The Multiple Risk Factor Intervention Trial (MRFIT) -- Boondoggle!
The Multiple Risk Factor Intervention Trial (MRFIT) -- Boondoggle!
Over a period of several years, 12,866 men at increased risk of death from CHD were recruited across the USA (Multiple Risk Factor Intervention Trial Research Group, 1982). They had no clinical evidence of CHD but were designated as being at increased risk because their levels of 3 risk factors - cigarette smoking, serum cholesterol and diastolic blood pressure - were sufficiently high to place them in the upper 10% of a risk score distribution based on data from the Framingham study. Half were assigned to a special intervention group (SI) and were treated conventionally with drugs for their hypertension, encouraged to stop smoking and consume less cholesterol and saturated fats. The other men were a "usual care" (UC) group and received no special treatment other than that provided by their personal physicians.
The men were examined annually and followed for an average of 7 years each. The three risk factors declined in both groups but the reductions were larger throughout the trial in the SI group, being significant at P<0.01 at each annual visit. For example, after 6 years, 50% of SI men who were smokers had quit compared with 29% of the UC. Diastolic blood pressure fell in the two groups by 10.5 and 7.3 respectively. Plasma cholesterol fell in the two groups by 12.1 and 7.5 mg/dl respectively, which primarily represented changes in low-density lipoprotein cholesterol and not high-density lipoprotein cholesterol. The unexpected decline in cholesterol in the UC group and a smaller than predicted decline in the SI group meant that the SI-UC difference was about half of that expected. At the end of the follow-up period, the mortality rates were SI 41.2 and UC 40.4/1000. The CHD death rates were 17.9 and 19.3/1000. Neither death rates from CHD nor any other cause were reported as significantly different in the two groups.
The investigators were reluctant to accept their own results and examined sub-groups within their study. They found that SI men with hypertension as an important risk factor and with resting ECG abnormalities had a substantially raised mortality. This, they consider, would have been due to an unexpected deleterious effect of the SI program, particularly toxic effects of the diuretics used. They reported this at a news conference which presented their findings (Kolata, 1982).
After removal of the men with resting ECG abnormalities from their results, total mortality rates for SI and UC men were 37.2 and 39.5/1000 and for CHD 14.8 and 18.8/1000. Again, none of these differences were significant.
The original goal of the MRFIT was to determine whether reduction of the risk factors smoking, cholesterol and elevated blood pressure in high-risk but otherwise healthy men would reduce CHD mortality, non-fatal MI or CHD, cardiovascular mortality and mortality from all causes (Zukel, Paul and Schnaper, 1981). Their paper answers these questions thus:
"In conclusion we have shown that it is possible to apply an intensive long-term intervention program against three coronary risk factors with considerable success in terms of risk factor changes. The overall results do not show a beneficial effect on CHD or total mortality from this multifactor intervention. (Multiple Risk Factor Intervention Trial Research Group, 1982)
In other words, they found that changing the "risk factors" does not apparently change the risks. This necessarily means that the "risk factors" are not as important as was thought. Indeed, it should be concluded that the "risk factors" were no such thing, at least as far as this trial is concerned.
Roger W. Sherwin, Ph.D. - Dr. Sherwin is the J. S. Copes Professor and Chair of the Department of Epidemiology, TSPHTM. He received his B.A., M.A., M.B., and B.Chir. from Cambridge University, England. He was recruited to Tulane in 1999. While at Johns Hopkins University he served as clinic physician for the Baltimore Center of the Diet-Heart Feasibility Study and designed the first randomized trial of maternal nutritional supplementation during pregnancy. At the University of Maryland School of Medicine he was Principal Investigator of the Baltimore Center of the Multiple Risk Factor Intervention Trial (MRFIT). He served on several national MRFIT committees and was the first chairman of the Intervention Committee, which was responsible for the implementation of the complex intervention program. In 1982 he became the first chairman of the Planning Committee of the Diabetic Control and Complications Trial (DCCT). In 1986 he was the Principal Investigator of the Baltimore Center of the Study of Osteoporotic Fractures for which he recruited 2,400 subjects. In 1991 he became Principal Investigator of the Baltimore Center of the Cholesterol and Recurrent Events (CARE) Trial of pravastatin. In 1991 he recruited 120 subjects for the Postmenopausal Estrogen/Progesterone Intervention Trial (PEPI). In 1993 he was funded as Principal Investigator of the Baltimore alendronate trial.
Roger Sherwin
Dr.
Sherwin received his medical degree from
Cambridge University with residency training
in Internal Medicine and Geriatrics in
London. He then underwent 5 years of
fellowship training in Medical Genetics,
Cardiology and Biostatistics at Johns Hopkins
University School of Medicine and School of
Hygiene and Public Health.
In 1966 he was appointed to the faculty of the Department of Biochemistry at Johns Hopkins where he taught and conducted research on nutrition and fetal growth. He designed the first randomized clinical trial of the effect of nutritional supplementation during pregnancy on birth weight and postnatal development.
In 1970 he joined the faculty of the Department of Preventive Medicine at the University of Maryland School of Medicine. He taught in all 4 years of the medical curriculum and developed a program of research into the prevention of cardiovascular disease. In 1983 he helped to develop and initiate a master’s and doctoral program in Epidemiology and Preventive Medicine in which he participated for the next 15 years. During this time, the focus of his research broadened to include the prevention and treatment of osteoporosis.
In 1999 he joined the new Department of Epidemiology at the Tulane School of Public Health and Tropical Medicine and became the first Joseph S. Copes Professor and Chair. He continues to teach and collaborate in the research of faculty and students.
Research Interests:
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Cardiovascular epidemiology
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Nutritional epidemiology
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Reproductive epidemiology
-
Experimental epidemiology
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Scientific Inference
Selected Publications:
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Sherwin R. W.: The epidemiology of atherosclerosis and coronary heart disease. Postgraduate Medicine 1974; 56:81-87.
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Sherwin, R. W.: Controlled trials of the diet-heart hypothesis: some comments on the experimental unit. American Journal of Epidemiology f1978; 109:92-99.
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Sherwin, R. W., Kaelber, C. T., Kezdi, P., Kjelsberg, M. O. and Thomas, H. E.: The Multiple Risk Factor Intervention Trial (MRFIT) II. The development of the protocol. Preventive Medicine 1981; 10:402-425.
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Sherwin, R. W., Wentworth, D. NH., Cutler, J. A., Hulley, S. B., Kuller, L. H. and Stamler, J.: Serum cholesterol levels and cancer mortality in 361,662 men screened for the Multiple Risk Factor Intervention Trial. Journal of the American Medical Association 1987; 257:943-948.
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Sherwin, R. W.: Myocardial damage, thiazides, hypokalemia, and sudden death. Clinical Nutrition 1987; 6:65-69.
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