Age, period, cohort and geographical area effects on the relationship between risk factors and coronary heart disease mortality. 15-year follow-up of the European cohorts of the Seven Countries study.

The effects of three major risk factors (i.e. serum cholesterol, systolic blood pressure and smoking habits) on prediction of coronary heart disease (CHD) mortality in relation to three nuisance variables--i.e. geographical location, age of subject at examination and period of examination--are analyzed using data from three different 5-year apart examinations of the Seven Countries Study and observations on CHD mortality in the corresponding 15-year follow-up period. First, a cross-classification exploratory analysis including both CHD-free subjects at entry and prevalence subjects, by different geographical areas, age classes and examination times is presented. Secondly, a logistic regression including the three major risk factors and the three nuisance variables, regarded both as confounders and effect modifiers is discussed. The prevalence status of the subjects is also considered as a nuisance variable in this second analysis. Results showed that: (a) there is a highly significant (p less than 0.001) marked decrease in the association between cholesterol level and CHD mortality with increasing age of subject; (b) a decreasing association with coronary heart disease mortality as age increases also holds for smoking habits (p less than 0.05). This association, however, tends to be reinforced with time (p less than 0.05), i.e. the relative risk of heavy smokers vs non-smokers is four times bigger in the period 1970-75, than in the period 1960-65, age and all other factors being equal; (c) a possible dependence of the association between systolic blood pressure and CHD on geographical area is suggested, although this finding could be the result of chance with a 10% probability.