Effect of autonomic nervous system dysfunction on the circadian pattern of myocardial ischemia in diabetes mellitus

Institute for the Prevention of Cardiovascular Disease, Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215.

OBJECTIVES. The aim of this study was to determine the prevalence and characteristics of ambulatory myocardial ischemia in patients with diabetes mellitus and to delineate the relation between the presence and severity of autonomic nervous system dysfunction and the incidence and time of onset of myocardial ischemia. BACKGROUND. Conflicting data exist with regard to the circadian pattern of myocardial infarction and other cardiovascular events, such as ambulatory ischemia, in diabetes. METHODS. We performed ambulatory electrocardiographic monitoring in 60 patients with diabetes and coronary artery disease. Autonomic nervous system testing was performed in a subgroup of 25 patients with myocardial ischemia after discontinuation of all antianginal medications. RESULTS. Thirty-eight of 60 patients had evidence of ambulatory ischemia; 91% of all ischemic episodes were asymptomatic. The 25 patients with ambulatory ischemia who underwent autonomic nervous system testing had a peak incidence of ischemia between 6 AM and noon (46 of 133 ischemic episodes, p < 0.007), compared with the other three 6-h periods. Fifteen of the 25 patients had no or mild autonomic nervous system dysfunction and demonstrated a similar peak incidence of ischemia between 6 AM and noon (p = 0.0009). However, the 10 patients with moderate to severe autonomic nervous system dysfunction did not experience a morning peak of ischemia, and the number of ischemic episodes was distributed evenly throughout the day (p = 0.4). CONCLUSIONS. Silent ischemia is highly prevalent among patients with diabetes and coronary artery disease. Time of onset of ischemia in diabetic patients follows a circadian distribution, with a peak incidence in the morning hours. However, patients with significant autonomic nervous system dysfunction did not demonstrate such a peak, suggesting that alterations in sympathovagal balance may have an effect on the circadian pattern of cardiovascular events.

This article has been cited by other articles:

				A. H. Lauruschkat, B. Arnrich, A. A. Albert, J. A. Walter, B. Amann, U. P. Rosendahl, T. Alexander, and J. Ennker Prevalence and Risks of Undiagnosed Diabetes Mellitus in Patients Undergoing Coronary Artery Bypass Grafting Circulation, October 18, 2005; 112(16): 2397 - 2402. [Abstract] [Full Text] [PDF]

				J. S. Rana, K. J. Mukamal, J. P. Morgan, J. E. Muller, and M. A. Mittleman Circadian Variation in the Onset of Myocardial Infarction: Effect of Duration of Diabetes Diabetes, June 1, 2003; 52(6): 1464 - 1468. [Abstract] [Full Text] [PDF]

				A. I. Vinik, R. E. Maser, B. D. Mitchell, and R. Freeman Diabetic Autonomic Neuropathy Diabetes Care, May 1, 2003; 26(5): 1553 - 1579. [Abstract] [Full Text] [PDF]

				F. B. Sozzi, A. Elhendy, J. R.T.C. Roelandt, R. T. van Domburg, A. F.L. Schinkel, E. C. Vourvouri, J. J. Bax, J. De Sutter, A. Borghetti, and D. Poldermans Prognostic Value of Dobutamine Stress Echocardiography in Patients With Diabetes Diabetes Care, April 1, 2003; 26(4): 1074 - 1078. [Abstract] [Full Text] [PDF]

				P. N. Ruygrok, M. W.I. Webster, V. de Valk, G.-A. van Es, J. A. Ormiston, M.-A. M. Morel, and P. W. Serruys Clinical and Angiographic Factors Associated With Asymptomatic Restenosis After Percutaneous Coronary Intervention Circulation, November 6, 2001; 104(19): 2289 - 2294. [Abstract] [Full Text] [PDF]

				P. A. Carson, C. M. O'Connor, A. B. Miller, S. Anderson, R. Belkin, G. W. Neuberg, J. H. Wertheimer, D. Frid, A. Cropp, and M. Packer Circadian rhythm and sudden death in heart failure: Results from prospective randomized amlodipine survival trial J. Am. Coll. Cardiol., August 1, 2000; 36(2): 541 - 546. [Abstract] [Full Text] [PDF]

				J W Sayer, B Marchant, S V Gelding, J A Cooper, and A D Timmis Autonomic dysfunction is related to impaired pancreatic beta cell function in patients with coronary artery disease Heart, February 1, 2000; 83(2): 210 - 216. [Abstract] [Full Text]

				R. W. Nesto and S. Zarich Acute Myocardial Infarction in Diabetes Mellitus : Lessons Learned From ACE Inhibition Circulation, January 13, 1998; 97(1): 12 - 15. [Full Text] [PDF]

				T. B. Investigators Influence of Diabetes on 5-Year Mortality and Morbidity in a Randomized Trial Comparing CABG and PTCA in Patients With Multivessel Disease : The Bypass Angioplasty Revascularization Investigation (BARI) Circulation, September 16, 1997; 96(6): 1761 - 1769. [Abstract] [Full Text]

				M. Chiariello and C. Indolfi Silent Myocardial Ischemia in Patients With Diabetes Mellitus Circulation, June 15, 1996; 93(12): 2089 - 2091. [Full Text]

				E. Braunwald Morning Resistance to Thrombolytic Therapy Circulation, March 1, 1995; 91(5): 1604 - 1606. [Full Text]