Objectives: To examine the generalisability of multivariate risk functions from diverse populations in three contexts: ordering risk, magnitude of relative risks, and estimation of absolute risk. Design: Meta-analysis of prospective cohort studies. Patients: Participants from various epidemiological studies. Main outcome measure: Death from coronary heart disease (CHD). Results: The analysis included 105 420 men and 56 535 women 35-74 years of age and free of CHD at baseline from 16 observational studies with a total of 27 analytical groups. The area under the receiver operating characteristic curve (AUC) was used to judge the ability of the multivariate risk function to order risk correctly. AUCs ranged from 0.60 to 0.80. The AUCs differed significantly between the studies (p < 0.01) but were very similar for different risk functions applied to the same population, indicating similar ability to rank risk for different models. The magnitudes of the relative risks associated with major risk factors (age, systolic blood pressure, serum total cholesterol, smoking, and diabetes) varied significantly across studies (p < 0.05 for homogeneity). The prediction of absolute risk was not very accurate in most of the cases when a model derived from one study was applied to a different study. Conclusions: When considered qualitatively, the major risk factors are associated with CHD mortality in a diverse set of populations. However, when considered quantitatively, there was significant heterogeneity in all three aspects: ordering risk, magnitude of relative risks, and estimation of absolute risk. C oronary heart disease (CHD) is a leading cause of death in many countries. Prospective studies around the world have identified major risk factors for developing CHD and, based on these risk factors, functions have been developed to predict the occurrence of CHD in individual patients. Although many researchers have examined whether a risk function based on a single population is valid when applied to other populations, 1-12 most have involved a small number of studies and the various aspects of predictive accuracy have not been systematically examined. In this report we examine the predictive accuracy of risk functions using three successively stronger sets of criterion: ordering risk, estimating relative risk, and estimating absolute risk.The lowest level of validity for a predictive function is its ability to rank individual patients within a population according to their risk, differentiating patients with higher risk from those at lower risk levels. The absolute level of risk is not a concern; only the ordering is important. Several reports have examined the ability of a single risk function to order risk across studies and judged the validity of the risk function by this criterion. Estimating relative risk is more difficult than ordering. A more stringent criterion would require that the model parameters relating risk factors to disease be the same in different populations. Comparisons in the literature based on this criteri...

In a prospective study of more than 10,000 Yugoslav men residing in Bosnia and Croatia, who were first examined in 1964--1965, consumption of alcoholic beverages was related inversely to the subsequent appearance of coronary heart disease clinically manifest as myocardial infarction or nonsudden coronary heart disease death. Consumption of alcoholic beverages was not so related to sudden cardiac death. Men who drank most frequently had half the subsequent incidence of overall coronary heart disease as men who seldom or never drank. This finding was true for urban residents only. Serum cholesterol and Quetelet index were also related to coronary heart disease in urban areas but not in rural areas. The inverse relation of alcohol consumption to coronary heart disease incidence was statistically significant even after taking into account differences in blood pressure, serum cholesterol levels, cigarette smoking and other variables. The apparent absence of protection against sudden death may be due to chance or it may reflect the deleterious effects of high alcohol consumption on the myocardial cells and increased vulnerability to lethal arrhythmias in an especially lean population. There is, in fact, a specific association of recent drunkenness with sudden death in this population. Conceivably, the acute effect of heavy drinking may be a dominant factor in the incidence of sudden death for this population.

In a 7-year follow-up of 11,121 Yugoslav men first examined in 1964-1965 when they were 35-62 years old, it was found that the incidence of coronary heart disease (CHD) was one-fourth that of a comparable Framingham (USA) group. Incidence in rural men was only 59% of urban men. In both urban and rural groups, men with higher blood pressures had greater CHD incidence, and cigarette smoking was also associated with greater incidence. In the urban but not the rural groups serum cholesterol and weight/height were also CHD risk factors. Levels of serum cholesterol and weight were lower in urban Yugoslavia than Framingham and lowest in rural Yugoslavia. At the same levels of these characteristics Framingham incidence was 3 times that in Yugoslavia. At the very low rural levels of weight and blood pressure CHD incidence was the same in urban as rural Yugoslav groups.

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