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Serum Cholesterol Levels and Six-Year Mortality from Stroke in 350,977 Men Screened for the Multiple Risk Factor Intervention Trial

List of authors.
  • Hiroyasu Iso, M.D.,
  • David R. Jacobs, Jr., Ph.D.,
  • Deborah Wentworth, M.P.H.,
  • James D. Neaton, Ph.D.,
  • Jerome D. Cohen, M.D.,
  • and for the MRFIT Research Group*

Abstract

We examined the relation between the serum total cholesterol level and the risk of death from stroke during six years of follow-up in 350,977 men, 35 to 57 years of age, who had no history of heart attack and were not currently being treated for diabetes mellitus. The diagnosis of stroke and the type of stroke were obtained from death certificates.

Using proportional-hazards regression to control for age, cigarette smoking, diastolic blood pressure, and race or ethnic group, we found that the six-year risk of death from Intracranial hemorrhage (International Classification of Diseases, ninth edition [ICD-9], categories 431 and 432) was three times higher in men with serum cholesterol levels under 4.14 mmol per liter (160 mg per deciliter) than in those with higher cholesterol levels (P = 0.05 by omnibus test across five cholesterol levels). On the other hand, a positive association was observed between the serum cholesterol level and death from nonhemorrhagic stroke (P = 0.007). The inverse association of the serum cholesterol level with the risk of death from intracranial hemorrhage was confined to men with diastolic blood pressure ≥90 mm Hg, in whom death from intracranial hemorrhage is relatively common.

We conclude that there is an inverse relation between the serum cholesterol level and the risk of death from hemorrhagic stroke in middle-aged American men, but that its public health impact is overwhelmed by the positive association of higher serum cholesterol levels with death from nonhemorrhagic stroke and total cardiovascular disease (ICD-9 categories 390 through 459). (N Engl J Med 1989; 320:904–10.)

Funding and Disclosures

Supported in part by grants (HL28715 and HL23727) from the National Heart, Lung, and Blood Institute. Dr. Iso's work was supported by a grant (DGB 33914) from the Fulbright Program.

We are indebted to Drs. Henry Blackburn, Aaron R. Folsom, and Gregory L. Burke for valuable discussion and to Mr. James T. Huber for assistance in the validation data processing.

Author Affiliations

From the Division of Epidemiology (H.I., D.R.J.) and the Division of Biometry (D.W., J.D.N.), School of Public Health, University of Minnesota, Minneapolis, and the Preventive Cardiology Programs, St. Louis University Medical Center, St. Louis (J.D.C.). Address reprint requests to Ms. Wentworth at the Division of Biometry, School of Public Health, University of Minnesota, A-460 Mayo Memorial Bldg., Box 197, 420 Delaware St. S.E., Minneapolis, MN 55455.

*Members of the MRFIT Research Group are listed in the Appendix.

Appendix

The principal investigators and senior staff of the clinical coordinating, and support centers and the National Heart, Lung, and Blood Institute and the members of the MRFIT policy advisory board and mortality review committee are as follows: American Health Foundation, New York: C.B. Arnold, M.D., M.P.H. (principal investigator), R. Mandriota, M.S., M.Ed., R.P. Ames, M.D., and J. Ruff Eisenbach, R.N.; Boston University, Boston: H.E. Thomas, Jr., M.D. (principal investigator), W.B. Kannel, M.D. (co-principal investigator), R. Rotondo, M.A., and J. Connors, R.D.; Cox Heart Institute, Kettering, Ohio: P. Kezdi, M.D. (principal investigator), E.L. Stanley, M.D. (co-principal investigator), W.L. Black, M.D., and F.A. Ernst, Ph.D.; Dade County Department of Public Health, Miami: G. Christakis, M.D., M.P.H. (principal investigator), J.M. Burr, M.D. (co-principal investigator), T.A. Gerace, Ph.D. (coprincipal investigator), and M.E. Wilcox, R.D., M.Ed.; Dalhousie University, Halifax, Nova Scotia (MRFIT Electrocardiographic Center): P.M. Rautaharju, M.D., Ph.D. (principal investigator), and H. Wolf, Ph.D.; Harvard University, Boston: R.C. Benfari, Ph.D. (principal investigator), K.M. McIntyre, M.D., J.D. (co-principal investigator), O. Paul, M.D. (co-principal investigator), E. Danielson, M.A., and J. Ockene, Ph.D.; Institutes of Medical Sciences, San Francisco Central Laboratory, San Francisco: G.M. Widdowson, Ph.D. (co-principal investigator), G.Z. Williams, M.D. (co-principal investigator), S.B. Hulley, M.D., M.P.H. (co-principal investigator), and M.L. Kuehneman (laboratory manager); Institutes of Medical Sciences, University of California, San Francisco and Berkeley, Calif.: J. Billings, Ph.D., M.P.H. (principal investigator), S.B. Hulley, MD., M.P.H. (co-principal investigator), W.M. Smith, M.D., M.P.H. (co-principal investigator), and S.L. Syme, Ph.D. (co-principal investigator); Kaiser Foundation Research Institute, Portland, Oreg.: J.B. Wild, M.D. (principal investigator), M. Greenlick, Ph.D. (co-principal investigator), J. Grover, M.D. (co-principal investigator), and S. Lamb; Lankenau Hospital, Philadelphia: W. Holmes, Ph.D. (principal investigator), J.E. Pickering, M.D. (co-principal investigator), E.L. Duffy, R.D., and G.B. Rubel, R.D.; National Center for Disease Control, Atlanta: G.R. Cooper, Ph.D., M.D. (principal investigator), and D.T. Miller, Ph.D.; New Jersey Medical School, Newark, N.J.: N.L. Lasser, M.D., Ph.D. (principal investigator), N. Hymowitz, Ph.D. (co-principal investigator), K.C. Mezey, M.D., and B. Munves, Ph.D., R.D.; Northwestern University, Chicago: J. Stamler, M.D. (principal investigator), D. Moss, M.S., R.D., V. Persky, M.D., E. Robinson, M.S., R.D., and L. Van Horn, Ph.D., R.D.; Rush–Presbyterian–St. Luke's Medical Center, Chicago: J.A. Schoenberger, M.D. (principal investigator), J.C. Schoenenberger, Ph.D., R.B. Shekelle, Ph.D., G.S. Neri, M.D., and T.A. Dolecek, M.S., R.D.; Rutgers Medical School, Piscataway, N.J.: N.H. Wright, M.D., M.P.H. (principal investigator), S.A. Kopel, Ph.D. (co-principal investigator), K. R. Suckerman, Ph.D., and M. Schorin, M.P.H. R.D.; St. Joseph's Hospital, Chicago: D.M. Berkson, M.D. (principal investigator), G. Lauger, M.S., S. Grujic, M.D., and D. Obradovic, M.D.; St. Louis Heart Association, St. Louis: N. Simon, M.D. (principal investigator), J.D. Cohen, M.D. (co-principal investigator), E. Bunkers, R.D., and B. Ronchetto, R.N.; University of Alabama, Birmingham, Ala.: H.W. Schnaper, M.D. (principal investigator), G.H. Hughes, Ph.D. (co-principal investigator), A. Oberman, M.D., and C.C. Hill, Ph.D.; University of California, Davis, Calif.: N.O. Borhani, M.D. (principal investigator), C. Sugars, R.D., K. Kirkpatrick, and M. Lee, M.D.; University of Chicago, Chicago: L. Cohen, M.D. (principal investigator), J. Morgan, Ph.D. (co-principal investigator), G. Grundmann, M.S., R.D., and T.D. Vestal, P.A.; University of Maryland, Baltimore: R.W. Sherwin, M.B., B. Chir. (principal investigator), M.S. Sexton, Ph.D., M.P.H. (co-principal investigator), P.C. Dischinger, Ph.D., and M.B. Pilkington, R.N., M.S.N.; University of Minnesota, Minneapolis: R.H. Grimm, Jr., M.D., M.P.H. (principal investigator), M. Mittelmark, Ph.D. (co-principal investigator), R.S. Crow, M.D. (co-principal investigator), H. Blackburn, M.D. (co-principal investigator), and D.Jacobs, Ph.D. (co-investigator); University of Minnesota Coordinating Center, Minneapolis: M.O. Kjelsberg, Ph.D. (principal investigator), G.E. Bartsch, Sc.D. (co-principal investigator), J.D. Neaton, Ph.D. (co-principal investigator), and D.N. Wentworth, M.P.H.; University of Minnesota Electrocardiographic Coding Center, Minneapolis: R.J. Prineas, M.B., Ph.D. (director), and R.C. Crow, M.D. (associate director); University of Minnesota Nutrition Coding Center, Minneapolis: I.M. Buzzard, Ph.D. (director), and P.V. Grambsch (former director); University of Pittsburgh, Pittsburgh: L.H. Kuller, M.D., D.P.H. (principal investigator), R. McDonald, M.D. (co-principal investigator), A. Caggiula, Ph.D., R.D. (co-principal investigator), and L. Falvo-Gerard, M.N., M.P.H. (co-principal investigator); University of South Carolina, Columbia, S.C.: W.K. Giese, Ph.D. (principal investigator), J.F. Martin, M.D. (co-principal investigator), J.A. Keith, Ph.D. (coprincipal investigator), and H.H. Harrison, R.N.; University of Southern California, Los Angeles: E. Fishman, M.D. (principal investigator), L. Wampler, Ph.D., G. Newmark, M.A., R.D., and F. Rosenfield, M.P.H.; National Heart, Lung, and Blood Institute, Bethesda, Md.: W.T. Friedewald, M.D. (program director), CD. Furberg, M.D. (project office director), J.A. Cutler, M.D. (scientific project officer), E.R. Passamani, M.D. (former scientific project officer), and CT. Kaelber, M.D. (former scientific project officer); MRFIT Policy Advisory Board: W. Insull, Jr., M.D., (chairperson), J.W. Farquhar, M.D., C.D. Jenkins, Ph.D., E. Rapaport, M.D., D.J. Thompson, Ph.D., H.A. Tyroler, M.D., P.W. Willis III, M.D., W.T. Friedewald, M.D., and W. Zukel, M.D.; MRFIT Mortality Review Committee: J.T. Doyle, M.D. (chairman), H.B. Burchell, M.D., P.N. Yu, M.D., P.W. Willis III, M.D. (former member).

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