Progression of Carotid Intima-Media Thickness as Predictor of Vascular Events: Results from the IMPROVE Study

Objective —To investigate whether several different measures of carotid intima-media thickness (C-IMT) progression are associated with subsequent vascular events (VEs), and whether such associations are independent of baseline carotid atherosclerotic profile and Framingham risk factors (FRFs). Approach and Results — A longitudinal cohort study (the IMPROVE study) was carried out in 7 centers in 5 European countries (Finland, France, Italy, the Netherlands and Sweden). 3482 subjects (median age 64.1 years; 47.8% men) with at least three vascular risk factors were recruited and monitored for a post-progression median follow-up of 21.5 months, during which time 129 subjects suffered a first VE (incidence of 20.4 per 1000 person-years). The 15th month progression of mean and maximum C-IMT of the left and right common carotids, bifurcations, internal carotid arteries and their composite measures, as well as the fastest IMTmax progression (Fastest-IMTmax-progr) detected in the whole carotid tree regardless of location, were used in the statistical analyses. All C-IMT measures showed significant progression during the first 15 months (P<0.001), but only the Fastest-IMTmax-progr was significantly associated with the risk of subsequent VEs. The Fastest-IMTmax-progr association persisted after Bonferroni correction for multiple comparisons and after adjustments for FRFs and pharmacological treatments (all P<0.005). The use of the Framingham Risk Score in place of FRFs provided almost identical results (P=0.003). Conclusions—The Fastest-IMTmax-progr, a novel approach to assess C-IMT progression, identifies focal increases of carotid IMT and, in contrast to other progression variables, is associated with cardiovascular risk.