Fastest Carotid IMT progression: a marker of focal Intima-Media Thickness progression associated with vascular events

Introduction: While the one-time measurement of Intima-Media Thickness (C-IMT) is a well recognized surrogate marker of subclinical atherosclerosis, the association of C-IMT progression with subsequent vascular events has been to date less consistent. We describe here the fastest C-IMT progression (Fastest-IMTprogr), a new index of focalized increase of C-IMT, potentially associated with the risk of vascular events. Methods: The Fastest-IMTprogr defined as the highest focal C-IMT increase occurring in any spot of the carotids over a definite time period, was compared with conventional progression variables (i.e. segment-specific progressions and progressions of IMTmax, IMTmean and IMTmean-max, of the whole carotid tree). Data from the IMPROVE study (3703 subjects from 5 European countries) were used. The association with vascular events, the multivariate association with conventional vascular risk factors (VRFs) and the signal-to- noise ratio (average annual progression over measurement error) were compared. In order to assess whether carotid IMT progression is a focal or diffuse phenomenon, we compared the within-subject variance, among the different segments, computed at baseline and at 15 months, as it is expected that a focal progression would result in an increase over time of the variance among IMTs of different carotid segments, whereas a diffuse progression would not. Results: As compared to conventional progression variables, the Fastest-IMTprogr showed: a) a stronger association with combined vascular events (age and gender adjusted hazard ratio 2.02, 95% confidence interval 1.33-3.06, p=0.0009), b) a stronger multivariate association with VRFs (R2=0.24 vs. 0.11, using the progression of mean common carotid) and c) a greater signal-to-noise ratio (4.8 times greater than that of the IMTmean-max progression, the second best performing variable). Moreover, the variability among carotid segments increased significantly by about 5% a year, thus pointing to a focalized dynamics for atherosclerosis progression. Conclusions: The Fastest-IMTprogr performed much better than all the other IMT-progression variables considered. This new index is able to grasp short-term focal IMT increases (which remain mostly hidden to conventional approaches) and appears to be a key risk factor for vascular events.