Michael M. Sabetai

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.

Effect of Image Normalization on Carotid Plaque Classification and the Risk of Ipsilateral Hemispheric Ischemic Events: Results from the Asymptomatic Carotid Stenosis and Risk of Stroke Study:

The aim of this study was to determine the effect of image normalization on plaque classification and the risk of ipsilateral ischemic neurologic events in patients with asymptomatic carotid stenosis. The first 1,115 patients recruited to the Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study with a follow-up of 6 to 84 months (mean 37.1 months) were included in this study. Duplex ultrasonography was used for grading the degree of internal carotid artery stenosis and for plaque characterization (types 1–5), which was performed before and after image normalization. One hundred sixteen ipsilateral ischemic hemispheric events occurred. Image normalization resulted in 60% of plaques being reclassified. Before image normalization, a high event rate was associated with all types of plaque. After image normalization, 109 (94%) of the events occurred in patients with plaque types 1 to 3. For patients with European Carotid Stenosis Trial (ECST) 70 to 99% diameter stenosis (equivalent to North American Symptomatic Carotid Endarterectomy Trial [NASCET] 50–99%) with plaque types 1 to 3, the cumulative stroke rate was 14% at 7 years (2% per year), and for patients with plaque types 4 and 5, the cumulative stroke rate was 0.9% at 7 years (0.14% per year). The results suggest that asymptomatic patients with plaque types 4 and 5 classified as such after image normalization are at low risk irrespective of the degree of stenosis.

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.

Juxtaluminal hypoechoic area in ultrasonic images of carotid plaques and hemispheric symptoms

OBJECTIVES The aim was to determine the diagnostic value of a juxtaluminal black (hypoechoic) area without a visible echogenic cap (JBA) in ultrasonic images of internal carotid artery plaques. METHODS Ultrasonic images of plaques from 324 patients with asymptomatic (n = 139) and symptomatic (n = 185) internal carotid 50% to 99% stenosis in relation to the bulb (European Carotid Surgery Trial) referred for duplex scanning were studied. The JBA in mm(2) and the gray-scale median (GSM) were obtained after image normalization. Cut-off points for GSM and JBA (combined highest sensitivity with highest specificity) were determined from receiver operator characteristic (ROC) curves. RESULTS JBA >or= 8 mm(2) was associated with a high prevalence of symptomatic plaques in all grades of stenosis. In a multiple logistic regression model, increasing stenosis (mild, moderate, severe), GSM <or= 15 and JBA >or= 8 mm(2) were independent predictors of the presence of hemispheric symptoms. This model could identify a high-risk group of 188 plaques that contained 142 (77%) of the 185 symptomatic plaques (odds ratio [OR], 6.7; 95% confidence interval [CI], 4.08-10.91), (P < .001), (sensitivity: 77%; specificity 66%; positive predictive value 75%; negative predictive value 68%). CONCLUSIONS The results of this study indicate the diagnostic value and for the first time suggest a cut-off point of 8 mm(2) for JBA. This cut-off point needs to be validated in other groups and then applied to prospective studies of asymptomatic patients.

Computerized texture analysis of carotid plaque ultrasonic images can identify unstable plaques associated with ipsilateral neurological symptoms.

We estimated the value of objective, computerized texture analysis of ultrasonic images in distinguishing carotid plaques associated with neurological ipsilateral symptoms (amaurosis fugax [AmF; n = 30], transient ischemic attack [TIA; n = 52], and stroke [n = 55]) from asymptomatic plaques (n = 51). We performed 3 case-control studies (1/symptom with asymptomatic plaques as control). On logistic regression, AmF was independently associated with severity of stenosis, percentage of pixels with gray levels 0 to 10 (PPCS1; measure of echolucency), and spatial gray level dependence matrices (SGLDM) information measure of correlation (IMC-1; texture); TIAs with PPCS1 (echolucency), SGLDM correlation, and skewness (both texture); and stroke with PPCS1, SGLDM correlation, and percentage of pixels with gray levels 11 to 20 (PPCS2; echolucency). The area under the curve of the regression-derived predicted probability for AmF, TIA, and stroke was 0.92, 0.82, and 0.85, respectively (all P < .001). Texture analysis can identify carotid plaques associated with a neurological event, improving the diagnostic value of echolucency measures. Texture analyses could be applied to natural history studies.

Long-term response to subtotal colectomy in colonic inertia

The purpose of this study was to determine the long-term outcome of patients who had previously undergone subtotal colectomy for severe idiopathic constipation at the University of Florida between 1983 and 1987. In addition, we aimed to determine whether preoperative motility abnormalities of the upper gastrointestinal tract are more common among those patients who have significant postoperative complications after subtotal colectomy. We valuated 13 patients who underwent subtotal colectomy for refractory constipation between 1983 and 1987 at the University of Florida. Preoperatively, all patients exhibited a pattern consistent with colonic inertia as demonstrated by means of radiopaque markers. Each patient was asked to quantitate the pain intensity and frequency of their bowel movements before and after surgery. In seven patients an ileosigmoid anastomosis was performed, whereas in six patients an ileorectal anastomosis was used. Abdominal pain decreased after subtotal colectomy. Patients with abnormal upper gastrointestinal motility preoperatively experienced greater postoperative pain than those with normal motility regardless of the type of anastomosis. In addition, the number of postoperative surgeries was similar in those patients with abnormal upper motility compared to those with normal motility. Overall, the total number of bowel movements per week increased from 0.5 ± 0.03 preoperatively to 15 ± 4.5 (P < 0.007) postoperatively. The results of our study suggest that patients with isolated colonic inertia have a better long-term outcome from subtotal colectomy than patients with additional upper gastrointestinal motility abnormalities associated with their colonic inertia.