© American Diabetes Association ®, Inc., 2006
Screening for Coronary Disease in Diabetes: When and How
IN BRIEF Coronary atherosclerosis and silent ischemia are highly prevalent in patients with diabetes. Identification of subclinical atherosclerosis and ischemia in asymptomatic patients with diabetes is valuable for risk stratification and for guiding therapy. This article reviews methods of screening and proposes how to implement them in practice.
Cardiovascular disease is the leading cause of death in patients with diabetes, accounting for as many as 80% of deaths in these patients.1 The risk of myocardial infarction (MI) in patients with diabetes is similar to that of patients without diabetes who have had a previous MI.2 Autopsy studies have identified a high prevalence of coronary atherosclerosis in patients with diabetes, even among those without clinical coronary heart disease (CHD). Goraya et al.3 found advanced coronary lesions in nearly three-fourths of individuals with diabetes who did not have clinically apparent CHD; > 50% of asymptomatic individuals had multivessel disease. The prevalence of coronary calcification is similar in asymptomatic individuals with type 2 diabetes and individuals without diabetes who have symptomatic CHD.4 Hence, diabetes is considered to be a "CHD equivalent."5 Furthermore, the prevalence of silent ischemia among asymptomatic individuals with diabetes is high, ranging from 20 to > 50% of patients.6,7 The question thus arises as to whether asymptomatic patients with diabetes should be screened for CHD and, if so, when and by which modality.
If we approach all patients with diabetes as if they have already been diagnosed with CHD, what is the rationale for trying to detect the presence of CHD? The reason is that there are important prognostic, management, and therapeutic implications from identifying CHD in patients with diabetes. Patients with diabetes and CHD carry a significantly worse prognosis than those a with diabetes who do not have CHD.2 In addition to risk stratification, detecting CHD may improve patient motivation to adhere to medical therapy.8 From a management perspective, patients with highrisk characteristics on testing for ischemia may belong to a subset that would benefit from coronary angiography and revascularization. With regard to medical therapy, the knowledge that a patient with diabetes has CHD may indicate the need to initiate or intensify pharmacological therapy with ß-blockers (if ischemia is present), statins, or ACE inhibitors. Current National Cholesterol Education Program guidelines recommend an LDL cholesterol goal of < 100 mg/dl for patients with diabetes without CHD; if CHD is present, the LDL goal is < 70 mg/dl.9 Not all patients with diabetes are considered candidates for ACE inhibitor therapy; those with CHD should be treated with these agents.10 Hence, detecting CHD with or without ischemia helps refine the management of asymptomatic patients with diabetes.
Existing guidelines for screening Guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) and the American Diabetes Association (ADA) recommend graded exercise testing in asymptomatic patients with diabetes who plan to begin a moderate- to highintensity exercise program and are at increased risk for CHD based on one or more of the following factors: age > 35 years, age > 25 years and type 2 diabetes of > 10 years' duration or type 1 diabetes of > 15 years' duration, any additional risk factors for CHD, and the existence of microvascular disease, such as proliferative retinopathy or nephropathy (including microalbuminuria), autonomic neuropathy, or peripheral vascular disease.11,12 The greater the number of risk factors, the higher the pretest probability, thus increasing the likelihood that screening will result in useful prognostic information. The diagnostic accuracy of stress testing is improved when combined with imaging. The ACC Foundation and American Society of Nuclear Cardiology have deemed it appropriate to perform single-photon emission computed tomography (SPECT) myocardial perfusion imaging for asymptomatic individuals with diabetes.13 It is also considered appropriate to repeat a SPECT study in patients with diabetes at least 2 years after a previously normal SPECT study.
Exercise treadmill testing In another study of asymptomatic, higher-risk patients with diabetes, Bacci et al.15 found the positive predictive accuracy of the exercise treadmill test to be 79%. Those with false-negative tests tended to have a longer duration of diabetes and a higher prevalence of peripheral vascular disease.
Nuclear stress imaging
Rajagopalan et
al.18 examined the
relationship of ischemia by SPECT with angiographic findings and total
mortality in 1,427 asymptomatic patients with diabetes who did not have known
CHD. The average age of subjects was 60 years, and the median duration of
diabetes was 10 years. Eighteen percent had high-risk stress SPECT results,
defined as a summed stress score De Lorenzo et al.19 also evaluated the utility of SPECT imaging in screening asymptomatic subjects with diabetes. One hundred and eighty asymptomatic patients with diabetes underwent 2-day stress SPECT testing and were followed for 36 ± 18 months. Twenty-six percent of patients had perfusion defects, and clinical variables were not associated with the type of defect or subsequent events. "Hard" events were defined as MI or death due to a cardiac cause; "total" events included MI, cardiac death, or revascularization. Two percent of hard events and 5% of total events per year occurred in patients who had a normal SPECT. By comparison, these numbers increased to 9% of hard events and 38% of total events in those with an abnormal SPECT. Thus, the presence of an abnormal SPECT test in these asymptomatic patients seemed to provide added prognostic value over clinical predictors alone. In a multicenter cohort consisting of 370 asymptomatic patients with diabetes who also had at least two additional cardiac risk factors, Valensi et al.20 identified silent ischemia in 35% of patients using stress SPECT imaging as well as electrocardiographic stress testing. These patients were followed for 38 ± 23 months, with a significant association found between positive stress results and subsequent cardiac events. The prevalence of silent ischemia was 43% among patients > 60 years of age versus 30% in patients < 60 years of age. Interestingly, the association between the presence of silent ischemia and subsequent cardiac events was statistically significant in the patients > 60 years old but not in those < 60 years old.
Stress echocardiography Elhendy et al.22 followed 563 patients with diabetes who also had known or suspected CAD and had undergone exercise stress echocardiography over a median follow-up period of 3 years. Event rates were not well predicted by prior angina or stress-induced angina. Patients with multiple wall motion abnormalities had the highest event rates, and echocardiographic abnormalities in a multivessel distribution during exercise provided prognostic information beyond that afforded by clinical and exercise data alone. Conversely, patients with a normal exercise echocardiogram had no events at 2 years. The event rate increased to 7.6% at 5 years, suggesting that, as with nuclear stress testing, the frequency of such stress testing should be in the range of every 2-3 years for the reassessment of risk in patients with diabetes.
Most MIs originate from atherosclerotic plaque that is not obstructive and therefore would not be detected by a test for myocardial ischemia.23 In addition, patients with diabetes and a normal SPECT have a higher event rate than patients without diabetes who have a normal SPECT.24 These facts provide the rationale to search noninvasively for the presence of subclinical atherosclerosis. The two imaging modalities most commonly evaluated for this purpose are coronary artery calcium (CAC) scanning and measurement of carotid intimamedia thickness (cIMT).
CAC
In a study by Raggi et
al.,28 10,377
asymptomatic patients (903 of whom had type 2 diabetes) were followed for a
mean of 5 years after undergoing CAC screening. The primary end point of the
study was all-cause mortality. On average, patients with diabetes had a higher
CAC score than patients without diabetes, and for every increase in CAC score,
there was a greater increase in mortality for subjects with diabetes than for
those without. Notably, patients both with and without diabetes who were found
to have no coronary calcification had a low risk of death (
cIMT Few prospective studies exist using cIMT measurements to predict cardiac events in patients with diabetes. Yamasaki et al.35 followed 287 patients with type 2 diabetes for 3 years and determined that baseline cIMT independently predicted nonfatal CHD events.
Identification of subclinical atherosclerosis and ischemia in asymptomatic patients with diabetes is worthwhile for risk stratification and for guiding therapy. Current guidelines fail to identify an unacceptably large proportion of patients, yet evidence is not currently sufficient to define the optimal screening strategy for asymptomatic patients with diabetes in terms of clinical and cost-effectiveness outcomes. In the absence of such evidence, we propose an approach, based on our synthesis of the current evidence, to identify more highrisk individuals in a presymptomatic phase (Figure 1). We acknowledge that further research is needed to define the optimal approach.
We recommend that patients with type 1 or type 2 diabetes who are
Subclinical atherosclerosis and silent ischemia in asymptomatic patients with diabetes is common. Screening patients according to traditional risk factors and current guidelines alone will frequently fail to identify CHD, thus losing the opportunity for early diagnosis and intensified management. A more aggressive approach to identifying asymptomatic coronary disease should therefore be considered in this patient population.
Yasmine S. Ali, MD, is a fellow in cardiovascular medicine, and David J. Maron, MD, is an associate professor of medicine in the Division of Cardiovascular Medicine at Vanderbilt University Medical Center in Nashville, Tenn. Note of disclosure: Dr. Maron is an employee of and stockholder in Cardiovascular Services of America, which provides outpatient cardiac catheterization and computed tomography angiography services.
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