Cross-sectional analysis of baseline data to identify the major determinants of carotid intima-media thickness in a European population: the IMPROVE study

The 'IMPROVE study' was designed to investigate whether cross-sectional carotid artery intima-media thickness (IMT) and overall IMT progression are predictors of new vascular events in European individuals at high risk of cardiovascular diseases. This paper reports the results of the baseline analyses aimed at identifying the major determinants of increased carotid IMT (C-IMT). IMPROVE is a prospective, multicentre, longitudinal, observational study. A total of 3711 subjects (age range 54-79 years) with at least three vascular risk factors (VRFs) were recruited in seven centres in Finland, France, Italy, the Netherlands, and Sweden. Collected variables included clinical, biochemical, genetic, socioeconomic, psychological, nutritional, and educational data, personal and family history of diseases, drug intake, and physical activity. By multiple linear regression analysis, C-IMT was positively associated with latitude, age, gender, pulse pressure, pack-years, and hypertension, and inversely with educational level (all P < 0.0001 for IMTmean-max). Latitude was the strongest independent determinant of C-IMT (partial r(2) for IMTmean-max = 0.109, P < 0.0001) and alone accounted for nearly half of the variation explained by the regression model (partial r(2) for IMTmean-max = 0.243, P < 0.0001). The geographical gradient for C-IMT paralleled the well-known north-to-south cardiovascular mortality gradient (r(2) for IMTmean = 0.96). Latitude is an important determinant of C-IMT, which is not explained by between-country differences in established VRFs. Other unknown contributory mechanisms such as heritable, nutritional, or environmental factors may be important in the genesis of this geographical gradient.