Journal of Cardiovascular Imaging

  • 제23권4호
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  • Pages.233-243
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  • 2015
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  • 2586-7210(pISSN)
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  • 2586-7296(eISSN)
한국심초음파학회 (Korean Society of Echocardiography)
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EFFECT OF DIPEPTIDYL PEPTIDASE-4 INHIBITOR ON ALL-CAUSE MORTALITY AND CORONARY REVASCULARIZATION IN DIABETIC PATIENTS

  • Park, Hyo Eun (Division of Cardiology, Healthcare System Gangnam Center, Seoul National University Hospital) ;
  • Jeon, Jooyeong (Master in Statistics, Department of Statistics, Sungkyunkwan University) ;
  • Hwang, In-Chang (Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital) ;
  • Sung, Jidong (Division of Cardiology, Department of Internal Medicine, Sungkyunkwan University College of Medicine, Samsung Medical Center) ;
  • Lee, Seung-Pyo (Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital) ;
  • Kim, Hyung-Kwan (Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital) ;
  • Cho, Goo-Yeong (Division of Cardiology, Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Sohn, Dae-Won (Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital) ;
  • Kim, Yong-Jin (Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital)
  • 투고 : 2015.08.04
  • 심사 : 2015.11.18
  • 발행 : 2015.12.27
⟨ 이전 논문 다음 논문 ⟩

초록

BACKGROUND: Anti-atherosclerotic effect of dipeptidyl peptidase-4 (DPP-4) inhibitors has been suggested from previous studies, and yet, its association with cardiovascular outcome has not been demonstrated. We aimed to evaluate the effect of DPP-4 inhibitors in reducing mortality and coronary revascularization, in association with baseline coronary computed tomography (CT). METHODS: The current study was performed as a multi-center, retrospective observational cohort study. All subjects with diabetes mellitus who had diagnostic CT during 2007-2011 were included, and 1866 DPP-4 inhibitor users and 5179 non-users were compared for outcome. The primary outcome was all-cause mortality and secondary outcome included any coronary revascularization therapy after 90 days of CT in addition to all-cause mortality. RESULTS: DPP-4 inhibitors users had significantly less adverse events [0.8% vs. 4.4% in users vs. non-users, adjusted hazard ratios (HR) 0.220, 95% confidence interval (CI) 0.102-0.474, p = 0.0001 for primary outcome, 4.1% vs. 7.6% in users vs. non-users, HR 0.517, 95% CI 0.363-0.735, p = 0.0002 for secondary outcome, adjusted variables were age, sex, presence of hypertension, high sensitivity C-reactive protein, glycated hemoglobin, statin use, coronary artery calcium score and degree of stenosis]. Interestingly, DPP-4 inhibitor seemed to be beneficial only in subjects without significant stenosis (adjusted HR 0.148, p = 0.0013 and adjusted HR 0.525, p = 0.0081 for primary and secondary outcome). CONCLUSION: DPP-4 inhibitor is associated with reduced all-cause mortality and coronary revascularization in diabetic patients. Such beneficial effect was significant only in those without significant coronary stenosis, which implies that DPP-4 inhibitor may have beneficial effect in earlier stage of atherosclerosis.

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참고문헌

  1. Kim YG, Hahn S, Oh TJ, Kwak SH, Park KS, Cho YM. Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: a systematic review and meta-analysis. Diabetologia 2013;56:696-708. https://doi.org/10.1007/s00125-012-2827-3
  2. Mason RP, Jacob RF, Kubant R, Ciszewski A, Corbalan JJ, Malinski T. Dipeptidyl peptidase-4 inhibition with saxagliptin enhanced nitric oxide release and reduced blood pressure and sICAM-1 levels in hypertensive rats. J Cardiovasc Pharmacol 2012;60:467-73. https://doi.org/10.1097/FJC.0b013e31826be204
  3. Yousefzadeh P, Wang X. The effects of dipeptidyl peptidase-4 inhibitors on cardiovascular disease risks in type 2 diabetes mellitus. J Diabetes Res 2013;2013:459821.
  4. Liu L, Liu J, Wong WT, Tian XY, Lau CW, Wang YX, Xu G, Pu Y, Zhu Z, Xu A, Lam KS, Chen ZY, Ng CF, Yao X, Huang Y. Dipeptidyl peptidase 4 inhibitor sitagliptin protects endothelial function in hypertension through a glucagon-like peptide 1-dependent mechanism. Hypertension 2012;60:833-41. https://doi.org/10.1161/HYPERTENSIONAHA.112.195115
  5. Heo KS, Fujiwara K, Abe J. Glucagon-like peptide-1 and its cardiovascular effects. Curr Atheroscler Rep 2012;14:422-8. https://doi.org/10.1007/s11883-012-0265-9
  6. Chrysant SG, Chrysant GS. Clinical implications of cardiovascular preventing pleiotropic effects of dipeptidyl peptidase-4 inhibitors. Am J Cardiol 2012;109:1681-5. https://doi.org/10.1016/j.amjcard.2012.01.398
  7. Patil HR, Al Badarin FJ, Al Shami HA, Bhatti SK, Lavie CJ, Bell DS, O’Keefe JH. Meta-analysis of effect of dipeptidyl peptidase-4 inhibitors on cardiovascular risk in type 2 diabetes mellitus. Am J Cardiol 2012;110:826-33. https://doi.org/10.1016/j.amjcard.2012.04.061
  8. Monami M, Ahren B, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and cardiovascular risk: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2013;15:112-20. https://doi.org/10.1111/dom.12000
  9. Dai Y, Dai D, Mercanti F, Ding Z, Wang X, Mehta JL. Dipeptidyl peptidase-4 inhibitors in cardioprotection: a promising therapeutic approach. Acta Diabetol 2013;50:827-35. https://doi.org/10.1007/s00592-013-0496-4
  10. UK Prospective Diabetes Study (UKPDS) Group. 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;352:837-53. https://doi.org/10.1016/S0140-6736(98)07019-6
  11. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854-65. https://doi.org/10.1016/S0140-6736(98)07037-8
  12. Macfarlane DP, Paterson KR, Fisher M. Oral antidiabetic agents as cardiovascular drugs. Diabetes Obes Metab 2007;9:23-30.
  13. Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA 1979;241:2035-8. https://doi.org/10.1001/jama.1979.03290450033020
  14. Schernthaner G. Cardiovascular mortality and morbidity in type-2 diabetes mellitus. Diabetes Res Clin Pract 1996;31 Suppl:S3-13. https://doi.org/10.1016/0168-8227(96)01224-7
  15. Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I; SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369:1317-26. https://doi.org/10.1056/NEJMoa1307684
  16. White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, Perez AT, Fleck PR, Mehta CR, Kupfer S, Wilson C, Cushman WC, Zannad F; EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013;369:1327-35. https://doi.org/10.1056/NEJMoa1305889
  17. Kwon S. Payment system reform for health care providers in Korea. Health Policy Plan 2003;18:84-92. https://doi.org/10.1093/heapol/18.1.84
  18. Cho I, Shim J, Chang HJ, Sung JM, Hong Y, Shim H, Kim YJ, Choi BW, Min JK, Kim JY, Shim CY, Hong GR, Chung N. Prognostic value of multidetector coronary computed tomography angiography in relation to exercise electrocardiogram in patients with suspected coronary artery disease. J Am Coll Cardiol 2012;60:2205-15. https://doi.org/10.1016/j.jacc.2012.08.981
  19. Villines TC, Hulten EA, Shaw LJ, Goyal M, Dunning A, Achenbach S, Al-Mallah M, Berman DS, Budoff MJ, Cademartiri F, Callister TQ, Chang HJ, Cheng VY, Chinnaiyan K, Chow BJ, Delago A, Hadamitzky M, Hausleiter J, Kaufmann P, Lin FY, Maffei E, Raff GL, Min JK; CONFIRM Registry Investigators. Prevalence and severity of coronary artery disease and adverse events among symptomatic patients with coronary artery calcification scores of zero undergoing coronary computed tomography angiography: results from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry. J Am Coll Cardiol 2011;58:2533-40. https://doi.org/10.1016/j.jacc.2011.10.851
  20. Chow BJ, Small G, Yam Y, Chen L, McPherson R, Achenbach S, Al-Mallah M, Berman DS, Budoff MJ, Cademartiri F, Callister TQ, Chang HJ, Cheng VY, Chinnaiyan K, Cury R, Delago A, Dunning A, Feuchtner G, Hadamitzky M, Hausleiter J, Karlsberg RP, Kaufmann PA, Kim YJ, Leipsic J, LaBounty T, Lin F, Maffei E, Raff GL, Shaw LJ, Villines TC, Min JK; CONFIRM Investigators. Prognostic and therapeutic implications of statin and aspirin therapy in individuals with nonobstructive coronary artery disease: results from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry) registry. Arterioscler Thromb Vasc Biol 2015;35:981-9. https://doi.org/10.1161/ATVBAHA.114.304351
  21. Shah S, Bellam N, Leipsic J, Berman DS, Quyyumi A, Hausleiter J, Achenbach S, Al-Mallah M, Budoff MJ, Cademartiri F, Callister TQ, Chang HJ, Chow BJ, Cury RC, Delago AJ, Dunning AL, Feuchtner GM, Hadamitzky M, Karlsberg RP, Kaufmann PA, Lin FY, Chinnaiyan KM, Maffei E, Raff GL, Villines TC, Gomez MJ, Min JK, Shaw LJ; CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter Registry) Investigators. Prognostic significance of calcified plaque among symptomatic patients with nonobstructive coronary artery disease. J Nucl Cardiol 2014;21:453-66. https://doi.org/10.1007/s12350-014-9865-9
  22. Hulten E, Villines TC, Cheezum MK, Berman DS, Dunning A, Achenbach S, Al-Mallah M, Budoff MJ, Cademartiri F, Callister TQ, Chang HJ, Cheng VY, Chinnaiyan K, Chow BJ, Cury RC, Delago A, Feuchtner G, Hadamitzky M, Hausleiter J, Kaufmann PA, Karlsberg RP, Kim YJ, Leipsic J, Lin FY, Maffei E, Plank F, Raff GL, Labounty TM, Shaw LJ, Min JK; CONFIRM Investigators. Usefulness of coronary computed tomography angiography to predict mortality and myocardial infarction among Caucasian, African and East Asian ethnicities (from the CONFIRM [Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter] Registry). Am J Cardiol 2013;111:479-85. https://doi.org/10.1016/j.amjcard.2012.10.028
  23. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990;15:827-32. https://doi.org/10.1016/0735-1097(90)90282-T
  24. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-59. https://doi.org/10.1056/NEJMoa0802743
  25. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-89. https://doi.org/10.1056/NEJMoa0806470
  26. Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol 2009;53(5 Suppl):S35-42. https://doi.org/10.1016/j.jacc.2008.09.055
  27. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007;132:2131-57. https://doi.org/10.1053/j.gastro.2007.03.054
  28. Drucker DJ. The biology of incretin hormones. Cell Metab 2006;3:153-65. https://doi.org/10.1016/j.cmet.2006.01.004
  29. Neumiller JJ, Wood L, Campbell RK. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus. Pharmacotherapy 2010;30:463-84. https://doi.org/10.1592/phco.30.5.463
  30. Schweizer A, Dejager S, Foley JE, Couturier A, Ligueros-Saylan M, Kothny W. Assessing the cardio-cerebrovascular safety of vildagliptin: meta-analysis of adjudicated events from a large Phase III type 2 diabetes population. Diabetes Obes Metab 2010;12:485-94. https://doi.org/10.1111/j.1463-1326.2010.01215.x
  31. Zhong J, Rao X, Rajagopalan S. An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control: potential implications in cardiovascular disease. Atherosclerosis 2013;226:305-14. https://doi.org/10.1016/j.atherosclerosis.2012.09.012
  32. Anagnostis P, Athyros VG, Adamidou F, Panagiotou A, Kita M, Karagiannis A, Mikhailidis DP. Glucagon-like peptide-1-based therapies and cardiovascular disease: looking beyond glycaemic control. Diabetes Obes Metab 2011;13:302-12. https://doi.org/10.1111/j.1463-1326.2010.01345.x
  33. Wang XM, Yang YJ, Wu YJ. The emerging role of dipeptidyl peptidase-4 inhibitors in cardiovascular protection: current position and perspectives. Cardiovasc Drugs Ther 2013;27:297-307. https://doi.org/10.1007/s10557-013-6459-8
  34. Monami M, Vitale V, Ambrosio ML, Bartoli N, Toffanello G, Ragghianti B, Monami F, Marchionni N, Mannucci E. Effects on lipid profile of dipeptidyl peptidase 4 inhibitors, pioglitazone, acarbose, and sulfonylureas: meta-analysis of placebo-controlled trials. Adv Ther 2012;29:736-46. https://doi.org/10.1007/s12325-012-0045-5
  35. Rizzo M, Rizvi AA, Spinas GA, Rini GB, Berneis K. Glucose lowering and anti-atherogenic effects of incretin-based therapies: GLP-1 analogues and DPP-4-inhibitors. Expert Opin Investig Drugs 2009;18:1495-503. https://doi.org/10.1517/14728220903241633
  36. Panchapakesan U, Mather A, Pollock C. Role of GLP-1 and DPP-4 in diabetic nephropathy and cardiovascular disease. Clin Sci (Lond) 2013;124:17-26. https://doi.org/10.1042/CS20120167
  37. Ogawa S, Ishiki M, Nako K, Okamura M, Senda M, Mori T, Ito S. Sitagliptin, a dipeptidyl peptidase-4 inhibitor, decreases systolic blood pressure in Japanese hypertensive patients with type 2 diabetes. Tohoku J Exp Med 2011;223:133-5. https://doi.org/10.1620/tjem.223.133
  38. Makdissi A, Ghanim H, Vora M, Green K, Abuaysheh S, Chaudhuri A, Dhindsa S, Dandona P. Sitagliptin exerts an antinflammatory action. J Clin Endocrinol Metab 2012;97:3333-41. https://doi.org/10.1210/jc.2012-1544
  39. Terasaki M, Nagashima M, Watanabe T, Nohtomi K, Mori Y, Miyazaki A, Hirano T. Effects of PKF275-055, a dipeptidyl peptidase-4 inhibitor, on the development of atherosclerotic lesions in apolipoprotein E-null mice. Metabolism 2012;61:974-7. https://doi.org/10.1016/j.metabol.2011.11.011
  40. Vittone F, Liberman A, Vasic D, Ostertag R, Esser M, Walcher D, Ludwig A, Marx N, Burgmaier M. Sitagliptin reduces plaque macrophage content and stabilises arteriosclerotic lesions in Apoe (-/-) mice. Diabetologia 2012;55:2267-75. https://doi.org/10.1007/s00125-012-2582-5
  41. Barbieri M, Rizzo MR, Marfella R, Boccardi V, Esposito A, Pansini A, Paolisso G. Decreased carotid atherosclerotic process by control of daily acute glucose fluctuations in diabetic patients treated by DPP-IV inhibitors. Atherosclerosis 2013;227:349-54. https://doi.org/10.1016/j.atherosclerosis.2012.12.018
  42. Matsubara J, Sugiyama S, Akiyama E, Iwashita S, Kurokawa H, Ohba K, Maeda H, Fujisue K, Yamamoto E, Kaikita K, Hokimoto S, Jinnouchi H, Ogawa H. Dipeptidyl peptidase-4 inhibitor, sitagliptin, improves endothelial dysfunction in association with its anti-inflammatory effects in patients with coronary artery disease and uncontrolled diabetes. Circ J 2013;77:1337-44. https://doi.org/10.1253/circj.CJ-12-1168
  43. Fan J, Watanabe T. Inflammatory reactions in the pathogenesis of atherosclerosis. J Atheroscler Thromb 2003;10:63-71. https://doi.org/10.5551/jat.10.63

피인용 문헌

  1. Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care vol.354, pp.None, 2016, https://doi.org/10.1136/bmj.i3477