Silent myocardial ischemia (SMI) is common in patients with diabetes (1–4). The prognostic value of SMI, evidenced by exercise electrocardiogram (ECG) stress test (5) and thallium 201 myocardial scintigraphy (6), as well as their association (7) in asymptomatic diabetic patients, has recently been demonstrated. About 50% of the patients with SMI exhibit angiographically normal coronary arteries (1,2). In these patients, endothelial dysfunction and abnormalities of coronary microcirculation may be involved (8). So far, the respective roles played by these functional disorders, by the demonstrated silent coronary stenoses, or by both in the poor prognosis of SMI are still unknown.
The aim of this study was to determine the prognostic value of silent coronary stenoses in patients with diabetes. We prospectively recruited 362 asymptomatic patients with diabetes, without prior myocardial infarction, with at least one additional risk factor, and with a normal resting ECG. All of them underwent a myocardial scintigraphy after an exercise or a pharmacological (dipyridamole infusion) stress test to detect SMI. The patients with SMI subsequently underwent a coronary angiography to detect coronary stenosis, as previously reported (2). A total of 345 (95.3%) patients were followed-up for 41 ± 24 months (mean ± SD) with regard to the occurrence of major cardiac events (death of cardiac origin, myocardial infarction, unstable angina, heart failure, and secondary need for coronary revascularization).
The diabetic patients (190 men and 172 women, 10 type 1 and 352 type 2 diabetes) were 58.5 ± 9.1 years of age. The prevalence of peripheral or carotid occlusive arterial disease was 6%. There was evidence of SMI in 121 (33.4%) patients. A coronary angiography was performed in 92 subjects (44 had significant coronary stenoses [>70%]). A major cardiac event occurred in 23 patients (3 cardiac deaths, 11 myocardial infarctions, 5 unstable angina, 3 congestive heart failures, and 1 noninitial revascularisation procedure). The rate of silent coronary stenoses was significantly higher in the patients with major cardiac events than in those without (13/23 [57%] vs. 29/322 [9%]), with an odds ratio of 13.1 (95% CI 5.3–32.6, P < 0.001). SMI (3.6 [1.5–8.5], P = 0.003) and peripheral or carotid occlusive arterial disease (3.8 [1.1–12.3], P = 0.049) were less strong predictors of major cardiac events. The traditional cardiovascular risk factors, even combined, were not predictive of major cardiac events. According to the Kaplan-Meier analysis, a major cardiac event occurred in 30.9% of the patients with SMI and coronary stenoses, 1.4% of the patients with SMI but without coronary stenosis, and 4.0% of the patients without SMI (log rank 42.5, P < 0.0001) (Fig. 1).
This study shows for the first time that 1) the presence of silent coronary stenoses with SMI is the main predictive factor for subsequent major cardiac events in diabetic patients and 2) patients with a normal myocardial scintigraphy and those with an abnormal scintigraphy but without coronary stenosis have a close prognosis.
Kaplan-Meier survival curves for the occurrence of major cardiac events according to the absence or presence of SMI or silent coronary stenoses (CS). Log rank 42.5, P < 0.0001.
Kaplan-Meier survival curves for the occurrence of major cardiac events according to the absence or presence of SMI or silent coronary stenoses (CS). Log rank 42.5, P < 0.0001.
References
Address correspondence to Dr. Emmanuel Cosson, Department of Endocrinology-Diabetology-Nutrition, Hôpital Jean Verdier, Avenue du 14 Juillet, 93143 Bondy Cedex, France. E-mail: [email protected].
