Asymptomatic Patients Undergoing Carotid Endarterectomy Research Articles

Increased Piezo1 expression in myofibroblasts in patients with symptomatic carotid atherosclerotic plaques undergoing carotid endarterectomy: A pilot study.

We aimed to investigate Piezo1 expression in myofibroblasts in symptomatic and asymptomatic patients undergoing carotid endarterectomy and its relationship with atherosclerotic plaque formation. This cross-sectional study analyzed carotid plaques of 17 randomly selected patients who underwent carotid endarterectomy from May 2015 to August 2017. In total, 51 sections (the most stenotic lesion, and the sections 5-mm proximal and distal) stained with hematoxylin-eosin and elastica-Masson were examined. Immunohistochemistry was performed using antibodies to Piezo1. The Piezo1 score of a section was calculated semiquantitatively, averaged across 30 randomly selected myofibroblasts in the fibrous cap of the plaque. Of 17 patients (mean age: 74.2 ± 7.1 years), 15 were men, 9 had diabetes mellitus, and 13 had hypertension. Symptomatic patients had higher mean Piezo1 score than asymptomatic patients (1.78 ± 0.23 vs 1.34 ± 0.17, p < .001). Univariate linear regression analyses suggested an association between plaque rupture, thin-cap fibroatheroma and microcalcifications and the Piezo1 score (p = .001, .008, and 0.003, respectively). Increased Piezo1 expression of myofibroblasts may be associated with atherosclerotic carotid plaque instability. Further study is warranted to support this finding.

Long-term outcomes of symptomatic and asymptomatic patients undergoing carotid endarterectomy in an average-volume community hospital

Background Long-term benefit of carotid endarectomy has not yet been fully investigated in average volume centers. Thus our purpose is to evaluate long-term results of carotid endarterectomies at a medium-volume hospital. Methods A retrospective analysis of carotid artery stenosis operated between 2008 and 2017 in a community hospital was done. Demographic and postoperative outcomes were evaluated in short and long-term by Kaplan–Meier survival analysis. Results 167 procedures in 159 patients were included. Average age was 72 years, and 65% were men. Twenty-nine percent of the patients were symptomatic and the rest asymptomatic. Median hospitalization was 3 (IQR 3–4) days and the mean follow-up was 56 months. No hospital mortality was recorded. At 120-month follow-up, freedom of stroke was 97.4%, death 97.3%, restenosis, 98.7% and all combined events 92.9% (log rank p = .042) Combined event-free survival was 84.4% in symptomatic patients, and 96.1% in asymptomatic patients (log rank p = .025). Conclusions In a medium-volume hospital combined event-free survival was 84.4% in symptomatic patients and 96.1% in asymptomatic at a 10-year follow-up.

Timing of procedural stroke and death in asymptomatic patients undergoing carotid endarterectomy: individual patient analysis from four RCTs.

The effectiveness of carotid endarterectomy (CEA) for stroke prevention depends on low procedural risks. The aim of this study was to assess the frequency and timing of procedural complications after CEA, which may clarify underlying mechanisms and help inform safe discharge policies. Individual-patient data were obtained from four large carotid intervention trials (VACS, ACAS, ACST-1 and GALA; 1983-2007). Patients undergoing CEA for asymptomatic carotid artery stenosis directly after randomization were used for the present analysis. Timing of procedural death and stroke was divided into intraoperative day 0, postoperative day 0, days 1-3 and days 4-30. Some 3694 patients were included in the analysis. A total of 103 patients (2·8 per cent) had serious procedural complications (18 fatal strokes, 68 non-fatal strokes, 11 fatal myocardial infarctions and 6 deaths from other causes) [Correction added on 20 April, after first online publication: the percentage value has been corrected to 2·8]. Of the 86 strokes, 67 (78 per cent) were ipsilateral, 17 (20 per cent) were contralateral and two (2 per cent) were vertebrobasilar. Forty-five strokes (52 per cent) were ischaemic, nine (10 per cent) haemorrhagic, and stroke subtype was not determined in 32 patients (37 per cent). Half of the strokes happened on the day of CEA. Of all serious complications recorded, 44 (42·7 per cent) occurred on day 0 (20 intraoperative, 17 postoperative, 7 with unclear timing), 23 (22·3 per cent) on days 1-3 and 36 (35·0 per cent) on days 4-30. At least half of the procedural strokes in this study were ischaemic and ipsilateral to the treated artery. Half of all procedural complications occurred on the day of surgery, but one-third after day 3 when many patients had been discharged.

The Role of the Model of End-Stage Liver Disease Score in Predicting Outcomes of Carotid Endarterectomy.

The Model of End-Stage Liver Disease (MELD) score has been traditionally utilized to prioritize for liver transplantation; however, recent literature has shown its value in predicting surgical outcomes for patients with hepatic dysfunction. The benefit of carotid endarterectomy in asymptomatic patients is dependent on low perioperative morbidity. Our objective was to use MELD score to predict outcomes in asymptomatic patients undergoing carotid endarterectomy. Patients undergoing carotid endarterectomy were identified in the National Surgical Quality Improvement Program data sets from 2005 to 2012. The Model of End-Stage Liver Disease score was calculated using serum bilirubin, creatinine, and the international normalized ratio (INR). Patients were grouped into low (<9), moderate (9-14), and high (15+) MELD classifications. The effect of the MELD score on postoperative morbidity and mortality was assessed by multivariable logistic and gamma regressions and propensity matching. There were 7966 patients with asymptomatic carotid endarterectomy identified. The majority 5556 (70%) had a low MELD score, 1952 (25%) had a moderate MELD score, and 458 (5%) had a high MELD score. High MELD score was independently predictive of postoperative death, increased length of stay, need for transfusion, pulmonary complications, and a statistical trend toward increased cardiac arrest/myocardial infarction. The Model of End-Stage Liver Disease score did not affect postoperative stroke, wound complications, or operative time. High MELD score places asymptomatic patients undergoing carotid endarterectomy at a higher risk of adverse outcomes in the 30 days following surgery. This provides further empirical evidence for risk stratification when considering treatment for these patients. Outcomes of medical management or carotid stenting should be investigated in high-risk patients.

The Nature of Iron Deposits Differs between Symptomatic and Asymptomatic Carotid Atherosclerotic Plaques.

Iron within atherosclerotic plaque has been implicated as a catalyst of oxidative stress that causes progression of plaque, and plaque rupture. Iron is believed to accumulate within plaque by incorporation of erythrocytes following plaque rupture and hemorrhage. There is only indirect evidence to support this hypothesis. Plaque specimens were obtained from ten symptomatic and fifteen asymptomatic patients undergoing carotid endarterectomy at a single institution. Plaques were sectioned for study using synchrotron radiation induced X-ray fluorescence the study the distribution of zinc, calcium and iron. Histologic staining was carried out with Prussian Blue, and immunohistochemical staining was done to localize macrophages with CD68. Data were compared against patient clinical variables. Ten symptomatic (15 ± 10 days between index symptoms and surgery) and fifteen asymptomatic carotid plaques were studied. Zinc and calcium co-localized in mineralized areas of symptomatic and asymptomatic plaque. Iron was identified away from zinc and calcium in both symptomatic and asymptomatic plaques. Within the symptomatic plaques, iron was found within the thrombus associated with plaque rupture and hemorrhage. It did not stain with Prussian Blue, but was found in association with CD68 positive macrophages. In symptomatic plaques, the abundance of iron showed an association with the source patient’s LDL cholesterol (R2 = 0.39, Significance F = 0.05). Iron in asymptomatic plaque was present as hemosiderin/ferritin that stained positive with Prussian Blue, and was observed in association with CD68 positive macrophages. Iron in acutely symptomatic plaques is found within thrombus, in the presence of macrophages. The abundance of iron in symptomatic plaques is associated with the source patient’s LDL cholesterol. Within asymptomatic plaques, iron is found in association with macrophages, as hemosiderin/ferritin.

Role of preoperative serum creatinine and estimated glomerular filtration rate values in asymptomatic patients undergoing carotid endarterectomy.

The aim of this study was to evaluate the effect of chronic kidney disease (CKD), assessed by preoperative estimated glomerular filtration rate (eGFR) and serum creatinine (Cr), on postoperative outcomes and long-term survival in asymptomatic patients undergoing carotid endarterectomy (CEA). We examined data about patients that underwent CEA between January 2002 and September 2014 in our Institution. Retrospective analysis to assess preoperative comorbidities and postoperative complications was performed. Modification of Diet in Renal Disease (MDRD) formula was used to calculate eGFR. Patients were divided into four groups based on values of preoperative eGFR: group A (≥90 mL/min/1.73 m2), group B (89-60 mL/min/1.73 m2), group C (59-30 mL/min/1.73 m2) and group D (≤29 mL/min/1.73 m2), and into two groups based on preoperative Cr values: group 1 (<1.5 mg/dL) and group 2 (≥1.5 mg/dL). Primary outcomes were death or the development of one or more postoperative major complications within 30 days after surgery, for each group. Survival curves of Kaplan-Meier were plotted for each group of patients to assess long-term mortality. During the study period, 853 CEAs in 808 patients were performed, of which 682 CEA in 645 patients for asymptomatic carotid artery stenosis. Symptomatic patients (19.58%) and patients receiving hemodialysis (0.46%) were excluded. Among CEAs analyzed, 678 (99.4%) had preoperative Cr values recorded and 637 (93.4%) had preoperative eGFR values recorded. The number of patients in each group according to eGFR values was 84 (13.2%) for group A, 250 (39.3%) for group B, 271 (42.5%) for group C and 32 (5.0%) for group D; according to Cr values was 609 (89.8%) for group 1 and 69 (10.2%) for group 2. One death and 24 (3.52%) postoperative major complications, of which 20 postoperative neurological events (NE) and 4 postoperative myocardial infarctions (MI), occurred within 30 days after surgery. The median follow-up was 55 months (IQR 27-84). Regarding general population, multivariate analysis with age found no significant correlation between Cr and primary outcomes, to the contrary of eGFR (OR=1.02; CI: 1.01-1.02; P<0.0001). No significant differences were observed concerning primary outcomes according to eGFR and Cr groups. Five-year survival rates for groups A, B, C and D were 98±0.02%, 90±0.02%, 80±0.03% and 56±0.12% respectively (P<0.0001) and 88±0.02% and 62±0.08% for group 1 and 2 respectively (P<0.0001). eGFR and Cr classes are not a dependable method in evaluating postoperative complications risk after CEA in asymptomatic patients, although preoperative eGFR values influence 30-days morbility. Both eGFR and Cr groups are reliable predictors to discriminate among asymptomatic patients candidates for CEA, based on their life expectancy.

Risk index for predicting perioperative stroke, myocardial infarction, or death risk in asymptomatic patients undergoing carotid endarterectomy

The latest guidelines recommend performance of carotid endarterectomy (CEA) on asymptomatic patients with high-grade carotid stenosis, only if the combined perioperative stroke, myocardial infarction (MI), or death risk is ≤3%. Our objective was to develop and validate a risk index to estimate the combined risk of perioperative stroke, MI, or death in asymptomatic patients undergoing elective CEA. Asymptomatic patients who underwent an elective CEA (n= 17,692) were identified from the 2005-2010 National Surgical Quality Improvement Program, a multicenter, prospective database. Multivariable logistic regression analysis was performed with primary outcome of interest being the composite of any stroke, MI, or death during the 30-day periprocedural period. Bootstrapping was used for internal validation. A risk index was created by assigning weighted points to each predictor using the β-coefficients from the regression analysis. Fifty-eight percent of the patients were men with a median age of 72 years. Thirty-day incidences of stroke, MI, and death were 0.9% (n= 167), 0.6% (n= 108), and 0.4% (n= 72), respectively. The combined 30-day stroke, MI, or death incidence was 1.8% (n= 324). On multivariable analysis, six independent predictors were identified and a risk index created by assigning weighted points to each predictor using the β-coefficients from the regression analysis. The predictors included age in years (<60: 0 point; 60-69: -1 point; 70-79: -1 point; ≥80: 2 points), dyspnea (2 points), chronic obstructive pulmonary disease (3 points), previous peripheral revascularization or amputation (3 points), recent angina within 1 month (4 points), and dependent functional status (5 points). Patients were classified as low (<3%),intermediate (3%-6%), or high (>6%) risk for combined 30-day stroke, MI, or death, based on a total point score of<4, 4-7, and >7, respectively. There were 15,249 patients (86.2%) in the low-risk category, 2233 (12.6%) in the intermediate-risk category, and 210 (1.2%) in the high-risk category. The validated risk index can help identify asymptomatic patients who are at greatest risk for 30-day stroke, MI, and death after CEA, thereby aiding patient selection.

Abstract 421: Biomarkers of Atherosclerotic Plaque Instability in Carotid Artery Stenosis

Objective: Atherosclerotic plaque instability has been linked to cardiovascular events. We hypothesized that novel serum and intraplaque markers of plaque instability could be identified through analysis of serum and atherosclerotic plaques obtained from symptomatic and asymptomatic patients undergoing carotid endarterectomy (CEA). Methods: Under an IRB approved protocol, 6 symptomatic patients (5 transient ischemic attack, 1 amaurosis fugax) and their age- and gender-matched controls were analyzed for intraplaque markers of plaque instability. 8 symptomatic patients and their age- and gender-matched controls were analyzed for serum activity of proteolytic enzymes MMP-2 and MMP-9. Plaques were removed intraoperatively, placed in RNAlater and processed immediately after CEA. Blood samples were drawn prior to incision to determine serum activity of MMP-2 and MMP-9 using gelatin zymography. Intraplaque expression of MMP-2, MMP-9, proteolytic enzymes (uPA, tPA and PAI-1) and inflammatory markers (TF, TSP-1, and TNF-α) were evaluated by Western blot analysis. Results: The activity of proteolytic enzymes MMP-2 and MMP-9 detected in serum was significantly higher in symptomatic patients when compared to asymptomatic controls, with a 1.5- and 2.2-fold increase, respectively (P&lt;0.05, n=8). The activity of MMP-2 and MMP-9 detected in plaque was also elevated in the symptomatic group, with a 9.04 and 15.3-fold increase, respectively. Intraplaque expression of uPA (9.6-fold increase) and PAI-1 (28% decrease) was found in symptomatic patients. The expression of inflammatory markers TF and TSP-1 was elevated in symptomatic patients (2.7- and 4.2-fold, respectively) (All P&lt;0.05, n=6). There was not a statistically significant difference in levels of tPA and TNF-α (P=0.075 and 0.345, respectively). Conclusion: Levels of matrix metalloproteinases, proteolytic enzymes and inflammatory markers found in serum and plaque samples of symptomatic and asymptomatic patients may be different. Testing for biomarkers may help diagnose atherosclerotic plaque instability and identify patients at high risk for cerebrovascular events.

Carotid endarterectomy in asymptomatic patients with limited life expectancy.

Data from randomized trials assert that asymptomatic patients undergoing carotid endarterectomy (CEA) must live 3 to 5 years to realize the benefit of surgery. We examined how commonly CEA is performed among asymptomatic patients with limited life expectancy. Within the American College of Surgeons National Quality Improvement Project we identified 8 conditions associated with limited life expectancy based on survival estimates using external sources. We then compared rates of 30-day stroke, death, and myocardial infarction after CEA between asymptomatic patients with and without life-limiting conditions. Of 12,631 CEAs performed in asymptomatic patients, 2525 (20.0%) were in patients with life-limiting conditions or diagnoses. The most common conditions were severe chronic obstructive pulmonary disease and American Society of Anesthesiologists Class IV designation. Patients with life-limiting conditions had significantly higher rates of perioperative complications, including stroke (1.8% versus 0.9%, P<0.001), death (1.4% versus 0.3%, P<0.001), and stroke/death (2.9% versus 1.1%, P<0.001). Even after adjustment for other comorbidities, patients with life-limiting conditions were nearly 3 times more likely to experience perioperative stroke or death than those without these conditions (OR, 2.8; 95% CI, 2.1-3.8; P<0.001). CEA is performed commonly in asymptomatic patients with life-limiting conditions. Given the high rates of postoperative stroke/death in these patients as well as their limited life expectancy, the net benefit of CEA in this population remains uncertain. Health policy research examining the role of CEA in asymptomatic patients with life-limiting conditions is necessary and may serve as a potential source for significant healthcare savings in the future.

Non-cholesterol sterols in serum and endarterectomized carotid arteries after a short-term plant stanol and sterol ester challenge

Background and Aims It is not known whether dietary intake of plant stanols or sterols changes the composition of arterial sterols. Therefore, we compared serum and carotid artery cholesterol and non-cholesterol sterols after plant stanol (staest) or sterol (steest) ester feeding in endarterectomized patients. Methods and Results Elderly statin-treated asymptomatic patients undergoing carotid endarterectomy were randomized double-blind to consume staest ( n = 11) or steest ( n = 11) spread (2 g of stanol or sterol/day) for four weeks preoperatively. Non-cholesterol sterols from serum and carotid artery tissue were analysed with gas-liquid chromatography. Staest spread lowered serum total (17.2%), VLDL, and LDL cholesterol and serum triglycerides, while steest spread lowered serum total (13.8%) and LDL cholesterol levels from baseline ( p < 0.05 for all). Serum cholestanol and avenasterol were decreased in both groups, but campesterol and sitosterol were decreased by staest and increased by steest from baseline ( p < 0.05 from baseline and between the groups). Serum sitostanol to cholesterol ratio was increased by staest, but in arterial tissue this ratio was similar in both groups. On staest, lathosterol, campesterol, and sitosterol, and on steest sitosterol and avenasterol correlated significantly between serum and arterial tissue. Cholesterol metabolism, eg. lathosterol/campesterol, suggested that plant sterols were reduced in serum and in arterial tissue during staest. Conclusion The novel observations were that plant stanol ester consumption, in contrast to plant sterols, tended to reduce carotid artery plant sterols in statin-treated patients. Furthermore, despite increased serum sitostanol contents during plant stanol ester consumption, their arterial levels were unchanged suggesting that sitostanol is not taken up into the arterial wall.

Increased Activity of the Ubiquitin-Proteasome System in Patients With Symptomatic Carotid Disease Is Associated With Enhanced Inflammation and May Destabilize the Atherosclerotic Plaque: Effects of Rosiglitazone Treatment

We evaluated ubiquitin-proteasome activity in carotid plaques of asymptomatic and symptomatic patients and the effect of rosiglitazone, a peroxisome proliferator-activated receptor-gamma activator, in symptomatic plaques. The role of the ubiquitin-proteasome system, the major pathway for non-lysosomal intracellular protein degradation in eucaryotic cells, in the progression of atherosclerotic plaque to instability is unclear. Plaques were obtained from 40 symptomatic and 38 asymptomatic patients undergoing carotid endarterectomy. Symptomatic patients received 8 mg rosiglitazone (n = 20) or placebo (n = 20) for 4 months before scheduled endarterectomy. Plaques were analyzed for macrophages (CD68), T-lymphocytes (CD3), inflammatory cells (HLA-DR), ubiquitin-proteasome activity, nuclear factor kappa B (NFkB), inhibitory kappa B (IkB)-beta, nitrotyrosine, matrix metalloproteinase (MMP)-9, and collagen content (immunohistochemistry and enzyme-linked immunosorbent assay). Compared with asymptomatic plaques, symptomatic plaques had more macrophages, T-lymphocytes, and HLA-DR+ cells (p < 0.001); more ubiquitin-proteasome activity and NFkB (p < 0.001); and more markers of oxidative stress (nitrotyrosine and O2- production) and MMP-9 (p < 0.01) along with a lesser collagen content and IkB-beta levels (p < 0.001). Compared with placebo-treated plaques, rosiglitazone-treated symptomatic plaques presented fewer inflammatory cells (p < 0.01); less ubiquitin, proteasome 20S, and NFkB (p < 0.01); less nitrotyrosine and O2- production (p<0.01); and greater collagen content (p<0.01), indicating a more stable plaque phenotype. Ubiquitin-proteasome overactivity is associated with enhanced inflammatory reaction in symptomatic plaques. The inhibition of ubiquitin-proteasome activity in lesions of symptomatic patients by rosiglitazone is associated with plaque stabilization, possibly by down-regulating NFkB-mediated inflammatory pathways.

Statins are Associated with Better Outcomes After Carotid Endarterectomy in Symptomatic Patients

Conclusion: Statin therapy appears to have a protective effect in symptomatic patients undergoing carotid endarterectomy. Summary: Pleiotropic effects of statins are widely appreciated. Statins are associated with a reduction in mortality in non cardiac surgery. This study determined the effect of statin use at the time of hospital admission in patients undergoing carotid endarterectomy. The authors sought to determine whether statin use at the time of hospital admission in patients undergoing carotid endarterectomy was associated with a reduction of in-hospital adverse outcomes. All carotid endarterectomy cases were identified in four western Canadian provinces from January 2000 to December 2001. Charts were abstracted for data describing patient characteristics, surgical indication for endarterectomy, statin treatment, and in-hospital outcomes with respect to death, ischemic stroke, as well as cardiac outcomes. There were 3,360 patients included in the data base. Logistic regression analysis was used to compare outcomes of patients on statins versus those not on statins and to account for differences in patient characteristics. Propensity score analysis was used to account for factors that may influence patient treatment with statins. At the time of hospital admission, 815 of 2,031 symptomatic patients and 665 of 1,252 asymptomatic patients were on a statin medication. Symptomatic patients on statins had reduced in-hospital mortality and in-hospital ischemic stroke and death rates. There was no difference in in-hospital cardiac outcomes. (Adjusted odd ratios 0.25 {CI, 0.07 to 0.90}, 0.55 {CI, 0.32 to 0.95}, 0.87 {CI, 0.49 to 1.54}, respectively). Improvement in outcome of symptomatic patients was robust when tested with propensity score analysis. The association between outcomes and statin use was not seen in asymptomatic patients. Comment: The study adds to the growing impression that statins improve perioperative outcomes in patients undergoing vascular surgery. The lack of effect of statins in the asymptomatic patients undergoing carotid endarterectomy may be the result of an inability to detect the statin effect due to the low frequency of adverse events in the asymptomatic patients. Since this was not a randomized study, statins, however, may just be serving as a marker of overall better perioperative care. Results of this observational study and others like it will need to be confirmed in large multi-center randomized trials specifically addressing perioperative use of statins to improve operative outcomes.

Association Between Prostaglandin E Receptor Subtype EP4 Overexpression and Unstable Phenotype in Atherosclerotic Plaques in Human

We recently demonstrated that inducible cyclooxygenase/PGE synthase-1 (COX-2/mPGES-1) are overexpressed in symptomatic plaques in association with PGE2-dependent metalloproteinase (matrix metalloproteinase [MMP]) biosynthesis and plaque rupture. However, it is not known which of the 4 PGE2 receptors (EP1-4) mediates macrophage metalloproteinase generation. The aim of this study was to characterize EP1-4 expression in plaques from symptomatic and asymptomatic patients undergoing carotid endarterectomy and correlate it with the extent of inflammatory infiltration, COX-2/mPGES-1 and MMP expression and clinical features of patients' presentation. Plaques were analyzed for COX-2, mPGES-1, EP1-4, MMP-2, and MMP-9 by immunohistochemistry, reverse-transcription polymerase chain reaction and Western blot; zymography was used to detect MMP activity. We observed strong EP4 immunoreactivity, only very weak staining for EP2, and no expression of EP1 and EP3 in atherosclerotic plaques. EP4 was more abundant in MMP-rich symptomatic lesions, whereas EP2 was no different between symptomatic and asymptomatic plaques. Finally, MMP induction by PGE2 in vitro was inhibited by the EP4 antagonist L-161 982, but not by its inactive analog L-161 983 or by the EP2 antagonist AH6809. This study shows that EP4 overexpression is associated with enhanced inflammatory reaction in atherosclerotic plaques. This effect might contribute to plaque destabilization by inducing culprit metalloproteinase expression.

Heat shock protein 60 and 70 expression is related to carotid plaque stability

Abstract Introduction: Heat Shock Proteins (HSP) are stress proteins expressed in times of cellular injury. We hypothesized that there would be expression of heat shock proteins 60 and 70 incited by endothelial damage in carotid plaque specimens. We also compared the level of HSP expression between symptomatic and asymptomatic plaques. Methods: Eighteen carotid plaque specimens from were obtained from 10 symptomatic and 8 asymptomatic patients undergoing carotid endarterectomy. Internal carotid artery (ICA) from an autopsy specimen was used as a control. Plaques were fixed in formalin and immunostained for HSP 60 and 70 expression. An intensity staining index (ISI) was calculated via digital image analysis to quantify HSP expression. Statistical significance was determined using ANOVA and a student’s t-test with a 95% confidence interval. Results: HSP 70 expression was greatly enhanced in all carotid plaques (ISI = 70) compared with ICA control (ISI = 0.61). HSP 60 expression was also greater in carotid plaques (ISI = 68) compared with control (ISI = 48). HSP 60 and 70 expression was significantly greater in symptomatic versus asymptomatic patients. HSP 60 and 70 expression was higher in the necrotic core of the plaques compared with their fibrous tissue cap (p Conclusions: HSP 60 and 70 expression is increased in carotid plaques compared to ICA control. The increased expression of HSP 60 and 70 in asymptomatic plaques, preferentially located in the necrotic core, indicates that these stress proteins may play a role in the stabilization of carotid plaques.

Quality Improvement Guidelines for the Performance of Cervical Carotid Angioplasty and Stent Placement: Developed by a Collaborative Panel of the American Society of Interventional and Therapeutic Neuroradiology, the American Society of Neuroradiology, and the Society of Interventional Radiology

John D. Barr, MD, John J. Connors, III, MD, David Sacks, MD, Joan C. Wojak, MD, Gary J. Becker, MD, John F. Cardella, MD, Bohdan Chopko, MD, PhD, Jacques E. Dion, MD, Allan J. Fox, MD, Randall T. Higashida, MD, Robert W. Hurst, MD, Curtis A. Lewis, MD, MBA, Terence A.S. Matalon, MD, Gary M. Nesbit, MD, J. Arliss Pollock, MD, Eric J. Russell, MD, David J. Seidenwurm, MD, and Robert C. Wallace, MD, for the ASITN, ASNR, and SIR Standards of Practice Committees

Expression of inflammatory mediators and adhesion molecules in human atherosclerotic plaque.

The mechanisms that cause carotid atherosclerotic plaque to become symptomatic remain unclear. Evidence suggests that mediators of inflammation not only are instrumental in the formation of plaque but also may be involved in the rapid progression of atheromatous lesions, leading to plaque fissuring and intraluminal thrombosis. This article reviews the current evidence for the role of inflammatory mediators in atherosclerotic plaque production and maturation. It also includes studies performed in our laboratory to determine if known components of the inflammatory pathway, including cytokines and leukocyte adhesion molecules, are preferentially expressed on symptomatic versus asymptomatic carotid plaques. Carotid plaques from symptomatic and asymptomatic patients undergoing carotid endarterectomy with lesions of greater than 70% stenosis were snap-frozen and stored at -70 degrees C until analysis. Immunofluorescent studies were performed to measure endothelial expression of intercellular adhesion molecule-1 (ICAM-1). ICAM-1 expression was measured in a blinded fashion as percent of luminal endothelial surface of plaque sections. In situ hybridization also was performed to measure expression of message for tumor necrosis factor alpha (TNF-alpha) and ICAM-1 in the plaque by comparing mean optical density between the symptomatic and asymptomatic patients. There was increased expression of ICAM-1 on the endothelial surface in high-grade regions (28%) versus low-grade regions (11%), of plaques from symptomatic patients. There was also a trend toward greater expression of ICAM-1 in the high-grade region of symptomatic plaques versus the high-grade region of asymptomatic plaques. In situ hybridization revealed increased mRNA for TNF-alpha and ICAM-1 in the body of the plaque, preferentially in the high-grade region of plaques from symptomatic patients. The data obtained suggest that a local increase of endothelial inflammatory mediator expression correlates with the clinical setting of thromboembolic ischemia and may play a role in conversion of atheromatous plaque to a prothrombotic state. The data also indicate that this line of investigation deserves further exploration because it may be useful in identifying new mechanisms in patients at risk for stroke and in suggesting possible novel strategies for intervention.