F.E., a 54-year-old man with a history of type 2 diabetes, hypertension, and Reiter’s syndrome with prior hospitalizations for pneumonia and sepsis presented to the hospital emergency room complaining of chest pain, weakness, and fatigue. His chest pain was pleuritic in nature, worsening with movement and deep breathing. When he was motionless, the pain completely resolved.

F.E.’s electrocardiogram showed Q waves in leads II, III, and aVF, a new right bundle branch block, and mild ST segment elevation in leads V4 through V6. An urgent echocardiogram was ordered to differentiate between pericarditis and ischemia. The echocardiogram showed marked motion abnormalities in the inferior posterior, lateral wall. An initial troponin I was 238 ng/ml (normal range 0–2.5 ng/ml).

The patient was taken for emergent cardiac catheterization. This demonstrated an occluded right coronary artery that was opened with primary angioplasty and stent placement.

  1. Is silent ischemia or atypical presentation of myocardial ischemia more common in diabetes?

  2. What other disease states may predispose to the development of atypical chest pain syndromes?

  3. What is the proposed mechanism for atypical or silent ischemia in diabetes?

  4. Which patients with diabetes should undergo myocardial assessment?

Manifestations of coronary artery disease (CAD) include overt, typical chest pain syndromes, atypical symptomatic ischemia, and asymptomatic or unnoticed ischemia. Previously unrecognized CAD may become apparent with abnormalities on a resting electrocardiogram including electrocardiographic left ventricular hypertrophy, nonspecific ST and T wave abnormalities, Q waves and interventricular conduction delays including bundle branch block. Silent CAD may also be recognized during an asymptomatic positive stress test.

For several years, it has been postulated that people with diabetes have a higher prevalence of asymptomatic or atypical CAD. The literature is far from clear on this point. What appears undeniable is that diabetes is an independent risk factor for the development of early CAD. In addition, the diagnosis of type 2 diabetes carries with it an increased risk of abnormal lipid profiles and hypertension (Syndrome X), both of which are independent risk factors for CAD. People with type 1 diabetes often lack other associated risk factors for atherosclerosis. Duration of diabetes seems to be the predominant predictor of CAD in these patients.

Silent myocardial ischemia was examined in the Framingham study.1 In this cohort of 5,209 men and women, unrecognized anterior and inferior myocardial infarctions (MIs) were established by comparing biennial electrocardiograms.

More than 25% of all MIs in the Framingham cohort were discovered retrospectively, only after clear evidence of myocardial damage was noted on these routine electrocardiograms. Of these unrecognized MIs, 48% in men and 46% in women were actually silent. The remaining unrecognized MIs were so atypical that neither the patient nor the attending physician entertained MI as a possible diagnosis.

Women had a higher incidence of unrecognized infarction than men (35 vs. 28%) at all age levels. Hypertension was the only CAD risk factor, in both men and women, that was statistically correlated with unrecognized MI. This was a consistent finding even after excluding those patients with coexisting diabetes. In the cohort with diabetes, MI was unrecognized in 39% of men, a clear excess. In women, only 17% of the MIs were unrecognized, less than half the rate noted in the nondiabetic population. The authors offered no theory for these divergent findings.

Other studies have demonstrated an increased incidence of unrecognized CAD in patients with diabetes. In a case-control study, 41 of 132 patients with diabetes and 42 of 140 control subjects matched for age, sex, and risk factors other than diabetes, were noted to have electrocardiographic stress test evidence of myocardial ischemia.2 To rule out possible false-positive stress tests, 36 of the 41 patients with diabetes and 34 of 42 control patients underwent coronary angiography. This demonstrated significant coronary narrowing in 39% of those with diabetes and in only 18% of the control subjects (P < 0.05). Other studies have demonstrated similar correlations between diabetes and silent or atypical ischemia.

Autonomic and sensory dysfunction have been postulated as possible mechanisms for unrecognized ischemia in patients with diabetes. A case-control study involving 32 diabetic patients and 36 control subjects, all with typical anginal symptoms, tested this hypothesis by studying the anginal perceptual threshold, defined as the time from onset of 0.1 mV ST segment depression to the onset of anginal symptoms during treadmill stress testing.3 The results indicated that the perception of angina was significantly (P < 0.001) delayed in patients with diabetes compared to the control group, despite the fact that ST segment depression occurred earlier in the diabetic group. Further studies on patients with diabetes demonstrated significant autonomic dysfunction in the heart rate response to Valsalva and deep breathing, which were directly correlated with increased anginal perceptual threshold.

  1. Atypical or silent presentations of CAD may be more frequent in patients with diabetes.

  2. Comorbid states such as hypertension may predispose patients with diabetes to a higher incidence of atypical or silent myocardial ischemia.

  3. Autonomic dysfunction may in part explain altered anginal perception in diabetes.

  4. The American Diabetes Association 1998 consensus statement on Diagnosis of Coronary Heart Disease in People With Diabetes4 recommended the following indications for cardiac stress testing:

      A. Typical or atypical cardiac symptoms

      B. Resting electrocardiograph suggestive of ischemia or infarction

      C. Peripheral or carotid occlusive arterial disease

      D. Sedentary lifestyle, age >35 years, and plans to begin a vigorous exercise program

      E. Two or more of the risk factors listed below in addition to diabetes

        1. Total cholesterol >240 mg/dl, LDL cholesterol >160 mg/dl, or HDL cholesterol <35 mg/dl

        2. Blood pressure >140/90 mmHg

        3. Smoking

        4. Family history of premature CAD

        5. Positive micro/macroalbuminuria test

Craig D. Wittlesey, MD, is co-director of the Central Washington Providence Diabetes Care Center in Wapato, Wash.

Kannel WB: Silent myocardial ischemia and infarction: insights from the Framingham Study.
Cardiol Clin
Naka M, Hiramatsu K, Aizawa T, Momose A, Yoshizawa K, Shigematsu S, Ishihara F, Niwa A, Yamada T: Silent myocardial ischemia in patients with non-insulin-dependent diabetes mellitus as judged by treadmill exercise testing and coronary angiography.
Am Heart J
Gamini A, Kopelman P, Ingram D, Swash M, Mills P, Timmis A: Exertional myocardial ischemia in diabetes.
Am Coll Cardiol
American Diabetes Association: Diagnosis of coronary heart disease in people with diabetes (Consensus Statement).
Diabetes Care