Сердечно-сосудистые риски у больных сахарным диабетом 2 типа

Сердечно-сосудистые заболевания по-прежнему являются ведущей причиной высоких показателей смертности у  лиц с сахарным диабетом (СД). В настоящей статье рассмотрен вопрос о влиянии СД на сердечно-сосудистые риски. Отражена распространенность и значимость основных и дополнительных факторов риска сердечно-сосудистых заболеваний в развитии макрососудистых осложнений при СД. В  контексте влияния на  сердечно-сосудистые риски рассмотрены эффективность и безопасность основных современных противодиабетических препаратов. Показано преимущество дапаглифлозина — перорального противодиабетического препа рата нового поколения, обладающего надежным и безопасным противодиабетическим действием и  способностью к  коррекции основных факторов сердечно-сосудистого риска (ожирение, артериальная гипертензия).

1. IDF Diabetes Atlas, 8th edition. Brussels: International Diabetes Federation; 2017. Available from: https://www.idf.org/e-library/epidemiologyresearch/diabetesatlas/134-idf-diabetes-atlas-8th-edition.html.

2. Дедов ИИ, Шестакова МВ, Викулова ОК. Эпидемиология сахарного диабета в Российской Федерации: клинико-статистический анализ по данным Федерального регистра сахарного диабета. Сахарный диабет. 2017;1(20):13-41.

3. Nwaneri C, Cooper H, Bowen-Jones D. Mortality in type 2 diabetes mellitus: magnitude of the evidence from a systematic review and meta-analysis. The British Journal of Diabetes & Vascular Disease. 2013;4(13):192-207. doi:10.1177/1474651413495703.

4. Sarwar N, Gao P, Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215-22. doi:10.1016/S0140-6736(10)60484-9.

5. Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. British Medical Journal. 2006;332:73-8. doi:10.1136/bmj.38678.389583.7C.

6. Kannel WB, McGee DL. Diabetes and cardiovascular disease: the Framingham study. JAMA. 1979;241:2035-8.

7. Haffner SM, Lehto S, Ronnemaa T. Mortality from coronary artery disease in subject with type 2 diabetes and nondiabetic subjects with and without myocardial infarction. The New England Journal of Medicine. 1998;339:229-34. doi:10.1056/NEJM199807233390404.

8. Demidova TYu. Vascular complications of type 2 diabetes beyond that of glycemic control. Diabetes Mellitus. 2010;3:111-6. (In Russ.) Демидова ТЮ. Сосудистые осложнения СД 2 типа за гранью гликемического контроля. Сахарный диабет. 2010;3:111-6.

9. Boyer JK, Thanigaraj S, Schechtman KB, Peґrez JE. Prevalence of Ventricular Diastolic Dysfunction in Asymptomatic, Normotensive Patients With Diabetes Mellitus. The American Journal of Cardiology. 2004;93:870-5. doi:10.1016/j.amjcard.2003.12.026.

10. Poirier P, Bogaty P, Garneau C, et al. Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy. Diabetes Care. 2001;24:5-10. 11. Bell DS. Diabetic cardiomyopathy: a unique entity or a complication of coronary artery disease? Diabetes Care. 1995;18:708-14.

11. Sarma S, Mentz RJ, Kwasny MJ, et al. Association between diabetes mellitus and post-discharge outcomes in patients hospitalized with heart failure: findings from the EVEREST trial. European Journal of Heart Fail. 2013;15:194-202.

12. Greenberg BH, Abraham WT, Albert NM, et al. Influence of diabetes on characteristics and outcomes in patients hospitalized with heart failure: a report from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF). American Heart Journal. 2007;154:271-8. doi:10.1016/j.ahj.2007.05.001.

13. Hamm CW, Bassand JP, Agewall S, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). European Heart Journal 2011; 23(32): 2999-3054. doi:10.1093/eurheartj/ehr236.

14. O’Donoghue ML, Vaidya A, Afsal R, et al. An Invasive or Conservative Strategy in Patients With Diabetes Mellitus and Non-ST-Segment Elevation Acute Coronary Syndromes. JACC. 2012;2(60):106-11. doi:10.1016/j.jacc.2012.02.059.

15. Turnbull FM, Abraira C, Anderson RJ, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009;52:2288-98. doi:10.1007/s00125-009-1470-0.

16. UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:83753. doi:10.1016/S0140-6736(98)07019-6.

17. Gotto AM, Bailey K, Gohdes D, et al. The Action to Control Cardiovascular Risk in Diabetes Study Group (2008) Effects of intensive glucose lowering in type 2 diabetes. The N Engl J Med. 2008;358:2545-59. doi:10.1056/NEJMoa0802743.

18. Chalmers J, MacMahon S, Patel A, et al. The ADVANCE Collaborative Group (2008) Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. The N Engl J Med. 2008;358:2560-72. doi:10.1056/NEJMoa0802987.

19. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. The N Engl J Med. 2009;360:129-39. doi:10.1056/NEJMoa0808431.

20. Riddle MC, Ambrosius WT, Brillon DJ, et al. Action to Control Cardiovascular Risk in Diabetes Investigators. Epidemiologic relationships between A1C and all-cause mortality during a median 3,4-year follow-up of glycemic treatment in the ACCORD trial. Diabetes Care. 2010,33:983-90. doi:10.2337/dc09-1278.

21. Center for Drug Evaluation and Research. Guidance for Industry Diabetes Mellitus: Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes, 2008. http://www.fda.gov/downloads/drugs/guidancecomplianceregulato ryinformation/guidances/ucm071627.pdf.

22. Gerstein H, Yusuf S, Riddle MC, et al. ORIGIN Trial Investigators, Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: the ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention). Am Heart J. 2008;1(155):26-32.

23. Gerstein H, Bosch J, Dagenais GR, et al. ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. The N Engl J Med. 2012;367:31928. doi:10.1056/NEJMoa1203858.

24. Marso SP, McGuire DK, Zinman B, et al. Design of DEVOTE (Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events) — DEVOTE 1. Am Heart J. 2016;179:175-83. doi:10.1016/j.ahj.2016.06.004.

25. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. The N Engl J Med. 2007;356(24):2457-71. doi:10.1056/NEJMoa072761.

26. Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly medicare patients treated with rosiglitazone or pioglitazone. JAMA. 2010;304(4):411-8. doi:10.1001/jama.2010.920.

27. Lincoff AM, Woski K, Nichols SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007;298(10):1180-8. doi:10.1001/jama.298.10.1180.

28. Marso SP, Poulter NR, Nissen SE, et al. Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial. Am Heart J. 2013;166(5):823-30. doi:10.1016/j.ahj.2013.07.012.

29. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. The N Engl J Med. 2015;373(23):2247-57. doi:10.1056/NEJMoa1509225.

30. Scirica BM, Braunwald E, Raz I, et al. Heart Failure, Saxagliptin, and Diabetes Mellitus: Observations from the SAVOR-TIMI 53 Randomized Trial. Circulation. 2014;130(18):1579-88. doi:10.1161/CIRCULATIONAHA.114.010389.

31. White WB, Cannon CP, Heller SR, et al. Alogliptin after Acute Coronary Syndrome in Patients with Type 2 Diabetes. The N Engl J Med. 2013;369(14):1327-35. doi:10.1056/NEJMoa1305889.

32. Green JB, Bethel МА, Armstrong PW, et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. The N Engl J Med. 2015;373(3):232-42. doi:10.1056/NEJMoa1501352.

33. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. The N Engl J Med. 2015;373(22):2117-28. doi:10.1056/NEJMoa1504720.

34. Neal B, Perkovic V, de Zeeuw D, et al. Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS)-a randomized placebocontrolled trial. Am Heart J. 2013;166(2):217-23. doi:10.1016/j.ahj.2013.05.007.

35. Wiviott SD, Raz I, Bonaca MP, et al. The Design and Rationale for the Dapagliflozin Effect on Cardiovascular Events (DECLARE) — TIMI 58 Trial. Am Heart J. 2018;200(2):83-9. doi.org/10.1016/j.ahj.2018.01.012.

36. Raz I, Mosenzon O, Bonaca MP. DECLARE-TIMI 58: Participants’ baseline characteristics. Diabetes, Obesity and Metabоlism. 2018;20(5):1102-10. doi:10.1111/dom.13217.

37. Уразгильдеева СА, Малыгина ОФ. Особенности лечения дислипидемии у больных сахарным диабетом 2-го типа. Медицинский совет. 2016;3:48-53.

38. Rabkin SW, Mathewson FA, Hsu P-H. Relation of body weight to development of ischemic heart disease in a cohort of young North American men after a 26 year observation period: the Manitoba Study. The American Journal of Cardiology. 1977;39:452-8.

39. Hubert HB, Feinleib M, McNamara PM, et al. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation. 1983;67:968-77.

40. Wilson PWF, D’Agostino RB, Sullivan L, et al. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. The Archives of Internal Medicine. 2002;162:1867-72.

41. Бутрова СА. От эпидемии ожирения к эпидемии сахарного диабета. Consilium medicum. 2003;5(9):524-8.

42. Клинические рекомендации ЕОК/ЕОА по диагностике и лечению диспилипидемий 2016. Российский кардиологический журнал. 2017;22(5):7-77. doi:10.15829/1560-4071-2017-5-7-77.

43. Wing RR, Bolin P, Brancati FL. The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. The New England Journal of Medicine. 2013;369(2):145–54. doi:10.1056/NEJMoa1212914.

44. Дедов ИИ, Мельниченко ГА, Шестакова МВ, и др. Лечение морбидного ожирения у взрослых. Ожирение и метаболизм. 2018;15(1):53-70. doi:10.14341/OMET2018153-70.

45. Garvey WT, Mechanick JI, Brett EM, et al. AACE/ACE Comprehensive Clinical Practice Guidelines for Medicare Care of Patients with Obesity. Endocrine Practice. 2016;22(3):1-203. doi:10.4158/EP161365.GL.

46. Bolinder J, Ljunggren Ö, Johansson L, et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes, Obesity and Metabоlism. 2014;16(2):159-69. doi:10.1111/dom.12189.

47. Sawicki PT, Heise T, Berger М. Antihypertensive treatment and mortality in diabetic patients. What is the evidence? Diabetologia. 1997;40(2):134-7. doi:10.1007/s001250051429.

48. Sundström J, Sheikhi R, Östgren CJ, et al. Blood pressure levels and risk of cardiovascular events and mortality in type-2 diabetes: cohort study of 34 009 primary care patients. Journal of Hypertension. 2013;31(8):1603-10. doi:10.1097/HJH.0b013e32836123aa.

49. Rothwell PM, Howard SC, Dolan E, et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010;375:895-905. doi:10.1016/S0140-6736(10)60308-X.

50. Adler AI, Stratton IM, Neil HA, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. 2000;321(7258):412-9. doi:10.1136/bmj.321.7258.412.

51. Mancia G, Fagard R, Narkiewicz K. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Journal of Hypertension. 2013;31(7):1281-357. doi:10/1097/01.hjh.0000431740.32696.сс.

52. Рекомендации по лечению артериальной гипертонии ESH/ ESC, 2013. Российский кардиологический журнал. 2014;19(1):5-94.

53. Van Liefde I, Vauquelin G. Sartan — AT1 receptor interactions: evidence for insurmountable antagonism and inverse agonism. Molecular and Cellular Endocrinology. 2009;302(2):237-57.

54. Кисляк ОА, Мышляева ТО, Малышева НВ, и др. Сахарный диабет 2 типа, артериальная гипертензия и риск сердечно-сосудистых осложнений. Сахарный диабет. 2008;1:45-9.

55. Weber M, Mansfield T, T’joen C, et al. Dapagliflozin for reduction of blood pressure in diabetic patients inadequately controlled with combination antihypertensive regimen. American Heart Association. 2013;74(18):2191-209.

56. Del Prato S, Nauck M, Durán-Garcia S, et al. Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data. Diabetes, Obesity and Metabоlism. 2015;17(6):581-90. doi:10.1111/dom.12459.

57. Vasilakou D, Karagiannis T, Athanasiadou E, et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Annals of Internal Medicine. 2013;159(4):262-74. doi:10.7326/0003-4819-159-4-201308200-00007.

58. Lambers Heerspink HJ, de Zeeuw D, Wie L, et al. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes, Obesity and Metabоlism. 2013;15(9):853-62. doi:10.1111/dom.12127.

59. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;25(106):3143-421.

60. Buse JB, Ginsberg HN, Bakris GL, et al. American Heart Association; American Diabetes Association. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Circulation. 2007;115(1):114-26. doi: 10.1161/CIRCULATIONAHA.106.179294.

61. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): casecontrol study. Lancet. 2004;364(9438):937-52. doi:10.1016/S0140-6736(04)17018-9.

62. Howard BV, Robbins DC, Sievers ML, et al. LDL cholesterol as a strong predictor of coronary heart disease in diabetic individuals with insulin resistance and low LDL: The Strong Heart Study. Arteriosclerosis, thrombosis and vascular biology. 2000;3(20):830-5.

63. Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;9607(371):117-25. doi:10.1016/S0140-6736(08)60104-X.

64. Catapano AL, Graham I, De Backer G. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. The European Heart Journal. 2016;39(37):2999-3058. doi:10.1093/eurheartj/ehw272.

65. Ежов МВ, Сергиенко ИВ, Аронов ДМ, и др. Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации VI пересмотр. Атеросклероз и дислипидемии. 2017;3:5-22.

66. Дедов ИИ, Шестакова МВ, Майоров АЮ, и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом.8-й выпуск. Сахарный диабет. 2017;20(1):1-112. doi:10.14341/DM20171S8.

67. Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial). The American Journal of Cardiology. 2003;92:152-60. doi:10.1185/030079903125002405.

68. Karlson BW, Palmer MK, Nicholls SJ, et al. A VOYAGER Meta-Analysis of the Impact of Statin Therapy on Low-Density Lipoprotein Cholesterol and Triglyceride Levels in Patients With Hypertriglyceridemia. The American Journal of Cardiology. 2016;117(9):1444-8. doi:10.1016/j.amjcard.2016.02.011.

69. Hardy E, Ptaszynska A, de Bruin TWA, et al. Changes in lipid profiles of patients with type 2 diabetes mellitus on dapagliflozin therapy. Diabetologia. 2013;56(1):p-379.

70. Мкртумян АМ, Давыдов АЛ, Подачина СВ, Щукина ВН. Влияние постпрандиальной гликемии на сердечно-сосудистую заболеваемость больных сахарным диабетом типа 2 и ее коррекция. Consilium medicum. 2004;6(9):640-5.

71. Haheim LL, Holme I, Hjermann I, et al. Nonfasting serum glucose and the risk of fatal stroke in diabetic and nondiabetic subjects. 18-year follow-up of the Oslo Study. Stroke. 1995;26:774-7.

72. Cavalot F, Petrelli A, Traversa M, et al. Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study. The Journal of Clinical Endocrinology and Metabolism. 2006;91:813-9. doi:10.1210/jc.2005-1005.

73. Muggeo M, Verlato G, Bonora E, et al. Long-term instability of fasting plasma glucose predicts mortality in elderly NIDDM patients: the Verona diabetes study. Diabetologia. 1995;38:672-9.

74. Feng-fei Li, Gu Gao, Qian Li, et al. Influence of Dapagliflozin on Glycemic Variations in Patients with Newly Diagnosed Type 2 Diabetes Mellitus. Journal of Diabetes Research. 2016;5347262. doi:10.1155/2016/5347262.

75. Wilding JPH, Norwood Р, T’joen С, et al. A Study of Dapagliflozin in Patients With Type 2 Diabetes Receiving High Doses of Insulin Plus Insulin Sensitizers. Applicability of a novel insulin-independent treatment. Diabetes Care. 2009;32(9):1656-62. doi:10.2337/dc09-0517.

76. Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. The New England Journal of Medicine. 2003;348(5):383-93. doi:10.1056/NEJMoa021778.

77. Ferrannini E, Ramos SJ, Salsali A, et al. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010;33(10):2217-24. doi:10.2337/dc10-0612.

78. Bailey CJ, Gross JL, Pieters A, et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, doubleblind, placebo-controlled trial. Lancet. 2010;9733(375):2223-33. doi:10.1016/S0140-6736(10)60407-2.

79. Wilding JPH, Woo V, Soler NG, et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Annals of Internal Medicine. 2012;156(6):405-15. doi:10.7326/0003-4819-156-6201203200-00003.

80. Nauck MA, Del Prato S, Meier JJ, et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care. 2011;34(9):2015-22. doi:10.2337/dc11-0606.

81. Salsali A, Rohwedder K, Mansfield TA, et al. Durability of dapagliflozin treatment response in patients with T2DM: 2-year results. 72nd Annual Meeting of the American Diabetes Association. 2012:p-1030.

82. Bailey CJ, Gross JL, Hennicken D, et al. Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, doubleblind, placebo-controlled 102-week trial. BMC Medicine. 2013;11(1):p-43. doi:10.1186/1741-7015-11-43.

83. Bolinder J, Ljunggren O, Johansson L, et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over LONG-TERM DAPAGLIFLOZIN EFFICACY AND SAFETY 1695 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes, Obesity and Metabоlism. 2014;16(2):159-69. doi:10.1111/dom.12189.

84. Sonesson С, Johansson РА, Johnsson Е, Gause-Nilsson I. Cardiovascular effects of dapagliflozin in patients with type 2 diabetes and different risk categories: a meta-analysis. Cardiovascular Diabetology. 2016;15 (1):37р. doi:10.1186/s12933016-0356-y.