To examine whether a significant circadian variation of transient myocardial ischemia exists and to better understand the character of such variation, 32 patients with chronic stable symptoms of coronary artery disease underwent one or more days of ambulatory monitoring of ischemic ST segment changes during daily life. A total of 251 episodes of ischemic ST segment depression occurred in 24 (75%) of the 32 patients with a median duration of 5 min (range 1 to 253). A significant circadian increase in ischemic activity was found with 39% of episodes and 46% of total ischemic time occurring between 6 A.M. and 12 P.M. (p < .05 and p = .02, respectively). In 21 patients with-ST segment depression during the 6 hr after waking and the 6 hr before sleep, 68% of episodes occurred in the morning compared with 32% in the evening. There were no significant differences in heart rate at onset, heart rate at 1 min before onset, and activity score associated with ST segment depression. The proportion of minutes showing ST segment depression when the heart rate was above the lowest rate associated with ST segment depression was significantly greater in the morning compared with the evening (26% vs 15%; p = .03). Thus the early morning increase in ST segment depression does not appear to be explained by differences in extrinsic activity and/or stress measured by physical activity score and heart rate response. More importantly, this phenomenon is often ignored by the usual patterns of drug administration for angina. This may have clinical relevance, since the observed circadian variation coincides with that reported for onset of acute myocardial infarction and sudden death. Circulation 75, No. 2, 395-400, 1987. PATIENTS with coronary artery disease suffer symptoms and damage to left ventricular myocardium through the development of active myocardial ischemia. Recently, ambulatory monitoring of the electrocardiogram during daily life has been used to detect transient myocardial ischemia in patients with coronary artery disease and has shown that these ischemic episodes are often asymptomatic, surprisingly prolonged, and frequently not associated with stress.1-5 At the same time, clinical studies have demonstrated circadian variations in the onset of myocardial infarction'IO and of other manifestations of cardiovascular function, including plasma catecholamine levels, arte-

Cholesterol lowering with lovastatin appears to be effective in eliminating myocardial ischemia during daily life in a significant proportion of patients.

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