We evaluated the effectiveness of the current American Diabetes Association guidelines for the detection of coronary artery disease (CAD) in asymptomatic patients with type 2 diabetes and assessed whether a more aggressive diagnostic strategy would permit detection of silent CAD at an earlier stage. The prevalence of myocardial perfusion defects and CAD in asymptomatic diabetic patients was high independent of risk factor profile, and an aggressive diagnostic approach in patients who would normally be excluded from screening permitted identification of CAD at an earlier stage, when coronary anatomy is more likely to respond to treatment.
Type 2 diabetes mellitus is strongly associated with the development of coronary artery disease (CAD) that is often detected in an advanced stage, when major complications (ie, silent myocardial infarction [MI] or myocardial dysfunction) have already occurred. However, CAD in asymptomatic type 2 diabetes mellitus patients is commonly missed.1 When CAD is finally diagnosed, the extensive atherosclerotic involvement of the coronary arteries imposes a high mortality rate despite interventional or surgical revascularization procedures.2-4
In light of these observations, it is extremely important to detect CAD in asymptomatic type 2 diabetes mellitus patients at an early stage, when coronary anatomy is probably more favorable for revascularization and when myocardial complications have not occurred. Current American Diabetes Association (ADA) guidelines recommend stress screening for asymptomatic diabetic patients with at least 2 additional risk factors.5 This recommendation is based on the assumption that this group of type 2 diabetes mellitus patients is characterized by a high prevalence of CAD. Unfortunately, this assumption is not supported by experimental or epidemiologic studies.
The current study included a large sample of adult asymptomatic type 2 diabetes mellitus patients aged 60 years and older. Regardless of the associated risk factor profile, all patients underwent stress myocardial contrast echocardiography (MCE)6 to identify asymptomatic patients with myocardial perfusion defects. The presence of myocardial perfusion abnormalities (at rest or induced by dipyridamole [Persantine]) was considered an indication to perform selective coronary angiography.
The goal of our study was to evaluate how effective ADA guidelines are in detecting type 2 diabetes mellitus patients with no symptoms. We also evaluated whether a more aggressive diagnostic strategy would allow for the detection of silent CAD at an earlier stage, when coronary anatomy would be more likely to respond to treatment.
Patients and methods
Our study included 1899 asymptomatic patients with type 2 diabetes who were eligible to receive dipyridamole testing and had no history of CAD, valvular heart disease, or cardiomyopathy. Demographic, clinical, and hematologic baseline data were collected (Table). Considering the risk factors outlined in the ADA's 2005 position statement,7 we divided the study population into 2 groups: group A included 1170 subjects with 2 or more risk factors for CAD, and group B included 729 subjects with 1 or no risk factors. Myocardial contrast echocardiography during dipyridamole infusion and at rest was performed on all patients. At a mean of 9 days after noninvasive testing, coronary angiography was performed on patients with perfusion defects.
Table. Clinical characteristics.
SD indicates standard deviation; CAD, coronary artery disease. Adapted from
J Am Coll Cardiol.
Scognamiglio R, Negut C, Ramondo A, et al. Detection of coronary artery disease in asymptomatic patients with type 2 diabetes mellitus. 2006;47(1):65-71.
"Diffuse disease" at angiography was defined as significant stenosis (≥ 50%) in ≥ 2 epicardial vessels with lesions in ≥ 2 segments of each vessel. To compare continuous variables between groups A and B, 2-sample test was used. To identify whether risk factors and clinical characteristics were independently correlated with significant CAD at angiography, we used multivariate Cox proportional hazards regression analysis. The chi-square test was used to compare the number of coronary vessels involved by CAD and the presence of occlusion and diffuse disease between the 2 groups. A value below .05 represented statistical significance.
In the 2 study groups, the prevalence of abnormal stress MCE results (59.4% in group A vs 60% in group B; = .96) and significant CAD (64.6% in group A vs 65.5% in group B) was not significantly different, regardless of the risk factor profile. Based on multivariate analysis, no clinical characteristics were shown to independently predict that a patient would have significant CAD as shown by angiography.
The angiographic characteristics of the coronary vessels, based on whether a traditional or aggressive diagnostic approach was used, are shown in the Figure. The overall prevalence of CAD was not significantly different between the 2 groups, but coronary anatomy differed. In fact, compared with group B, group A patients had a higher prevalence of 3-vessel disease (33.3% vs 7.6%; < .001), diffuse disease (54.9% vs 18.8%; < .001), and coronary vessel occlusion (31.2% vs 3.5%; < .001). On the other hand, the prevalence of 1-vessel disease was more frequent in group B than in group A (70.6% vs 46.3%; < .001).
Figure. Coronary angiographic characteristics according to "traditional" or
"aggressive" approach to diagnosing silent coronary artery disease in asymp-
tomatic patients with type 2 diabetes.
For 187 patients in group A and 32 patients in group B, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery could not be performed because of the coronary anatomy ( < .001). One hundred seventy-eight patients in group A and 122 patients in group B underwent PCI. The rate of successful PCI was higher in group B than in group A (91% vs 84%, respectively; < .001). Coronary artery bypass graft surgery was performed in 13.3% of cases in group A and in 11.4% of cases in group B. In group A, 73.3% of patients received complete revascularization of all myocardial areas, whereas 97.2% of group B patients received complete revascularization ( < .001).
Symptoms of myocardial ischemia are often absent or atypical in diabetic patients, and CAD is frequently detected in an advanced stage, characterized by extensive atherosclerotic obstructive coronary disease. Notably, asymptomatic patients with type 2 diabetes without a prior MI have a cardiovascular survival rate similar to that of nondiabetic patients who have had a previous MI.8 Because of this high risk of CAD and the poor outcome among asymptomatic patients with type 2 diabetes, clinicians should use aggressive strategies to diagnose CAD to reduce or prevent cardiovascular morbidity and mortality in these patients.
Regardless of risk factor profile, our study showed that the prevalence of CAD and myocardial perfusion defects in asymptomatic diabetic patients is high. Using only risk factor profiles for diagnosis did not help to identify the subgroup of patients with a significantly higher prevalence of myocardial perfusion abnormalities or obstructive CAD. When an aggressive diagnostic approach was used in patients who would normally be excluded from screening by current ADA guidelines (patients with ≤ 1 risk factor for CAD),7 we found a similar prevalence of CAD but coronary vessel anatomy more likely to respond to revascularization (a higher prevalence of 1-vessel disease and a lower prevalence of occlusion, diffuse disease, and 3-vessel disease). With this diagnostic approach, the chance of achieving adequate revascularization was greatly increased. In patients assigned to a traditional diagnostic strategy, any type of revascularization was often impossible, incomplete, or unsuccessful. The actual prevalence of CAD in asymptomatic patients with diabetes mellitus is not clear, but our data seem to be in line with postmortem studies.9
Epicardial coronary stenosis, as well as microvascular disease, including hyperfibrinogenemia, abnormal myocardial capillaries and small intramural arteries, increased platelet aggregability, endothelial dysfunction, and small vessel disease, causes myocardial perfusion defects in type 2 diabetes patients.10,11 Therefore, in asymptomatic diabetic patients, the strategies used to diagnose myocardial perfusion defects may also be useful in diagnosing a coronary microvascular disease that indicates an early sign of an atherogenic process.12 A perfusion defect shown in a patient without critical epicardial stenosis should not be considered a false-positive result, but instead an early clinical marker of microvascular disease, and for this group of patients, intense, aggressive therapy might be recommended.
The subjects in this study were representative of typical type 2 diabetes patients with no cardiovascular symptoms. With an aggressive diagnostic strategy, a large number of asymptomatic type 2 diabetes patients with perfusion defects and significant CAD may be identified independently of their risk factor profile. Patients with type 2 diabetes and a low risk factor profile who may have unidentified CAD are often missed when using current ADA guidelines.5,7 In this subset of patients, with no more than 1 risk factor for CAD, abnormal MCE results represent a strong clinical indication to perform selective coronary angiography. The criterion of more than 2 associated risk factors as an indication for coronary angiography does not help to identify asymptomatic patients with a higher prevalence of CAD; instead, it is only related to more severe CAD with coronary anatomy unfavorable to successful myocardial revascularization. In addition, when results of perfusion stress testing are positive in the absence of major epicardial coronary vessel stenosis, the demonstration of myocardial perfusion abnormalities is useful because it suggests an early stage of atherogenesis in the coronary arteries, which can be addressed by aggressive medical treatment.13
The diagnostic approach we proposed in our study permits the identification of an early phase of CAD in asymptomatic diabetic patients and favorable anatomy of coronary vessels (with a high prevalence of 1-vessel disease). It also provides the potential to improve the results of revascularization procedures. Together with the previously recommended aggressive multifactorial treatment, it has the potential to reduce the rate of cardiac events in asymptomatic diabetic patients. The 5-year follow-up phase of the study, which will be completed in 2008, will give us more data about the outcome of these patients and the economic implications of this large-scale screening approach.