Tofler, G. H., Muller, J. E., Stone, P. H., Forman, S., Solomon, R. E., Knatterud, G. L., Braunwald, E. Modifiers of timing and possible triggers of acute myocardial infarction in the Thrombolysis in Myocardial Infarction Phase II (TIMI II) Study Group Journal of the American College of Cardiology. 1992;20(5):1049-55.

OBJECTIVES: The aim of this study was to provide insight into the mechanism of acute myocardial infarction by determining the modifiers of timing and possible triggers of onset of infarction.

BACKGROUND: A higher frequency of onset of acute myocardial infarction has been reported in the morning with a peak in the 1st 3 h after awakening. This observation suggests that the onset of infarction may be triggered by activity in the morning and at other times of the day.

METHODS: The clinical history of the 3,339 patients entered into the Thrombolysis in Myocardial Infarction phase II study was analyzed to determine characteristics predicting a higher frequency of infarction between 6 AM and noon, and onset of infarction during exertion.

RESULTS: A higher proportion (34.4%) of infarctions began in the morning (6 AM to noon) compared with other times of the day. Characteristics independently predicting a higher frequency between 6 AM to noon were no beta-adrenergic blocking agent use in the 24 h before infarction, no discomfort other than the index pain in the preceding 48 h, occurrence of the infarction on a weekday and no history of current smoking. In 18.7% of patients, infarction occurred during moderate or marked physical activity. Independent predictors of exertion-related infarction included male gender, no history of current smoking, white race, no use of calcium channel blocking agents or nitrates in the preceding 24 h, the absence of either chest pain at rest in the 3 weeks before infarction or any pain in the preceding 48 h, the absence of new onset angina and the presence of exertional pain in the preceding 3 weeks. Compared with patients whose infarction occurred at rest or during mild activity, those with exertion-related infarction had fewer coronary vessels with > or = 60% stenosis (p = 0.002) and were more likely to have an occluded infarct-related vessel after thrombolytic therapy (p = 0.01).

CONCLUSIONS: Further study of the timing and activity at onset of infarction may provide insight into the pathophysiologic mechanisms causing acute myocardial infarction and provide clues to preventive measures.

Trial: TIMI 2B