Carotid atherosclerosis, a chronic inflammatory disease, is a risk factor for ischemic stroke, the third cause of death in developed countries. Degree of stenosis, evaluated by imaging techniques, is used to predict the risk of future cerebrovascular events and it is considered the most validated parameter to select asymptomatic patients eligible for carotid endarterectomy (CEA). However it has been observed that a subset of patients, particularly women, with lesions at an early stage of development undergoes sudden death. Therefore there is the need of more sensitive tools, that in addition to imaging techniques permit to identify plaques at high risk of clinical events. The identification of suitable biomarkers could provide a useful adjunctive criterion to ensure better risk stratification and optimize management of patients. The aim of this project is to identify inflammatory and immunological molecules in the blood of patients with carotid atherosclerosis as biomarkers of plaque activity associated with plaque morphology evaluated by ultrasound. Patients will be divided into two groups according to the presence or not of indication for CEA. A Doppler carotid ultrasound study will be used to determine a computer assisted (quantitative) index named Gray-Scale median (GSM). This score will be used to assess the carotid plaque echogenicity, that is associated to plaque characteristics. The panel of soluble molecules will include: 1) CD40L a protein by activated T lymphocytes and platelets; 2) endoglin, a biomarker of neoangiogenesis and endothelial dysfunction; 3) CD163 and CD14, two macrophage biomarkers, 4) E-selectin, an adhesion molecule expressed on endothelial cells; 5) MCP-1, one of the key chemokines that regulate migration and infiltration of monocytes/macrophages; 6) Adiponectin, a novel adipocyte-specific protein, which plays a role in the development of atherosclerosis.
On the basis of literature data, an ideal approach to evaluate plaque instability would provide information regarding both the morphology and activity of the plaque. The large majority of clinical studies focused on the association between biomarkers and subclinical atherosclerosis, that is carotid intima-media thickening, which represents an earlier stage of the disease. A restricted number of individuals is a common limitation in studies investigating multiple biomarkers of one pathological condition and we cannot exclude that larger sample size would yield more significant associations. The innovation of our proposal is that it is aimed to investigate inflammatory biomarkers that are associated with a higher atherosclerotic burden and features of plaque instability in patients with carotid atherosclerotic plaque, which represents an advanced stage of disease compared with carotid intima-media thickening.
Furthermore the monitoring of plaque development is a challenging clinical task which requires information obtained with different diagnostic tools. Studies on the associations of ultrasonographic features with multiple biomarkers in the blood are strongly encouraged to increase our knowledge of the complex pathophysiologic phenomena of carotid plaques and to aid the clinicians in the identification of patients eligible for CEA. The combination of degree of stenosis, with circulating biomarkers may provide a better insight into the development of atherosclerotic vascular disease, and will aid the clinicians to evaluate the response to pharmacological therapy and the surgeons to identify vulnerable plaques eligible for CEA. Ideally, the association of plaque activity evaluated by circulating biomarkers with plaque characteristics evaluated by ultrasound will enhance the value of echogenicity indices for an accurate morphologic characterization of vulnerable plaques and will accelerate incorporation of echogenicity as a non-invasive tool in individualized patient management.
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