The Fastest Progression of Carotid Intima Media Thickness is Associated with Increased Vascular Events in the IMPROVE Study

Background: The association between progression of Carotid Intima Media Thickness (C-IMT) and cardiovascular risk remains controversial and has not been examined in large epidemiological studies, specifically designed for this purpose. Methods: The 15-month C-IMT progression was measured in 3703 European high risk individuals (>3 vascular risk factors) enrolled in the IMPROVE Study. Progression of mean and maximum IMT of the left and right common carotids, bifurcations, internal carotid arteries and of the whole carotid tree, as well as the fastest IMT-progression detected in the whole carotid tree regardless of its location (Fastest-IMTprogr) were computed and used in the statistical analyses. A Cox proportional hazards model was used to assess the association between these variables and cardiovascular events occurred during the subsequent follow-up (median 21.8 months). Results: All ultrasonic variables significantly progressed during the 15th months, but only fastest IMT-progression was significantly associated with the incidence of vascular events. The unadjusted hazard ratios (HR) for combined events (coronary, cerebral and vascular events pooled together) were 1.18 [1.05-1.33] (p=0.005), 1.15 [1.01-1.30] (p=0.03) and 1.19 [1.06-1.33] (p=0.004) for one standard deviation increase of the Fastest-IMTprogr detected in carotid bifurcations, internal carotid arteries and the whole carotid tree, respectively. These associations remained significant, or nearly significant, after adjustment for age, sex and baseline-IMT (p=0.009, p=0.06 and p=0.01) as well as after further adjustment for latitude, HDL-C, LDL-C, systolic blood pressure, diabetes, hypertension, pack-years and pharmacological treatments (p=0.09, p=0.03 and p=0.04). Conclusions: The fastest carotid IMT-progression, being associated with an increased risk of CV events in high-risk European subjects, represents a novel risk marker and/or a potential target for therapy.