Alessandro Menotti a , Henry Blackburn a , Fulvia Seccareccia b , Daan Kromhout c , Aulikki Nissinen d , Martti Karvonen e , Flaminio Fidanza f , Simona Giampaoli b , Ratko Buzina g , Ivan Mohacek h , Srecko Nedeljkovic i , Christ Aravanis j , Anastasios Dontas k
11 December 1997
Background: This analysis explores whether ‘typical’ clinical manifestations of coronary heart disease (CHD) such as myocardial infarction and sudden death, relate to major cardiovascular risk factors in the same way as the ‘atypical’ manifestations, e.g. heart failure and chronic arrhythmias. Patients and Methods: Sixteen cohorts of men aged 40–59 in seven countries were examined, risk factors measured (age, systolic blood pressure, serum cholesterol and smoking habits) and 25-year mortality data collected in a systematic way. Cohorts were located in the US (n = 1), Finland (n = 2), the Netherlands (n = 1), Italy (n = 3), former Yugoslavia (n = 5), Greece (n = 2) and Japan (n = 2), with a total of 12,763 individuals. Ecological analysis based on regression equations and correlation among cohorts, and individual analyses based on proportional hazard models in pools of cohorts were conducted with typical and atypical CHD deaths as dependent variables. Results: The ecological analysis suggests a significant relationship of populational mean levels of serum cholesterol and of systolic blood pressure to age-adjusted death rates from typical CHD manifestations. The relationships for atypical CHD deaths were not statistically significant. In the ecological approach with multivariate analysis, none of the risk factors showed relevant associations with event rates, except serum cholesterol and typical CHD deaths. The ecological relationship of serum cholesterol to atypical CHD death rates was negative but not significant. On average, mean age at death was statistically higher among atypical CHD than typical CHD patients (70.2 vs. 65.8 years). In the individual multivariate analysis conducted on pools of countries, the relationship of risk factors with typical CHD deaths was direct and significant for age, systolic blood pressure, and smoking habits in Northern Europe and America and Southern Europe, but only for systolic blood pressure and smoking habits in Japan, whereas for atypical CHD, the predictive factors were age, systolic blood pressure and cigarette smoking in Northern Europe and America and Southern Europe, but only age in Japan. Conclusions: The usual relationship of blood pressure and smoking habits and the differential relationship of serum cholesterol with atypical CHD (negative or absent) versus typical CHD (direct and significant) could be explained by ‘two different diseases’ or by a mix of poorly classified conditions among the atypical cases.