REVIEW PAPER
The role of acetylsalicylic acid and circulating microRNAs in primary prevention of cardiovascular events in patients with Diabetes Mellitus Type 2 – A Review
Aleksandra Chabior 1, 2
,  
Justyna Pordzik 2, 1
,  
Marek Postuła 1, 2  
 
 
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1
Medical University, Warsaw, Poland
2
Department of Experimental and Clinical Pharmacology/Center for Preclinical Research and Technology (CePT), Medical University, Warsaw, Poland
 
KEYWORDS:
TOPICS:
ABSTRACT:
Introduction:
Type 2 diabetes mellitus (T2DM) is a common metabolic disorder, which carries a risk for atherosclerosis and cardiovascular impairment. The purpose of this review is to demonstrate the role of acetylsalicylic acid (ASA) in primary cardiovascular prevention in T2DM patients, as well as present an outline of microRNAs (miRNA) relevant to ASA therapy and should be evaluated as targets to improve treatment.

Brief description of state of knowledge:
Although the etiology of hypercoagulable state in T2DM is considered multifactorial, attention mainly focuses on platelet disturbances. Platelets in T2DM not only demonstrate intensified adhesion, activation, aggregation, and thrombin generation, but are likely to deliver miRNAs at specific sites of action in the cardiovascular system, hence contributing to the pathogenesis of cardiovascular events.

Objective:
Since cardiovascular disease (CVD) is currently the leading cause of mortality among T2DM patients, appropriate risk stratification and management is necessary to reduce morbidity and mortality in this group. A large number of T2DM patients show inadequate response to antiplatelet therapy, which currently revolves around ASA, despite compliance with treatment regimens proposed by the guidelines.

Conclusions:
The review shows that the use of ASA for primary prevention is beneficial in patients at high cardiovascular risk. However, it is important to select patients in whom ASA therapy will bring the most beneficial outcome with minimal risk for adverse effects. This can be potentially achieved with the use of unique biomarkers. The biologically diverse characteristics of miRNA make them a promising novel biomarker and potential tool for better risk stratification, as well as antiplatelet therapy optimization.

CORRESPONDING AUTHOR:
Marek Postuła   
Medical University, Warsaw, Poland
 
REFERENCES (73):
1. Fox CS, Golden SH, Anderson C, Bray GA, Burke LE, de Boer IH, Deedwania P, Eckel RH, Ershow AG, Fradkin J, Inzucchi SE, Kosiborod M, Nelson RG, Patel MJ, Pignone M, Quinn L, Schauer PR, Selvin E, Vafiadis DK; American Heart Association Diabetes Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Surgery and Anesthesia, Council on Quality of Care and Outcomes Research; American Diabetes Association. Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence: A Scientific Statement From the American Heart Association and the American Diabetes Association. Diabetes Care. 2015 Sep; 38(9):1777–803. doi: 10.2337/dci15–0012.
2. Kubisz P, Stanicakovs L, Stasko J, Galajda P, Mokan M. Endothelial and platelet markers in diabetes mellitus type 2. World J Diabetes. 2015 Apr 15;6(3):423–31.doi: 10.4239/wjd.v6.i3.423.
3. Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Eur Heart J. 2013 Aug; 34(31): 2436–43. doi: 10.1093/eurheartj/eht149.
4. Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998 Jul 23; 339(4): 229–34.
5. Pomero F, Di Minno MN, Fenoglio L, Gianni M, Ageno W, Dentali F. Is diabetes a hypercoagulable state? A critical appraisal. Acta Diabetol. 2015 Dec; 52(6): 1007–16. doi: 10.1007/s00592–015–0746–8.
6. Morel O, Jesel L, Abbas M, Morel N. Prothrombotic changes in diabetes mellitus. Semin Thromb Hemost. 2013 Jul; 39(5): 477–88. doi: 10.1055/s-0033–1343888.
7. Association AD. Standards of Medical Care in Diabetes-2016. Diabetes Care.2016; 39: 60–71.
8. Cardiovascular Disease and Risk Management. Diabetes Care. 2016; 39: 60–71.
9. Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, Rosenson RS, Williams CD, Wilson PW, Kirkman MS. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Circulation. 2010 Jun 22; 121(24): 2694–701. doi: 10.1161/CIR.0b013e3181e3b133.
10. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corrà U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FDR, Løchen ML, Löllgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WMM, Binno S; ESC Scientific Document Group. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016 Aug 1; 37(29): 2315–2381. doi: 10.1093/eurheartj/ehw106.
11. Halvorsen S, Andreotti F, ten Berg JM, Cattaneo M, Coccheri S, Marchioli R, Morais J, Verheugt FW, De Caterina R. Aspirin therapy in primary cardiovascular disease prevention: a position paper of the European Society of Cardiology working group on thrombosis. J Am Coll Cardiol. 2014 Jul 22; 64(3): 319–27. doi: 10.1016/j.jacc.2014.03.049.
12. Rollini F, Franchi F, Muñiz-Lozano A, Angiolillo DJ. Platelet function profiles in patients with diabetes mellitus. J Cardiovasc Transl Res. 2013 Jun; 6(3): 329–45. doi: 10.1007/s12265–013–9449–0.
13. Kumbhani DJ, Marso SP, Alvarez CA, McGuire DK. State-of-the-Art: Hypo-responsiveness to oral antiplatelet therapy in patients with type 2 diabetes mellitus. Curr Cardiovasc Risk Rep. 2015 Jan; 9: 4. doi: 10.1007/s12170–014–0430–5.
14. Yazbek N, Bapat A, Kleiman N. Platelet abnormalities in diabetes mellitus. Coron Artery Dis 2003; 14: 365–71. doi: 10.1097/01.mca.0000085138.16622.9e.
15. Postula M, Kaplon-Cieslicka A, Rosiak M, Kondracka A, Serafin A, Filipiak KJ, Czlonkowski A, Opolski G, Janicki PK. Genetic determinants of platelet reactivity during acetylsalicylic acid therapy in diabetic patients: evaluation of 27 polymorphisms within candidate genes. J Thromb Haemost. 2011; 9(11): 2291–301. doi: 10.1111/j.1538–7836.2011.04482.x.
16. Natarajan A, Zaman AG, Marshall SM. Platelet hyperactivity in type 2 diabetes: role of antiplatelet agents. Diab Vasc Dis Res. 2008; 5: 138–44. doi: 10.3132/dvdr.2008.023.
17. Ferroni P, Basili S, Falco A, Davi G. Platelet activation in type 2 diabetes mellitus. J Thromb Haemost. 2004; 2: 1282–91. doi: 10.1111/j.1538–7836.2004.00836.x.
18. McRedmond JP, Park SD, Reilly DF, Coppinger JA, Maguire PB, Shields DC, Fitzgerald DJ. Integration of proteomics and genomics in platelets: a profile of platelet proteins and platelet-specific genes. Mol Cell Proteomics. 2004 Feb; 3(2): 133–44. doi: 10.1074/mcp.M300063-MCP200.
19. Dangwal S, Thum T. MicroRNAs in platelet biogenesis and function. Thromb Haemost. 2012 Oct; 108(4): 599–604. doi: 10.1160/TH12–03–0211.
20. Wang K, Yuan Y, Cho JH, McClarty S, Baxter D, Galas DJ. Comparing the MicroRNA spectrum between serum and plasma. PLoS One. 2012; 7(7): e41561. Doi: 10.1371/journal.pone.0041561.
21. Shi R, Ge L, Zhou X, Ji WJ, Lu RY, Zhang YY, Zeng S, Liu X, Zhao JH, Zhang WC, Jiang TM, Li YM. Decreased platelet miR-223 expression is associated with high on-clopidogrel platelet reactivity. Thromb Res. 2013 Jun; 131(6): 508–13. doi: 10.1016/j.thromres.2013.02.015.
22. Choi JL, Li S, Han JY. Platelet function tests: a review of progresses in clinical application. Biomed Res Int. 2014; 2014: 456569. doi: 10.1155/2014/456569.
23. Iaconetti C, Sorrentino S, De Rosa S, Indolfi C. Exosomal miRNAs in Heart Disease. Physiology (Bethesda). 2016 Jan; 31(1): 16–24. doi: 10.1152/physiol.00029.2015.
24. Santilli F, Pignatelli P, Violi F, Davì G. Aspirin for primary prevention in diabetes mellitus: from the calculation of cardiovascular risk and risk/benefit profile to personalised treatment. Thromb Haemost. 2015 Nov; 114(5): 876–82. doi: 10.1160/TH15–03–0202.
25. Carr ME. Diabetes mellitus: a hypercoagulable state. J Diabetes Complications. 2001 Jan-Feb; 15(1): 44–54.
26. 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; 106: 3143–3421.
27. Angiolillo DJ, Bernardo E, Sabaté M, Jimenez-Quevedo P, Costa MA, Palazuelos J, Hernández-Antolin R, Moreno R, Escaned J, Alfonso F, Bañuelos C, Guzman LA, Bass TA, Macaya C, Fernandez-Ortiz A. Impact of platelet reactivity on cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol. 2007 Oct 16; 50(16): 1541–7. doi: 10.1016/j.jacc.2007.05.049.
28. Jung JH, Tantry US, Gurbel PA, Jeong YH. Current antiplatelet treatment strategy in patients with diabetes mellitus. Diabetes Metab J. 2015 Apr; 39(2): 95–113. doi: 10.4093/dmj.2015.39.2.95.
29. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23; 2 31(25): 232–5.
30. Nguyen KX, Marinac JS, Sun C. Aspirin for primary prevention in patients with diabetes mellitus. Fam Med. 2005 Feb; 37(2): 112–7.
31. Casado-Arroyo R, Sostres C, Lanas A. Optimizing the use of aspirin for cardiovascular prevention. Drugs. 2013 Jun; 73(8): 803–14. doi: 10.1007/s40265–013–0061-z.
32. Vandvik PO, Lincoff AM, Gore JM, Gutterman DD, Sonnenberg FA, Alonso-Coello P, Akl EA, Lansberg MG, Guyatt GH, Spencer FA. Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb; 141(2 Suppl): e637S-e668S. doi: 10.1378/chest.11–2306.
33. Davì G, Catalano I, Averna M, Notarbartolo A, Strano A, Ciabattoni G, Patrono C. Thromboxane biosynthesis and platelet function in type II diabetes mellitus. N Engl J Med. 1990 Jun 21; 322(25): 1769–74. doi: 10.1056/NEJM199006213222503.
34. Zhang C, Sun A, Zhang P, Wu C, Zhang S, Fu M, Wang K, Zou Y, Ge J. Aspirin for primary prevention of cardiovascular events in patients with diabetes: A meta-analysis. Diabetes Res Clin Pract. 2010 Feb; 87(2): 211–8. Doi: 10.1016/j.diabres.2009.09.029.
35. Bartolucci AA, Tendera M, Howard G. Meta-analysis of multiple primary prevention trials of cardiovascular events using aspirin. Am J Cardiol. 2011 Jun 15; 107(12): 1796–801. doi: 10.1016/j.amjcard.2011.02.325.
36. Bartolucci AA, Howard G. Meta-analysis of data from the six primary prevention trials of cardiovascular events using aspirin. Am J Cardiol. 2006 Sep 15; 98(6): 746–50. Epub 2006 Jul 26.
37. Butalia S, Leung AA, Ghali WA, Rabi DM. Aspirin effect on the incidence of major adverse cardiovascular events in patients with diabetes mellitus: a systematic review and meta-analysis. Cardiovasc Diabetol. 2011 Apr 1; 10: 25. doi: 10.1186/1475–2840–10–25.
38. Stavrakis S, Stoner JA, Azar M, Wayangankar S, Thadani U. Low-dose aspirin for primary prevention of cardiovascular events in patients with diabetes: a meta-analysis. Am J Med Sci. 2011 Jan; 341(1): 1–9. Doi: 10.1097/MAJ.0b013e3181f1fba8.
39. Sutcliffe P, Connock M, Gurung T, Freeman K, Johnson S, Kandala NB, Grove A, Gurung B, Morrow S, Clarke A. Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer: a systematic review and overview of reviews. Health Technol Assess. 2013 Sep; 17(43): 1–253. doi: 10.3310/hta17430.
40. Xie M, Shan Z, Zhang Y, Chen S, Yang W, Bao W, Rong Y, Yu X, Hu FB, Liu L. Aspirin for primary prevention of cardiovascular events: meta-analysis of randomized controlled trials and subgroup analysis by sex and diabetes status. PLoS One. 2014 Oct 31; 9(10): e90286. doi: 10.1371/journal.pone.0090286.
41. Webster R, Patel A, Selak V, Billot L, Bots ML, Brown A, Bullen C, Cass A, Crengle S, Raina Elley C, Grobbee DE, Neal B, Peiris D, Poulter N, Prabhakaran D, Rafter N, Stanton A, Stepien S, Thom S, Usherwood T, Wadham A, Rodgers A; SPACE Collaboration. Effectiveness of fixed dose combination medication (‘polypills’) compared with usual care in patients with cardiovascular disease or at high risk: A prospective, individual patient data meta-analysis of 3140 patients in six countries. Int J Cardiol. 2016 Feb 15; 205: 147–156. doi: 10.1016/j.ijcard.2015.12.015.
42. Kokoska LA, Wilhelm SM, Garwood CL, Berlie HD. Aspirin for primary prevention of cardiovascular disease in patients with diabetes: A meta-analysis. Diabetes Res Clin Pract. 2016 Oct; 120: 31–9. doi: 10.1016/j.diabres.2016.07.012.
43. De Berardis G, Sacco M, Evangelista V, Filippi A, Giorda CB, Tognoni G, Valentini U, Nicolucci A; ACCEPT-D Study Group. Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D): design of a randomized study of the efficacy of low-dose aspirin in the prevention of cardiovascular events in subjects with diabetes mellitus treated with statins. Trials. 2007 Aug 28;8:21.
44. Aung T, Haynes R, Barton J, Cox J, Murawska A, Murphy K, Lay M, Armitage J, Bowman L; ASCEND Study Collaborative Group. Cost-effective recruitment methods for a large randomised trial in people with diabetes: A Study of Cardiovascular Events iN Diabetes (ASCEND). Trials. 2016 Jun 13; 17(1): 286. doi: 10.1186/s13063–016–1354–9.
45. Derosa G, Mugellini A, Pesce RM, D’Angelo A, Maffioli P. A study about the relevance of adding acetylsalicylic acid in primary prevention in subjects with type 2 diabetes mellitus: effects on some new emerging biomarkers of cardiovascular risk. Cardiovasc Diabetol. 2015 Jul 30; 14: 95. doi: 10.1186/s12933–015–0254–8.
46. Kapłon-Cieślicka A, Rosiak M, Postuła M, Serafin A, Kondracka A, Opolski G, Filipiak KJ. Predictors of high platelet reactivity during aspirin treatment in patients with type 2 diabetes. Kardiol Pol. 2013; 71(9): 893–902. doi: 10.5603/KP.2013.0055.
47. Li L, Qu C, Wu X, Dai J, Lu Y, Gong Y, You R, Liu Y. Patterns and levels of platelet glycosylation in patients with coronary heart disease and type 2 diabetes mellitus. J Thromb Thrombolysis. 2018 Jan; 45(1): 56–65. Doi: 10.1007/s11239–017–1573–2.
48. Israels SJ, McNicol A, Dean HJ, Cognasse F, Sellers EA. Markers of platelet activation are increased in adolescents with type 2 diabetes. Diabetes Care. 2014 Aug; 37(8): 2400–3. doi: 10.2337/dc13–2718.
49. El-Mesallamy H, Hamdy N, Suwailem S, Mostafa S. Oxidative stress and platelet activation: markers of myocardial infarction in type 2 diabetes mellitus. Angiology. 2010 Feb-Mar; 61(1): 14–8. doi: 10.1177/0003319709340891.
50. Zhang X, McGeoch SC, Johnstone AM, Holtrop G, Sneddon AA, MacRury SM, Megson IL, Pearson DW, Abraham P, De Roos B, Lobley GE, O’Kennedy N. Platelet-derived microparticle count and surface molecule expression differ between subjects with and without type 2 diabetes, independently of obesity status. J Thromb Thrombolysis. 2014 May; 37(4): 455–63. doi: 10.1007/s11239–013–1000–2.
51. Liani R, Halvorsen B, Sestili S, Handberg A, Santilli F, Vazzana N, Formoso G, Aukrust P, Davì G. Plasma levels of soluble CD36, platelet activation, inflammation, and oxidative stress are increased in type 2 diabetic patients. Free Radic Biol Med. 2012 Apr 15; 52(8): 1318–24. doi: 10.1016/j.freeradbiomed.2012.02.012.
52. Kaudewitz D, Skroblin P, Bender LH, Barwari T, Willeit P, Pechlaner R, Sunderland NP, Willeit K, Morton AC, Armstrong PC, Chan MV, Lu R, Yin X, Gracio F, Dudek K, Langley SR, Zampetaki A, de Rinaldis E, Ye S, Warner TD, Saxena A, Kiechl S, Storey RF, Mayr M. Association of MicroRNAs and YRNAs With Platelet Function. Circ Res. 2016 Feb 5; 118(3): 420–432. doi: 10.1161/CIRCRESAHA.114.305663.
53. Nishiguchi T, Imanishi T, Akasaka T. MicroRNAs and cardiovascular diseases. Biomed Res Int. 2015: 682857. doi:10.1155/2015/682857.
54. Kondkar AA, Abu-Amero KK. Utility of circulating microRNAs as clinical biomarkers for cardiovascular diseases. Biomed Res Int. 2015:8 21823.doi:10.1155/2015/821823.
55. De Rosa S, Curcio A, Indolfi C. Emerging role of microRNAs in cardiovascular diseases. Circ J. 2014; 78(3): 567–75. Epub 2014 Feb 13.
56. Pordzik J, Pisarz K, De Rosa S, Jones AD, Eyileten C, Indolfi C, Malek L, Postula M. The Potential Role of Platelet-Related microRNAs in the Development of Cardiovascular Events in High-Risk Populations, Including Diabetic Patients: A Review. Front Endocrinol (Lausanne). 2018 Mar 20; 9: 74. doi: 10.3389/fendo.2018.00074.
57. Feje, Z, Póliska S, Czimmerer Z, Káplár M, Penyige A, Gál Szabó G, et al. Hyperglycemia suppresses microRNA expression in platelets to increase P2RY12 and SELP levels in type 2 diabetes mellitus. Thromb. Haemost. 2017; 117: 529–542. doi: 10.1160/TH16–04–0322.
58. Duan X, Zhan Q, Song B, Zeng S, Zhou J, Long Y, et al. Detection of platelet microRNA expression in patients with diabetes mellitus with or without ischemic stroke. J Diabetes Complications. 2017; 28: 705–710. doi: 10.1016/j.jdiacomp.2014.04.012.
59. Zhang YY, Zhou X, Ji WJ, Shi R, Lu RY, Li JL, et al. Decreased circulating microRNA-223 level predicts high on-treatment platelet reactivity in patients with troponin-negative non-ST elevation acute coronary syndrome. J. Thromb. Thrombolysis. 2014; 38: 65–72. doi: 10.1007/s11239–013–1022–9.
60. Zampetaki A, Willeit P, Drozdov I, Kiechl S, Mayr M. Profiling of circulating microRNAs: from single biomarkers to re-wired networks. Cardiovasc Res. 2012; 93: 555–562. doi: 10.1093/cvr/cvr266.
61. Zampetaki A, Willeit P, Tilling L, Drozdov I, Prokopi M, Renard JM, et al. Prospective study on circulating microRNAs and risk of myocardial infarction. J Am Coll Cardiol. 2012; 60: 290–299. doi: 10.1016/j.jacc.2012.03.056.
62. Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010; 107: 810–817. doi: 10.1161/CIRCRESAHA.110.226357.
63. Dangwal S, Stratmann B, Bang C, Lorenzen JM. Kumarswamy R, Fiedler J, et al. Impairment of Wound Healing in Patients With Type 2 Diabetes Mellitus Influences Circulating MicroRNA Patterns via Inflammatory Cytokines. Arterioscler Thromb Vasc Biol. 2015; 35: 1480–1488. doi: 10.1161/ATVBAHA.114.305048.
64. Fuentes E, Palomo I, Alarcón M. Platelet miRNAs and cardiovascular diseases. Life Sci. 2015; 133: 29–44. doi: 10.1016/j.lfs.2015.04.016.
65. Olivieri F, Spazzafumo L, Bonafè M, Recchioni R, Prattichizzo F, Marcheselli F, et al. MiR-21–5p and miR-126a-3p levels in plasma and circulating angiogenic cells: relationship with type 2 diabetes complications. Oncotarget. 2015; 6: 35372–82. doi: 10.18632/oncotarget.6164.
66. De Rosa S, Indolfi C. Circulating microRNAs as Biomarkers in Cardiovascular Diseases. EXS. 2015; 106: 139–149. doi:.1007/978–3–0348–0955–9_6.
67. Wang F, Chen C, Wang D. Circulating microRNAs in cardiovascular diseases: from biomarkers to therapeutic targets. Front Med. 2014 Dec; 8(4): 404–18. Doi: 10.1007/s11684–014–0379–2.
68. Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, Weber M, Hamm CW, Röxe T, Müller-Ardogan M, Bonauer A, Zeiher AM, Dimmeler S. Circulating microRNAs in patients with coronary artery disease. Circ Res. 2010 Sep 3; 107(5): 677–84. doi: 10.1161/CIRCRESAHA.109.215566.
69. Schulte C, Molz S, Appelbaum S, Karakas M, Ojeda F, Lau DM, Hartmann T, Lackner KJ, Westermann D, Schnabel RB, Blankenberg S, Zeller T. miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease. PLoS One. 2015 Dec 31; 10(12): e0145930. Doi: 10.1371/journal.pone.0145930.
70. Jansen F, Yang X, Proebsting S, Hoelscher M, Przybilla D, Baumann K, Schmitz T, Dolf A, Endl E, Franklin BS, Sinning JM, Vasa-Nicotera M, Nickenig G, Werner N. MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease. J Am Heart Assoc. 2014 Oct 27; 3(6): e001249. doi: 10.1161/JAHA.114.001249.
71. Wang L, Zhi H, Li Y, Ma G, Ye X, Yu X, Yang T, Jin H, Lu Z, Wei P. Polymorphism in miRNA-1 target site and circulating miRNA-1 phenotype are associated with the decreased risk and prognosis of coronary artery disease. Int J Clin Exp Pathol. 2014 Jul 15; 7(8): 5093–102.
72. Buraczynska M, Zukowski P, Wacinski P, Ksiazek K, Zaluska W. Polymorphism in microRNA-196a2 contributes to the risk of cardiovascular disease in type 2 diabetes patients. J Diabetes Complications. 2014 Sep-Oct; 28(5): 617–20. Doi: 10.1016/j.jdiacomp.2014.05.006.
73. Hira RS, Kennedy K, Nambi V, Jneid H, Alam M, Basra SS, Ho PM, Deswal A, Ballantyne CM, Petersen LA, Virani SS. Frequency and practice-level variation in inappropriate aspirin use for the primary prevention of cardiovascular disease: insights from the National Cardiovascular Disease Registry’s Practice Innovation and Clinical Excellence registry. J Am Coll Cardiol. 2015 Jan 20; 65(2): 111–21. doi: 10.1016/j.jacc.2014.10.035.
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