Beyond stenosis: Further progress in multi-modal evaluation of carotid disease

Abstract

According to estimates from the American Heart Association, someone has a stroke every 40 seconds. Stroke is a leading cause of disability in United States leading to $73.7 billion direct and indirect cost to the economy. Current approach to estimate an individual’s risk for a stroke involves identification of various risk factors such as diet, smoking, hypertension, dyslipidemia, physical inactivity, and diabetes mellitus. The risk of stroke is particularly increased in patients with two or more of these risk factors. Further risk stratification involves assessment of degree of carotid stenosis. It is well established that patients with substantial carotid stenosis have an increased risk of future strokes which can be reduced with carotid endarterectomy. More recently, it has become evident that structural information beyond luminal encroachment may aid in determination of stroke risk. Efforts are currently underway to develop imaging techniques which can provide information about plaque biologic activity and composition with the expectation that the additional information may improve the identification of high-risk plaques and allow for better targeting of therapies to reduce stroke. Among plaque characteristics associated with stroke, several stand-out as potentially important, including plaque echoluceny and plaque inflammation. Echolucency is assessed using B-mode ultrasound. Plaques that appear echolucent on US tend to be lipid-rich when examined histologically, while plaques that are echogenic have a higher content of fibrous tissue and calcification. Moreover, plaque echolucency has been shown to predict subsequent risk of CVA. Plaque inflammation can also be measured using non-invasive imaging techniques. FDGPET imaging is validated as a method for measuring carotid plaque inflammation. Several studies have demonstrated a good correlation between carotid PET measures of FDG uptake and histopathologic measures of macrophage infiltration and inflammatory gene expression seen in specimens subsequently removed at endarterectomy. The arterial FDG signal is reproducible, correlates well with atherosclerotic risk factors, and is modifiable by anti-atherosclerotic therapies. Furthermore, prior studies have observed a link between FDG uptake and atherothrombotic symptoms as well as subsequent atherothrombotic events. Paulmier et al compared cardiovascular events in patients with (n = 45) and without (n = 56) arterial FDG uptake, who had PET scans as a part of malignancy work-up. In this study, higher FDG uptake was observed in patients who had previous vascular events or a new event within 6 months after their PET scan. Rominger et al demonstrated in a series of 932 patients, that a high PET signal was an independent predictor for the occurrence of cardioor cerebrovascular events. In that study, the odds of experiencing a subsequent atherothrombotic event were increased 14-fold in patients with a high FDG-PET signal, even after correcting for atherosclerotic risk factors. However, the relationship between PET and structural imaging assessments of carotid plaques is not well established. In this issue of Journal of Nuclear Cardiology, Choi et al compared FDG uptake (using PET-CT) with high risk ultrasound characteristics (echolucency) of the carotid plaque. The authors found significantly higher FDG uptake in echolucent plaques as compared to calcified plaques or carotids vessels without plaques (P 0.05). These findings are consistent with prior observations by Graebe et al wherein a negative correlation between the extent of echolucency (measured as gray scale median) and FDG uptake was observed (r = -0.56, P 0.01). An important difference between the two studies is that the findings by Graebe et al were observed in symptomatic patients, while the present study involved patients who were asymptomatic. The observed association between FDG uptake and echolucency is encouraging, and advances the case that From the Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA. Reprint requests: Ahmed Tawakol, MD, Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; atawakol@partners.org. J Nucl Cardiol 2011;18:204–6. 1071-3581/$34.00 Copyright 2011 American Society of Nuclear Cardiology. doi:10.1007/s12350-011-9341-8