This statement is an update of the 1970 Inter-Society Commission for Heart Disease Resources ( ICHD ) report, "Primary Prevention of the Atherosclerotic Diseases." The charge to the Study Group was to assess relevant new data and, where the evidence is less than definitive, to formulate conclusions and recommendations based on best judgment. Current developments are reviewed, and issues raised in response to the earlier recommendations are considered. Recommendations are intended to serve as a guide for individual behavior, physician practice, and the formulation of public health policy.

Comparing the effects of long-term beta-blocker trials on nonfatal myocardial infarction (MI) is difficult because of differences in diagnostic criteria and in methods of reporting and classifying events. Analysis of available data indicates that the relative effect of beta blockers on the incidence of nonfatal MI is not different among the reviewed long-term trials. Pooling of trial results indicates that beta-blocker therapy has a beneficial effect on nonfatal MI incidence that is of the same magnitude (25%) as that for all-cause mortality.

Treatment with oral beta 1 blockade started after recovery from acute myocardial infarction and continued for approximately 2 years reduces total mortality by about 25%. It is unclear how long oral treatment should be maintained, nor is it known if stopping beta blockade increases the risk of sudden death or reinfarction. Acute i.v. administration of beta blockers has been shown to reduce indexes of infarct size. The effect of this reduction on short- and long-term survival is promising, but not conclusive.

It seems clear that beta blockers can limit infarct size in man and reduce mortality after a myocardial infarction. Early mortality also seems to be reduced by beta blockade in patients in whom infarct size was not limited. Thus, infarct size limitation is not the only mechanism for an effect of beta blockade on early infarction mortality. The favorable effect of early initiation of beta blockade on long-term survival might, however, suggest an importance of infarct size limitation for prognosis. More studies are needed to evaluate the role of infarct size limitation for long-term prognosis.

Morbidity and mortality differences between populations, between ethnic groups and between individuals are not satisfactorily explained by the variation of risk factors. Differences in genetic susceptibility might be responsible for a part of the unexplained variation of coronary heart disease (CHD) rates. Genetic factors are also significant in determining the level of risk factors in individuals. Ample evidence links genetic factors to the levels of serum cholesterol, blood pressure and diabetes. Marked sex differences in CHD mortality also indicate the role of heredity in the development of the disease. The male:female ratio varies widely between different countries, as well as between different ethnic groups. These variations are difficult to explain by variation in environmental and behavioral differences between males and females alone. The degree of atherosclerosis in males and females varies, depending on the anatomic location of the atherosclerosis. Inherited disorders of metabolism and the variability of anatomic patterns provide additional indications of the role of genetics. The data accumulated in the Israeli Ischemic Heart Disease Study over 15 years reveal an ethnic variation of risk factors coupled with remarkably larger variation in disease rates. Patterns of incidence assessed in the national mortality data of the Israeli study and in histologic findings in the coronary arteries of infants from different ethnic groups are compatible with a hypothesis that ethnic and sex differences in early structural changes of the coronary arteries partly determine the susceptibility of the latter to the development of atherosclerosis. In conclusion, findings from our studies and the review of the evidence from genetic epidemiologic investigations indicate a significant role of genetics in determining the degree, time course and severity of the atherosclerotic process and of the occurrence of symptomatic CHD. This important role of the genetic component is relevant to preventive strategies offered as tools for reducing the burden of CHD. Research into genetic determinants of both susceptibility to atherosclerosis or clinical manifestation of CHD and individual response to preventive measures should be encouraged.

Myocardial ischemia has, for many decades, been viewed as an all-or-none process that causes myocardial necrosis when prolonged and severe, but whose effects are transient when it is brief or mild. In view of the evidence that the ischemic process may "hit, run and stun," perhaps our thinking about the consequences of myocardial ischemia should be expanded. According to this formulation, an ischemic insult not of sufficient severity of duration to produce myocardial necrosis may acutely affect myocardial repolarization and cause angina (hit); but these changes wane rapidly (run), when the balance between myocardial oxygen supply and demand has been reestablished. However, the ischemia may interfere with normal myocardial function, biochemical processes and ultrastructure for prolonged periods (stun). The severity and duration of these postischemic changes depend on the length and intensity of the ischemia, as well as on the condition of the myocardium at the onset of the ischemic episode. Furthermore, it is likely that when the myocardium is repeatedly stunned, it may exhibit chronic postischemic left ventricular dysfunction, an ill-defined condition. If prolonged, chronic postischemic left ventricular dysfunction can progress to myocardial scarring and ischemic cardiomyopathy, it may be important to determine how often it can be ameliorated by permanent improvement of myocardial perfusion by surgical treatment.