Carotid atherosclerosis progression varies according to baseline thickness in placebo and pravastatin treated subjects

Carotid intima-media thickness (IMT) is a surrogate measurement of early atherosclerosis. Disease progression is estimated by monitoring annual increase of an average of IMTs from different carotid segments (up to twelve). This procedure does not allow to investigate whether progression is focused in one or a few spots, and whether the effect of hypolipemic treatment is more effective on large plaques. Any attempt to monitor IMT increase on the single thickest segment (t-Max) has so far yielded poor results, far measurement inaccuracy and systematic effects like 'regression toward the mean'. We analyzed data on 301 asymptomatic hypercholesterolemic (mean age 55 years, 51% male. 154 placebo and 147 Pravastatin treated) from the Carotid Atherosclerosis Italian Ultrasound Study to evaluate single-segment progressions. In order to balance regression toward the mean, we excluded baseline measurements in computing progressions, and we adopted a system of weights to reduce the impact of measurement errors. The 3599 baseline IMTs (range 0.31 - 3.54 mm) where grouped into quintiles, and 3 years progression was calculated. IMTs in the upper quintile (>1.32 mm) tended to regress significantly also in the placebo group (-0.097 mm/yr. , p<0.0001), and the most significant effect of Pravastatin was observed on IMTs between 1.0 and 1.3 mm (0.021 mm/yr. reduction, p<0.0001), while in very thin or very thick segments this effect was less marked. These results are quite robust with respect to the procedures or weights employed, and strongly suggest a form of remodeling in larger plaques of asymptomatic hypercholesterolemic subjects with mild atherosclerosis. Pravastatin effect, although observed in all thickness categories, appears to be more marked (about threefold) on segments with mildly elevated IMT.