Stratification of patients with type 2 diabetes mellitus for painless ischemic heart disease

Aims.
Development of assessment model for type 2 diabetes mellitus (DM) patient stratification for painless ischemic heart disease(IHD).
Materials and methods.
258 patients with DM type 2 participated in this study (109 male and 149 female) of mean age 58.4?8.5 withDM experience of 7.9?6.1 years. All participants were subdivided into three groups: first - DM type 2 without history of painless IHD(138 individuals); second - DM type 2 with diagnosed painless IHD (50 individuals); third - DM type 2 with painful myocardialischemia. We assessed "classic" risk factors for IHD, immediately connected with DM comorbidity, as well as "additional" risk factors,potentially capable of provoking both painless and painful IHD. In addition, we screened our patients for structural abnormalitiesof heart by means of echocardiography. Painless IHD was diagnosed by treadmill-tests or Holter monitoring with submaximal exercise.Accumulated data was statistically processed with the use of Spearman's rank correlation, as well as binary logistic regression method.Results were deemed statistically significant at р<0,05.
Results.
At the first stage all risk factors were analyzed according to Spearman's rank correlation coefficient. We identified 21 parameterwith average (r=0,5-0,7) and high (r>0,7) correlation strength. Next we isolated 11 independent variables with highest predictivevalidity for painless IHD. Based on binary logistic regression method we calculated prediction coefficients and developed a specialmodel, valid for prediction of painless IHD. After adjustment with account of type I and type II errors (with 50/50 ration), predictivevalidity of our model reached 76% with confidence limit of 95%.
Conclusion.
Only 11 of all assessed risk factors ("classic", "specific" and "additional") showed to have high predictive validity fordevelopment of IHD. Based upon our data, we offer an assessment model suitable for identification of patients at high risk of IHDdevelopment in everyday clinical practice.

diabetes mellitus type 2, silent myocardial ischemia, risk factors, cardiovascular diseases, screening method

1. Colagiuri S, Best J. Lipid-lowering therapy in people with type 2 diabetes. Curr Opin Lipidol. 2002 Dec;13(6):617-623.

2. Rydén L, Standl E, Bartnik M, Van den Berghe G, Betteridge J, de Boer MJ, Cosentino F, Jönsson B, Laakso M, Malmberg K, Priori S, Ostergren J, Tuomilehto J, Thrainsdottir I, Vanhorebeek I, Stramba-Badiale M, Lindgren P, Qiao Q, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers J, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo J, Zamorano JL, Deckers JW, Bertrand M, Charbonnel B, Erdmann E, Ferrannini E, Flyvbjerg A, Gohlke H, Juanatey JR, Graham I, Monteiro PF, Parhofer K, Pyörälä K, Raz I, Schernthaner G, Volpe M, Wood D; Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC); European Association for the Study of Diabetes (EASD). Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. 2007 Jan;28(1):88-136.

3. Лупанов ВП, Наумов ВГ. Безболевая ишемия миокарда: диа- гностика и лечение. Сердце. 2002;1(6):276-282.

4. Верткин АЛ, Ткачева ОН, Новикова ИМ. Безболевая ишемия и диабетическая автономная нейропатия. Русский медицинский журнал. 2005; 13(20):1036-1038.

5. Gutterman DD. Silent myocardial ischemia. Circ J. 2009 May;73(5):785-797. Epub 2009 Mar 13.

6. Zellweger MJ. Prognostic significance of silent coronary artery disease in type 2 diabetes. Herz. 2006 May;31(3):240-245.

7. Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Heller GV, Iskandrian AE, Wittlin SD, Filipchuk N, Ratner RE, Inzucchi SE; DIAD Investigators. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009 Apr 15;301(15):1547-1555.

8. Cohn PF, Fox KM, Daly C. Silent Myocardial Ischemia. Circulation. 2003 Sep 9;108(10):1263-1277.

9. Machecourt J, Vanzetto G, Fagret D. Strategy of investigation of coronary artery disease in diabetes: from screening to suspicion of acute coronary syndromes. Arch Mal Coeur Vaiss. 2004 Dec;97 Spec No 3:41-46.

10. Оганов РГ, Поздняков ЮМ, Акчурин РС и др. Комитет экспертов ВНОК. Диагностика и лечение стабильной стенокардии. Российские рекомендации (второй пересмотр). Кардиоваскулярная терапия и профилактика. 2008;7(6):5-25.

11. Executive summary: Standards of medical care in diabetes-- 2010. Diabetes Care. 2010 Jan;33 Suppl 1:S4-10.

12. Yildirimtürk O, Kiliçgedik M, Tuğcu A, Aytekin V, Aytekin S. The relationship of microalbuminuria with left ventricular functions and silent myocardial ischemia in asymptomatic patients with type 2 diabetes. Turk Kardiyol Dern Ars. 2009 Mar;37(2):91-97.

13. Gazzaruso C, Solerte SB, De Amici E, Mancini M, Pujia A, Fratino P, Giustina A, Garzaniti A. Association of the metabolic syndrome and insulin resistance with silent myocardial ischemia in patients with type 2 diabetes mellitus. Am J Cardiol. 2006 Jan 15;97(2):236-239. Epub 2005 Dec 1.

14. Дедов ИИ, Мельниченко ГА. Клинические рекомендации. Эндокринология. М: ГЭОТАР-Медиа; 2008.

15. Кишкун АА. Руководство по лабораторным методам диагно- стики. М: ГЭОТАР-Медиа; 2007.

16. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004 Jun;27(6):1487-1495.

17. Ткачева ОН, Зорина СА, Хайбулина ЭТ, Ибраги- мова ЛМ, Полупанова ЮС, Верткин АЛ. Диабетическая автономная нейропатия: распространенность, патогенез, лечение. Русский медицинский журнал. 2005;13(20):1329-1333.

18. Ahmed AH, Shankar K, Eftekhari H, Munir M, Robertson J, Brewer A, Stupin IV, Casscells SW. Silent myocardial ischemia: Current perspectives and future directions. Exp Clin Cardiol. 2007 Winter;12(4):189-196.

19. Chyun DA, Melkus GD, Katten DM, Price WJ, Davey JA, Grey N, Heller G, Wackers FJ. The association of psychological factors, physical activity, neuropathy, and quality of life in type 2 diabetes. Biol Res Nurs. 2006 Apr;7(4):279-288.

20. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple method for the estimation of free testosterone in serium. J Clin Endocrinol Metab. 1999 Oct;84(10):3666-3672.

21. Рыбакова МК, Алехин МН, Митьков ВВ. Практическое руководство по ультразвуковой диагностике. Эхокардиография. М: Издательский дом Видар-М; 2008.

22. Беленков ЮН, Оганов РГ. Руководство по амбулаторно-поликлинической кардиологии. М: ГЭОТАР-Медиа; 2007.

23. Zweig MH., Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 1993 Apr;39(4):561-577.

24. Davis J, Goadrich M. The Relationship Between Precision-Recall and ROC Curves. Proc. Of 23 International Conference on Machine Learning, Pittsburgh, PA, 2006.

25. Александров АА. Клинические горизонты кардиопротекции: «кальциевый след» триметазидина. Consilium Medicum. 2005;7(9):757-763.