Since the classical risk factors show poor correlation with C-IMT, 12–18 more important determinants of the development of atherosclerosis apparently exist. An appealing facet of vascular imaging as a surrogate endpoint for cardiovascular disease is that it assesses the atherosclerotic disease process itself, which includes the net effect of hereditary and environmental factors, either known or yet to be discovered. Indeed, plasma biomarkers have come under scrutiny since a few of those considered to be among the most reliable intermediate endpoints (LDL-C or HDL-C) have failed to predict clinical benefit following pharmacological intervention in the causal pathway. Recently, evaluation of determinants of C-IMT in a high-risk population has gained particular attention for a variety of reasons. To address this issue, we designed ‘the IMPROVE study’, a longitudinal cohort study carried out in a European sample of persons with at least three VRFs. Although commonly accepted, this assumption has not yet been rigorously tested. Monitoring of IMT in clinical trials, however, is based on the assumption that not only cross-sectional IMT, but also IMT progression, is a predictor of new vascular events. A variety of compounds with different mechanisms of action reduce C-IMT progression, albeit to different extents. Overall, attempts to delay IMT progression, or even to induce IMT regression, by using ‘anti-atherosclerotic’ agents, have provided encouraging results. 3, 11 Against this background, this ultrasound variable has been widely used in clinical trials, as a substitute for angiography, to investigate the effectiveness of pharmacological and dietary intervention. 2 In addition, in view of its correlation with coronary atherosclerosis 3–6 and its capacity to predict incident coronary events, 7–10 carotid IMT (C-IMT) has been proposed as a surrogate marker of coronary atherosclerosis. 1 Intima–media thickness (IMT) of extracranial carotid arteries, measured by high-resolution B-mode ultrasound, is the most widely accepted non-invasive marker of subclinical atherosclerosis, which has been used in clinical and epidemiological studies to investigate the effects of established and non-traditional vascular risk factors (VRFs), as well as the association with end-organ damage in high-risk patients. Therefore, identification of markers of subclinical arterial disease is fundamental. The early recognition and treatment of patients at high risk of atherosclerosis is a major goal to reduce the incidence of atherothrombotic events. The geographical gradient for C-IMT paralleled the well-known north-to-south cardiovascular mortality gradient ( r 2 for IMT mean = 0.96).Ītherosclerosis, Risk factors, Ultrasound, B-mode, Geographical gradient, Latitude Introduction Latitude was the strongest independent determinant of C-IMT (partial r 2 for IMT mean–max = 0.109, P < 0.0001) and alone accounted for nearly half of the variation explained by the regression model (partial r 2 for IMT mean–max = 0.243, P < 0.0001). By multiple linear regression analysis, C-IMT was positively associated with latitude, age, gender, pulse pressure, pack-years, and hypertension, and inversely with educational level (all P < 0.0001 for IMT mean–max). Collected variables included clinical, biochemical, genetic, socioeconomic, psychological, nutritional, and educational data, personal and family history of diseases, drug intake, and physical activity. A total of 3711 subjects (age range 54–79 years) with at least three vascular risk factors (VRFs) were recruited in seven centres in Finland, France, Italy, the Netherlands, and Sweden.
IMPROVE is a prospective, multicentre, longitudinal, observational study.
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