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Commentary: insights from cross-population studies: Rose revisited.

The serum cholesterol concentrations of the local (mainly rural) population samples in the Seven Countries Study appear to have truly reflected the national differences (though not necessarily the national averages), since they correlate so remarkably well with the national differences in mortality. The high correlations also vindicate the use of national mortality rates, since errors in the data would tend to weaken the correlation estimates rather than create false-positive associations. Laboratory biases are excluded by using a central laboratory, and a false-positive correlation would seem possible only if there had been a tendency in countries with a high incidence of coronary heart disease to select population samples with unrepresentatively high cholesterol concentrations or vice versa in countries with a low incidence of the disease. Nevertheless, the strong inverse correlation of cholesterol concentration with senility and illdefined causes of death indicates that this is also a broad marker of medicosocial conditions and not only of dietary fat. The results support and extend the conclusion from the Seven Countries Study that differences in serum cholesterol concentration account for most of the difference in mortality from coronary heart disease between these countries. Differences in blood pressure might also contribute, but any such effect is overshadowed by the strength of the cholesterol prediction; furthermore, the comparison might be confused by measurement biases. All the correlations (for cholesterol concentration and both systolic and diastolic blood pressures) grew steadily stronger with time, and the cholesterol concentrations in the late 1950s gave an almost perfect prediction of the international differences in mortality from coronary heart disease in the mid1970s. With data from only seven countries it would be unwise to put too much reliance on the time trend, which was consistent with a delay of 10 years or more between exposure of a population to given concentrations of cholesterol or blood pressure and the maximum effect on mortality from coronary heart disease; the decline in American rates in the 1970s brought them into line with what would have been predicted by the cholesterol concentration more than a decade earlier. The situation is, however, complicated by continuing changes in the levels of these and other coronary risk factors. This makes it all the more surprising that a single examination can permit such accurate long-term prediction. Longitudinal surveys such as the Framingham study5 have found that in individuals the predictive ability of the serum cholesterol concentration is much less in older than in younger people, which seems to be at variance with the present findings. Possibly the determination of individual risk has a different basis from the determination of rates in populations. Some clarification might come from comparing short-term and longterm predictive power within the same individuals. The results do not support the view that low mean concentrations of cholesterol imply a higher national risk of cancer: the trend is in fact rather strongly in the reverse direction. Data extraction and computing were undertaken by Miss Linda Colwell.