P, Isles C. A coronary primary prevention study of Scottish men aged 45–64 years: trial design. J Clin Epidemiol. 1992; 45:849–860.Zilberberg MD: The clinical research enterprise: time to change course? JAMA. 2011; 305: pp. 604-605.Zilberberg MD: The clinical research enterprise: time to change course? JAMA. 2011; 305: pp. 604-605.Greenhalgh T, et al: Evidence based medicine: a movement in crisis? BMJ. 2014; 348: pp. g3725.Greenhalgh T, et al: Evidence based medicine: a movement in crisis? BMJ. 2014; 348: pp. g3725.Wilke RA, Xu H, Denny JC, et al: The emerging role of electronic medical records in pharmacogenomics. Clin Pharmacol Ther. 2011; 89: pp. 379-386.Wilke RA, Xu H, Denny JC, et al: The emerging role of electronic medical records in pharmacogenomics. Clin Pharmacol Ther. 2011; 89: pp. 379-386.Dai L, Gao X, Guo Y, Xiao J, Zhang Z. Bioinformatics clouds for big data manipulation. Biol Direct, 7 (2012), p. 43.Dai L, Gao X, Guo Y, Xiao J, Zhang Z. Bioinformatics clouds for big data manipulation. Biol Direct, 7 (2012), p. 43.Harris PA, Taylor R, Thielke R, et al: Research Electronic Data Capture (REDCap) – A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009; 42: pp. 377-381.Harris PA, Taylor R, Thielke R, et al: Research Electronic Data Capture (REDCap) – A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009; 42: pp. 377-381.Lunshof JE, and Gurwitz D: Pharmacogenomic testing: knowing more, doing better. Clin Pharmacol Ther. 2012; 91: pp. 387-389.Lunshof JE, and Gurwitz D: Pharmacogenomic testing: knowing more, doing better. Clin Pharmacol Ther. 2012; 91: pp. 387-389.

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