Ultrasound and atherosclerosis. Evaluation of methods, risk factors and intervention.

The importance of studying cardiovascular disease before the process leads to hard end-points has been recognised, and methods to quantify early atherosclerosis have been taken in use in many research centres around the world. An ultrasound method with a computer assisted image analysing system was developed in co-operation with the Wallenberg Laboratory for Cardiovascular Research and Chalmers University of Technology in Gothenburg, Sweden. The objectives of the studies were to determine the validity and reproducibility of the method, to describe the associations between known cardiovascular risk factors and as well ultrasound-determined degree of atherosclerosis cross-sectionally as progression of these parameters, and to elucidate the effects of multifactorial intervention on cardiovascular risk factors. The method proved valid and reproducible when evaluating early atherosclerosis, reflected by intima-media thickness (IMT) in the Carotid artery. Measurements of IMT in the Femoral artery and plaque size were less reproducible. In multiple regression models, ultrasound-determined degree of atherosclerosis cross-sectionally, as well as change in the degree, correlated to known cardiovascular risk factors with small differences between men and women. However, in general, the degrees of explanation were low in the multiple regression models, and the strongest determinator of progression in IMT, plaque occurrence and degree of stenosis were the baseline values, reflecting regression towards the mean. In a small pilot study, multifactorial intervention on cardiovascular risk factors resulted in no measurable effect on ultrasound-determined progression of atherosclerosis. Using the experience gained from our studies, the ultrasound method is well-suited for application in research on atherosclerosis progression and regression. In prospective studies, to avoid regression towards the mean, duplicate investigations at baseline and follow-up are recommended. In intervention studies, a more aggressive pharmacological treatment than what was the case in our study, should be applied after proper sample size calculations