Predictive Value of Cardiac Autonomic Neuropathy in Diabetic Patients With or Without Silent Myocardial Ischemia

OBJECTIVE: The aim of this study was to determine the predictive value of silent myocardial ischemia (SMI) and cardiac autonomic neuropathy (CAN) in asymptomatic diabetic patients. RESEARCH DESIGN AND METHODS: We recruited 120 diabetic patients with no history of myocardial infarction or angina, a normal 12-lead electrocardiogram (ECG), and two or more additional risk factors. SMI assessment was carried out by means of an ECG stress test, a thallium-201 myocardial scintigraphy with dipyridamole, and 48-h ECG monitoring. CAN was searched for by standardized tests evaluating heart rate variations. Accurate follow-up information for 3-7 years (mean 4.5) was obtained in 107 patients. RESULTS: There was evidence of SMI in 33 patients (30.7%). CAN was detected in 33 of the 75 patients (38.9%) who were tested, and a major cardiac event occurred in 11 of them. Among these 75 patients, the proportion of major cardiac events in the SMI+ patients was not significantly higher than that in the SMI- patients (6 of 25 vs. 5 of 50 patients), whereas it was significantly higher in the CAN+ patients than in the CAN- patients (8 of 33 vs. 3 of 42 patients; P = 0.04), with a relative risk of 4.16 (95% CI 1.01-17.19) and was the highest in the patients with both SMI and CAN (5 of 10 patients). After adjusting for SMI, there was a significant association between CAN and major cardiac events (P = 0.04). CONCLUSIONS: In asymptomatic diabetic patients, CAN appears to be a better predictor of major cardiac events than SMI. The risk linked to CAN appears to be independent of SMI and is the highest when CAN is associated with SMI.