THE INVERSE RELATION OF AVERAGE POPULATION BLOOD-PRESSURE AND STROKE MORTALITY-RATES IN THE 7 COUNTRIES STUDY - A PARADOX

This study attempts to explain the unexpected finding of an inverse po pulation (ecological) relationship between mean systolic blood pressur e levels and stroke death rates in 25 years follow-up of the Seven Cou ntries Study, a cross-cultural study of cardiovascolar disease. Sixtee n cohorts of all men aged 40-59 in seven countries (one cohort in the USA, two in Finland, one in the Netherlands, three in Italy, two in Cr oatia (former Yugoslavia), three in Serbia (former Yugoslavia), two in Greece, two in Japan) were surveyed from 1958 to 1964. Risk factors a nd personal characteristics were measured and follow-up for vital stat us and cause of death was then carried out over 25 years. Analyses wer e based on comparisons of mean levels of risk factors and death rates within and among the 16 cohorts. Mean entry population levels of systo lic blood pressure among the cohorts were strongly and inversely relat ed with their 25-year stroke death rates (R -0.55; CI -0.81 and -0.06; p = 0.0276). Within cohorts in contrast, the individual relation of b lood pressure and stroke was strongly positive and significant in 14 o f the 16 cohorts. Mean population levels of serum cholesterol were inv ersely and strongly related to stroke death rates (R -0.79; CI -0.92 a nd -0.46; p = 0.0003), while the partial correlation coefficient of sy stolic blood pressure, computed in models including serum cholesterol, became small and not significant (-0.05; CI -0.55 and +0.48; p = 0.85 37). Age at death for stroke (average 68.9 +/- 7.1 years) was signific antly higher than age at death from myocardial infarction and sudden d eath (average 65.8 +/- 7.8 years) suggesting a competition effect betw een the conditions. Multivariate models including population average s ystolic blood pressure and serum cholesterol provided no added explana tion for the lack of direct and significant relationship of population blood pressure with stroke death rates. They were based on these vari ables: age at stroke death, age at myocardial infarction death or and sudden death, death rates from myocardial infarction and sudden death, the interaction term of systolic blood pressure with serum cholestero l and the multivariate coefficients for systolic blood pressure from C ox models run in individuals. Similar findings were obtained using dia stolic instead of systolic blood pressure and excluding the Japanese c ohorts. The paradox of the inverse ecologic relation of population blo od pressure and stroke mortality and a direct relation for individual is only partly explained by the cofounding effect of population mean s erum cholesterol levels. An effect of low cholesterol levels on excess stroke mortality cannot be excluded. A major limitation of the study was our inability to segregate thrombotic from heamorrhagic strokes.