Circulation, Vol 82, 897-902, Copyright © 1990 by American Heart Association
PM Ridker, JE Manson, JE Buring, JE Muller and CH Hennekens
Increased platelet aggregation in the morning and upon assuming an upright
posture may account at least in part for the observed circadian variation
in onset of acute myocardial infarction. The Physicians' Health Study, a
randomized, double-blind, placebo-controlled trial of alternate-day aspirin
intake (325 mg) among 22,071 US male physicians, afforded the opportunity
to assess this circadian pattern and examine whether it is altered by
aspirin therapy. During a 5-year period of follow-up, 342 cases of nonfatal
myocardial infarction were confirmed, of which the time of onset was
available in 211 (62%). The placebo group showed a bimodal circadian
variation in onset of myocardial infarction with a primary peak between
4:00 AM and 10:00 AM (p less than 0.001). In the aspirin group, however,
this circadian variation was minimal (p = 0.16), due primarily to a marked
reduction in the morning peak of infarction. Specifically, aspirin was
associated with a 59.3% reduction in the incidence of infarction during the
morning waking hours, compared with a 34.1% reduction for the remaining
hours of the day. The greater reduction was observed during the 3-hour
interval immediately after awakening, a period with a risk of infarction
twice that of any other comparable time interval (p less than 0.001).
Aspirin intake was associated with a mean reduction in the incidence of
infarction of 44.8% over the entire 24-hour cycle. These data support the
hypothesis that increased platelet aggregability in the morning and upon
arising contributes to the occurrence of myocardial infarction and that
aspirin reduces the risk of infarction by inhibiting platelet aggregation
during these critical periods.
ARTICLES
Circadian variation of acute myocardial infarction and the effect of low-dose aspirin in a randomized trial of physicians
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02146.
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