Moderate Carotid Stenosis Research Articles

Aggressive lipid-lowering is more effective than moderate lipid-lowering treatment in carotid plaque stabilization

Atherosclerotic plaque stabilization is a promising strategy to prevent cerebrovascular events in patients with carotid atherosclerosis. Vascular calcification inhibitors, known osteopontin (OPN) and osteoprotegerin (OPG), have emerged as novel cardiovascular biomarkers. This open-label, prospective study aimed to examine whether aggressive lipid-lowering therapy with atorvastatin is more effective than moderate lipid-lowering in increasing carotid plaque echogenicity, assessed by Gray-Scale Median (GSM) score and suppressing serum OPN and OPG levels in patients with moderate carotid stenosis. One hundred forty patients (64 males, 76 females), aged 50 to 75 years, with carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial [NASCET]: 30%-60% for symptomatic and 30%-70% for asymptomatic), but without indications for surgical intervention, were enrolled. Patients with coronary heart disease, renal failure, hypothyroidism, osteoporosis, and ongoing use of statins were excluded. Patients were randomly assigned to: Group A (N = 70): Moderate lipid-lowering therapy with low-dose of atorvastatin (10 mg-20 mg) to target LDL-C <100 mg/dL. Group B (N = 70): Aggressive lipid-lowering therapy with high-dose of atorvastatin (80 mg) to target LDL-C <70 mg/dL. Blood pressure, lipid and glycemic indexes, hsCRP, serum OPN, and OPG were measured at baseline and after 12 months as well as the GSM score. Independent samples t test, paired samples t test, Pearson correlation, and multiple regression analysis were used (P < .05). There were no significant differences between groups at baseline. Three patients in group A experienced either cerebrovascular or cardiac ischemic attacks, while two patients in group B underwent coronary angioplasty during follow-up. Group B showed a more pronounced improvement in total cholesterol and LDL-cholesterol compared with group A (P < .05). Moreover, atorvastatin treatment suppressed serum hsCRP, OPN, and OPG levels from baseline in both groups (P < .001). Notably, aggressive treatment decreased OPN (P = .012) and OPG (P = .025) levels to a greater degree compared with moderate treatment. Similarly, GSM score was remarkably increased in both groups, but that augmentation was greater in group B (from 66.39 +/- 23.66 to 100.4 +/- 25.31) than in group A (from 64.4 +/- 23.62 to 85.39 +/- 20.21) (P = .024). No change in the degree of carotid stenosis was noted in both treatment arms. Importantly, the aforementioned reduction in OPN (r = -0.517, P = .024) and OPG (r = -0.312, P = .008) levels was inversely associated with GSM score changes in univariate and standard multiple regression analysis (R(2) = 0.411, P = .021). Among patients with moderate carotid stenosis, an aggressive atorvastatin regimen enhanced carotid plaque echogenicity and reduced serum OPN and OPG levels to a greater extent than respective moderate atorvastatin therapy. Most importantly, those atorvastatin-induced effects were associated with OPN and OPG suppression in a dose-dependent manner.

Preoperative screening and management of carotid artery disease in patients undergoing cardiac surgery

Carotid artery stenosis (CAS) is a well-known risk factor for perioperative stroke in cardiac surgery. It is unclear whether preoperative carotid screening should be applied to all patients. Carotid intervention concomitantly with cardiac operations is also controversial. Our objective was to identify the prevalence of significant CAS and its related risk factors by applying a protocol of preoperative carotid screening to all patients undergoing cardiac surgery. We studied 307 patients who were primarily screened preoperatively by duplex Doppler ultrasonography. Catheter carotid angiography or transcranial Doppler was performed on equivocal cases. Univariate and multivariate analyses were applied across selected parameters to identify risk factors for significant CAS (> 70%). The prevalence of CAS and perioperative stroke rates were determined. Twenty-two patients with severe and 18 with moderate carotid stenosis were identified. Further radiological evaluation with catheter carotid angiography and transcranial Doppler confirmed the presence of significant CAS in 20 patients who underwent carotid stenting or endarterectomy before the open heart surgery. The cardiac surgeon was free to modify the surgical technique according to the preoperative assessment. No patient had major stroke perioperatively, while two minor strokes with complete neurologic recovery have been documented. The history of stroke and the presence of bruit on clinical examination were the only significant predictors of severe carotid disease. Careful clinical examination together with detailed previous history taking can identify the majority of patients with CAS. Further data are required for the construction of a scientifically valid policy as a guideline.

Moderate Carotid Artery Stenosis: MR Imaging–depicted Intraplaque Hemorrhage Predicts Risk of Cerebrovascular Ischemic Events in Asymptomatic Men

To investigate the association between magnetic resonance (MR) imaging-depicted intraplaque hemorrhage (IPH) in the carotid artery wall and the risk of future ipsilateral cerebrovascular events in men with asymptomatic moderate carotid stenosis by using a rapid three-dimensional T1-weighted fat-suppressed spoiled gradient-echo sequence. The institutional ethics review board approved this retrospective chart review and waived the requirement for written informed consent. All patients gave informed verbal consent at follow-up telephone interviews. Ninety-one men (mean age, 74.8 years; range, 47-88 years) who attended a vascular clinic between 2003 and 2006, who had asymptomatic carotid stenosis (50%-70% at Doppler ultrasonography), and who had undergone MR imaging for IPH detection were retrospectively identified. Seventy-five men with 98 eligible carotid arteries were included in the study. Patients were followed for a minimum of 1 year (mean follow-up, 24.92 months; range, 12-43 months). Kaplan-Meier survival and univariate Cox regression analyses were conducted to compare future ipsilateral cerebrovascular event rates between carotid arteries with and those without MR-depicted IPH. Of the 98 carotid arteries included, 36 (36.7%) had MR-depicted IPH. Six cerebrovascular events (two strokes and four transient ischemic attacks) occurred in the carotid arteries with IPH, as compared with no clinical events in the carotid arteries without IPH. Univariate Cox regression analysis confirmed that MR-depicted IPH was associated with an increased risk of cerebrovascular events (hazard ratio, 3.59; 95% confidence interval: 2.48, 4.71; P < .001). MR-depicted IPH negatively predicted outcomes (negative predictive value = 100%). In this cohort with asymptomatic moderate carotid stenosis, MR-depicted IPH was associated with future ipsilateral cerebrovascular events. Conversely, patients without MR-depicted IPH remained asymptomatic during follow-up. The absence of IPH at MR imaging, therefore, may be a reassuring marker of plaque stability and of a lower risk of thromboembolism.

Predictors of shunt during carotid endarterectomy with routine electroencephalography monitoring

The routine use of intraoperative electroencephalography (EEG) monitoring with selective shunt placement during carotid endarterectomy (CEA) has been shown to be safe and effective. We attempt to identify the anatomic and clinical factors associated with significant EEG changes requiring shunt placement during CEA. Between January 2005 and June 2007, 242 CEAs were performed with selective shunt placement for significant EEG changes. Risk factors assessed include severity of both ipsilateral and contralateral disease, presence of ipsilateral preoperative symptoms, hypertension, coronary artery disease, diabetes, age, gender, and preemptive intraoperative blood pressure manipulation to >or=20% above baseline before cross-clamping. Data were analyzed with the chi(2) test (P < .05 was significant). CEA was performed for asymptomatic disease in 177 of 242 patients (73.1%). The perioperative stroke rate was 0.8% (2 of 242), and the overall morbidity rate was 4.5%. No patients died. Significant EEG changes requiring shunt occurred in 35 patients (14.46%). Factors associated with carotid shunt placement were moderate ipsilateral carotid artery stenosis (50% to 79%) compared with severe (>or=80%) disease (30.6% vs 11.7%, P = .003) and degree of contralateral carotid stenosis (0% to 49%, 10.8%; 50% to 79%, 10.9%; 80% to 99%, 23.2%; occlusion, 50%; P = .0003). Presence of symptoms, gender, age, hypertension, diabetes, or coronary artery disease, and preemptive intraoperative manipulation of blood pressure were not significant predictors of shunt placement. CEA performed with routine EEG monitoring and selective shunt placement is associated with a low risk of perioperative stroke. Identified predictors of significant EEG changes were anatomic factors including degree of contralateral carotid artery disease and moderate ipsilateral carotid artery stenosis (50% to 79%). Although contralateral carotid occlusion has been accepted as indication for shunt placement in the absence of cerebral monitoring, this study suggests that high-grade contralateral disease and moderate ipsilateral carotid stenosis are associated with cerebral ischemia resulting in EEG changes and should prompt consideration for nonselective shunting.

Clinical analysis of microsurgical carotid endarterectomy for carotid stenosis and occlusion

To evaluate the clinical effects of carotid endarterectomy for carotid stenosis and occlusion. From August 2005 to November 2008 moderate and severe carotid stenosis or occlusion were found in 16 patients by Doppler ultrasonography (DUS), MRA, CTA, DSA. The stenosis degree ranged from 60% to 99% in 14 patients and complete occlusion in 2 patients. Twelve patients underwent standard carotid endarterectomy (sCEA) in whom 2 patients were placed carotid shunt and 1 patient underwent carotid patch angioplasty. Four patients underwent eversion carotid endarterectomy (eCEA). All operations were performed by microscope. There was no stroke, transient ischemic attack and mortality perioperatively and during follow-up from 1 month to 3 years. The ICA flow detected by follow-up duplex scan and MRA was unobstructed. The primary cerebral ischemic symptoms were obviously improved or disappeared after operation. The postoperative complications included one case of upper gastrointestinal hemorrhage and one case of hoarseness and bucking, which disappeared after medical treatment. CEA is an effective way for treating carotid stenosis. Different operative methods and techniques deal with different carotid lesions to achieve better effect. Microsurgical technique is useful for exposure of high ICA bifurcation and avoid effectively cranial nerve injury and other complications.

Prevalence of Carotid Stenosis in a High-Risk Caribbean Population

The purpose of this study was to determine the prevalence of carotid stenosis among patients presenting to the University Hospital of West Indies (UHWI) Accident and Emergency Department (A&E) with an ischemic stroke or transient ischemic attack (TIA). Beginning in August 2006, all patients presenting to the UHWI A&E with an acute stroke or TIA were screened for enrollment. Patients were excluded if they had a hemorrhagic stroke or if informed consent could not be obtained. Demographic and clinical information were collected by chart review and interviewer-administered questionnaires. All participants had noncontrast head computed tomography (CT) and bilateral carotid duplex ultrasounds. 133 patients were enrolled in the study. 90% presented with a stroke and 10% with a TIA. Mean age was 64 years, 52% were male, 96% self-identified as black. 78% had diabetes mellitus or hypertension or both, 27% were current or past smokers. 65.1% had a normal carotid ultrasound, 28.5% had <50% stenosis, 1.6% had 50% to 69% stenosis, 0.8% had >or=70% stenosis to near occlusion, 1.6% had near occlusion and 1.6% total occlusion. The prevalence of moderate or high-grade carotid stenosis in this high-risk black Caribbean population presenting with an ischemic stroke or a TIA is 5.6%. This is lower than that described in other populations. Further studies are needed to determine the cost-effectiveness of routine screening for carotid stenosis in this population.

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

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. 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. 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). 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.

Imaging of early inflammation in low-to-moderate carotid stenosis by 18-FDG-PET

It is not clear if 18FDG-PET can be useful for detection of inflammation in low to moderate carotid stenosis. We studied 15 patients scheduled for endarterectomy with contralateral carotids with less than 50% stenosis. 18-FDG-PET was performed prior to CEA and 3 months following surgery. FDG-uptake values were calculated based on maximum standardized uptake value (SUV) and corresponding uptake ratios. We confirmed by CD68 macrophage staining that FDG accumulation corresponds to active inflammation (R=0.8 p less than 0.005). We found significant correlation between the FDG-uptake in the carotids scheduled for CEA and contralateral carotids with low to moderate stenosis (R=0.9 p less than 0.001). The FDG uptake ratio in the contralateral arteries remained stable on the follow-up imaging (1.15+/-0.2 vs. 1.14+/-0.1, R=0.7 p=0.006). We did not find correlation between FDG uptake and symptomatic or asymptomatic patients, degree of carotid stenosis and vascular risk factors. This is a prospective, preliminary in vivo study demonstrating that low to moderate carotid atherosclerosis can be detected using 18-FDG-PET imaging and highlights the truly systemic nature of atherosclerosis.

Classification of Carotid Stenosis by Millimeter CT Angiography Measures: Effects of Prevalence and Gender

Previous studies quantifying moderate and severe carotid stenosis by direct millimeter measures on CT angiography (CTA) did not consider how prevalence and gender may influence classification cutoff values. Three hundred nineteen carotid arteries were evaluated in consecutive patients with known or suspected carotid artery disease. Millimeter measures were obtained of the stenotic carotid bulb lumen and distal internal carotid artery (ICA). Interclass correlation coefficients (ICC) defined interobserver and intraobserver agreement. North American Symptomatic Carotid Endarterectomy Trial (NASCET)-style percent stenosis ratios were calculated per carotid artery and used in linear regression and receiver operating characteristic (ROC) curve analysis to define equivalent millimeter quantification and classification values. Likelihood ratios and prevalence-specific positive/negative predictive values (PPV/NPV) were calculated to determine the most appropriate millimeter cutoff values to classify stenosis. Interobserver agreement was excellent for stenosis measures (0.90) and good for distal ICA measures (0.79). Gender-specific regression curves and ROC curves indicated that millimeter stenosis is an excellent tool to quantify and classify carotid stenosis. Assuming a 10% prevalence of severe stenosis, we found that the cutoff value maximizing NPV and PPV was 1.1 mm for both genders (female: PPV = 86.2, NPV = 97.7; male: PPV = 83.2, NPV = 95.9). Assuming a 40% prevalence of moderate stenosis, we found that the cutoff values differed between genders: female = 2.0 mm (PPV = 91.3, NPV = 91.5), male = 2.1 mm (PPV = 91.6, NPV = 92.4). Specific millimeter cutoffs will vary depending upon the clinical scenario, prevalence, and gender. Direct millimeter stenosis measures are an excellent tool to classify moderate and severe carotid artery stenosis. Millimeter classification cutoff values that best approximate NASCET classifications vary depending on prevalence and gender.

Dynamic cerebral autoregulation in carotid stenosis before and after carotid stenting

Impaired dynamic cerebral autoregulation (DCA) has been shown in patients with severe (> or =70%) internal carotid artery (ICA) stenosis, but DCA in moderate (50% to 69%) ICA stenosis, especially its response to carotid revascularization, has rarely been reported. Our study aimed to characterize DCA in severe and moderate ICA stenosis before and after carotid stenting. This study included 21 patients with ICA stenosis > or =50% who received carotid stenting. Data of arterial blood pressure and cerebral blood flow velocity of the middle cerebral artery, measured by transcranial Doppler, were collected for 10 minutes < or =24 hours before and after stenting. The DCA index, represented as aMx, was assessed by calculating the Pearson product-moment correlation coefficient of spontaneous arterial blood pressure and cerebral blood flow velocity fluctuations. The relationship between aMx and stenotic severity and also alternations of aMx before and after stenting were assessed. Carotid stenting was effective to improve the DCA in the stenting side but not in the contralateral nonstenting side. In considering individual ICAs, the average aMx (mean +/- SD) increased significantly from ICA stenosis <50% (0.117 +/- 0.091) to 50% to 69% (0.349 +/- 0.144), 70% to 99% (0.456 +/- 0.147), and total occlusion (0.557 +/- 0.210; P < .05, P < .01, and P < .01, compared with 50% to 69%, 70% to 99%, or total occlusion with <50% stenosis). The correlation between the degree of ICA stenosis and the aMx was also significant (r = 0.693, P < .005). The aMx improved significantly in the stented side after carotid stenting in both moderate and severe ICA stenosis, and this finding was not affected by age, sex, risk factors, or clinical symptoms. In addition to patients with severe carotid stenosis, patients with moderate carotid stenosis may also have impaired DCA that can be restored after carotid stenting.

Does metabolic syndrome predict silent carotid stenosis in coronary patients?

The metabolic syndrome (MS) is a clustering of risk factors whose association with cardiovascular diseases and type 2 diabetes has been well documented [1]. Nevertheless, the clinical value of diagnosing MS remains controversial, as there is no accordance between different series in the predictive value for adverse cardiovascular outcomes [2], and the ability of MS to improve risk prediction beyond that achieved by conventional cardiovascular risk factors has not been clearly shown. The need for studies targeted on selected patient subgroups has been recently highlighted; in this perspective, a valuable approach may emerge from considering MS as a possible indicator of multi-site advanced atherosclerosis among patients at high cardiovascular risk. In this observational, case–control study we restricted our analysis to the subgroup of patients with a recent first clinical manifestation of coronary artery disease (CAD) and without a previous cerebrovascular event or documentation of carotid examination. The aim of our study was to evaluate the association between MS and the presence of silent carotid stenosis[50% obtained by means of ultrasonographic screening. A sample of 168 consecutive referred patients with coronary angiography after a first manifestation of CAD (acute coronary syndrome in 52%, stable angina in 34% and silent myocardial ischemia in 14% of cases, respectively) was considered. The patients had a mean age of 65 ± 8 years, in 31% of cases were active smokers, and in 26% of cases presented a depressed left ventricular dysfunction. The prevalence of conventional cardiovascular risk factors was as follows: hypercholesterolemia 60%, hypertension 63%, diabetes 30% and family history of vascular events 53%. The patients were studied while in hospital by color Doppler ultrasonographic examinations of both carotid arteries; an intima-media thickness (IMT)\1.00 mm identified absence of lesions, while an increased IMT identified carotid atherosclerosis. The severity of carotid atherosclerosis was evaluated by using both the percentage diameter stenosis and parameters of the flow velocity pattern. The greatest stenosis observed on the right or left side identified patients with at least moderate ([50% diameter stenosis) carotid stenosis. A morphologic evaluation of carotid plaques to differentiate stable from unstable lesions was not performed. The MS was diagnosed according to the 2001 NCEP guidelines [3] when three or more of the following factors were present: waist circumference[102 and 88 cm in men and women, respectively, triglycerides C150 mg/dL, highdensity lipoprotein cholesterol (HDL-C)\40 and 50 mg/dL in men and women, respectively; blood pressure C130/ C85 mmHg, and fasting glucose C110 mg/dL. The odds ratio (OR) with confidence interval (CI) 95% for the presence of[50% carotid stenosis in patients with MS and other cardiovascular risk factors was calculated. Globally, 149 patients out of 168 (89%) had carotid atherosclerosis, with [50 and [70% carotid stenosis in 38 (23%) and 11 (7%) cases, respectively. No carotid occlusion was documented. The MS (Fig. 1) was detected in 26.3% of patients with[50% carotid stenosis and 26.9% of controls (OR 0.97; 95% CI 0.43, 2.20). Among other cardiovascular risk factors, only hypertension (OR 2.15; 95% CI 0.94, 4.91) and an age over 65 years (OR 2.96; 95% CI 1.37, 6.36) increased the odds of having a [50% carotid stenosis. M. Ambrosetti (&) R. F. E. Pedretti Division of Cardiology, IRCCS Fondazione Salvatore Maugeri, Institute of Tradate (VA), Via Roncaccio, 16, 21049 Tradate, Italy e-mail: m.ambrosetti@clinicaleterrazze.com

Detection of intraplaque hemorrhage by magnetic resonance imaging in symptomatic patients with mild to moderate carotid stenosis predicts recurrent neurological events

Carotid endarterectomy is beneficial in severe (>70%) symptomatic carotid stenosis. The risk of stroke in moderate carotid stenosis (50%-69%) is modest, and so the role of carotid endarterectomy in this group is unclear. Intraplaque hemorrhage is associated with advanced atherosclerosis and can be detected in the carotid arteries by magnetic resonance imaging. This study evaluates whether magnetic resonance imaging detected intraplaque hemorrhage (MR IPH) can identify patients with symptomatic mild to moderate carotid stenosis who are at higher risk of ipsilateral transient ischemic attack (TIA) and stroke. Prospective longitudinal cohort study of symptomatic patients with mild to moderate (30%-69%) carotid stenosis followed up for 2 years after imaging for IPH using magnetic resonance imaging. Sixty four participants were followed up for a median of 28 months (interquartile range 26-30) after MRI of the carotid arteries. Thirty-nine (61%) ipsilateral arteries showed intraplaque hemorrhage. During follow-up, five ipsilateral strokes and a total of 14 ipsilateral ischemic events were observed. Thirteen of these ischemic events, of which five were strokes, occurred in those with ipsilateral carotid intraplaque hemorrhage (hazard ratio = 9.8, 95% confidence interval 1.3-75.1, P = .03). MR IPH is a good predictor of ipsilateral stroke and TIA in patients with symptomatic mild to moderate (30%-69%) carotid stenosis. This technique could help in the selection of patients for carotid endarterectomy.

Overexpression of hypoxia/inflammatory markers in atherosclerotic carotid plaques

Hypoxia, angiogenesis and inflammation leads to plaque progression and remodelling and may significantly contribute towards plaque rupture and subsequent cerebrovascular events. Our aim was to study, markers of hypoxia and inflammation previously identified by microarray analysis, in atherosclerotic carotid arteries with low to moderate stenosis. We hoped to describe different cellular populations expressing the studied markers. The location of selected inflammatory molecules obtained as vascular transplants from organ donors were analysed by immunohistochemistry with monoclonal and polyclonal antibodies. Paraffin-embedded sections were cut and probed with antibodies recognizing active B and T-lymphocytes (CD30), hypoxia-inducible factor-1alpha, endoglin (CD105), Interleukin-6 and C-reactive protein. We observed a notable overexpression of HIF-1alpha in inflammatory and hypoxic areas of carotid arteries in all types of lesions from type II-V taken from the patients with carotid stenosis less than 50%. This suggests that HIF-1alpha may have a putative role in atherosclerosis progression and angiogenesis. Dynamic changes in the non-occluding plaques may explain some of the clinical events in patients with low to moderate carotid stenosis.

Revascularización de la arteria carótida interna

Carotid endarterectomy remains the standard revascularization technique for the prevention of ischemic stroke resulting from severe carotid stenosis. Surgery is highly beneficial in patients with a symptomatic stenosis of 70% or greater that is not a total or near-total occlusion. The benefit becomes more diluted in patients with a symptomatic 50-69% stenosis, and surgery has no effect, or even increases the risk of stroke, in those with a less than 50% stenosis. Surgery has also been shown to reduce the risk of stroke in asymptomatic patients with a 60-99% stenosis, but the absolute benefit is only 1% per year. There is no clear evidence that surgery benefits asymptomatic women at 5-year follow-up, and the benefit is unknown in asymptomatic patients aged over 75 years. Decision-making must take individual factors into consideration, particularly in patients with an asymptomatic (60-99%) or a moderate (50-69%) symptomatic carotid stenosis, so that the risk-benefit ratio of surgery can be optimized. Current data do not support the preferential use of carotid stenting over carotid endarterectomy in patients with a symptomatic or asymptomatic carotid stenosis who are good candidates for surgery. In those who are not good surgical candidates, carotid stenting might be equivalent to surgery, but whether or not any form of carotid revascularization is superior to medical treatment alone remains unknown.

Non-Coronary Arterial Disease (VII): Internal Carotid Artery Revascularization

Carotid endarterectomy remains the standard revascula-rization technique for the prevention of ischemic stroke resulting from severe carotid stenosis. Surgery is highly beneficial in patients with a symptomatic stenosis of 70% or greater that is not a total or near-total occlusion. The benefit becomes more diluted in patients with a symptomatic 50%-69% stenosis, and surgery has no effect, or even increases the risk of stroke, in those with a less than 50% stenosis. Surgery has also been shown to reduce the risk of stroke in asymptomatic patients with a 60%-99% stenosis, but the absolute benefit is only 1% per year. There is no clear evidence that surgery benefits asymptomatic women at 5-year follow-up, and the benefit is unknown in asymptomatic patients aged over 75 years. Decision-making must take individual factors into consideration, particularly in patients with an asymptomatic (60%–99%) or a moderate (50%–69%) symptomatic carotid stenosis, so that the risk–benefit ratio of surgery can be optimized. Current data do not support the preferential use of carotid stenting over carotid endarterectomy in patients with a symptomatic or asymptomatic carotid stenosis who are good candidates for surgery. In those who are not good surgical candidates, carotid stenting might be equivalent to surgery, but whether or not any form of carotid revascularization is superior to medical treatment alone remains unknown.

Response to Letter by Karapanayiotides and Devuyst

Response: We thank Drs Karapanayiotides and Devuyst for their interest in our recent study, which gives us the opportunity to discuss our results further. We would like firstly to point out that our model should in no way be used yet for clinical decision-making because further refinement is required to this idealized model as well as testing on more patient data. The title of the article is not misleading and states exactly what has been performed in the study. We are not sure how Drs Karapanayiotides and Devuyst conclude that the model “would better represent atheromatous disease in the common carotid artery, distal internal carotid artery, the coronaries or the lower limb arteries?” …

How Critical Is Fibrous Cap Thickness to Carotid Plaque Stability?

Acute cerebral ischemic events are associated with rupture of vulnerable carotid atheroma and subsequent thrombosis. Factors such as luminal stenosis and fibrous cap thickness have been thought to be important risk factors for plaque rupture. We used a flow-structure interaction model to simulate the interaction between blood flow and atheromatous plaque to evaluate the effect of the degree of luminal stenosis and fibrous cap thickness on plaque vulnerability. A coupled nonlinear time-dependent model with a flow-plaque interaction simulation was used to perform flow and stress/strain analysis in a stenotic carotid artery model. The stress distribution within the plaque and the flow conditions within the vessel were calculated for every case when varying the fibrous cap thickness from 0.1 to 2 mm and the degree of luminal stenosis from 10% to 95%. A rupture stress of 300 kPa was chosen to indicate a high risk of plaque rupture. A 1-sample t test was used to compare plaque stresses with the rupture stress. High stress concentrations were found in the plaques in arteries with >70% degree of stenosis. Plaque stresses in arteries with 30% to 70% stenosis increased exponentially as fibrous cap thickness decreased. A decrease of fibrous cap thickness from 0.4 to 0.2 mm resulted in an increase of plaque stress from 141 to 409 kPa in a 40% degree stenotic artery. There is an increase in plaque stress in arteries with a thin fibrous cap. The presence of a moderate carotid stenosis (30% to 70%) with a thin fibrous cap indicates a high risk for plaque rupture. Patients in the future may be risk stratified by measuring both fibrous cap thickness and luminal stenosis.

Dipyridamole Decreases Protease-Activated Receptor and Annexin-V Binding on Platelets of Poststroke Patients with Aspirin Nonresponsiveness

Background: Although controversial, the phenomenon of aspirin resistance (AR) has been correlated in some small studies with poor clinical outcomes in patients with coronary artery disease. Even less is known regarding the role of AR in the poststroke population. The reason for and the underlying mechanism of AR is unknown. We hypothesized that excessive formation of thrombin on the platelet surface may contribute to this phenomenon and assessed how dipyridamole affects multiple platelet and thrombin generation biomarkers in AR patients after ischemic stroke. Methods: Whole blood samples from 20 poststroke AR patients were pretreated with dipyridamole, simulating the therapeutic range, and then incubated for 45 min at 37°C. Platelet characteristics were assessed by aggregometry, cartridge-based analyzer, and receptor expression by flow cytometry. Markers of thrombin generation were measured in the autologous plasma by ELISA. Results: Pretreatment of blood with dipyridamole resulted in 22–26% diminished expression of intact PAR-1 receptor (p = 0.021 and p = 0.024) and 28–31% decrease of annexin V binding (p = 0.031 and p = 0.02) after incubation with 2 µg/ml and 4 µg/ml of dipyridamole, respectively. Platelet aggregation and thrombin generation markers were not affected in vitro by dipyridamole. Conclusions: Dipyridamole may be capable of overcoming increased prothrombinase complex formation and be in part able to compensate for AR in patients with moderate carotid stenosis. This phenomenon may explain the clinical advantages of Aggrenox^®, known to reduce ischemic events in poststroke patients as proven in clinical trials, though an additional antithrombotic benefit beyond the platelet inhibition by aspirin alone.

Determination of Carotid Artery Atherosclerotic Lesion Type and Distribution in Hypercholesterolemic Patients With Moderate Carotid Stenosis Using Noninvasive Magnetic Resonance Imaging

Determination of Carotid Artery Atherosclerotic Lesion Type and Distribution in Hypercholesterolemic Patients With Moderate Carotid Stenosis Using Noninvasive Magnetic Resonance Imaging

Markers of lacunar stroke in patients with moderate internal carotid artery stenosis

The benefits of surgical correction of moderate internal carotid artery stenosis have been demonstrated only in symptomatic subjects. It is debatable whether patients with lacunar infarct ipsilateral to a moderate carotid stenosis may be considered symptomatic like those with large-artery stroke. The aim of the study was to seek markers capable of differentiating patients with lacunar or non-lacunar stroke ipsilateral to a moderate internal carotid artery stenosis. We enrolled 95 patients with a first stroke ipsilateral to a moderate (50-69 %) stenosis of the internal carotid artery and divided them into lacunar and non-lacunar stroke based on clinical presentation and neuroradiological findings; 34 subjects with asymptomatic moderate carotid stenosis and 31 normal individuals were also studied. Baseline characteristics; risk factors, cerebrovascular reactivity to hypercapnia evaluated by means of the breath-holding index (BHI), the presence and severity of carotid stenosis and intimamedia thickness (IMT) of the common carotid arteries were determined. There were 36 patients with lacunar and 59 with non-lacunar stroke. Degree of stenosis, and IMT and BHI ipsilateral to symptomatic stenosis were found to be significant independent predictors as each 10 % increase of stenosis carried a 4.3 higher probability of non-lacunar stroke (95 % CI: 1.91-9.51); each decimillimeter increment in IMT increased this probability by 1.45 (95 % CI: 1.10-1.92); and the risk odds ratio associated with each 0.1 increase in BHI was 1.88 (95 % CI: 1.33-2.66). A decrease in BHI of 0.1 thus carried a 90% greater probability of having a lacunar stroke. The results show that patients with moderate internal carotid artery stenosis and lacunar stroke can be differentiated from those with non-lacunar stroke on the basis of distinctive ultrasonographic findings. Further studies are needed to clarify whether our findings have pathogenetic implications and may be of help for the planning of different therapeutic strategies in patients with moderate internal carotid stenosis and lacunar or non-lacunar ipsilateral stroke.