Thomas J. Tegos

Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification

BACKGROUND The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis. METHODS This was a prospective, multicenter, cohort study of patients undergoing medical intervention for vascular disease. Hazard ratios for ICA stenosis, clinical features, and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic (CORI) events were calculated using proportional hazards models. RESULTS A total of 1121 patients with 50% to 99% asymptomatic ICA stenosis in relation to the bulb (European Carotid Surgery Trial [ECST] method) were followed-up for 6 to 96 months (mean, 48). A total of 130 ipsilateral CORI events occurred. Severity of stenosis, age, systolic blood pressure, increased serum creatinine, smoking history of more than 10 pack-years, history of contralateral transient ischemic attacks (TIAs) or stroke, low grayscale median (GSM), increased plaque area, plaque types 1, 2, and 3, and the presence of discrete white areas (DWAs) without acoustic shadowing were associated with increased risk. Receiver operating characteristic (ROC) curves were constructed for predicted risk versus observed CORI events as a measure of model validity. The areas under the ROC curves for a model of stenosis alone, a model of stenosis combined with clinical features and a model of stenosis combined with clinical, and plaque features were 0.59 (95% confidence interval [CI] 0.54-0.64), 0.66 (0.62-0.72), and 0.82 (0.78-0.86), respectively. In the last model, stenosis, history of contralateral TIAs or stroke, GSM, plaque area, and DWAs were independent predictors of ipsilateral CORI events. Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke, with predicted risk close to observed risk. Of the 923 patients with ≥ 70% stenosis, the predicted cumulative 5-year stroke rate was <5% in 495, 5% to 9.9% in 202, 10% to 19.9% in 142, and ≥ 20% in 84 patients. CONCLUSION Cerebrovascular risk stratification is possible using a combination of clinical and ultrasonic plaque features. These findings need to be validated in additional prospective studies of patients receiving optimal medical intervention alone.

Reproducibility of Computer-Quantified Carotid Plaque Echogenicity Can We Overcome the Subjectivity?

Background and Purpose We sought to assess the reproducibility, interobserver variability, and application to clinical studies of a new method for the quantitative assessment of carotid plaque echogenicity. Methods Carotid plaques were scanned with the use of ultrasound, and their images were stored in a computer. They were normalized by assigning certain gray values to blood and adventitia, and the gray scale median (GSM) was used to quantify their echogenicity. The variability between storage media, between degrees of magnification, and between probes was assessed. The method was applied to 232 asymptomatic carotid plaques causing 60% to 99% stenosis in relation to the presence of ipsilateral CT-demonstrated brain infarcts. In all parts of the study the plaque GSM was measured before and after normalization to evaluate its effect. Interobserver agreement for the scanning process was assessed. Results The GSM mean difference before and after normalization for variability studies of storage media, degrees of magnification, and probes was −14.5 and −0.12, 2.24 and 1.68, and −8.3 and −0.7, respectively. The median GSM of plaques associated with ipsilateral nonlacunar silent CT-demonstrated brain infarcts was 14, and that of plaques that were not so associated was 30 (P =0.003). The interobserver GSM difference was −0.05 (95% CI, −1.7 to 1.6). Conclusions Our method decreases the variability between storage media and between probes but not the variability between degrees of magnification. It separates echomorphologically the carotid plaques associated with silent nonlacunar CT-demonstrated brain infarcts from plaques that are not so associated.

Hemispheric symptoms and carotid plaque echomorphology.

PURPOSE In patients with carotid bifurcation disease, the risk of stroke mainly depends on the severity of the stenosis, the presenting hemispheric symptom, and, as recently suggested, on plaque echodensity. We tested the hypothesis that asymptomatic carotid plaques and plaques of patients who present with different hemispheric symptoms are related to different plaque structure in terms of echodensity and the degree of stenosis. METHODS Two hundred sixty-four patients with 295 carotid bifurcation plaques (146 symptomatic, 149 asymptomatic) causing more than 50% stenosis were examined with duplex scanning. Thirty-six plaques were associated with amaurosis fugax (AF), 68 plaques were associated with transient ischemic attacks (TIAs), and 42 plaques were associated with stroke. B-mode images were digitized and normalized using linear scaling and two reference points, blood and adventitia. The gray scale median (GSM) of blood was set to 0, and the GSM of the adventitia was set to 190 (gray scale range, black = 0; white = 255). The GSM of the plaque in the normalized image was used as the objective measurement of echodensity. RESULTS The mean GSM and the mean degree of stenosis, with 95% confidence intervals, for plaques associated with hemispheric symptoms were 13.3 (10.6 to 16) and 80.5 (78.3 to 82.7), respectively; and for asymptomatic plaques, the mean GSM and the mean degree of stenosis were 30.5 (26.2 to 34.7) and 72. 2 (69.8 to 74.5), respectively. Furthermore, in plaques related to AF, the mean GSM and the mean degree of stenosis were 7.4 (1.9 to 12. 9) and 85.6 (82 to 89.2), respectively; in those related to TIA, the mean GSM and the mean degree of stenosis were 14.9 (11.2 to 18.6) and 79.3 (76.1 to 82.4), respectively; and in those related to stroke, the mean GSM and the mean degree of stenosis were 15.8 (10.2 to 21.3) and 78.1 (73.4 to 82.8), respectively. CONCLUSION Plaques associated with hemispheric symptoms are more hypoechoic and more stenotic than those associated with no symptoms. Plaques associated with AF are more hypoechoic and more stenotic than those associated with TIA or stroke or those without symptoms. Plaques causing TIA and stroke have the same echodensity and the same degree of stenosis. These findings confirm previous suggestions that hypoechoic plaques are more likely to be symptomatic than hyperechoic ones. They support the hypothesis that the pathophysiologic mechanism for AF is different from that for TIA and stroke.

Silent embolic infarcts on computed tomography brain scans and risk of ipsilateral hemispheric events in patients with asymptomatic internal carotid artery stenosis

OBJECTIVES This study tested the hypothesis that silent embolic infarcts on computed tomography (CT) brain scans can predict ipsilateral neurologic hemispheric events and stroke in patients with asymptomatic internal carotid artery stenosis. METHODS In a prospective multicenter natural history study, 821 patients with asymptomatic carotid stenosis graded with duplex scanning who had CT brain scans were monitored every 6 months for a maximum of 8 years. Duplex scans were reported centrally, and stenosis was expressed as a percentage in relation to the normal distal internal carotid criteria used by the North American Symptomatic Carotid Endarterectomy Trialists. CT brain scans were reported centrally by a neuroradiologist. In 146 patients (17.8%), 8 large cortical, 15 small cortical, 72 discrete subcortical, and 51 basal ganglia ipsilateral infarcts were present; these were considered likely to be embolic and were classified as such. Other infarct types, lacunes (n = 15), watershed (n = 9), and the presence of diffuse white matter changes (n = 95) were not considered to be embolic. RESULTS During a mean follow-up of 44.6 months (range, 6 months-8 years), 102 ipsilateral hemispheric neurologic events (amaurosis fugax in 16, 38 transient ischemic attacks [TIAs], and 47 strokes) occurred, 138 patients died, and 24 were lost to follow-up. In 462 patients with 60% to 99% stenosis, the cumulative event-free rate at 8 years was 0.81 (2.4% annual event rate) when embolic infarcts were absent and 0.63 (4.6% annual event rate) when present (log-rank P = .032). In 359 patients with <60% stenosis, embolic infarcts were not associated with increased risk (log-rank P = .65). In patients with 60% to 99% stenosis, the cumulative stroke-free rate was 0.92 (1.0% annual stroke rate) when embolic infarcts were absent and 0.71 (3.6% annual stroke rate) when present (log-rank P = .002). In the subgroup of 216 with moderate 60% to 79% stenosis, the cumulative TIA or stroke-free rate in the absence and presence of embolic infarcts was 0.90 (1.3% annual rate) and 0.65 (4.4% annual rate), respectively (log-rank P = .005). CONCLUSION The presence of silent embolic infarcts can identify a high-risk group for ipsilateral hemispheric neurologic events and stroke and may prove useful in the management of patients with moderate asymptomatic carotid stenosis.

The objective characterisation of ultrasonic carotid plaque features.

OBJECTIVE To determine the influence of ultrasonic carotid plaque morphology on the incidence of ipsilateral hemispheric symptoms (IHS). DESIGN Cross-sectional study. MATERIALS A consecutive series of 80 patients (96 plaques) with more than 50% ICA stenosis was studied. METHODS B mode ultrasonic images were captured and transferred to a computer on magneto-optic disk and standardised using linear scaling so that adventitia would have a grey scale median (GSM) value of 185-195 and blood 0-5. The GSM and the percentage of echolucent pixels (PEP) in plaques were determined to measure echodensity. Homogeneity, entropy, and contrast were also determined to measure spatial distribution (heterogeneity) of grey shades in each plaque. Each measurement was correlated to presence or absence of IHS. RESULTS Twenty-five plaques were associated with IHS and 71 plaques were asymptomatic. In symptomatic plaques the mean of GSM was 23 and the mean of PEP was 70%, compared to 38 and 55% respectively in asymptomatic plaques (p = 0.02; Wilcoxon test). Sixty per cent of symptomatic plaques were associated with a homogeneity, entropy, and contrast values of > 0.2, < 2.95, < 150 respectively as compared to 40% in asymptomatic plaques. Multiple regression analysis revealed that the GSM and the PEP were the most significant variables (p = 0.001) that are related to presence or absence of IHS. CONCLUSION This study indicates that computer aided analysis of ultrasonic B mode features of carotid plaques could identify a potentially high-risk subgroup (patients with IHS). A GSM less than 40 or PEP greater than 50% is a good predictor of IHS related to carotid plaques. The fact that these measurements are operator independent and performed after image standardisation should encourage their use in multicenter clinical trials where different operators and equipment are used.

The Genesis of Atherosclerosis and Risk Factors: A Review

Atherosclerosis constitutes the most common medical and surgical problem. This can be mani fested clinically as stroke, coronary artery disease, or peripheral vascular disease. In the present review the microscopic appearance of the normal arterial wall, the definition of atherosclerosis and the five theories of atherogenesis are described. These are: the lipid theory, the hemody namic theory, the fibrin incrustation theory, the nonspecific mesenchymal hypothesis and the response to injury hypothesis. Based on the above theories the sequence of events in athero genesis is analyzed. The classification of the atherosclerotic lesions according to Stary (types I-VI) and their characteristics appear in a table. The epidemiology and the role of the following risk factors are presented in detail: age, sex, lipid abnormalities, cigarette smoking, hyperten sion, diabetes mellitus, physical inactivity, alcohol consumption, obesity, and hemostatic factors. In addition, less common genetically determined associations like homocystinuria, Tangier disease, Hutchinson-Gilford syndrome (progeria), Werners syndrome, radiation induced ather osclerosis and the implications of Chlamydia pneumoniae on the arterial wall are discussed.

Comparability of the ultrasonic tissue characteristics of carotid plaques.

Hypoechoic carotid atherosclerotic plaques on ultrasonographic examination were found to be associated with cerebrovascular events. This underlines the need for an accurate evaluation of their echotexture characteristics. The objective of this study was to further validate a proposed method of normalization aiming to facilitate the comparability of these characteristics. The sonographic examination involved imaging of carotid plaques using duplex technique and capturing, digitization, and normalization in a computer in a standard way. In the first part, the interobserver and interscanner variability and the gain‐level variability within the ultrasound unit were examined, before and after normalization, in terms of plaque echotexture. The second part investigated the effect of normalization on the echotexture of 419 symptomatic and asymptomatic plaques. Our results indicated that the normalization reduced the interscanner variability and the gain‐level variability. The interobserver variability was excellent. In addition, this process further distinguished the echotexture characteristics of symptomatic and asymptomatic carotid plaques, which encourages the use of this method in natural history studies in persons with asymptomatic carotid atherosclerotic disease, aiming to identify those at higher risk for stroke. These patients might benefit from a carotid endarterectomy.

Echogenicity of B-mode Sonographic Images of the Carotid Artery Work in Progress

Objective. The echogenicity of the carotid atheromatous plaque estimated from B‐mode sonographic images may be related to plaque content and has been analyzed with a number of techniques. The purpose of this study was to compare plaque with surrounding muscle tissue echogenicity and to validate the use of first‐order mathematical descriptors as determinants of tissue echogenicity. Methods. We estimated echogenicity descriptors for regions in the following 3 distinct areas of a typical B‐mode sonographic image of a diseased carotid artery: plaque, blood, and sternocleidomastoid muscle. Two‐dimensional B‐mode sonographic images from 19 symptomatic and asymptomatic plaques (17 subjects) were interrogated, in which the following estimators were calculated: minimal, maximal, mean, and median gray levels, SD of gray levels, coefficient of variation, and gray level skewness, kurtosis, entropy, and energy. Plaque echogenicity was estimated at systole and diastole for studying the effect of the phase of the cardiac cycle. To assess the effect of different fascial tissue–muscle fiber composition on the first‐order mathematical descriptors, we estimated echogenicity at 3 different sites within the muscle tissue. Results. Compared with the echogenicity of surrounding muscle tissue, plaque echogenicity was characterized by (1) significantly lower (Student t test, P < .05) gray level mean, median, SD, and entropy; (2) significantly higher (Student t test, P < .05) coefficient of variation, gray level skewness, and kurtosis; and (3) similar minimal and maximal gray levels and gray level energy. The phase of the cardiac cycle, systole or diastole, did not affect the estimation of plaque echogenicity. Echogenicity was found to vary within the muscle tissue. The coefficient of variation was significantly higher in the asymptomatic plaques in the small group that was investigated. Conclusions. First‐order statistical descriptors may be used to characterize atheromatous plaques and the surrounding muscle tissue.

Platelet Activation During Carotid Endarterectomy And the Antiplatelet effect of Dextran 40

Objective: To determine changes in platelet activation during carotid endarterectomy (CEA) and the antiplatelet effect of Dextran 40. Methods: Prospective study in 40 patients undergoing CEA. Platelet activity was measured by whole blood flow cytometry and platelet aggregometry during CEA. The expression of P-selectin and the PAC-1 antigen were used as markers of platelet activation and aggregation. Patients received aspirin (75-300 mg) preoperatively and 5,000 units unfractionated heparin during surgery. High intensity transient signals (HITS) in the ipsilateral middle cerebral artery were monitored using transcranial Doppler (TCD) perioperatively. Results: P-Selectin expression increased after carotid clamping (P < 0.01) and clamp release (P < 0.05). There was higher expression of PAC-1 after carotid clamping (p < 0.05). Spontaneous and ADP-induced platelet aggregation increased after carotid clamping (P< 0.01) and release (P < 0.01). TCD monitoring showed an increased HITS count from preoperative levels, after clamp release (P < 0.01) and during recovery (P < 0.01). After the operation, patients with more than 50 HITS per 30 min were started on an infusion of dextran 40 (n = 6). P-selectin expression decreased 24 h after dextran 40 (P < 0.01). Conclusion: Significant platelet activation and aggregation occurs during CEA despite the current use of antiplatelet treatment. Dextran 40 had an antiplatelet effect after CEA providing further evidence that it may contribute to reducing thromboembolic complications.

Types of neurovascular symptoms and carotid plaque ultrasonic textural characteristics.

The aim of this study was to identify the echo morphology and stenosis of carotid plaques that corresponded to ipsilateral asymptomatic status, amaurosis fugax, hemispheric transient ischemic attack, and stroke. One hundred ninety‐two plaques (150 patients), producing stenosis in the range of 50% to 99% and associated with various neurovascular manifestations, were studied. These plaques were imaged on duplex scans, and a series of textural features was produced in a computer to distinguish quantitatively their various echo patterns. Amaurosis fugax corresponded to dark, severely stenosed atheromas (90%); hemispheric transient ischemic attack and stroke corresponded to plaques with intermediate echoic characteristics and intermediate stenosis (80%); and asymptomatic status corresponded to bright, moderately stenosed plaques (70%; P < .05). The significance of these findings is discussed.