To determine for a group of men at high risk of death from coronary heart disease whether a special intervention program to lower serum cholesterol, reduce blood pressure, and eliminate cigarette smoking would result in a significant reduction in mortality from coronary heart disease.
BACKGROUND:
Research findings from prospective epidemiological studies in a number of populations in the United States over the past 40 years have convincingly established that elevated blood cholesterol, elevated blood pressure, and cigarette smoking are risk factors associated with accelerated development of myocardial infarction, sudden death, and death from coronary heart disease. These are not the only risk factors associated with premature development of CHD, but these factors are modifiable and provide a strong expectation that a reduction of these factors should have a beneficial result of reducing the rate of development of premature heart attacks.
A multifactor approach to risk factor reduction closely resembles the type of intervention that would be carried out by a physician in his treatment of a patient. The general concept for such a trial was endorsed by the Arteriosclerosis Task Force in its 1970 report to the Institute.
Volunteers were selected for the trial through a series of three screening visits, which began in November 1973 and were completed by February 28, 1976. From among 361,662 men seen at first screening, 12,866 were found to be eligible and were randomized into the trial. Half of the participants were assigned to the special intervention group and half to the usual care group. The special intervention group was advised to follow an eating pattern designed to result in a nutrient intake of 30 percent to 35 percent of calories from fat, with 10 (later 8) percent from saturated and 10 percent from polyunsaturated fat; approximately 300 (later 250) mg of cholesterol; and modification of carbohydrates as needed for individual requirements. This group was also encouraged to cease cigarette smoking by a combination of techniques, including counseling and audio-visual aids. Hypertension management was based on a stepped-care program of weight reduction and drugs similar to that used in the Hypertension Detection and Follow-up Program. Those in the usual care group were referred to their personal physician or other source of care for such management of their risk factors as considered appropriate by these providers. The primary endpoint was death due to coronary heart disease. Men in both the special intervention and usual care groups returned for assessment of changes in risk factor levels annually. A medical history was taken and a physical examination performed. An electrocardiogram was also obtained for centralized reading to identify non-fatal myocardial infarction as an additional endpoint.
Participating in the study were 22 clinical centers across the United States, a coordinating center, central laboratory, two ECG reading centers, and lipid standardization laboratory, as well as a drug distribution center. The trial has concluded, with the main mortality results published in September l982. Active follow-up was terminated on schedule on February 28, l982, with final determination of vital status as of that date accomplished for 99.6 percent of the study population.
DESIGN NARRATIVE:
A randomized, non-blind design with two groups and fixed sample size. The experimental group underwent a modified-fat diet, antihypertensive therapy, and education related to lifestyle and smoking. Those in the control group were referred to their own physicians for treatment.
Post-trial mortality surveillance of the 12,300 participants still living at the end of active intervention in February 1982 continued through June 1998 under grant support (R01HL43232). Use of the National Death Index for mortality surveillance of the 361,662 men screened for the MRFIT continued thorough July 1998 under grant support (R01HL28715). Recent analyses focus on the relationship of dietary factors, such as sodium, during the trial with post-trial mortality. Papers are in progress on further predictors of diabetes mellitus; indicators of cardiovascular disease morbidity and risk of death; and prognostic importance of changes in indices of left ventricular hypertrophy and ischemia.
Men, ages 35-57. One or more of three risk factors--hypertension, hypercholesterolemia, and cigarette smoking.
Free from coronary heart disease.