Carotid intima-media thickness: studies into methodological aspects

Carotid artery intima-media thickness (CIMT) is widely used in observational and intervention studies. Despite the long history and its frequent use there is little uniformity in the measurement of CIMT. This diversity may have substantial effects on published results of studies and on the interpretation thereof. In this thesis we aimed to study several methodological aspects of CIMT measurements to facilitate an evidence-based decision making with respect to CIMT measurements. In chapter 2, two online techniques to measure CIMT, an automated RF approach and a manual B-mode approach, were compared. CIMT measured with B-mode showed stronger relations with established risk factors and was more strongly associated with risk of future cardiovascular events whereas in individuals with a thin CIMT (<0.9 mm) automated RF provided stronger relations with risk factors and stronger associations with future events, indicating that type of study population and expected presence of local atherosclerotic abnormalities should be considered in the choice of technique. The pros and cons of two different CIMT outcome measures (the mean common CIMT and mean maximum CIMT) were considered in chapter 3. As most parameters (apart from logistics) between both measures were equal, the decisive aspect that remained was the congruency of the result of the outcome measure with event data. The congruency showed a complementary value of both measures, favoring the use of both measures. Since the measurement of the mean maximum CIMT also includes measurement of the mean common CIMT, the balance tips towards the mean maximum CIMT measurement as the choice of outcome. Completeness of CIMT data at different walls, segments and angles of the carotid artery was studied in a population with familial hypercholesterolemia (FH) and in a population with mixed dyslipidemia (MD) in chapter 4. With the current ultrasound protocols and equipment it is possible to obtain high levels of complete CIMT information from nearly all walls, segments and angles. Apart from the study population, the completeness depended on the body mass index and waist circumference. In chapter 5 ultrasound protocols were compared on reproducibility, progression rates of CIMT and treatment effects in four different study populations. Ultrasound protocols that included measurements of both walls at multiple (? 2) angles for both the mean common CIMT and the mean maximum CIMT overall provided the best balance of the parameters mentioned above. In chapter 6, we showed that the quantification of the effect of an intervention did not appear to be affected by the type of reading approach (reading in batch versus reading in consecutive order). However, the absolute observed CIMT progression rates might be biased in a non-batch approach. Finally, all findings were put in perspective and implications of choices on sample size were discussed in chapter 8. If one aims to design a study with a sample size that is large enough to demonstrate a statistically significant effect of the intervention on both the mean maximum CIMT as the mean common CIMT, the differences in magnitude of progression rate and precision of the estimates of both outcome measures should be considered.