Luther T. Clark, MD, is chief, Division of Cardiovascular Medicine, State University of New York Downstate Medical Center, Brooklyn.

Cardiovascular disease is a leading cause of death for persons with diabetes, accounting for almost 80% of mortality in this group in the United States. Persons with diabetes are at high risk for symptomatic and asymptomatic ischemic events. Despite the large number of studies conducted to date, however, the optimal approach to evaluation and detection of asymptomatic ischemia in patients with diabetes remains a topic of continuing debate. In 1998, the American Diabetes Association issued guidelines for diagnostic testing for detection of coronary disease in patients with type 2 diabetes.^1,2 These guidelines recommended stress testing only in those asymptomatic patients with diabetes with an abnormal resting electrocardiogram, evidence of peripheral vascular disease, or 2 or more other risk factors for coronary artery disease.

The variety of noninvasive techniques currently available for detecting asymptomatic ischemia include exercise-electrocardiography, nuclear imaging, exercise stress echocardiography, and dobutamine stress echocardiography (DSE). Dobutamine stress echocardiography is widely used and accepted as an accurate and reliable noninvasive tool for diagnostic and prognostic assessment of coronary artery disease for both those with and without diabetes.

In their study “Stress echocardiography in diabetes mellitus,” Chaowalit and Pellikka evaluate the long-term prognostic value of DSE in 2349 patients with diabetes mellitus followed for up to 13.2 years. The average follow-up was 5.4 ± 2.2 years for mortality and 3.9 ± 2.7 years for morbidity. Age, failure to achieve target heart rate, and the percentage of ischemic segments were independent predictors of both morbidity and mortality. The investigators used clinical and DSE parameters to develop a model for further stratification of patients into 3 risk categories, with separate risk categories for mortality and morbidity. The 5-year survival in the 3 mortality risk categories were 70%, 57%, and 46%, and in the 3 morbidity categories were 94%, 87%, and 76%.

This is an interesting study that demonstrates the important observation that the presence, extent, and severity of inducible ischemia and inadequate chronotropic response during DSE predict unfavorable outcomes during long-term follow-up. These findings add to the known diagnostic and short-term prognostic value of DSE in the evaluation of patients with coronary artery disease. The practical utility of these findings and the incremental value provided by the risk categorization scheme, however, are unclear. Patients in each of the 3 risk categories were shown to be at very high risk and deserving of maximum intensity of risk reduction therapy, ongoing monitoring, and surveillance.

Further prospective studies of the important issue of evaluation for ischemia in asymptomatic individuals with diabetes are needed. One promising ongoing study is the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study.³ Detection of Ischemia in Asymptomatic Diabetics is a prospective study of 1123 patients with type 2 diabetes, aged 50 to 75 years, with no known or suspected coronary artery disease. Following a baseline stress myocardial perfusion imaging study, participants will be monitored for occurrence of cardiac events for up to 5 years. In the initial phase of the DIAD study, significant silent ischemia was determined to be present in 22% of asymptomatic individuals with diabetes. The ultimate significance of this finding and the relative risks of this group compared with those without silent ischemia await completion of the 5-year follow-up phase of the study, which is anticipated to be in 2007.

The take-home messages are as follows: DSE provides useful information for prediction of long-term morbidity and mortality as well as diagnostic and short-term prognosis in patients with diabetes. Risk categories can be developed by combining clinical and DSE parameters. However, these risk categories do not appear to provide incremental risk predictive value or additional information that would impact diagnostic or treatment regimens. Patients with diabetes are at high risk for development of cardiovascular events. Results of DSE and other forms of diagnostic stress testing of asymptomatic individuals with diabetes provide important clinical information, but debate continues as to which asymptomatic patients with diabetes should have these studies performed in the first place.

References
1. Consensus development conference on the diagnosis of coronary heart disease in people with diabetes: February 10-11, 1998, Miami, Florida. American Diabetes Association. Diabetes Care. 1998;21: 1551-1559.

2. Redberg RF, Greenland P, Fuster V, et al. Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group III: risk assessment in persons with diabetes. Circulation. 2002;105:e144-e152.

3. Wackers FJ, Young LH, Inzucchi SE, et al. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study. Diabetes Care. 2004;27:1954-1961.