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Circadian Variation in the Frequency of Onset of Acute Myocardial Infarction
List of authors.Abstract
To determine whether the onset of myocardial infarction occurs randomly throughout the day, we analyzed the time of onset of pain in 2999 patients admitted with myocardial infarction. A marked circadian rhythm in the frequency of onset was detected, with a peak from 6 a.m. to noon (P<0.01). In 703 of the patients, the time of the first elevation in the plasma creatine kinase MB (CK-MB) level could be used to time the onset of myocardial infarction objectively. CK-MB—estimated timing confirmed the existence of a circadian rhythm, with a threefold increase in the frequency of onset of myocardial infarction at peak (9 a.m.) as compared with trough (11 p.m.) periods. The circadian rhythm was not detected in patients receiving beta-adrenergic blocking agents before myocardial infarction but was present in those not receiving such therapy.
If coronary arteries become vulnerable to occlusion when the intima covering an atherosclerotic plaque is disrupted, the circadian timing of myocardial infarction may result from a variation in the tendency to thrombosis. If the rhythmic processes that drive the circadian rhythm of myocardial-infarction onset can be identified, their modification may delay or prevent the occurrence of infarction. (N Engl J Med 1985; 313:1315–22.)
Appendix
The Multicenter Investigation of the Limitation of Infarct Size involved the following centers, laboratories, and investigators:
Clinical Centers: Barnes Hospital, Washington University School of Medicine, St. Louis, Mo.: principal investigators, Allan S. Jaffe, M.D., Robert Roberts, M.D.; co-investigator, Edward Geltman, M.D.; nuclear medicine coordinator, Dan Biello, M.D.; research nurse coordinator, Rosanne Wettach, R.N., M.N.P.; data coordinators, Ava Ysaguire, Susan Payne, Linda Wilson. Massachusetts General Hospital, Boston, Mass.: principal investigators, Herman K. Gold, M.D., Robert C. Leinbach, M.D.; Tsunehiro Yasuda, M.D.; research nurse coordinators, Wendy Werner, R.N., Mary McHugh, R.N.; data coordinator, Harry Garabedian. Medical Center Hospital of Vermont, University of Vermont College of Medicine, Burlington: principal investigator, Daniel S. Raabe, Jr., M.D.; Walter Gundel, M.D.; research nurse coordinators, Marian Dornell, R.N., Maureen Hawley, R.N., Patricia Beecher, R.N., Kathleen Cornell, R.N., Karen Helminger, R.N.; data coordinator, Raina Maynard. Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.: principal investigator, Eugene Braunwald, M.D.; clinical unit directors, Peter H. Stone, M.D., Joseph S. Alpert, M.D., Robert Rude, M.D.; research nurse coordinators, Nancy E. Taplin, R.N., Kathryn Shea, R.N., Debbie Shiner, R.N. Parkland Memorial Hospital, University of Texas Health Science Center at Dallas: principal investigator, James T. Willerson, M.D.; clinical unit director, Robert E. Rude, M.D.; Charles Croft, M.D., Robert Dillon, M.D., Kevin Wheelan, M.D., Christopher Wolfe, M.D.; research nurse coordinators, Barbara Moses, R.N., Sandra Cochran, R.N.; Marvin Akers, R.N., Joan Reinert Corey, R.N., Vicki Gillespie, R.N., Barbara Fitzpatrick, R.N.; unit clerk, Kris Kraft.
Creatine Kinase Core Laboratory: Washington University School of Medicine, St. Louis, Mo.: principal investigators, Burton E. Sobel, M.D., Robert Roberts, M.D.; Allan Jaffe, M.D.; laboratory coordinator, Cynthia Ritter; laboratory technician, Steven Mumm.
Cardiovascular Pathology Core Laboratory: Duke University Medical Center, Durham, N.C.: principal investigators, Donald B. Hackel, M.D., Raymond E. Ideker, M.D., Ph.D., Keith A. Reimer, M.D., Ph.D., Eileen Mikat, Ph.D.
Technetium-99m Pyrophosphate Myocardial Scintigram Core Laboratory: University of Texas Health Science Center at Dallas: principal investigator, James T. Willerson, M.D.; laboratory director, Samuel E. Lewis, M.D.; laboratory codirector, Robert W. Parkey, M.D.; laboratory coordinator, Irma Dobbins.
Holter Recording Core Laboratory: Washington University School of Medicine, St. Louis, Mo.: principal investigator, Lewis J. Thomas, Jr., M.D.; co-principal investigator, Robert Roberts, M.D.; laboratory director, Kenneth W. Clark; laboratory coordinator, Kathleen Madden; biostatistician, J. Phillip Miller.
Radionuclide Ventriculogram Core Laboratory: Massachusetts General Hospital, Boston: principal investigator, H. William Strauss, M.D.; co-principal investigator, Nathaniel M. Alpert, M.D.; clinical director, Nuclear Medicine Division, Kenneth A. McKusick, M.D.; Tsunehiro Yasuda, M.D.; laboratory coordinator, Karen Kelly; laboratory coordinators and nuclear medicine technicians, Annali Kiers, Leander Blakeman, Merrill Griff.
ECG Core Laboratory: Harvard Medical School and Brigham and Women's Hospital, Boston, Mass.: principal investigator, Eugene Braunwald, M.D.; laboratory directors, Zoltan G. Turi, M.D., John D. Rutherford, M.D.; laboratory codirector, James E. Muller, M.D.; laboratory codirector for ETT analysis, Peter H. Stone, M.D.; laboratory coordinators, Gail Z. Alymer, Susan G. Albert, P.A., Jennifer Forage, Michael Miller; programmer analysts, Neil Rhodes, Matthew Levine, Jeremy Pool, John Rees; computer operators, Jane Soukup, David Mayberry.
Data Coordinating Center: Research Triangle Institute, Research Triangle Park, N.C.: principal investigator, W. Kenneth Poole, Ph.D.; co-principal investigator, Tyler D. Hartwell, Ph.D.; project coordinator, biostatistician, Corette Parker, M.S.P.H.; data coordinators, Connie Hobbs, Norma Fox, M.P.H., Susan Warwick, R.N.; data-management coordinator, Priscilla Rigby, R.N.; computer programmers, Thomas S. Farrell, Debra Fleischman; statisticians, Nancy Gustafson, M.S., Susan K. Settergren, M.S., B.J.G. York, M.S., James H. Crowder, M.P.H., Carolyn Stuart, M.S.P.H., Vicki Davis, M.S.; statistical clerk, Lee Larsen.
Clinical Coordinating Center: Harvard Medical School and Brigham and Women's Hospital, Boston, Mass.: principal investigator, Eugene Braunwald, M.D.; James E. Muller, M.D.; Zoltan G. Turi, M.D.; project coordinator, Ellenjane Scheiner; financial administrator, Norman R. Stein.
Program Office: Cardiac Diseases Branch, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, Bethesda, Md.: project officers, Thomas Robertson, M.D., Eugene R. Passamani, M.D., Michael B. Mock, M.D.; clinical trials nurse administrator, Suzanne M. Mullin, R.N., M.P.H.; contracting officer, Roland Castle; contract officer, Patrick M. Sullivan; biostatisticians, K. Gordan Lan, Ph.D., David DeMets, Ph.D., James Ware, Ph.D.
MILIS Policy Advisory Board: William L. Ashburn, M.D., Eugene Braunwald, M.D., Paul Canner, Ph.D., Robert L. Frye, M.D. (chairman), Lawrence E. Hinkle, Jr., M.D., Andrew Z. Keller, D.M.D., Paul Meier, Ph.D., Leroy Walters, Ph.D., Nanette Wenger, M.D.
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