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Concurrent Morning Increase in Platelet Aggregability and the Risk of Myocardial Infarction and Sudden Cardiac Death

List of authors.
  • Geoffrey H. Tofler, M.B.,
  • Damian Brezinski,
  • Andrew I. Schafer, M.D.,
  • Charles A. Czeisler, Ph.D., M.D.,
  • John D. Rutherford, M.B.,
  • Stefan N. Willich, M.D.,
  • Ray E. Gleason, Ph.D.,
  • Gordon H. Williams, M.D.,
  • and James E. Muller, M.D.

Abstract

We have previously reported that the frequencies of myocardial infarction and of sudden cardiac death are highest during the period from 6 a.m. to noon. Since platelet aggregation may have a role in triggering these disorders, we measured platelet activity at 3-hour intervals for 24 hours in 15 healthy men. In vitro platelet responsiveness to either adenosine diphosphate (ADP) or epinephrine was lower at 6 a.m. (before the subjects arose) than at 9 a.m. (60 minutes after they arose). The lowest concentration of these agents required to produce biphasic platelet aggregation decreased (i.e., aggregability increased) from a mean ±SEM of 4.7±0.6 to 3.7±0.6 μM (P<0.01) for ADP and from 3.7±0.8 to 1.8±0.5 μM (P<0.01) for epinephrine. The period from 6 to 9 a.m. was the only interval in the 24-hour period during which platelet aggregability increased significantly.

We subsequently studied 10 subjects on alternate mornings after they arose at the normal time and after delayed arising. The morning increase in platelet aggregability was not observed when the subjects remained supine and inactive.

Thus, there is a temporal association between increased platelet aggregability in the morning and an increased frequency of myocardial infarction and of sudden cardiac death. Demonstration of this association does not establish a cause–effect relation, but together with other evidence linking platelets to these disorders, it may provide insight into the mechanisms precipitating myocardial infarction and sudden cardiac death and aid in the design of more effective preventive measures. (N Engl J Med 1987; 316:1514–8.)

Funding and Disclosures

Supported in part by grants (HL-27465, 705861, and 9535 A607606) from the National Institutes of Health, a General Clinical Research Grant (RRO 2635), and grants from Miles Laboratories and the Squibb Research Foundation. Dr. Schafer is an Established Investigator of the American Heart Association. Mr. Brezinski is the recipient of an American Heart Association Fellowship and an Alpha Omega Alpha Student Research (Johns Hopkins Medical Institutions) Fellowship.

We are indebted to Dr. Kenneth Bauer for consultation, to Ms. Gail Aylmer and Mrs. Dorothy Curtis for assistance in conducting the study, to the nursing and laboratory staffs of the General Clinical Research Center, and to Ms. Kathleen Carney for preparation of the manuscript.

Author Affiliations

From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston. Address reprint requests to Dr. Tofler at Harvard Medical School, 164 Longwood Ave., Boston, MA 02115.