Хроническая обструктивная болезнь легких и сердечно-сосудистая коморбидность

В последние годы пришло большее понимание гетерогенности и сложности хронической обструктивной болезни легких (ХОБЛ) с точки зрения интегральной клинической оценки тяжести, патофизиологии и взаимосвязи с другой патологией. Типичный пациент ХОБЛ страдает в среднем 4 и более сопутствующими заболеваниями и каждый день примерно треть пациентов принимают от 5 до 10 различных препаратов. Механизмы взаимовлияния ХОБЛ и сердечно-сосудистых заболеваний (ССЗ) включают влияние системного воспаления, гипервоздушности (гиперинфляции) легких и бронхиальной обструкции. Риск развития CCЗ у пациентов с ХОБЛ в среднем в 2–3 раза выше, чем у лиц сопоставимого возраста в общей популяции даже с учетом риска табакокурения. Распространенность ишемической болезни сердца, сердечной недостаточности и нарушений ритма среди больных ХОБЛ значительно выше, чем в общей популяции. В статье подробно обсуждается безопасность назначения различных групп препаратов для терапии ССЗ у пациентов с ХОБЛ. Достичь успеха в понимании и ведении пациентов с ХОБЛ и ССЗ возможно при использовании интегрального мультидисциплинарного подхода.  

1. GOLD. Global Strategy for the Diagnosis, Management and Prevention of COPD (2019 report). [Av. at: https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf ]

2. Miller J, Edwards LD, Agusti A, Bakke P, Calverley PMA, Celli B et al. Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort. Respiratory Medicine. 2013;107(9):1376–84. DOI: 10.1016/j.rmed.2013.05.001

3. Hollingworth K, Mullerova H, Landis S, Aisanov Z, Davis K, Ichinose M et al. Health behaviors and their correlates among participants in the Continuing to Confront COPD International Patient Survey. International Journal of Chronic Obstructive Pulmonary Disease. 2016;11:881–90. DOI: 10.2147/COPD.S102280

4. Miravitlles M, Roche N, Cardoso J, Halpin D, Aisanov Z, Kankaanranta H et al. Chronic obstructive pulmonary disease guidelines in Europe: a look into the future. Respiratory Research. 2018;19(1):11. DOI: 10.1186/s12931-018-0715-1

5. Barr RG, Celli BR, Mannino DM, Petty T, Rennard SI, Sciurba FC et al. Comorbidities, Patient Knowledge, and Disease Management in a National Sample of Patients with COPD. The American Journal of Medicine. 2009;122(4):348–55. DOI: 10.1016/j.amjmed.2008.09.042

6. Арутюнов Г. П., Корсунская М. И., Чернявская Т. К., Вершинин А. А., Розанов А. В., Баланина Н. О. Клиническая эффективность и безопасность длительной комбинированной блокады действия ренин-ангиотензинальдостероновой системы у больных с хроническими обструктивными болезнями легких. Терапевтический архив. 2000;72(10):52-6

7. Mannino DM, Thorn D, Swensen A, Holguin F. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. European Respiratory Journal. 2008;32(4):962–9. DOI: 10.1183/09031936.00012408

8. Divo M, Cote C, de Torres JP, Casanova C, Marin JM, Pinto-Plata V et al. Comorbidities and Risk of Mortality in Patients with Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine. 2012;186(2):155–61. DOI: 10.1164/rccm.201201-0034OC

9. Martinez CH, Han MK. Contribution of the Environment and Comorbidities to Chronic Obstructive Pulmonary Disease Phenotypes. Medical Clinics of North America. 2012;96(4):713–27. DOI: 10.1016/j.mcna.2012.02.007

10. National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. – Atlanta (GA): Centers for Disease Control and Prevention (US);

11. Vanfleteren LEGW, Spruit MA, Groenen M, Gaffron S, van Empel VPM, Bruijnzeel PLB et al. Clusters of Comorbidities Based on Validated Objective Measurements and Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine. 2013;187(7):728–35. DOI: 10.1164/rccm.201209-1665OC

12. Mullerova H, Agusti A, Erqou S, Mapel DW. Cardiovascular Comorbidity in COPD. Chest. 2013;144(4):1163–78. DOI: 10.1378/chest.12-2847

13. Agarwal SK, Heiss G, Barr RG, Chang PP, Loehr LR, Chambless LE et al. Airflow obstruction, lung function, and risk of incident heart failure: the Atherosclerosis Risk in Communities (ARIC) study. European Journal of Heart Failure. 2012;14(4):414–22. DOI: 10.1093/eurjhf/hfs016

14. Wannamethee SG, Shaper AG, Papacosta O, Lennon L, Welsh P, Whincup PH. Lung function and airway obstruction: associations with circulating markers of cardiac function and incident heart failure in older men—the British Regional Heart Study. Thorax. 2016;71(6):526– 34. DOI: 10.1136/thoraxjnl-2014-206724

15. Simbirtseva A. S., Rylova N. V. Prognostic role of clinical phenotypes and verified flora in patients with pneumonia associated with decompensated CHF. Russian Heart Failure Journal. 2015;16 (6):331–8. [Russian: Симбирцева А. С., Рылова Н. В. Прогностическая роль клинических фенотипов и верифицированной флоры у пациентов с пневмонией на фоне декомпенсации ХСН. Журнал Сердечная Недостаточность. 2015;16(6):331–8]. DOI: 10.18087/rhfj.2015.6.2174

16. Tockman MS, Pearson JD, Fleg JL, Metter EJ, Kao SY, Rampal KG et al. Rapid decline in FEV1. A new risk factor for coronary heart disease mortality. American Journal of Respiratory and Critical Care Medicine. 1995;151(2):390–8. DOI: 10.1164/ajrccm.151.2.7842197

17. Li J, Agarwal SK, Alonso A, Blecker S, Chamberlain AM, London SJ et al. Airflow Obstruction, Lung Function, and Incidence of Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2014;129(9):971–80. DOI: 10.1161/CIRCULATIONAHA.113.004050

18. Pai JK, Pischon T, Ma J, Manson JE, Hankinson SE, Joshipura K et al. Inflammatory Markers and the Risk of Coronary Heart Disease in Men and Women. New England Journal of Medicine. 2004;351(25):2599– 610. DOI: 10.1056/NEJMoa040967

19. Gan WQ. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax. 2004;59(7):574–80. DOI: 10.1136/thx.2003.019588

20. Patel ARC, Kowlessar BS, Donaldson GC, Mackay AJ, Singh R, George SN et al. Cardiovascular Risk, Myocardial Injury, and Exacerbations of Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine. 2013;188(9):1091–9. DOI: 10.1164/rccm.201306-1170OC

21. Симбирцева А. С., Арутюнов Г. П., Былова Н. А. Прогностические модели комбинированного учета симптомов и риска летального исхода в течение года у пациентов с внегоспитальной пневмонией и декомпенсацией ХСН. Журнал Сердечная Недостаточность. 2017;18(1):72-80. DOI: 10.18087/rhfj.2017.1.2317

22. Katsouyanni K, Zmirou D, Spix C, Sunyer J, Schouten JP, Ponka A et al. Short-term effects of air pollution on health: a European approach using epidemiologic time series data. The APHEA Project. Air Pollution Health Effects--A European Approach. Public Health Reviews. 1997;25(1):7–18; discussion 19-28. PMID: 9170962

23. Samet JM, Dominici F, Curriero FC, Coursac I, Zeger SL. Fine Particulate Air Pollution and Mortality in 20 U.S. Cities, 1987–1994. New England Journal of Medicine. 2000;343(24):1742–9. DOI: 10.1056/NEJM200012143432401

24. Arutyunov G. P., Bylova N. A., Rumyancev S. A. Extracardial manifestations in chronic heart failure. -М.: Akrihin; 171 p. [Russian: Арутюнов Г. П., Былова Н. А., Румянцев С. А. Внекардиальные проявления при хронической сердечной недостаточности. – М.: Акрихин, 2013. 171с]. ISBN 978-5-905757-33-4

25. van Eeden SF, Tan WC, Suwa T, Mukae H, Terashima T, Fujii T et al. Cytokines Involved in the Systemic Inflammatory Response Induced by Exposure to Particulate Matter Air Pollutants (PM (10)). American Journal of Respiratory and Critical Care Medicine. 2001;164(5):826– 30. DOI: 10.1164/ajrccm.164.5.2010160

26. Suwa T, Hogg JC, Quinlan KB, Ohgami A, Vincent R, van Eeden SF. Particulate air pollution induces progression of atherosclerosis. Journal of the American College of Cardiology. 2002;39(6):935–42. DOI: 10.1016/S0735-1097(02)01715-1

27. Tan WC, Qiu D, Liam BL, Ng TP, Lee SH, van EEDEN SF et al. The Human Bone Marrow Response to Acute Air Pollution Caused by Forest Fires. American Journal of Respiratory and Critical Care Medicine. 2000;161(4):1213–7. DOI: 10.1164/ajrccm.161.4.9904084

28. Arutyunov G.P. Diabetes mellitus and atherosclerosis. What is the optimal strategy to contain the atherosclerotic process? Russian Heart Journal. 2004;3(1):36–40. [Russian: Арутюнов Г.П. Сахарный диабет и атеросклероз. Какова оптимальная стратегия сдерживания атеросклеротического процесса? Сердце: журнал для практикующих врачей. 2004;3(1):36-40]

29. O’Donnell DE, Fluge T, Gerken F, Hamilton A, Webb K, Aguilaniu B et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. The European Respiratory Journal. 2004;23(6):832–40. PMID: 15218994

30. Casanova C, Cote C, de Torres JP, Aguirre-Jaime A, Marin JM, PintoPlata V et al. Inspiratory-to-Total Lung Capacity Ratio Predicts Mortality in Patients with Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine. 2005;171(6):591–7. DOI: 10.1164/rccm.200407-867OC

31. De Troyer A. Effect of hyperinflation on the diaphragm. The European Respiratory Journal. 1997;10(3):708–13. PMID: 9073010

32. Krieger BP. Hyperinflation and Intrinsic Positive End-Expiratory Pressure: Less Room to Breathe. Respiration. 2009;77(3):344–50. DOI: 10.1159/000192790

33. Thurlbeck W, Simon G. Radiographic appearance of the chest in emphysema. American Journal of Roentgenology. 1978;130(3):429–40. DOI: 10.2214/ajr.130.3.429

34. Wigh RE. On Defining Microcardia: Application in Pulmonary Emphysema. Southern Medical Journal. 1978;71(2):150–4. DOI: 10.1097/00007611-197802000-00020

35. Hutsebaut J, Scano G, Garcia-Herreros P, Degre S, De Coster A, Sergysels R. Hemodynamic Characteristics in Chronic Obstructive Lung Disease as Related to Cardiac Size. Respiration. 1981;41(1):25– 32. DOI: 10.1159/000194355

36. Vassaux C, Torre-Bouscoulet L, Zeineldine S, Cortopassi F, Paz-Diaz H, Celli BR et al. Effects of hyperinflation on the oxygen pulse as a marker of cardiac performance in COPD. European Respiratory Journal. 2008;32(5):1275–82. DOI: 10.1183/09031936.00151707

37. Watz H, Waschki B, Meyer T, Kretschmar G, Kirsten A, Claussen M et al. Decreasing Cardiac Chamber Sizes and Associated Heart Dysfunction in COPD. Chest. 2010;138(1):32–8. DOI: 10.1378/chest.09-2810

38. Sin DD. Chronic Obstructive Pulmonary Disease as a Risk Factor for Cardiovascular Morbidity and Mortality. Proceedings of the American Thoracic Society. 2005;2(1):8–11. DOI: 10.1513/pats.200404-032MS

39. Lindberg A, Larsson L-G, Ronmark E, Lundback B. Co-morbidity in Mild-to-Moderate COPD: Comparison to Normal and Restrictive Lung Function. COPD: Journal of Chronic Obstructive Pulmonary Disease. 2011;8(6):421–8. DOI: 10.3109/15412555.2011.629858

40. Chen W, Thomas J, Sadatsafavi M, FitzGerald JM. Risk of cardiovascular comorbidity in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. The Lancet Respiratory Medicine. 2015;3(8):631–9. DOI: 10.1016/S2213-2600(15)00241-6

41. Onishi K, Yoshimoto D, Hagan G, Jones P. Prevalence of airflow limitation in outpatients with cardiovascular diseases in Japan. International Journal of Chronic Obstructive Pulmonary Disease. 2014;9:563–8. DOI: 10.2147/COPD.S59962

42. Vanfleteren LEGW, Spruit MA, Wouters EFM, Franssen FME. Management of chronic obstructive pulmonary disease beyond the lungs. The Lancet Respiratory Medicine. 2016;4(11):911–24. DOI: 10.1016/S2213-2600(16)00097-7

43. Арутюнов А.Г., Рылова А.К., Арутюнов Г.П. Регистр госпитализированных пациентов с декомпенсацией кровообращения (Павловской Регистр). Сообщение 1. Современная клиническая характеристика пациента с декомпенсацией кровообращения. Клинические фенотипы пациентов. Журнал Сердечная Недостаточность. 2014;15(1):23-32

44. Арутюнов А.Г., Рылова А.К., Арутюнов Г.П. Регистр госпитализированных пациентов с декомпенсацией кровообращения (регистр Павловской больницы). Сообщение 2. Клиническое значение и прогностическая роль некоторых параметров, определяемых при физикальном и инструментальном обследовании пациентов с декомпенсацией кровообращения. Журнал Сердечная Недостаточность. 2014;15(2):67-75. DOI: 10.18087/rhfj.2014.2.1934

45. Арутюнов А. Г., Драгунов Д. О., Арутюнов Г. П., Рылова А. К., Пашкевич Д. Д., Витер К. В. и др. Первое открытое исследование синдрома острой декомпенсации сердечной недостаточности и сопутствующих заболеваний в Российской Федерации. Независимый регистр ОРАКУЛ-РФ. Кардиология. 2015;55(5):12-21. DOI: 10.18565/cardio.2015.5.12–21

46. Чучалин А.Г., Арутюнов Г.П., Синопальников А.И., Авдеев С.Н., Зырянов С.К., Арутюнов А.Г. и др. Согласованная позиция экспертов по лечению пневмонии у пациентов с декомпенсацией кровообращения. Журнал Сердечная Недостаточность. 2016;17(3):212-28. DOI: 10.18087/rhfj.2016.3.2202

47. Simbirtseva A.S. Community-acquired pneumonia in patients with decompensated chronic heart failure. Therapy. 2017;2(12):43–51. [Russian: Симбирцева А.С. Внегоспитальная пневмония у пациентов с декомпенсацией хронической сердечной недостаточности. Терапия. 2017;2(12):43-51.]

48. Almagro P, Lopez Garcia F, Cabrera Fj, Montero L, Morchon D, Diez J et al. Comorbidity and gender-related differences in patients hospitalized for COPD. The ECCO study. Respiratory Medicine. 2010;104(2):253–9. DOI: 10.1016/j.rmed.2009.09.019

49. Antonelli-Incalzi R, Imperiale C, Bellia V, Catalano F, Scichilone N, Pistelli R et al. Do GOLD stages of COPD severity really correspond to differences in health status? The European Respiratory Journal. 2003;22(3):444–9. PMID: 14516133

50. Baty F, Putora PM, Isenring B, Blum T, Brutsche M. Comorbidities and Burden of COPD: A Population Based Case-Control Study. PLoS ONE. 2013;8(5):e63285. DOI: 10.1371/journal.pone.0063285

51. Blanchette C, Roberts M, Petersen H, Dalal A, Mapel D. Economic burden of chronic bronchitis in the United States: a retrospective casecontrol study. International Journal of Chronic Obstructive Pulmonary Disease. 2011;6:73–81. DOI: 10.2147/COPD.S15882

52. Cazzola M, Calzetta L, Bettoncelli G, Cricelli C, Romeo F, Matera MG et al. Cardiovascular disease in asthma and COPD: A populationbased retrospective cross-sectional study. Respiratory Medicine. 2012;106(2):249–56. DOI: 10.1016/j.rmed.2011.07.021

53. Curkendall SM, deLuise C, Jones JK, Lanes S, Stang MR, Goehring E et al. Cardiovascular Disease in Patients with Chronic Obstructive Pulmonary Disease, Saskatchewan Canada cardiovascular disease in COPD patients. Annals of Epidemiology. 2006;16(1):63–70. DOI: 10.1016/j.annepidem.2005.04.008

54. Chen Y, Li Q, Johansen H. Age and sex variations in hospital readmissions for COPD associated with overall and cardiac comorbidity. The International Journal of Tuberculosis and Lung Disease: The Official Journal of the International Union Against Tuberculosis and Lung Disease. 2009;13(3):394–9. PMID: 19275803

55. Finkelstein J, Cha E, Scharf SM. Chronic obstructive pulmonary disease as an independent risk factor for cardiovascular morbidity. International Journal of Chronic Obstructive Pulmonary Disease. 2009;4:337–49. PMID: 19802349

56. Garcia Rodriguez LA, Wallander M-A, Tolosa LB, Johansson S. Chronic obstructive pulmonary disease in UK primary care: incidence and risk factors. COPD. 2009;6(5):369–79. PMID: 19863366

57. Holguin F, Folch E, Redd SC, Mannino DM. Comorbidity and Mortality in COPD-Related Hospitalizations in the United States, 1979 to 2001. Chest. 2005;128(4):2005–11. DOI: 10.1378/chest.128.4.2005

58. Huiart L, Ernst P, Suissa S. Cardiovascular Morbidity and Mortality in COPD. Chest. 2005;128(4):2640–6. DOI: 10.1378/chest.128.4.2640

59. Kollert F, Muller C, Tippelt A, Jorres RA, Heidinger D, Probst C et al. Anaemia in chronic respiratory failure: Anaemia in chronic respiratory failure. International Journal of Clinical Practice. 2011;65(4):479–86. DOI: 10.1111/j.1742-1241.2011.02631.x

60. Konecny T, Park JY, Somers KR, Konecny D, Orban M, Soucek F et al. Relation of Chronic Obstructive Pulmonary Disease to Atrial and Ventricular Arrhythmias. The American Journal of Cardiology. 2014;114(2):272–7. DOI: 10.1016/j.amjcard.2014.04.030

61. Lange P, Mogelvang R, Marott JL, Vestbo J, Jensen JS. Cardiovascular Morbidity in COPD: A Study of the General Population. COPD: Journal of Chronic Obstructive Pulmonary Disease. 2011;7(1):5–10. DOI: 10.3109/15412550903499506

62. Lin P-J, Shaya FT, Scharf SM. Economic implications of comorbid conditions among Medicaid beneficiaries with COPD. Respiratory Medicine. 2010;104(5):697–704. DOI: 10.1016/j.rmed.2009.11.009

63. Mapel DW, Dedrick D, Davis K. Trends and cardiovascular co-morbidities of COPD patients in the Veterans Administration Medical System, 1991-1999. COPD. 2005;2(1):35–41. PMID: 17136959

64. Miniati M, Monti S, Pavlickova I, Bottai M. Survival in COPD: Impact of Lung Dysfunction and Comorbidities. Medicine. 2014;93(12):e76. DOI: 10.1097/MD.0000000000000076

65. Schneider C, Bothner U, Jick SS, Meier CR. Chronic obstructive pulmonary disease and the risk of cardiovascular diseases. European Journal of Epidemiology. 2010;25(4):253–60. DOI: 10.1007/s10654010-9435-7

66. Sidney S, Sorel M, Quesenberry CP, DeLuise C, Lanes S, Eisner MD. COPD and Incident Cardiovascular Disease Hospitalizations and Mortality: Kaiser Permanente Medical Care Program. Chest. 2005;128(4):2068–75. DOI: 10.1378/chest.128.4.2068

67. Sin DD, Man SFP. Why Are Patients With Chronic Obstructive Pulmonary Disease at Increased Risk of Cardiovascular Diseases?: The Potential Role of Systemic Inflammation in Chronic Obstructive Pulmonary Disease. Circulation. 2003;107(11):1514–9. DOI: 10.1161/01.CIR.0000056767.69054.B3

68. Sode BF, Dahl M, Nordestgaard BG. Myocardial infarction and other co-morbidities in patients with chronic obstructive pulmonary disease: a Danish Nationwide Study of 7.4 million individuals. European Heart Journal. 2011;32(19):2365–75. DOI: 10.1093/eurheartj/ehr338

69. Huang B, Yang Y, Zhu J, Liang Y, Zhang H, Tian L et al. Clinical Characteristics and Prognostic Significance of Chronic Obstructive Pulmonary Disease in Patients With Atrial Fibrillation: Results From a Multicenter Atrial Fibrillation Registry Study. Journal of the American Medical Directors Association. 2014;15(8):576–81. DOI: 10.1016/j.jamda.2014.04.009

70. Brusselle GG, Joos GF, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. The Lancet. 2011;378(9795):1015–26. DOI: 10.1016/S0140-6736(11)60988-4

71. Papaioannou AI, Mazioti A, Kiropoulos T, Tsilioni I, Koutsokera A, Tanou K et al. Systemic and airway inflammation and the presence of emphysema in patients with COPD. Respiratory Medicine. 2010;104(2):275–82. DOI: 10.1016/j.rmed.2009.09.016

72. Reed RM, Eberlein M, Girgis RE, Hashmi S, Iacono A, Jones S et al. Coronary Artery Disease Is Under-diagnosed and Undertreated in Advanced Lung Disease. The American Journal of Medicine. 2012;125(12):1228.e13-1228.e22. DOI: 10.1016/j.amjmed.2012.05.018

73. Arnett DK, Goodman RA, Halperin JL, Anderson JL, Parekh AK, Zoghbi WA. AHA/ACC/HHS Strategies to Enhance Application of Clinical Practice Guidelines in Patients with Cardiovascular Disease and Comorbid Conditions: From the American Heart Association, American College of Cardiology, and US Department of Health and Human Services. Circulation. 2014;130(18):1662–7. DOI: 10.1161/CIR.0000000000000128

74. Козлова Л. И., Айсанов З. Р., Чучалин А. Г. В чем опасность длительного применения β-блокаторов у больных ишемической болезнью сердца с сопутствующей хронической обструктивной болезнью легких. Терапевтический архив. 2005;77(3):18-23. PMID: 15881093

75. Симбирцева А. С., Арутюнов Г. П., Джандарова Д. Т., Швыдкая М. Г., Орлов С. Ю., Гришина А. В. и др. Сравнение микробиологического состава мокроты и биоптатов главных бронхов у пациентов с пневмонией на фоне декомпенсации хронической сердечной недостаточности. Журнал Сердечная Недостаточность. 2016;17(4):250-8. DOI: 10.18087/rhfj.2016.4.2268

76. Franssen FME, Soriano JB, Roche N, Bloomfield PH, Brusselle G, Fabbri LM et al. Lung Function Abnormalities in Smokers with Ischemic Heart Disease. American Journal of Respiratory and Critical Care Medicine. 2016;194(5):568–76. DOI: 10.1164/rccm.2015122480OC

77. Garcia Rodriguez LA, Wallander M-A, Martin-Merino E, Johansson S. Heart failure, myocardial infarction, lung cancer and death in COPD patients: A UK primary care study. Respiratory Medicine. 2010;104(11):1691–9. DOI: 10.1016/j.rmed.2010.04.018

78. Patel ARC, Donaldson GC, Mackay AJ, Wedzicha JA, Hurst JR. The Impact of Ischemic Heart Disease on Symptoms, Health Status, and Exacerbations in Patients With COPD. Chest. 2012;141(4):851–7. DOI: 10.1378/chest.11-0853

79. MacDonald MI, Shafuddin E, King PT, Chang CL, Bardin PG, Hancox RJ. Cardiac dysfunction during exacerbations of chronic obstructive pulmonary disease. The Lancet Respiratory Medicine. 2016;4(2):138–48. DOI: 10.1016/S2213-2600(15)00509-3

80. Campo G, Pavasini R, Malagu M, Mascetti S, Biscaglia S, Ceconi C et al. Chronic Obstructive Pulmonary Disease and Ischemic Heart Disease Comorbidity: Overview of Mechanisms and Clinical Management. Cardiovascular Drugs and Therapy. 2015;29(2):147–57. DOI: 10.1007/s10557-014-6569-y

81. Roca M, Verduri A, Corbetta L, Clini E, Fabbri LM, Beghe B. Mechanisms of acute exacerbation of respiratory symptoms in chronic obstructive pulmonary disease. European Journal of Clinical Investigation. 2013;43(5):510–21. DOI: 10.1111/eci.12064

82. Donaldson GC, Hurst JR, Smith CJ, Hubbard RB, Wedzicha JA. Increased Risk of Myocardial Infarction and Stroke Following Exacerbation of COPD. Chest. 2010;137(5):1091–7. DOI: 10.1378/chest.09-2029

83. Onishi K. Total management of chronic obstructive pulmonary disease (COPD) as an independent risk factor for cardiovascular disease. Journal of Cardiology. 2017;70(2):128–34. DOI: 10.1016/j.jjcc.2017.03.001

84. Rothnie KJ, Smeeth L, Herrett E, Pearce N, Hemingway H, Wedzicha J et al. Closing the mortality gap after a myocardial infarction in people with and without chronic obstructive pulmonary disease. Heart. 2015;101(14):1103–10. DOI: 10.1136/heartjnl-2014-307251

85. Cooper BG. An update on contraindications for lung function testing. Thorax. 2011;66(8):714–23. DOI: 10.1136/thx.2010.139881

86. McAllister DA, Maclay JD, Mills NL, Leitch A, Reid P, Carruthers R et al. Diagnosis of myocardial infarction following hospitalisation for exacerbation of COPD. European Respiratory Journal. 2012;39(5):1097–103. DOI: 10.1183/09031936.00124811

87. Pavasini R, d’Ascenzo F, Campo G, Biscaglia S, Ferri A, Contoli M et al. Cardiac troponin elevation predicts all-cause mortality in patients with acute exacerbation of chronic obstructive pulmonary disease: Systematic review and meta-analysis. International Journal of Cardiology. 2015;191:187–93. DOI: 10.1016/j.ijcard.2015.05.006

88. Neukamm AMC, Hoiseth AD, Hagve T-A, Soyseth V, Omland T. Highsensitivity cardiac troponin T levels are increased in stable COPD. Heart. 2013;99(6):382–7. DOI: 10.1136/heartjnl-2012-303429

89. Lee HM, Lee J, Lee K, Luo Y, Sin DD, Wong ND. Relation Between COPD Severity and Global Cardiovascular Risk in US Adults. Chest. 2012;142(5):1118–25. DOI: 10.1378/chest.11-2421

90. Bhatt SP, Dransfield MT. Chronic obstructive pulmonary disease and cardiovascular disease. Translational Research. 2013;162(4):237–51. DOI: 10.1016/j.trsl.2013.05.001

91. Goudis CA, Konstantinidis AK, Ntalas IV, Korantzopoulos P. Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease. International Journal of Cardiology. 2015;199:264–73. DOI: 10.1016/j.ijcard.2015.06.096

92. Buch P, Friberg J, Scharling H, Lange P, Prescott E. Reduced lung function and risk of atrial fibrillation in the Copenhagen City Heart Study. The European Respiratory Journal. 2003;21(6):1012–6. PMID: 12797497

93. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology. 2014;64(21):e1–76. DOI: 10.1016/j.jacc.2014.03.022

94. Knuiman M, Briffa T, Divitini M, Chew D, Eikelboom J, McQuillan B et al. A cohort study examination of established and emerging risk factors for atrial fibrillation: the Busselton Health Study. European Journal of Epidemiology. 2014;29(3):181–90. DOI: 10.1007/s10654-0139875-y

95. Miyazaki M, Nakamura H, Chubachi S, Sasaki M, Haraguchi M, Yoshida S et al. Analysis of comorbid factors that increase the COPD assessment test scores. Respiratory Research. 2014;15(1):13. DOI: 10.1186/1465-9921-15-13

96. Atzema CL, Lam K, Young C, Kester-Greene N. Patients with Atrial Fibrillation and an Alternative Primary Diagnosis in the Emergency Department: A Description of their Characteristics and Outcomes. Academic Emergency Medicine. 2013;20(2):193–9. DOI: 10.1111/acem.12078

97. Steer J, Gibson J, Bourke SC. The DECAF Score: predicting hospital mortality in exacerbations of chronic obstructive pulmonary disease. Thorax. 2012;67(11):970–6. DOI: 10.1136/thoraxjnl-2012-202103

98. Ekstrom MP, Jogreus C, Strom KE. Comorbidity and Sex-Related Differences in Mortality in Oxygen-Dependent Chronic Obstructive Pulmonary Disease. PLoS ONE. 2012;7(4):e35806. DOI: 10.1371/journal.pone.0035806

99. Terzano C, Romani S, Conti V, Paone G, Oriolo F, Vitarelli A. Atrial fibrillation in the acute, hypercapnic exacerbations of COPD. European Review for Medical and Pharmacological Sciences. 2014;18(19):2908– 17. PMID: 25339486

100. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal. 2016;37(27):2129–200. DOI: 10.1093/eurheartj/ehw128

101. Mentz RJ, Kelly JP, von Lueder TG, Voors AA, Lam CSP, Cowie MR et al. Noncardiac Comorbidities in Heart Failure with Reduced Versus Preserved Ejection Fraction. Journal of the American College of Cardiology. 2014;64(21):2281–93. DOI: 10.1016/j.jacc.2014.08.036

102. Kwon B-J, Kim D-B, Jang S-W, Yoo K-D, Moon K-W, Shim BJ et al. Prognosis of heart failure patients with reduced and preserved ejection fraction and coexistent chronic obstructive pulmonary disease. European Journal of Heart Failure. 2010;12(12):1339–44. DOI: 10.1093/eurjhf/hfq157

103. Dal Negro RW, Bonadiman L, Turco P. Prevalence of different comorbidities in COPD patients by gender and GOLD stage. Multidisciplinary Respiratory Medicine. 2015;10(1):24. DOI: 10.1186/s40248-0150023-2

104. Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. The Lancet. 2007;370(9589):786–96. DOI: 10.1016/S0140-6736(07)61382-8

105. Nieminen MS, Brutsaert D, Dickstein K, Drexler H, Follath F, Harjola V-P et al. EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population. European Heart Journal. 2006;27(22):2725–36. DOI: 10.1093/eurheartj/ehl193

106. Abroug F, Ouanes-Besbes L, Nciri N, Sellami N, Addad F, Hamda KB et al. Association of Left-Heart Dysfunction with Severe Exacerbation of Chronic Obstructive Pulmonary Disease: Diagnostic Performance of Cardiac Biomarkers. American Journal of Respiratory and Critical Care Medicine. 2006;174(9):990–6. DOI: 10.1164/rccm.200603-380OC

107. Yu T-C, Zhou H, Suh K, Arcona S. Assessing the importance of predictors in unplanned hospital readmissions for chronic obstructive pulmonary disease. ClinicoEconomics and Outcomes Research. 2015;7:37– 51. DOI: 10.2147/CEOR.S74181

108. Regan EA, Lynch DA, Curran-Everett D, Curtis JL, Austin JHM, Grenier PA et al. Clinical and Radiologic Disease in Smokers with Normal Spirometry. JAMA Internal Medicine. 2015;175(9):1539–49. DOI: 10.1001/jamainternmed.2015.2735

109. Minasian AG, van den Elshout FJ, Dekhuijzen PR, Vos PJ, Willems FF, van den Bergh PJ et al. Serial pulmonary function tests to diagnose COPD in chronic heart failure. Translational Respiratory Medicine. 2014;2(1):12. DOI: 10.1186/s40247-014-0012-5

110. Guder G, Brenner S, Stork S, Hoes A, Rutten FH. Chronic obstructive pulmonary disease in heart failure: accurate diagnosis and treatment. European Journal of Heart Failure. 2014;16(12):1273–82. DOI: 10.1002/ejhf.183

111. Brenner S, Guder G, Berliner D, Deubner N, Frohlich K, Ertl G et al. Airway obstruction in systolic heart failure – COPD or congestion? International Journal of Cardiology. 2013;168(3):1910–6. DOI: 10.1016/j.ijcard.2012.12.083

112. Горелик И. Л., Калманова Е. Н., Айсанов З. Р., Чучалин А. Г. Функционально-структурные изменения сердца при хронической обструктивной болезни легких в сочетании с ишемической болезнью сердца. Пульмонология. 2010;1:100-5

113. Hawkins NM, Virani S, Ceconi C. Heart failure and chronic obstructive pulmonary disease: the challenges facing physicians and health services. European Heart Journal. 2013;34(36):2795–807. DOI: 10.1093/eurheartj/eht192

114. Sacks CA, Jarcho JA, Curfman GD. Paradigm Shifts in HeartFailure Therapy — A Timeline. New England Journal of Medicine. 2014;371(11):989–91. DOI: 10.1056/NEJMp1410241

115. Lahousse L, Verhamme KM, Stricker BH, Brusselle GG. Cardiac effects of current treatments of chronic obstructive pulmonary disease. The Lancet Respiratory Medicine. 2016;4(2):149–64. DOI: 10.1016/S2213-2600(15)00518-4

116. Lohse MJ, Engelhardt S, Eschenhagen T. What Is the Role of β-Adrenergic Signaling in Heart Failure? Circulation Research. 2003;93(10):896–906. DOI: 10.1161/01.RES.0000102042.83024.CA

117. Gershon A, Croxford R, Calzavara A, To T, Stanbrook MB, Upshur R et al. Cardiovascular Safety of Inhaled Long-Acting Bronchodilators in Individuals with Chronic Obstructive Pulmonary Disease. JAMA Internal Medicine. 2013;173(13):1175–85. DOI: 10.1001/jamainternmed.2013.1016

118. Dong Y-H, Chang C-H, Gagne JJ, Hsu C-L, Lai M-S. Comparative Cardiovascular and Cerebrovascular Safety of Inhaled Long-Acting Bronchodilators in Patients with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2016;36(1):26–37. DOI: 10.1002/phar.1684

119. Bermingham M, O’Callaghan E, Dawkins I, Miwa S, Samsudin S, McDonald K et al. Are beta2-agonists responsible for increased mortality in heart failure? European Journal of Heart Failure. 2011;13(8):885– 91. DOI: 10.1093/eurjhf/hfr063

120. Anthonisen NR, Connett JE, Enright PL, Manfreda J. Hospitalizations and Mortality in the Lung Health Study. American Journal of Respiratory and Critical Care Medicine. 2002;166(3):333–9. DOI: 10.1164/rccm.2110093

121. Ogale SS, Lee TA, Au DH, Boudreau DM, Sullivan SD. Cardiovascular Events Associated with Ipratropium Bromide in COPD. Chest. 2010;137(1):13–9. DOI: 10.1378/chest.08-2367

122. Tashkin DP, Leimer I, Metzdorf N, Decramer M. Cardiac safety of tiotropium in patients with cardiac events: a retrospective analysis of the UPLIFT® trial. Respiratory Research. 2015;16(1):65. DOI: 10.1186/s12931-015-0216-4

123. Verhamme KMC, Afonso ASM, van Noord C, Haag MD, Koudstaal PJ, Brusselle GGO et al. Tiotropium Handihaler and the risk of cardioor cerebrovascular events and mortality in patients with COPD. Pulmonary Pharmacology & Therapeutics. 2012;25(1):19–26. DOI: 10.1016/j.pupt.2011.10.004

124. D’Urzo T, Kerwin E, Chapman K, Decramer M, DiGiovanni R, D’Andrea P et al. Safety of inhaled glycopyrronium in patients with COPD: a comprehensive analysis of clinical studies and post-marketing data. International Journal of Chronic Obstructive Pulmonary Disease. 2015;10:1599–612. DOI: 10.2147/COPD.S81266

125. Kerwin EM, D’Urzo AD, Gelb AF, Lakkis H, Gil EG, Caracta CF. Efficacy and Safety of a 12-week Treatment with Twice-daily Aclidinium Bromide in COPD Patients (ACCORD COPD I). COPD: Journal of Chronic Obstructive Pulmonary Disease. 2012;9(2):90–101. DOI: 10.3109/15412555.2012.661492

126. Trivedi R, Richard N, Mehta R, Church A. Umeclidinium in patients with COPD: a randomised, placebo-controlled study. European Respiratory Journal. 2014;43(1):72–81. DOI: 10.1183/09031936.00033213

127. Wedzicha JA, Banerji D, Chapman KR, Vestbo J, Roche N, Ayers RT et al. Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD. New England Journal of Medicine. 2016;374(23):2222–34. DOI: 10.1056/NEJMoa1516385

128. Calzetta L, Rogliani P, Matera MG, Cazzola M. A Systematic Review with Meta-Analysis of Dual Bronchodilation With LAMA/LABA for the Treatment of Stable COPD. Chest. 2016;149(5):1181–96. DOI: 10.1016/j.chest.2016.02.646

129. White WB, Cooke GE, Kowey PR, Calverley PMA, Bredenbroker D, Goehring U-M et al. Cardiovascular Safety in Patients Receiving Roflumilast for the Treatment of COPD. Chest. 2013;144(3):758–65. DOI: 10.1378/chest.12-2332

130. Macie C, Wooldrage K, Manfreda J, Anthonisen N. Cardiovascular morbidity and the use of inhaled bronchodilators. International Journal of Chronic Obstructive Pulmonary Disease. 2008;3(1):163–9. PMID: 18488440

131. Macie C, Wooldrage K, Manfreda J, Anthonisen NR. Inhaled Corticosteroids and Mortality in COPD. Chest. 2006;130(3):640–6. DOI: 10.1378/chest.130.3.640

132. Vestbo J, Anderson JA, Brook RD, Calverley PMA, Celli BR, Crim C et al. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. The Lancet. 2016;387(10030):1817–26. DOI: 10.1016/S0140-6736(16)30069-1

133. Jara M, Lanes SF, Wentworth C, May C, Kesten S. Comparative Safety of Long-Acting Inhaled Bronchodilators: A Cohort Study Using the UK THIN Primary Care Database. Drug Safety. 2007;30(12):1151–60. DOI: 10.2165/00002018-200730120-00007

134. Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S et al. A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease. New England Journal of Medicine. 2008;359(15):1543–54. DOI: 10.1056/NEJMoa0805800

135. Wedzicha JA, Calverley PMA, Seemungal TA, Hagan G, Ansari Z, Stockley RA. The Prevention of Chronic Obstructive Pulmonary Disease Exacerbations by Salmeterol/Fluticasone Propionate or Tiotropium Bromide. American Journal of Respiratory and Critical Care Medicine. 2008;177(1):19–26. DOI: 10.1164/rccm.200707973OC

136. Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B et al. Tiotropium Respimat Inhaler and the Risk of Death in COPD. New England Journal of Medicine. 2013;369(16):1491–501. DOI: 10.1056/NEJMoa1303342

137. Calverley PMA, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW et al. Cardiovascular events in patients with COPD: TORCH Study results. Thorax. 2010;65(8):719–25. DOI: 10.1136/thx.2010.136077

138. Singh S, Loke YK, Enright P, Furberg CD. Pro-arrhythmic and proischaemic effects of inhaled anticholinergic medications. Thorax. 2013;68(1):114–6. DOI: 10.1136/thoraxjnl-2011-201275

139. Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular Effects of β-Agonists in Patients with Asthma and COPD. Chest. 2004;125(6):2309–21. DOI: 10.1378/chest.125.6.2309

140. Бокерия Л. А., Затевахин И. И., Кириенко А. И., Андрияшкин А. В., Андрияшкин В. В., Арутюнов Г. П. и др. Российские клинические рекомендации по диагностике, лечению и профилактике венозных тромбоэмболических осложнений (ВТЭО). Флебология. 2015;9(4-2):1-52.

141. Wilchesky M, Ernst P, Brophy JM, Platt RW, Suissa S. Bronchodilator Use and the Risk of Arrhythmia in COPD. Chest. 2012;142(2):298– 304. DOI: 10.1378/chest.10-2499

142. Шляхто Е.В. Кардиология: национальное руководство. 2-е издание. М.: ГЭОТАР-Медиа, 2015. 800с. ISBN 978-5-9704-2845-0

143. Sessler CN, Cohen MD. Cardiac Arrhythmias during Theophylline Toxicity. Chest. 1990;98(3):672–8. DOI: 10.1378/chest.98.3.672

144. Ohta K, Fukuchi Y, Grouse L, Mizutani R, Rabe KF, Rennard SI et al. A prospective clinical study of theophylline safety in 3810 elderly with asthma or COPD. Respiratory Medicine. 2004;98(10):1016–24. PMID: 15481279