Multiple Risk Factor Intervention Trials

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A risk factor is part of the chain of causation leading to a disease and is a strong and independent predictor of excess risk. The idea of a controlled experiment to intervene with people at high risk of heart attack due to multiple elevated risk factors arose in the late 1960s.

Major risk factors for coronary heart disease (CHD), high blood pressure, high blood cholesterol level, and cigarette smoking had already been established by careful observational studies. The great public health question of the day was whether dietary modification to lower blood cholesterol levels could prevent heart attacks. Medical leaders concluded that it would not be feasible to carry out a definitive trial on this question due to the costand because dietary intervention would inadvertently influence other lifestyle risk factors. The search began, therefore, for a feasible alternative strategy of prevention.

In theory, controlled interventions in people without manifest CHD, but who have more than one major risk factor would: (1) test the hypothesis of whether prevention of CHD, with a reduction in total mortality is at all possible; and (2) provide the best likelihood of demonstrating quickly and efficiently the possibility of a major reduction in the incidence of heart attacks.

The theory and practical aspects of the multiple risk factor intervention trials (MRFIT) were first developed by prevention strategists in the United States, Richard Remington, Jeremiah Stamler, and Henry Taylor, who submitted to the National Institutes of Health in 1969 the first MRFIT proposal, nicknamed "JUMBO" because of its complexity. Reviewers were unable to arrive at consensus on its support, but because of the urgent need to answer its fundamental questions the MRFIT idea was widely adopted.

The World Health Organization organized one model of a MRFIT in which workers at industrial sites in Belgium and Britain were randomly assigned to comparative health promotion programs. In the United States, the National Heart, Lung, and Blood Institute designed and organized a MRFIT which randomly assigned 12,866 men, thrity-five to fifty-seven years of age, with multiple elevated risk factors to special intervention programs (SI) or to "usual care" (UC). Similar programs were also pursued in Norway and other countries.

These ambitious MRFIT projects were carried out during the 1970s, coincident with a period of mass sociocultural change in health awareness and behavior, which, in turn, was accompanied by a precipitous fall in heart attack and stroke death rates in the industrial nations of the West. With the notable exception of the successful Oslo study, where, at the outset, cholesterol and smoking levels were extremely high and health awareness lower than elsewhere, the MRFIT studies were unable to demonstrate significantly reduced multiple risk factor levels or heart attack rates, over and above favorable changes occurring in their control groups. Thus, most of the scientific community regarded the MRFIT experiments as a failure. The investigators concluded, however, that the risk factor trends and heart attack rates were moving in a favorable directionthough within study designs too weak to reach significance. Long-term follow-up of the U.S. MRFIT and the Belgian MRFIT detected lower heart attack rates among the treated groups. Moreover, ongoing observational studies of U.S. MRFIT subjects greatly increased the understanding of relationships among lifestyle interventions, risk factors, and mortality.

The concept of reducing multiple risk factors to prevent heart attack and stroke remains intact because of the overwhelming observational evidence of the causal role of such risk factors. There is continued development of effective preventive practices and public health strategies for reducing risk levels, along with ongoing surveillance of population heart attack rates. Favorable national trends in health behaviors and multiple risk factor levels were accompanied by a steady and brisk decline in coronary death rates from the 1960s until the mid-1990s, when the rate of fall diminished. This was associated with a slowing of the reduction in risk factor levels, and with a failure of health promotion to reach underserved populations among the poor, the elderly, young people, and women. Preventive strategies are now directed not only at the highest multifactor risk segments of industrial societies but to whole countries at excess risk, and to the prevention of elevated multiple risk factors in the first placewhat is termed "primordial prevention."

Henry Blackburn

(see also: Cardiovascular Diseases; Chronic Illness; Framingham Study; Multifactorial Diseases; Noncommunicable Disease Control; Observational Studies; Risk Assessment, Risk Management )


Gotto, A. M. (1997). "The Multiple Risk Factor Intervention Trial (MRFIT): A Return to a Landmark Trial." JAMA 277:595597.

Multiple Risk Factor Intervention Trial Research Group (1982). "Multiple Risk Factor Intervention Trial: Risk Factor Changes and Mortality Results." JAMA 248:14651477.