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Рецепт. 2019; : 166-177

Динамика сердечно-сосудистогои пульмонального рисков у пациентовс хронической обструктивной болезнью легких при приеме аторвастатина

Шолкова М. В., Доценко Э. А., Бураков И. И.

Аннотация

Хроническая обструктивная болезнь легких (ХОБЛ) имеет высокую коморбидность с кардиоваскулярной патологией. Статины (ингибиторы 3-гидрокси-3-метилглютарил-кофермента А-редуктазы) относятся к препаратам выбора при лечении дислипидемии и профилактике сердечно-сосудистых заболеваний. Цель исследования: оценить динамику сердечно-сосудистого и пульмонального рисков у пациентов с ХОБЛ при приеме аторвастатина. Материалы и методы. Исследование проводилось на базе учреждения здравоохранения«6-я городская клиническая больница». Было включено 75 пациентов с ХОБЛ и дислипидемией: 30 пациентов в дополнение к стандартной терапии ХОБЛ принимали аторвастатин в дозе 20 мг в день (группа 1) и 45 пациентов получали только стандартную терапию ХОБЛ (группа сравнения, группа 2). Пациенты наблюдались на протяжении 24 недель. Оценивались клинические показатели, уровень липидов, функция внешнего дыхания (ФВД), тест шестиминутной ходьбы (ШМТ), уровень сердечно-сосудистого риска по шкале SCORE и пульмонального риска по шкале BODE. Результаты. Через 24 недели в группе 1 наблюдалось снижение уровня общего холестерина (с 6,2 ммоль/л до 4,6 ммоль/л, р=0,036), холестерина липопротеинов низкой плотности (с 3,5 ммоль/л до 2,5 ммоль/л, р=0,039), триглицеридов (с 1,7 ммоль/л до 1,0 ммоль/л, р=0,027). Также у пациентов группы 1 было отмечено улучшение показателей ФВД и переносимости физической нагрузки по результатам ШМТ. Сердечно-сосудистый риск по шкале SCORE в группе 1 снизился с 12,0 [5,0; 15,0]% до 8,5 [4,5; 15,0]% через 24 недели (р=0,005), в группе 2 достоверно не изменился. Риск пульмонологической смерти по шкале BODE в группе 1 снизился с 2,5 [1,0; 4,0] до 1,0 [0; 3,0] балла (р=0,017). Различия между группами в отношении риска по шкале BODE при заключительном визите достигли уровня статистической значимости (р=0,035).Заключение. У пациентов с ХОБЛ применение аторвастатина может не только снижать сердечно-сосудистый риск, но и оказывать позитивное влияние на пульмонологическую патологию.

Список литературы

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10. Linder R., Rönmark E., Pourazar J., Behndig A., Blomberg A., Lindberg A. (2015) Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study. Respir Res, vol. 21, no 16, pp. 28. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337188/ (accessed 20 January 2019).

11. Maclay J.D., MacNee W. (2013) Cardiovascular disease in COPD: mechanisms. Chest, vol. 143, no 3, pp. 798-807.

12. Smith M.C., Wrobel M.C. (2014) Epidemiology and clinical impact of major comorbidities in patients with COPD. Int J Chron Obstruct Pulmon Dis, vol. 9, pp. 871-888.

13. Rothnie K.J., Yan R., Smeeth L., Quint J.K. (2015) Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis. BMJ Open, vol. 5, no 9, pp. e007824 Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567661/ (accessed 10 October 2018).

14. Conroy R.M., Pyörälä K., Fitzgerald A.P., Sans S., Menotti A.,De Backer G., De Bacquer D., Ducimetière P., Jousilahti U., Keil I., Njølstad R.G., Oganov T., Thomsen H.,Tunstall-Pedoe A., Tverdal H., Wedel P., Whincup L., Wilhelmsen I.M. Graham on behalf of the SCORE project group (2003) Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. European Heart Journal, vol. 24, issue 11, pp. 987-1003.

15. Cote C.G., Celli B.R. (2009) BODE index: a new tool to stage and monitor progression of chronic obstructive pulmonary disease. PneumonolAlergol Pol, vol. 77, no 3, pp. 305-313.

16. Catapano A.L., Graham I., De Backer G., Wiklund O., Chapman M.J., Drexel H., Hoes A.W., Jennings C.S., Landmesser U., Pedersen T.R., Reiner Ž., Riccardi G., Taskinen M.R., Tokgozoglu L., Verschuren W.M.M., Vlachopoulos C., Wood D.A., Zamorano J.L., Cooney M.T., ESC Scientific Document Group (2016) ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J, vol. 37, no 39, pp. 2999-3058.

17. Margaritis M., Channon K.M., Antoniades C. (2014) Statins as regulators of redox state in the vascular endothelium: beyond lipid lowering. Antioxid Redox Signal, vol. 20, no 8, pp. 1198-1215.

18. Oesterle A., Laufs U., Liao J.K. (2017) Pleiotropic Effects of Statins on the Cardiovascular System. Circ Res,

19. vol. 120, no 1, pp. 229-243.

20. Dang H., Song B., Dong R., Zhang H. (2018) Atorvastatin reverses the dysfunction of human umbilical vein endothelial cells induced by angiotensin II. ExpTher Med, vol. 16, no 6, pp. 5286-5297.

21. Kazi D.S., Penko J.M., Bibbins-Domingo K. (2017) Statins for Primary Prevention of Cardiovascular Disease: Review of Evidence and Recommendations for Clinical Practice. Med Clin North Am, vol. 101, no 4, pp. 689-699.

22. Halcox J.P., Banegas J.R., Roy C., Dallongeville J., De Backer G., Guallar E., Perk J., Hajage D., Henriksson K.M., Borghi C. (2017) Prevalence and treatment of atherogenic dyslipidemia in the primary prevention of cardiovascular disease in Europe: EURIKA, a cross-sectional observational study. BMC CardiovascDisord, vol. 17, no 1, pp. 160. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473961/ (accessed 14 February 2019).

23. Chuchalin A., Avdeev S., Aysanov Z., Belevskiy A., Leschenko I., Mescheryakova N., Ovcharenko S., Shmelev E. (2014) Rossiyskoe respiratornoe obschestvo. Federalnyie klinicheskie rekomendatsii po diagnostike i lecheniyu hronicheskoy obstruktivnoy bolezni legkih [Russian respiratory society. Federal clinical guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease]. Pulmonology, vol. 3, pp. 15-54.

24. Friedewald W.T., Levy R.I., Fredrickson D.S. (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. ClinChem, vol. 18, pp. 499-502.

25. Zhang W., Zhang Y., Li C.W., Jones P., Wang C., Fan Y. (2017) Effect of Statins on COPD: A Meta-Analysis of Randomized Controlled Trials. Chest, vol. 152, no 6, pp. 1159-1168.

26. John M., McKeever T.M., Haddad M.A., Hall I.P., Sayers I., Cockcroft J.R., Bolton C.E. (2016) Traditional and emerging indicators of cardiovascular risk in chronic obstructive pulmonary disease. ChronRespir Dis, vol. 13, no 3, pp. 247-55.

Recipe. 2019; : 166-177

Dynamics of Cardiovascular and Pulmonary Risks in Patientswith Chronic Obstructive Pulmonary Disease: Atorvastatin Effects

Sholkava M. ., Dotsenko E. ., Burakov I. .

Abstract

Chronic obstructive pulmonary disease (COPD) has a high comorbidity with cardiovascular disease. Statins (3-hydroxy-3-methylglutaryl-coenzyme A-reductase inhibitors) are the drugs of choice in the treatment of dyslipidemia and the prevention of cardiovascular diseases.Objective: to evaluate the dynamics of cardiovascular and pulmonary risks in patients with COPD while taking atorvastatin.Materials and methods. The study was conducted at the 6th City Clinical Hospital, Minsk. 75 patients with COPD and dyslipidemia were included: 30 patients in addition to the standard treatment for COPD took atorvastatin at a dose of 20 mg per day (group 1) and 45 patients received only standard treatment for COPD (comparison group, group 2). Patients were observed for 24 weeks. We evaluated the clinical indicators, lipid levels, respiratory function (spirometry), 6-minute walking test (6 MWT), cardiovascular risk on the SCORE scale and pulmonary risk on the BODE scale.Results. After 24 weeks in group 1, the level of total cholesterol has decreased (from 6.2 mmol/l to4.6 mmol/l, p=0.036), low-density lipoprotein cholesterol level has decreased (from 3.5 mmol/l to2.5 mmol/l, p=0.039), triglyceride level has decreased (from 1.7 mmol/l to 1.0 mmol/l, p=0.027). Also in patients of group 1 the respiratory function and exercise tolerance improved according to the results of 6 MWT. Cardiovascular risk according to the SCORE scale in group 1 decreased from 12.0 [5.0; 15.0]%, up to 8.5 [4.5; 15.0]% after 24 weeks (p=0.005), in group 2 did not change significantly. The risk of pulmonary death on the BODE scale in group 1 decreased from 2.5 [1.0; 4.0] to 1.0 [0; 3.0] points (p=0.017). Differences between groups regarding the risk on the BODE scale at the final visit reached a level of statistical significance (p=0.035).Conclusion. In patients with COPD, the use of atorvastatin may not only reduce the cardiovascular risk, but also have a positive effect on pulmonary pathology.
References

1. Gershon A.S., Thiruchelvam D., Chapman K.R., Aaron S.D., Stanbrook M.B., Bourbeau J., Tan W., To T., Canadian Respiratory Research Network (2018) Health Services Burden of Undiagnosed and Overdiagnosed COPD. Chest, vol. 153, no 6, pp. 1336-1346.

2. Landis S.H., Muellerova H., Mannino D.M., Menezes A.M., Han M.K., van der Molen T., Ichinose M., Aisanov Z., Oh Y.M., Davis K.J. (2014) Continuing to Confront COPD International Patient Survey: methods, COPD prevalence, and disease burden in 2012-2013. Int J Chron Obstruct Pulmon Dis, vol. 6, no 9, pp. 597-611.

3. Adeloye D., Basquill C., Papana A., Chan K.Y., Rudan I., Campbell H. (2015) An estimate of the prevalence of COPD in Africa: a systematic analysis. COPD, vol. 12, no 1, pp. 71-81.

4. Dzau V., Braunwald E. (1991) Resolved and unresolved issues in the prevention and treatment of coronary artery disease: a workshop consensus statement. Am Heart J., vol. 121, Issue 4, part 1, pp. 1244-1263.

5. Hikichi M., Hashimoto S., Gon Y. (2018) Asthma and COPD overlap pathophysiology of ACO. AllergolInt,

6. vol. 67, no 2, pp. 179-186.

7. Ukena C., Mahfoud F., Kindermann M., Kindermann I., Bals R., Voors A.A., van Veldhuisen D.J., Böhm M. (2010) The cardiopulmonary continuum systemic inflammation as 'common soil' of heart and lung disease. Int J Cardiol, vol. 145, no 2, pp. 172-176.

8. Trinkmann F., Saur J., Borggrefe M., Akin I. (2019) Cardiovascular Comorbidities in Chronic Obstructive Pulmonary Disease (COPD) - Current Considerations for Clinical Practice. J Clin Med, vol. 8, no 1, pii: E69. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352261/ (accessed 23 February 2019).

9. Kirkham P.A., Barnes P.J. (2013) Oxidative stress in COPD. Chest, vol. 144, no 1, pp. 266-273.

10. Linder R., Rönmark E., Pourazar J., Behndig A., Blomberg A., Lindberg A. (2015) Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study. Respir Res, vol. 21, no 16, pp. 28. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337188/ (accessed 20 January 2019).

11. Maclay J.D., MacNee W. (2013) Cardiovascular disease in COPD: mechanisms. Chest, vol. 143, no 3, pp. 798-807.

12. Smith M.C., Wrobel M.C. (2014) Epidemiology and clinical impact of major comorbidities in patients with COPD. Int J Chron Obstruct Pulmon Dis, vol. 9, pp. 871-888.

13. Rothnie K.J., Yan R., Smeeth L., Quint J.K. (2015) Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis. BMJ Open, vol. 5, no 9, pp. e007824 Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567661/ (accessed 10 October 2018).

14. Conroy R.M., Pyörälä K., Fitzgerald A.P., Sans S., Menotti A.,De Backer G., De Bacquer D., Ducimetière P., Jousilahti U., Keil I., Njølstad R.G., Oganov T., Thomsen H.,Tunstall-Pedoe A., Tverdal H., Wedel P., Whincup L., Wilhelmsen I.M. Graham on behalf of the SCORE project group (2003) Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. European Heart Journal, vol. 24, issue 11, pp. 987-1003.

15. Cote C.G., Celli B.R. (2009) BODE index: a new tool to stage and monitor progression of chronic obstructive pulmonary disease. PneumonolAlergol Pol, vol. 77, no 3, pp. 305-313.

16. Catapano A.L., Graham I., De Backer G., Wiklund O., Chapman M.J., Drexel H., Hoes A.W., Jennings C.S., Landmesser U., Pedersen T.R., Reiner Ž., Riccardi G., Taskinen M.R., Tokgozoglu L., Verschuren W.M.M., Vlachopoulos C., Wood D.A., Zamorano J.L., Cooney M.T., ESC Scientific Document Group (2016) ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J, vol. 37, no 39, pp. 2999-3058.

17. Margaritis M., Channon K.M., Antoniades C. (2014) Statins as regulators of redox state in the vascular endothelium: beyond lipid lowering. Antioxid Redox Signal, vol. 20, no 8, pp. 1198-1215.

18. Oesterle A., Laufs U., Liao J.K. (2017) Pleiotropic Effects of Statins on the Cardiovascular System. Circ Res,

19. vol. 120, no 1, pp. 229-243.

20. Dang H., Song B., Dong R., Zhang H. (2018) Atorvastatin reverses the dysfunction of human umbilical vein endothelial cells induced by angiotensin II. ExpTher Med, vol. 16, no 6, pp. 5286-5297.

21. Kazi D.S., Penko J.M., Bibbins-Domingo K. (2017) Statins for Primary Prevention of Cardiovascular Disease: Review of Evidence and Recommendations for Clinical Practice. Med Clin North Am, vol. 101, no 4, pp. 689-699.

22. Halcox J.P., Banegas J.R., Roy C., Dallongeville J., De Backer G., Guallar E., Perk J., Hajage D., Henriksson K.M., Borghi C. (2017) Prevalence and treatment of atherogenic dyslipidemia in the primary prevention of cardiovascular disease in Europe: EURIKA, a cross-sectional observational study. BMC CardiovascDisord, vol. 17, no 1, pp. 160. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473961/ (accessed 14 February 2019).

23. Chuchalin A., Avdeev S., Aysanov Z., Belevskiy A., Leschenko I., Mescheryakova N., Ovcharenko S., Shmelev E. (2014) Rossiyskoe respiratornoe obschestvo. Federalnyie klinicheskie rekomendatsii po diagnostike i lecheniyu hronicheskoy obstruktivnoy bolezni legkih [Russian respiratory society. Federal clinical guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease]. Pulmonology, vol. 3, pp. 15-54.

24. Friedewald W.T., Levy R.I., Fredrickson D.S. (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. ClinChem, vol. 18, pp. 499-502.

25. Zhang W., Zhang Y., Li C.W., Jones P., Wang C., Fan Y. (2017) Effect of Statins on COPD: A Meta-Analysis of Randomized Controlled Trials. Chest, vol. 152, no 6, pp. 1159-1168.

26. John M., McKeever T.M., Haddad M.A., Hall I.P., Sayers I., Cockcroft J.R., Bolton C.E. (2016) Traditional and emerging indicators of cardiovascular risk in chronic obstructive pulmonary disease. ChronRespir Dis, vol. 13, no 3, pp. 247-55.