Нарушение функции эндотелия является потенциальной основой патофизиологической связи между хронической обструктивной болезнью легких (ХОБЛ) и сердечно-сосудистыми заболеваниями. Известно, что вазорегулирующая функция эндотелия является прогностическим фактором риска возникновения сердечно-сосудистых событий. Изучение состояния сосудистой стенки, эндотелия, его функциональной активности представляет огромный интерес как органа-мишени при ХОБЛ и при ишемической болезни сердца (ИБС), и особый интерес у коморбидных пациентов, наиболее часто встречающихся в реальной клинической практике. Цель данной работы – оценка состояния сосудистой стенки у больных ХОБЛ и ИБС. Материалы и методы. Обследованы 108 больных ХОБЛ: 71 пациент с ХОБЛ без ИБС и 37 пациентов с ХОБЛ и ИБС. Диагноз ХОБЛ устанавливался в соответствии с критериями GOLD (2013) после проведения спирографического исследования. Критериями исключения являлись: возраст менее 40 и более 80 лет, наличие сахарного диабета, патология сосудов, хроническая почечная и печеночная недостаточности, хронические заболевания в фазе обострения, заболевания бронхов и легких другой этиологии. Для изучения функции эндотелия проводили пробы с реактивной гиперемией и нитроглицерином. Количество десквамированных эндотелиоцитов в крови определяли по методу J. Hladovec (1978). Заключение. Полученные данные свидетельствуют, что у коморбидных пациентов с ХОБЛ и ИБС имеются более выраженные нарушения вазорегулирующей функции эндотелия по сравнению с аналогичными показателями у больных ХОБЛ без ИБС. В то же время у пациентов с ХОБЛ без ИБС несколько более выражены повреждение сосудистой стенки и проявления ремоделирования плечевой артерии.
Chronic obstructive pulmonary disease is associated with increased cardiovascular mortality. Endothelial dysfunction may underpin this association. Vascular endothelial dysfunction is known to be an important prognostic marker for cardiovascular events. The aim of this study was to evaluate the state of the vascular wall in patients with chronic obstructive pulmonary disease (COPD) combined with chronic coronary artery disease (CAD). Materials and methods. The study included 108 patients: 37 patients with COPD and CAD and 71 patients with COPD without CAD. Endothelial function was studied in tests with reactive hyperemia and nitroglycerin. The number of blood plasma desquamated endotheliocytes were determined by the Hladovec method. In patients with COPD identified are signs of vascular wall remodeling: thickening wall of the brachial artery, reduction of the flow-mediated vasodilation. Patients with COPD in combination with CHD demonstrated higher impairments of the vasoregulatory dysfunction of endothelial of the vascular wall. Conclusion. In patients with COPD combined with chronic coronary heart disease more pronounced endothelial dysfunction with disturbance of endothelium-dependent vasomotor reactions.
Global Strategy for diagnosis, management and prevention of COPD. Scientific information and recommendations for COPD programs. Updated 2013. http://www.goldcopd.org/uploads/users/files/GOLD_Report_2013Feb13.pdf
2. Engstrom G, Lind P, Hedblad B, et al. Lung function and cardiovascular risk. Circulation. 2002;106(20):2555-60.
3. Sin DD, Wu L, Man SF. The relationship between reduced lung function and cardiovascular mortality: a population-based study and a systematic review of the literature. Chest. 2005;127(6):1952-9. https:// doi:10.1378/chest.127.6.1952
4. Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: role of comorbidities. Eur Respir J. 2006;28(6):1245-57. https://doi:10.1183/09031936.00133805
5. Macnee W, Maclay J, McAllister D. Cardiovascular injury and repair in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5(8):824-33. https://doi:10.1513/pats.200807-071TH
6. Decramer M, Janssens W. Chronic obstructive pulmonary disease and comorbidities. Lancet Respir Med. 2013;1(1):73-83. https://doi:10.1016/S2213-2600(12)70060-7
7. Pływaczewski R, Maciejewski J, Bednarek M, Zieliński J, et al. Causes of deaths in COPD patients in primary care setting - a 6-year follow-up. Pneumonol Alergol Pol. 2015;83(3):193-202. https://doi:10.5603/ PiAP.2015.0031
8. Curkendall SM, DeLuise C, Jones JK, et al. Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada: cardiovascular disease in COPD patients. Ann Epidemiol. 2006;16(1):63-70. https://doi:10.1016/j.annepidem.2005.04.008
9. Sabit R, Thomas P, Shale DJ, et al. The effects of hypoxia on markers of coagulation and systemic inflammation in patients with COPD. Chest. 2010;138(1):47-51. https://doi: 10.1378/chest.09-2764
10. MacNee W. Pulmonary and systemic oxidant/antioxidant imbalance in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2(1):50-60. https://doi: 10.1513/pats.200411-056SF
11. Watz H, Waschki B, Boehme C, et al. Extrapulmonary effects of chronic obstructive pulmonary disease on physical activity: a cross-sectional study. Am J Respir Crit Care Med. 2008;177(7):743-51. https://doi: 10.1164/rccm.200707-1011OC
12. Waschki B, Kirsten A, Holz O, et al. Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. Chest. 2011;140(2):331-42. https://doi: 10.1378/chest. 10-2521
13. Кароли Н.А., Ребров А.П. Вазорегулирующая активность эндотелия и легочная гипертензия. Терапевтический архив. 2004;76(12):39-44 [Karoli NA, Rebrov AP. Vasoregulating activity of the endothelium and pulmonary hypertension. Therapeutic Archive. 2004;76(12):39-44 (In Russ.)].
14. Rubinshtein R, Kuvin JT, Soffler M, et al. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J. 2010;31(9):1142-8. https://doi:10.1093/eurheartj/ehq010
15. Lind L, Berglund L, Larsson A, et al. Endothelial function in resistance and conduit arteries and 5-year risk of cardiovascular disease. Circulation. 2011;123:1545-51. https://doi:10.1161/CIRCULATIONAHA. 110.984047
16. Gokce N, Keaney JF Jr, Hunter LM, et al. Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study. Circulation. 2002;105(13):1567-72.
17. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340(8828):1111-5.
18. Кароли Н.А., Ребров А.П. Коморбидность у больных ХОБЛ: место кардиоваскулярной патологии. Рациональная фармакотерапия в кардиологии. 2009;4:9-16 [Karoli NA, Rebrov AP. Сomorbidity in patients with chronic obstructive pulmonary disease: a role of cardiovascular disorders. Racional'naja farmakoterapija v kardiologii. 2009;4:9-16 (In Russ.)].
19. Weidinger F, Frick M, Alber HF, et al. Association of wall thickness of the brachial artery measured with high-resolution ultrasound with risk factors and coronary artery disease. Am J Cardiol. 2002;89(9):1025-9.
20. Urban MH, Eickhoff P, Funk GK, et al. Increased brachial intima-media thickness is associated with circulating levels of asymmetric dimethylarginine in patients with COPD. Int J of COPD. 2017;12:169-76. https://doi: 10.2147/COPD.S118596
21. Chandra D, Gupta A, Strollo PJ Jr, Fuhrman CR, Leader JK, Bon J, Slivka WA, Shoushtari AH, Avolio J, Kip KE, Reis S, Sciurba FC. Airflow Limitation and Endothelial Dysfunction. Unrelated and Independent Predictors of Atherosclerosis. Am J Respir Crit Care Med. 2016;194(1):38-47. https://doi:10.1164/rccm.201510-2093OC
22. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26(5):1235-41.
23. Neunteufl T, Katzenschlager R, Hassan A, Klaar U, Schwarzacher S, Glogar D, Bauer P, Weidinger F. Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis. 1997;129(1):111-8.
24. Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, Widlansky ME, Tschakovsky ME, Green DJ. Assessment of flowmediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011;300(1):H2-12. https://doi: 10.1152/ajpheart.00471.2010
25. Clarenbach CF, Senn O, Sievi NA, Camen G, et al. Determinants of endothelial function in patients with COPD. Eur Respir J. 2013;42(5):1194-204. https://doi: 10.1183/09031936.00144612
26. Clarenbach CF, Sievi NA, Brock M, et al. Lung Volume Reduction Surgery and Improvement of Endothelial Function and Blood Pressure in Patients with Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial. Am J Respir Crit Care Med. 2015;192(3):307-14. https://doi:10.1164/rccm.201503-0453OC
27. Eickhoff P, Valipour A, Kiss D, Schreder M, Cekici L, Geyer K, Kohansal R, Burghuber OC. Determinants of systemic vascular function in patients with stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;178:1211-8. https://doi: 10.1164/rccm.200709-1412OC
28. Попова М.А., Долгополова Д.А., Терентьева Н.Н. Особенности эндотелиальной дисфункции у больных ишемической болезнью сердца, протекающей в коморбидности с хронической обструктивной болезнью легких. Ульяновский медико-биологический журнал. 2016;1:32-9 [Popova MA, Dolgopolova DA, Terent'eva NN. Features of endothelial dysfunction in patients with coronary heart disease occurring in comorbidity with chronic obstructive pulmonary disease. Ul'janovskij mediko-biologicheskij zhurnal. 2016;1:32-9 (In Russ.)].
________________________________________________
Global Strategy for diagnosis, management and prevention of COPD. Scientific information and recommendations for COPD programs. Updated 2013. http://www.goldcopd.org/uploads/users/files/GOLD_Report_2013Feb13.pdf
2. Engstrom G, Lind P, Hedblad B, et al. Lung function and cardiovascular risk. Circulation. 2002;106(20):2555-60.
3. Sin DD, Wu L, Man SF. The relationship between reduced lung function and cardiovascular mortality: a population-based study and a systematic review of the literature. Chest. 2005;127(6):1952-9. https:// doi:10.1378/chest.127.6.1952
4. Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: role of comorbidities. Eur Respir J. 2006;28(6):1245-57. https://doi:10.1183/09031936.00133805
5. Macnee W, Maclay J, McAllister D. Cardiovascular injury and repair in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5(8):824-33. https://doi:10.1513/pats.200807-071TH
6. Decramer M, Janssens W. Chronic obstructive pulmonary disease and comorbidities. Lancet Respir Med. 2013;1(1):73-83. https://doi:10.1016/S2213-2600(12)70060-7
7. Pływaczewski R, Maciejewski J, Bednarek M, Zieliński J, et al. Causes of deaths in COPD patients in primary care setting - a 6-year follow-up. Pneumonol Alergol Pol. 2015;83(3):193-202. https://doi:10.5603/ PiAP.2015.0031
8. Curkendall SM, DeLuise C, Jones JK, et al. Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada: cardiovascular disease in COPD patients. Ann Epidemiol. 2006;16(1):63-70. https://doi:10.1016/j.annepidem.2005.04.008
9. Sabit R, Thomas P, Shale DJ, et al. The effects of hypoxia on markers of coagulation and systemic inflammation in patients with COPD. Chest. 2010;138(1):47-51. https://doi: 10.1378/chest.09-2764
10. MacNee W. Pulmonary and systemic oxidant/antioxidant imbalance in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2(1):50-60. https://doi: 10.1513/pats.200411-056SF
11. Watz H, Waschki B, Boehme C, et al. Extrapulmonary effects of chronic obstructive pulmonary disease on physical activity: a cross-sectional study. Am J Respir Crit Care Med. 2008;177(7):743-51. https://doi: 10.1164/rccm.200707-1011OC
12. Waschki B, Kirsten A, Holz O, et al. Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. Chest. 2011;140(2):331-42. https://doi: 10.1378/chest. 10-2521
13. Karoli NA, Rebrov AP. Vasoregulating activity of the endothelium and pulmonary hypertension. Therapeutic Archive. 2004;76(12):39-44 (In Russ.)
14. Rubinshtein R, Kuvin JT, Soffler M, et al. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J. 2010;31(9):1142-8. https://doi:10.1093/eurheartj/ehq010
15. Lind L, Berglund L, Larsson A, et al. Endothelial function in resistance and conduit arteries and 5-year risk of cardiovascular disease. Circulation. 2011;123:1545-51. https://doi:10.1161/CIRCULATIONAHA. 110.984047
16. Gokce N, Keaney JF Jr, Hunter LM, et al. Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study. Circulation. 2002;105(13):1567-72.
17. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340(8828):1111-5.
18. Karoli NA, Rebrov AP. Сomorbidity in patients with chronic obstructive pulmonary disease: a role of cardiovascular disorders. Racional'naja farmakoterapija v kardiologii. 2009;4:9-16 (In Russ.)
19. Weidinger F, Frick M, Alber HF, et al. Association of wall thickness of the brachial artery measured with high-resolution ultrasound with risk factors and coronary artery disease. Am J Cardiol. 2002;89(9):1025-9.
20. Urban MH, Eickhoff P, Funk GK, et al. Increased brachial intima-media thickness is associated with circulating levels of asymmetric dimethylarginine in patients with COPD. Int J of COPD. 2017;12:169-76. https://doi: 10.2147/COPD.S118596
21. Chandra D, Gupta A, Strollo PJ Jr, Fuhrman CR, Leader JK, Bon J, Slivka WA, Shoushtari AH, Avolio J, Kip KE, Reis S, Sciurba FC. Airflow Limitation and Endothelial Dysfunction. Unrelated and Independent Predictors of Atherosclerosis. Am J Respir Crit Care Med. 2016;194(1):38-47. https://doi:10.1164/rccm.201510-2093OC
22. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26(5):1235-41.
23. Neunteufl T, Katzenschlager R, Hassan A, Klaar U, Schwarzacher S, Glogar D, Bauer P, Weidinger F. Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis. 1997;129(1):111-8.
24. Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, Widlansky ME, Tschakovsky ME, Green DJ. Assessment of flowmediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011;300(1):H2-12. https://doi: 10.1152/ajpheart.00471.2010
25. Clarenbach CF, Senn O, Sievi NA, Camen G, et al. Determinants of endothelial function in patients with COPD. Eur Respir J. 2013;42(5):1194-204. https://doi: 10.1183/09031936.00144612
26. Clarenbach CF, Sievi NA, Brock M, et al. Lung Volume Reduction Surgery and Improvement of Endothelial Function and Blood Pressure in Patients with Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial. Am J Respir Crit Care Med. 2015;192(3):307-14. https://doi:10.1164/rccm.201503-0453OC
27. Eickhoff P, Valipour A, Kiss D, Schreder M, Cekici L, Geyer K, Kohansal R, Burghuber OC. Determinants of systemic vascular function in patients with stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;178:1211-8. https://doi: 10.1164/rccm.200709-1412OC
28. Popova MA, Dolgopolova DA, Terent'eva NN. Features of endothelial dysfunction in patients with coronary heart disease occurring in comorbidity with chronic obstructive pulmonary disease. Ul'janovskij mediko-biologicheskij zhurnal. 2016;1:32-9 (In Russ.).
Авторы
Н.А. Кароли, А.П. Ребров
ФГБОУ ВО «Саратовский государственный медицинский университет им. В.И. Разумовского» Минздрава России, Саратов, Россия
________________________________________________
N.A. Karoli, A.P. Rebrov
V.I. Razumovsky Saratov State Medical University of the Ministry of Health of the Russian Federation, Saratov, Russia