Screening Asymptomatic Diabetics for Coronary Artery Disease using Diabetic Autonomic Neuropathy as Selection Criteria

Diabetics with Autonomic Neuropathy (DAN), or disease of the involuntary nervous system, represent a population at especially high risk for cardiovascular mortality, including death from Myocardial Infarction (heart attack) and Sudden death [2]. They stand to derive a mortality benefit from surgical revascularization (a bypass operation), however due to neuropathy they often do not exhibit symptomatic angina, i.e. these patients often do not have the symptoms of cherst pain. In failing to have symptomatic coronary artery disease (CAD) they are not subject to the same diagnostic procedures that symptomatic patients undergo that are required for the diagnosis and ultimately the management of CAD, most notably a stress test [5]. We propose that screening asymptomatic diabetics, (diabetic patients without chest pain) who have autonomic neuropathy, we will identify a substantional amount of CAD, including that which may constitute a requirement for surgical revascularization. It has been previously demonstrated that Type 2 Diabetics represent a population at significantly elevated risk for cardiovascular mortality and morbidity even in the absence of established Coronary artery disease. In fact their risk of cardiovascular events has been shown to be equivalent to patients with a history of MI, a mortality of 17% over 7 years of follow-up [1], and when limited to diabetics with autonomic neuropathy this number increases to 9% mortality over a 2 year period [6]. This may represent an association with more severe and long-standing diabetes, kidney disease and/or high blood pressure, or it may be reflective of independent pathological attributes of Cardiac autonomic dysfunction. Diabetics with an anginal syndrome and 3-vessel disease, or its equivalent, have previously been shown to derive a significant mortality benefit from surgical revascularization [3]. The enrollment criteria in the previously mentioned BARI trial included symptomatic angina, which itself excludes a substantial population of Diabetics at risk for Cardiovascular mortality. Previously published reports have identified that from 36 to 65% of Diabetics with Autonomic Neuropathy have silent ischemia i.e. these patients indeed had inadequate blood flow to supply their heart muscle, but failed to perceive the pain which can serve as a warning sign. However these studies failed to correlate the results of noninvasive testing with angiography, which is considered the gold standard in the diagnosis of CAD [4]. Unfortunately the prognosis of diabetics with DAN and silent ischemia has not been clearly identified, but the limited literature that has addressed this question has found a 30% event rate at 3 years [6]. By demonstrating an increased prevalence of CAD in asymptomatic diabetic patients with DAN we can resolve the results of studies done over a period of 20 years with varying sample size and methods. This study will be part of a two-part study with the latter portion aiming to randomize diabetics with DAN to observation or noninvasive examination for CAD and ultimately angiography and revascularization if indicated. The lack of reliable knowledge of the prevalence of 3-vessel CAD in this population precludes the design of a trial to identify a mortality benefit from screening asymptomatic diabetics with DAN. Here we aim to identify an estimate of 3 vessel CAD in this patient population and show that it is significantly larger than in diabetics without DAN. Therefore we hypothesize a 15% incidence of 3-vessel CAD in this population that will be significantly increased compared to appropriately matched diabetics without DAN.