Risk stratification in diabetic patients: a continuing challenge.

Our current paradigm for treating coronary artery disease (CAD) focuses on improving symptom status and correctly risk stratifying patients. Patients with severe symptoms, especially those with symptoms refractory to medical therapy, are candidates for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) to enhance quality of life. This issue generally does not apply to patients who are asymptomatic or have only mild symptoms (acknowledging that some patients who are mildly symptomatic will become asymptomatic following successful PCI or CABG). In these patients, the major issue to address is accurate risk stratification. The identification of any CAD can determine the intensity of treatment of risk factors, and the identification of severe (left main or 3-vessel) CAD can lead to consideration of CABG for improving survival. Selected subsets of patients who can be identified as those with higher risk on the basis of simple clinical characteristics theoretically might benefit from more aggressive risk stratification. Patients with diabetes represent such a higher-risk patient subset. Some form of heart disease or stroke accounts for 65% of deaths in diabetic patients. The CAD mortality rates in diabetics without clinically evident CAD have been reported to be as high as mortality rates in non-diabetics with established CAD, leading to the designation of diabetes as a ‘‘CAD risk equivalent.’’ In 2000, there were an estimated 171 million patients with diabetes worldwide, and this number is projected to increase to 366 million by the year 2030. Performing accurate risk stratification in asymptomatic or mildly symptomatic diabetic patients is an important health priority. Several studies applying a retrospective approach have examined the value of screening stress single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) in primarily asymptomatic diabetic patients. These studies reported a high yield of abnormal tests, ranging between 25% and 50%. SPECT MPI has also been shown to risk stratify these populations. However, a concern that has emerged from stress imaging studies in patients with diabetes (symptomatic or asymptomatic) is the inability to identify a true low-risk population. Annual cardiac death or myocardial infarction (MI) rates in retrospective studies of diabetic patients with normal or low-risk SPECT MPI scans were in the range of 2-3%, higher than the average annual hard event rate of 0.6% reported in general patient populations with normal or low-risk images. The Detection of Ischemia in Diabetics (DIAD) study represents the only prospective study designed to examine the nonselective application of stress SPECT MPI in asymptomatic diabetic patients. In contrast to the retrospective studies, patients enrolled in DIAD represented a substantially ‘‘healthier’’ population of asymptomatic diabetic patients. Only 16% of the patients randomized to the imaging arm had abnormal SPECT MPI, including just 1% with defects [10% of the left ventricle. The DIAD 5-year outcome has been recently published. The annual hard cardiac event rate was surprisingly low at 0.69%. Despite the low event rate, stress SPECT MPI was able to risk stratify the population. The only other large prospective study to screen asymptomatic diabetic patients for CAD using stress SPECT MPI was performed by Anand et al. Their study design employed a step-wise strategy, whereby all the patients underwent CT calcium scoring followed by stress SPECT MPI in those with Agatston From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN and Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA. Disclosures for Dr. Todd Miller: I receive research grants from Lantheus Medical Imaging and Molecular Insight Pharmaceuticals and have consulting agreements with TherOx, Inc. and The Medicines Company. Disclosures for Dr. Leslee J. Shaw: I receive research grants from GE Healthcare and Bracco Diagnostics, Inc. Received for publication Feb 11, 2009; final revision accepted Feb 11, 2009. Reprint requests: Todd D. Miller, MD, Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Gonda 5, 200 First Street SW, Rochester, MN 55905; miller.todd@mayo.edu. J Nucl Cardiol 2009;16:486–9. 1071-3581/$34.00 Copyright 2009 by the American Society of Nuclear Cardiology. doi:10.1007/s12350-009-9070-4