Atrial Fibrillation and Diabetes Mellitus: the Control of Thromboembolic Risk
https://doi.org/10.18087/cardio.2020.7.n1146
Abstract
Atrial fibrillation is one of the most common concomitant diseases in patients with diabetes mellitus (DM). Meta-analyses of multiple studies have shown that the risk of AF is higher for diabetic patients with impaired glucose homeostasis than for patients without DM. Patients with AF and DM were younger, more frequently had arterial hypertension, chronic kidney disease, heart failure, and ischemic heart disease, and stroke and were characterized with a more severe course of AF. The article discusses possible mechanisms of the mutually aggravating effects of DM and AF, scales for evaluating the risk of bleeding (CHADS2, CHA2DS2‑VASc, HAS-BLED), and the role of anticoagulants. A meta-analysis of 16 randomized clinical studies, including 9 874 patients, has demonstrated the efficacy of oral anticoagulants in prevention of stroke with an overall decrease in the relative risk by 62 % compared to placebo (95% confidence interval, from 48 to 72 ). For prevention of complications in patients with AF and DM, current antithrombotic therapies can be used, specifically the oral factor Xa inhibitor, rivaroxaban, which is the best studied in patients with AF and DM and represents a possible alternative to warfarin in such patients.
Keywords
Supporting agencies: The publication was supported by the company AO BAYER. PP-XAR-RU-0429-1
About the Authors
A. G. Obrezan
Saint-Petersburg University, Saint-Petersburg;
SOGAZ MEDI-CINE Clinic Group
Russian Federation
Russian Federation
MD, PhD, Head of department of Saint-Petersburg University, Head of the SOGAZ MEDICINE Clinic Group
N. V. Kulikov
Saint-Petersburg University, Saint-Petersburg
Russian Federation
Russian Federation
MD, graduate student of the therapy department of Saint-Petersburg University
SPIN: 8854-7836
References
1. Staerk L, Sherer JA, Ko D, Benjamin EJ, Helm RH. Atrial Fibrillation: Epidemiology, Pathophysiology, and Clinical Outcomes. Circulation Research. 2017;120(9):1501–17. DOI: 10.1161/CIRCRESAHA.117.309732
2. Lau DH, Nattel S, Kalman JM, Sanders P. Modifiable Risk Factors and Atrial Fibrillation. Circulation. 2017;136(6):583–96. DOI: 10.1161/CIRCULATIONAHA.116.023163
3. Obrezan A.G., Kulikov N.V. Chronic Heart Failure and Diabetes Mellitus: Pathogenesis and Possibilities of Treatment. Kardiologiia. 2018;58(7):85–94. DOI: 10.18087/cardio.2018.7.10156
4. Dedov I.I., Shestakova M.V., Vikulova O.K. Epidemiology of diabetes mellitus in Russian Federation: clinical and statistical report according to the federal diabetes registry. Diabetes mellitus. 2017;20(1):13–41. DOI: 10.14341/DM8664
5. Dedov I.I., Shestakova M.V., Galstyan G.R. The prevalence of type 2 diabetes mellitus in the adult population of Russia (NATION study). Diabetes mellitus. 2016;19(2):104–12. DOI: 10.14341/DM2004116-17
6. Naser N, Dilic M, Durak A, Kulic M, Pepic E, Smajic E et al. The Impact of Risk Factors and Comorbidities on The Incidence of Atrial Fibrillation. Materia Socio Medica. 2017;29(4):231–6. DOI: 10.5455/msm.2017.29.231-236
7. Lee Y-B, Han K, Kim B, Lee S-E, Jun JE, Ahn J et al. Risk of early mortality and cardiovascular disease in type 1 diabetes: a comparison with type 2 diabetes, a nationwide study. Cardiovascular Diabetology. 2019;18(1):157. DOI: 10.1186/s12933-019-0953-7
8. Pallisgaard JL, Schjerning A-M, Lindhardt TB, Procida K, Hansen ML, Torp-Pedersen C et al. Risk of atrial fibrillation in diabetes mellitus: A nationwide cohort study. European Journal of Preventive Cardiology. 2016;23(6):621–7. DOI: 10.1177/2047487315599892
9. Smith JG, Platonov PG, Hedblad B, Engström G, Melander O. Atrial fibrillation in the Malmö diet and cancer study: a study of occurrence, risk factors and diagnostic validity. European Journal of Epidemiology. 2010;25(2):95–102. DOI: 10.1007/s10654-009-9404-1
10. Huxley RR, Filion KB, Konety S, Alonso A. Meta-Analysis of Cohort and Case–Control Studies of Type 2 Diabetes Mellitus and Risk of Atrial Fibrillation. The American Journal of Cardiology. 2011;108(1):56–62. DOI: 10.1016/j.amjcard.2011.03.004
11. Echouffo-Tcheugui JB, Shrader P, Thomas L, Gersh BJ, Kowey PR, Mahaffey KW et al. Care Patterns and Outcomes in Atrial Fibrillation Patients With and Without Diabetes: ORBIT-AF Registry. Journal of the American College of Cardiology. 2017;70(11):1325–35. DOI: 10.1016/j.jacc.2017.07.755
12. Benjamin EJ, Levy D, Vaziri SM, D’Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA. 1994;271(11):840–4. DOI: 10.1001/jama.1994.03510350050036
13. Fox CS. Cardiovascular Disease Risk Factors, Type 2 Diabetes Mellitus, and the Framingham Heart Study. Trends in Cardiovascular Medicine. 2010;20(3):90–5. DOI: 10.1016/j.tcm.2010.08.001
14. Zhang H, Xu Q, Thakur A, Alfred MO, Chakraborty M, Ghosh A et al. Endothelial dysfunction in diabetes and hypertension: Role of microRNAs and long non-coding RNAs. Life Sciences. 2018;213:258– 68. DOI: 10.1016/j.lfs.2018.10.028
15. Silambarasan M, Tan J, Karolina D, Armugam A, Kaur C, Jeyaseelan K. MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction. International Journal of Molecular Sciences. 2016;17(4):518. DOI: 10.3390/ijms17040518
16. Beckman JA, Creager MA, Libby P. Diabetes and Atherosclerosis: Epidemiology, Pathophysiology, and Management. JAMA. 2002;287(19):2570–81. DOI: 10.1001/jama.287.19.2570
17. Karam BS, Chavez-Moreno A, Koh W, Akar JG, Akar FG. Oxidative stress and inflammation as central mediators of atrial fibrillation in obesity and diabetes. Cardiovascular Diabetology. 2017;16(1):120. DOI: 10.1186/s12933-017-0604-9
18. Zholbayeva A.Z., Tabina A.E., Golukhova E.Z. Molecular mechanisms of atrial fibrillation: „ideal” marker searching. Creative Cardiology. 2015;2:40–53.
19. Freestone B, Chong AY, Nuttall S, Blann AD, Lip GYH. Soluble E-selectin, von Willebrand Factor, Soluble Thrombomodulin, and Total Body Nitrate/Nitrite Product as Indices of Endothelial Damage/Dysfunction in Paroxysmal, Persistent, and Permanent Atrial Fibrillation. Chest. 2007;132(4):1253–8. DOI: 10.1378/chest.07-1185
20. Agostini S, Lionetti V. New insights into the non-hemostatic role of von Willebrand factor in endothelial protection. Canadian Journal of Physiology and Pharmacology. 2017;95(10):1183–9. DOI: 10.1139/cjpp-2017-0126
21. Scridon A, Girerd N, Rugeri L, Nonin-Babary E, Chevalier P. Progressive endothelial damage revealed by multilevel von Willebrand factor plasma concentrations in atrial fibrillation patients. Europace. 2013;15(11):1562–6. DOI: 10.1093/europace/eut121
22. Gusev E.I., Martynov M.Yu., Koltsov I.A., Yasamanova A.N., Fidler M.S., Tshukin I.A. Prognostic value of endothelial dysfunction and von Willebrand factor in acute and chronic hemispheric intracerebral hemorrhage. S.S. Korsakov Journal of Neurology and Psychiatry. 2019;119(8–2):46–52. DOI: 10.17116/jnevro201911908246
23. Jakobi AJ, Mashaghi A, Tans SJ, Huizinga EG. Calcium modulates force sensing by the von Willebrand factor A2 domain. Nature Communications. 2011;2(1):385. DOI: 10.1038/ncomms1385
24. Recommendations for diabetes, prediabetes and cardiovascular disease EASD/ESC. Russian Journal of Cardiology. 2014;19(3):7–61.
25. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983–8. DOI: 10.1161/01.STR.22.8.983
26. Wang TJ, Massaro JM, Levy D, Vasan RS, Wolf PA, D’Agostino RB et al. A Risk Score for Predicting Stroke or Death in Individuals With New-Onset Atrial Fibrillation in the Community: The Framingham Heart Study. JAMA. 2003;290(8):1049–56. DOI: 10.1001/jama.290.8.1049
27. Yang Y-W, Lee S-S, Chen C-C, Liu H-H, Tsai T-H, Lin T-H et al. CHADS2 scores as a predictor of ischemic stroke after radical prostatectomy. Cancer Medicine. 2016;5(1):3–8. DOI: 10.1002/cam4.557
28. Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining Clinical Risk Stratification for Predicting Stroke and Thromboembolism in Atrial Fibrillation Using a Novel Risk Factor-Based Approach: the euro heart survey on atrial fibrillation. Chest. 2010;137(2):263– 72. DOI: 10.1378/chest.09-1584
29. Jastrzębski M, Stec J, Fijorek K, Pavlinec C, Czarnecka D. CHADS2 and CHA2DS2-VASc scores predict long-term mortality in patients with typical atrial flutter after catheterablation. Kardiologia Polska. 2019;78(1):59–64. DOI: 10.33963/KP.15102
30. Zhu W, He W, Guo L, Wang X, Hong K. The HAS-BLED Score for Predicting Major Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation: A Systematic Review and Meta-analysis. Clinical Cardiology. 2015;38(9):555–61. DOI: 10.1002/clc.22435
31. Lip GYH, Skjøth F, Nielsen PB, Kjældgaard JN, Larsen TB. The HASBLED, ATRIA, and ORBIT Bleeding Scores in Atrial Fibrillation Patients Using Non-Vitamin K Antagonist Oral Anticoagulants. The American Journal of Medicine. 2018;131(5):574.e13-574.e27. DOI: 10.1016/j.amjmed.2017.11.046
32. Poli D, Antonucci E, Pengo V, Testa S, Palareti G. Comparison of HAS-BLED and HAS-BED Versus CHADS2 and CHA2DS2VASC Stroke and Bleeding Scores in Patients With Atrial Fibrillation. The American Journal of Cardiology. 2017;119(7):1012–6. DOI: 10.1016/j.amjcard.2016.12.007
33. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Heart Journal. 2016;37(38):2893–962. DOI: 10.1093/eurheartj/ehw210
34. Kirchhof P, Haas S, Amarenco P, Hess S, Lambelet M, van Eickels M et al. Impact of Modifiable Bleeding Risk Factors on Major Bleeding in Patients With Atrial Fibrillation Anticoagulated With Rivaroxaban. Journal of the American Heart Association. 2020;9(5):e009530. DOI: 10.1161/JAHA.118.009530
35. Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci A et al. Subclinical atrial fibrillation and the risk of stroke. The New England Journal of Medicine. 2012;366(2):120–9. DOI: 10.1056/ NEJMoa1105575
36. Tancredi M, Rosengren A, Svensson A-M, Kosiborod M, Pivodic A, Gudbjörnsdottir S et al. Excess Mortality among Persons with Type 2 Diabetes. The New England Journal of Medicine. 2015;373(18):1720–32. DOI: 10.1056/NEJMoa1504347
37. Lin H-J, Wolf PA, Kelly-Hayes M, Beiser AS, Kase CS, Benjamin EJ et al. Stroke Severity in Atrial Fibrillation: The Framingham Study. Stroke. 1996;27(10):1760–4. DOI: 10.1161/01.STR.27.10.1760
38. Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. European Heart Journal. 2018;39(16):1330– 93. DOI: 10.1093/eurheartj/ehy136
39. Bokeria L.A., Revishvili A.Sh., Golytsyn S.P., Egorov D.F., Popov S.V., Sulimov V.A. Clinical recommendations for electrophysiological studies, catheter ablation and the use of implantable antiarrhythmic devices. New revision - 2013. 596p. Av. at: https://vnoa.ru/upload/Recomend2013.pdf. https://vnoa.ru/upload/Recomend2013.pdf]
40. Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. European Heart Journal. 2020;41(2):255–323. DOI: 10.1093/eurheartj/ehz486
41. Joundi RA, Cipriano LE, Sposato LA, Saposnik G, on behalf of the Stroke Outcomes Research Working Group. Ischemic Stroke Risk in Patients With Atrial Fibrillation and CHA2DS2-VASc Score of 1: Systematic Review and Meta-Analysis. Stroke. 2016;47(5):1364– 7. DOI: 10.1161/STROKEAHA.115.012609
42. Avezum A, Oliveira GB de F, Diaz R, Hermosillo JAG, Oldgren J, Ripoll EF et al. Efficacy and safety of dabigatran versus warfarin from the RE-LY trial. Open Heart. 2018;5(1):e000800. DOI: 10.1136/openhrt-2018-000800
43. Bansilal S, Bloomgarden Z, Halperin JL, Hellkamp AS, Lokhnygina Y, Patel MR et al. Efficacy and safety of rivaroxaban in patients with diabetes and nonvalvular atrial fibrillation: The Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF Trial). American Heart Journal. 2015;170(4):675-682. e8. DOI: 10.1016/j.ahj.2015.07.006
44. Mak K-H. Coronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials. BMJ Open. 2012;2(5):e001592. DOI: 10.1136/bmjopen-2012-001592
45. Loke YK, Pradhan S, Yeong JK, Kwok CS. Comparative coronary risks of apixaban, rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison. British Journal of Clinical Pharmacology. 2014;78(4):707–17. DOI: 10.1111/bcp.12376
46. Mega JL, Braunwald E, Wiviott SD, Bassand J-P, Bhatt DL, Bode C et al. Rivaroxaban in patients with a recent acute coronary syndrome. The New England Journal of Medicine. 2012;366(1):9–19. DOI: 10.1056/NEJMoa1112277 47. Brambatti M, Darius H, Oldgren J, Clemens A, Noack HH, Brueckmann M et al. Comparison of dabigatran versus warfarin in diabetic patients with atrial fibrillation: Results from the RE-LY trial. International Journal of Cardiology. 2015;196:127–31. DOI: 10.1016/j.ijcard.2015.05.141
47. Ezekowitz JA, Lewis BS, Lopes RD, Wojdyla DM, McMurray JJV, Hanna M et al. Clinical outcomes of patients with diabetes and atrial fibrillation treated with apixaban: results from the ARISTOTLE trial. European Heart Journal - Cardiovascular Pharmacotherapy. 2015;1(2):86–94. DOI: 10.1093/ehjcvp/pvu024
48. Baker WL, Beyer‐Westendorf J, Bunz TJ, Eriksson D, Meinecke A, Sood NA et al. Effectiveness and safety of rivaroxaban and warfarin for prevention of major adverse cardiovascular or limb events in patients with non‐valvular atrial fibrillation and type 2 diabetes. Diabetes, Obesity and Metabolism. 2019;21(9):2107–14. DOI: 10.1111/dom.13787
49. Bansal N, Zelnick LR, Alonso A, Benjamin EJ, de Boer IH, Deo R et al. eGFR and Albuminuria in Relation to Risk of Incident Atrial Fibrillation: A Meta-Analysis of the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Clinical Journal of the American Society of Nephrology. 2017;12(9):1386– 98. DOI: 10.2215/CJN.01860217
50. Go AS, Fang MC, Udaltsova N, Chang Y, Pomernacki NK, Borowsky L et al. Impact of proteinuria and glomerular filtration rate on risk of thromboembolism in atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Circulation. 2009;119(10):1363–9. DOI: 10.1161/CIRCULATIONAHA.108.816082
51. Revishvili A.Sh., Shlyakhto E.V., Sulimov V.A., Rzaev F.G., Gorev M.V., Nardaya Sh.G. et al. Clinical recommendations RKO, VNOA and ASSH ‘Diagnosis and treatment of atrial fibrillation’ 2017. 211p. Av. at: http://webmed.irkutsk.ru/doc/pdf/af.pdf.
52. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC et al. 2019 AHA/ACC/HRS Focused Update of the 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 Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation. 2019;140(2):e125–51. DOI: 10.1161/CIR.0000000000000665
53. Obrezan A.G. Difficult issues of oral anticoagulant therapy in patients with atrial fibrillation. Bulletin of Arrhythmology. 2017;88:68–72.
54. Yao X, Tangri N, Gersh BJ, Sangaralingham LR, Shah ND, Nath KA et al. Renal Outcomes in Anticoagulated Patients With Atrial Fibrillation. Journal of the American College of Cardiology. 2017;70(21):2621–32. DOI: 10.1016/j.jacc.2017.09.1087
Review
For citations:
Obrezan A.G., Kulikov N.V. Atrial Fibrillation and Diabetes Mellitus: the Control of Thromboembolic Risk. Kardiologiia. 2020;60(7):108-114. (In Russ.) https://doi.org/10.18087/cardio.2020.7.n1146
Views:
2352
Email this article 
Post a Comment 
