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Circadian variations of transient myocardial ischemia and heart rate have been identified, but the rhythms and their response to beta blockade have not been fully characterized. Time-series analysis, a mathematical technique to describe oscillatory activity occurring within a continuous data set was used, to address these issues. Nine men with coronary artery disease underwent 72 hours of ambulatory electrocardiographic monitoring during therapy with placebo or metoprolol. During administration of placebo, ischemic time and heart rate showed a primary peak with a periodicity of approximately 24 hours with a tight coupling between the 2 variables and a secondary peak with a periodicity of 5 to 8 hours. During metoprolol therapy, heart rate and ischemic variation were reduced and the 24-hour periodicity for heart rate only remained. The 24-hour periodicity for ischemia was eliminated, but the data with 5- to 8-hour periodicity became the major component of the signal.

The usefulness of prolonged ambulatory electrocardiographic monitoring (AEM) for detecting ischemia was investigated in 17 asymptomatic men who had ischemic-type ST-segment depression (greater than or equal to 2.0 mm) during treadmill exercise testing. No patient took anti-ischemic medications and all patients underwent coronary angiography. A total of 1,154 hours (range 64 to 72 hours/patient) of high-quality AEM recordings was obtained. Silent ischemia (episodes of asymptomatic ischemic-type ST depression of 60 seconds or longer) occurred in 11 patients during daily activity detected by AEM. In 6 other patients, no myocardial ischemic episodes were found. But 1 of these patients withdrew after only 24 hours of AEM and the remaining 5 had no significant coronary artery disease (CAD). All 11 patients who had silent ischemia had significant CAD (at least 50% stenosis) on angiography. There was wide intrapatient variability in the frequency of silent ischemic episodes. Silent ischemia was identified in 6 of these 11 patients after 24 hours of AEM, in 2 after 48 hours and in 3 after 72 hours. Thus, asymptomatic men with positive exercise test responses and CAD have silent ischemic episodes during daily activity. AEM may be useful in helping to predict which patients with asymptomatic positive exercise test responses have CAD; however, extended AEM periods are required.