Intima-media thickness as an additive marker of cardiovascular risk

Objective: To elucidate whether carotid artery intima media thickness (IMT) detected by B-mode ultrasound can be considered as a clinically useful marker of cardiovascular risk. Methods: To address the study objectives the correlation between carotid IMT and vascular risk factors (VRFs), the IMT performance in the recognition of patients with and without history of vascular events, the association between carotid IMT and the extent of coronary atherosclerosis, and the carotid IMT capacity to predict new vascular events are discussed. Results: In large cross-sectional studies mainly performed in patients attending our Lipid Clinic, we have previously shown that carotid artery IMT correlates well with coronary VRFs.1,2 We have also shown that carotid IMT discriminates well between groups of patients with and without a history of events.1 In a later study, carried out by using Artificial neural networks as an innovative approach to perform statistical analyses, we have also shown that carotid IMT can significantly increase the capacity of VRFs to identify patients with and without a history of cardiovascular events even on an individual basis.3 More recently we have also investigated the relationship between carotid atherosclerosis detected by external B-mode ultrasound and coronary atherosclerosis measured by both quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). In this study, the highest correlation coefficients between carotid and coronary atherosclerosis were observed when both vascular districts were measured with ultrasound methods (external carotid B-mode ultrasound vs coronary IVUS). In the same study, carotid ultrasonic variables proved more effective than QCA to identify patients with a positive IVUS test. Finally, in a longitudinal - observational study, we have also shown that the combined use of the Framingham Risk Score (FRS) and ultrasonic measurements of carotid IMT significantly increases the ability of VRFs to predict cardiovascular events in patients at low/intermediate risk (FRS <20%). A prospective, multicenter, longitudinal, long-term, observational study (The IMPROVE study) is currently ongoing. It aims to investigate the association between carotid IMT-progression and the rate of new vascular events in subjects at high risk. The patients enrolment ended in April 2005 and a total of 3711 patients were recruited in 6 European countries (1095 in Italy, 504 in France and 2140 in northern Europe). Conclusions: Data will be presented clearly supporting the possibility of using carotid IMT not only as a marker of cardiovascular risk but also as a predictor of new events. These results, together with those reported by others, also support the possibility of using carotid IMT as a surrogate endpoint in pharmacological studies. Although this approach has been already used in a number of clinical trials to evaluate the effectiveness of anti atherosclerotic treatments, studies are needed to fully demonstrate that IMT-progression, like IMT measured in cross-sectional studies, is a predictor of new vascular events. The currently ongoing IMPROVE study will address also this still missing piece of information; results are expected for the end of 2008. References: 1. Baldassarre D, Amato M, Bondioli A, Sirtori CR, Tremoli E. Carotid artery intima-media thickness measured by ultrasonography in normal clinical practice correlates well with atherosclerosis risk factors. Stroke 2000;31:2426-2430. 2. Baldassarre D, Amato M, Pustina L, Tremoli E, Sirtori CR, Calabresi L, Franceschini G. Increased carotid artery intima-media thickness in subjects with primary hypoalphalipoproteinemia. Arterioscler Thromb Vasc Biol 2002;22:317-322. 3. Baldassarre D, Grossi E, Buscema M, Intraligi M, Amato M, Tremoli E, Pustina L, Castelnuovo S, Sirtori CR. Recognition of patients with cardiovascular disease by artificial neural networks. Ann of Med. 2004;36:630-640. Funding: Research describing correlations between carotid and coronary atherosclerosis is supported by the Italian Ministry of Health. The improve study is supported by European Union.