(Journal Article): The Association of Silent Coronary Artery Disease and Metabolic Syndrome in Chinese with Type 2 Diabetes Mellitus
 
Tsai JCR, Chang DM, Chung FM, Wu JC, Shin SJ, Lee YJ (Department of Clinical Research, Ping-Tung Christian Hospital, Ping-Tung 90000, Taiwan, t3275(at)ms25.hinet.net )
 
IN: Rev Diabetic Stud 2004; 1(1):18-28
Impact Factor(s) of Rev Diabetic Stud: 0.125 (2006)

Fulltext:    HTML  PDF

ABSTRACT: OBJECTIVES: Cardiovascular diseases account for approximately 75% of the deaths that occur in patients with diabetes. Because the clinical signs of coronary artery disease (CAD) in diabetic patients are hard to detect and routine screening is costly, it would be of great benefit to try to either prevent CAD from occurring or to detect it early and provide optimal care. Therefore, we analyzed the risk factors that might predict CAD in type 2 diabetes mellitus (T2DM) patients with no classical cardiac ischemic symptoms. METHODS: Using a resting 12-lead ECG, exercise tread-mill test, or thallium myocardial scintigraphy with exercise testing and dipyridamole injection, we screened diabetic patients already enrolled in a disease management program for possible CAD. We used diagnostic coronary angiography to confirm its presence. The definition and criteria of meta-bolic syndrome we used were modified from those outlined by the WHO classification and criteria of NCEP-ATP III. RESULTS: A total of 850 T2DM patients without clinical and electrocardiographic evidence of CAD were studied. Three hundred and sixty-eight asymptomatic patients with normal resting ECG were examined by exercise ECG test or thallium scintigraphy examination. Sixty patients considered to have a strong positive test or significant thallium myocardial ischemia received a diagnostic coronary angiography. Fifty-one were found to have significant coronary artery stenosis; 9 showed no significant ischemic lesion. While gender, patients’ age, known diabetes duration, serum uric acid level, smoking status, and the presence of WHO-metabolic syndrome defined hypertension and nephropathy were associated with silent CAD, logistic regression analysis found that the only predictor of silent CAD was the pres-ence of nephropathy. The components of NCEP-ATP III-metabolic syndrome were not found to be associated with silent CAD. CONCLUSIONS: A considerable proportion of T2DM patients have silent CAD. A diabetic patient with incipient or overt nephropathy should be examined for the presence of CAD. The definition of metabolic syndrome may be modified for early detection of CAD in patients with T2DM.

REFERENCES:

1. Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA 1979. 241:2035-2038. [DOD]
2. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993. 16:434-444. [DOD]
3. Hurst RT, Lee RW. Increased incidence of coronary atherosclerosis in type 2 diabetes mellitus: mechanisms and management. Ann Intern Med 2003. 139:824-834. [DOD]
4. Haffner SM, Lehto S, Ronnemaa T, Pyorala 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. 339:229-234. [DOD]
5. Nesto RW, Zarich S. Acute myocardial infarction in diabetes mellitus: lessons learned from ACE inhibition. Circulation 1998. 97:12-15. [DOD]
6. Jacoby RM, Nesto RW. Acute myocardial infarction in the diabetic patient: pathophysiology, clinical course and prognosis. J Am Coll Cardiol 1992. 20:736-744. [DOD]
7. Koistinen MJ. Prevalence of asymptomatic myocardial ischaemia in diabetic subjects. BMJ 1990. 301:92-95. [DOD]
8. MiSAD Group. Prevalence of unrecognized silent myocardial ischaemia and its association with atherosclerotic risk factors in noninsulin-dependent diabetes mellitus. Am J Cardiol 1997. 79:134-139. [DOD]
9. American Diabetes Association. Consensus development conference on the diagnosis of coronary heart disease in people with diabetes. Diabetes Care 1998. 21:1551-1559. [DOD]
10. Gibbons RJ, Balady GJ, Beasley JW, Bricker JT, Duvernoy WF, Froelicher VF, Mark DB, Marwick TH, McCallister BD, Thompson PD Jr, et al. ACC/AHA guidelines for exercise testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). J Am Coll Cardiol 1997. 30:260-311. [DOD]
11. Brun E, Nelson RG, Bennett PH, Imperatore G, Zoppini G, Verlato G, Muggeo M. Verona Diabetes Study. Diabetes duration and cause-specific mortality in the Verona Diabetes Study. Diabetes Care 2000. 23:1119-1123. [DOD]
12. Cohn PF. Prognosis for patients with different types of silent coronary artery disease. Circulation 1987. 75(3 Pt 2):II33-35. [DOD]
13. Weiner DA, Ryan TJ, Parsons L, Fisher LD, Chaitman BR, Sheffield LT, Tristani FE. Significance of silent myocardial ischemia during exercise testing in patients with diabetes mellitus: A report from the Coronary Artery Surgery Study (CASS) Registry. Am J Cardiol 1991. 68:729-734. [DOD]
14. Multiple Risk Factor Intervention Trial Research Group. Exercise electrocardiogram and coronary heart disease mortality in the Multiple Risk Factor Intervention Trial. Am J Cardiol 1985. 55:16-24. [DOD]
15. Laukkanen JA, Kurl S, Lakka TA, Tuomainen TP, Rauramaa R, Salonen R, Eranen J, Salonen JT. Exercise-induced silent myocardial ischemia and coronary morbidity and mortality in middle-aged men. J Am Coll Cardiol 2001. 38:72-79. [DOD]
16. Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z. Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. J Clin Invest 1985. 75:809-817. [DOD]
17. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991. 14:173-194.
18. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001. 24:683-689. [DOD]
19. Olijhoek JK, Van Der Graaf Y, Banga JD, Algra A, Rabelink TJ, Visseren FL for the SMART Study Group. The metabolic syndrome is associated with advanced vascular damage in patients with coronary heart disease, stroke, peripheral arterial disease or abdominal aortic aneurysm. Eur Heart J 2004. 25:342-348. [DOD]
20. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988. 37:1595-1607. [DOD]
21. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998. 15:539-553. [DOD]
22. Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Executive summary of the 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). JAMA 2001. 285:2486-2497. [DOD]
23. Lee YJ, Tsai JC. ACE gene insertion/deletion polymorphism associated with 1998 World Health Organization definition of metabolic syndrome in Chinese type 2 diabetic patients. Diabetes Care 2002. 25:1002-1008. [DOD]
24. Lee YJ, Chang DM, Tsai JC. Association of a 27-bp repeat polymorphism in intron 4 of endothelial constitutive nitric oxide synthase gene with serum uric acid levels in Chinese subjects with type 2 diabetes. Metabolism 2003. 52:1448-1453. [DOD]
25. Tan MS, Chang SY, Chang DM, Tsai JC, Lee YJ. Association of resistin gene 3'-untranslated region +62G-->A polymorphism with type 2 diabetes and hypertension in a Chinese population. J Clin Endocrinol Metab 2003. 88:1258-1263. [DOD]
26. World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Report of a WHO consultation, 1999.
27. Taskinen MR, Lahdenpera S, Syvanne M. New insights into lipid metabolism in non-insulin-dependent diabetes mellitus. Ann Med 1996. 28:335-340. [DOD]
28. Nesto RW, Watson FS, Kowalchuk GJ, Zarich SW, Hill T, Lewis SM, Lane SE. Silent myocardial ischemia and infarction in diabetics with peripheral vascular disease: assessment by dipyridamole thal-lium-201 scintigraphy. Am Heart J 1990. 120:1073-1077. [DOD]
29. Holley JL, Fenton RA, Arthur RS. Thallium stress testing does not predict cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. Am J Med 1991. 90:563-570. [DOD]
30. Inoguchi T, Yamashita T, Umeda F, Mihara H, Nakagaki O, Takada K, Kawano T, Murao H, Doi T, Nawata H. High incidence of silent myocardial ischemia in elderly patients with non insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 2000. 47:37-44. [DOD]
31. Earle KA, Mishra M, Morocutti A, Barnes D, Stephens E, Chambers J, Viberti GC. Microalbuminuria as a marker of silent myocardial ischaemia in IDDM patients. Diabetologia 1996. 39:854-856. [DOD]
32. Rutter MK, McComb JM, Brady S, Marshall SM. Silent myocardial ischemia and microalbuminuria in asymptomatic subjects with non-insulin-dependent diabetes mellitus. Am J Cardiol 1999. 83:27-31. [DOD]
33. Mykkanen L, Kuusisto J, Pyorala K, Laakso M. Cardiovascular disease risk factors as predictors of type 2 (non-insulin-dependent) diabetes mellitus in elderly subjects. Diabetologia 1993. 36:553-559. [DOD]
34. Gazzaruso C, Garzaniti A, Giordanetti S, Falcone C, De Amici E, Geroldi D, Fratino P. Assessment of asymptomatic coronary artery disease in apparently uncomplicated type 2 diabetic patients: a role for lipoprotein(a) and apolipoprotein(a) polymorphism. Diabetes Care 2002. 25:1418-1424. [DOD]
35. Airaksinen KE. Early diagnosis of silent coronary artery disease in diabetic sub-jects—are intense efforts worth while? Swiss Med Wkly 2001. 131:425-426. [DOD]
36. Heart Outcomes Prevention Evaluation Study Investiga-tors. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000. 355:253-259. [DOD]
37. Kendall MJ, Lynch KP, Hjalmarson A, Kjekshus J. Beta-blockers and sudden cardiac death. Ann Intern Med 1995. 123:358-367. [DOD]
38. Pyorala K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care 1997. 20:614-620. [DOD]
39. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003. 348:383-393. [DOD]
40. O'Malley PG, Feuerstein IM, Taylor AJ. Impact of electron beam tomography, with or without case management, on motivation, behavioral change, and cardiovascular risk profile: a randomized controlled trial. JAMA 2003. 289:2215-2223. [DOD]
41. Deckert T, Yokoyama H, Mathiesen E, Ronn B, Jensen T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen JS. Cohort study of predictive value of urinary albumin excretion for atherosclerotic vascular disease in patients with insulin dependent diabetes. BMJ 1996. 312:871-874. [DOD]
42. Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Intern Med 1997. 157:1413-1418. [DOD]
43. Rutter MK, Wahid ST, McComb JM, Marshall SM. Significance of silent ischemia and microalbuminuria in predicting coronary events in asymptomatic patients with type 2 diabetes. J Am Coll Cardiol 2002. 40:56-61. [DOD]
44. Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes 1983. 32 Suppl 2:64-78. [DOD]
45. Yudkin JS, Forrest RD, Jackson CA. Microalbuminuria as predictor of vascular disease in non-diabetic subjects. Islington Diabetes Survey. Lancet 1988. 2:530-533. [DOD]
46. Bigazzi R, Bianchi S, Baldari D, Campese VM. Microalbuminuria predicts cardiovascular events and renal insufficiency in patients with essential hypertension. J Hypertens 1998. 16:1325-1333. [DOD]
47. Jensen JS, Feldt-Rasmussen B, Strandgaard S, Schroll M, Borch-Johnsen K. Arterial hypertension, microalbuminuria, and risk of ischemic heart disease. Hypertension 2000. 35:898-903. [DOD]
48. Borch-Johnsen K, Feldt-Rasmussen B, Strandgaard S, Schroll M, Jensen JS. Urinary albumin excretion. An independent predictor of ischemic heart disease. Arterioscler Thromb Vasc Biol 1999. 19:1992-1997.
49. Jensen JS. Renal and systemic transvascular albumin leakage in severe atherosclerosis. Arterioscler Thromb Vasc Biol 1995. 15:1324-1329. [DOD]
50. Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 1989. 32:219-226. [DOD]
51. Valensi P, Sachs RN, Harfouche B, Lormeau B, Paries J, Cosson E, Paycha F, Leutenegger M, Attali JR. Predictive value of cardiac autonomic neuropathy in diabetic patients with or without silent myocardial ischemia. Diabetes Care 2001. 24:339-343. [DOD]
52. Airaksinen KE. Silent coronary artery disease in diabetes—a feature of autonomic neuropathy or accelerated atherosclerosis? Diabetologia 2001. 44:259-266. [DOD]
53. Airaksinen KE, Koistinen MJ. Association between silent coronary artery disease, diabetes, and autonomic neuropathy. Fact of fallacy? Diabetes Care 1992. 15:288-292. [DOD]
54. Gazzaruso C, Garzaniti A, Giordanetti S, Falcone C, Fratino P. Silent coronary artery disease in type 2 diabetes mellitus: the role of Lipoprotein(a), homocysteine and apo(a) polymorphism. Cardiovasc Diabetol 2002. 1:5.