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Objectives: The objectives of this study were 1) to determine the relationship between the amount of exercise-induced ischemic myocardium and the presence or absence of chest pain and ST segment depression, and 2) to define the incidence and characteristics of "truly silent ischemia," that is, ischemia that is not manifested by symptoms or electrocardiographic (ECG) findings., Background: There are no prior data relating ischemia to chest pain and ST depression. Thallium-201 imaging studies have evaluated perfusion but not ischemia. In contrast, supine bicycle stress echocardiography demonstrates exercise-induced ischemic dysfunction., Methods: Supine bicycle stress echocardiography and arteriography were performed in 130 patients and the severity and geographic extent of ischemic myocardium were compared in three groups. On exercise, Group I patients had both chest pain and ST segment depression (symptomatic ischemia), Group II patients ST depression without chest pain (asymptomatic ischemia) and Group III patients had neither chest pain nor ST depression (truly silent ischemia)., Results: There were no differences among groups in arteriographic characteristics. The incidence of "truly silent ischemia" was 43%. The number of abnormally contracting ischemic segments, average score per segment and sum of scores were virtually identical in Groups I and II and significantly greater than in Group III for the patients (p < 0.01 to < 0.0001), for the vessels as a group (p < 0.01 to < 0.0001) and for the left anterior descending (p < 0.01 to < 0.0001) and right (p < 0.05) coronary arteries. By multivariate analysis, positive findings on the stress ECG was the single most significant variable in relation to the amount of ischemia (p < 0.001); exercise chest pain had no significant relationship., Conclusions: Exercise-induced ST segment depression is the single most significant variable in relation to the amount of ischemic myocardium; exercise-induced chest pain is not related to the amount of ischemia. Patients with "truly silent ischemia" constitute almost 50% of patients with coronary artery disease and have less ischemia than do patients with ECG indications of ischemia, with or without chest pain.