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Background: Evidence to guide management of postdissection abdominal aortic aneurysms (PDAAA) is lacking. This study describes the outcomes of open repair of PDAAA., Methods: A retrospective cohort study was conducted of all consecutive patients treated with open repair for PDAAA after a Stanford type A or type B thoracic aortic dissection between January 2006 and December 2017 in two vascular referral centers. Preceding type B dissection treatment could include conservative or surgical management. Primary outcomes were 30-day mortality, complication rates, survival, and reintervention-free survival. Survival and reintervention-free survival were analyzed using the Kaplan-Meier method. Reintervention was defined as any endovascular or surgical intervention after the index procedure., Results: Included were 36 patients (27 men [75%]) with a median age of 64 years (range, 35-81 years). The 30-day mortality was 2.7%. The median follow-up was 16 months (range, 0-88 months). The postoperative course was uneventful in 21 patients (58%). The most frequent complications were postoperative bleeding requiring repeat laparotomy (n = 4), pneumonia (n = 3), congestive heart failure (n = 2), new-onset atrial fibrillation (n = 2), mesenteric ischemia requiring left hemicolectomy (n=1), and ischemic cerebrovascular accident (n = 1). Renal failure requiring hemodialysis developed in one patient. The overall survival at 1 year was 88.8%. Reintervention-free survival was 95.5% after 1 year and 88.6% after 2 years., Conclusions: Open repair of PDAAA can be performed with a low mortality rate and an acceptable complication rate, comparable with elective open repair of abdominal aortic aneurysms without dissection., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives To evaluate long-term outcome and quality of life after open and endovascular repair of ruptured abdominal aortic aneurysms. Methods All consecutive ruptured abdominal aortic aneurysm patients at the St. Antonius Hospital treated for ruptured abdominal aortic aneurysm between January 2005 and January 2015 were included. Mortality, morbidity, and re-interventions within 30 days and during follow-up were registered. Quality of life was measured with Short Form-36 questionnaire among survivors. Additional subgroup analysis between open repair and endovascular repair was performed. Results A total of 192 patients with ruptured abdominal aortic aneurysm were included: 76.6% (147/192) underwent open repair and 23.4% (45/192) endovascular repair. All-cause 30-day mortality rate was 31.3% (60/192), and 30-day morbidity rate was 70.3% (135/192). Median stay at the intensive care unit was two days for endovascular repair and four days for open repair ( p = 0.002). No other statistically significant differences between endovascular repair and open repair were observed. After a mean follow-up period of 62 months (range 9-126), 72.4% (76/105) of the responders had equivalent Short Form-36 scores as compared to the age-matched general Dutch population, and 84.2% (64/76) of the responders would choose surgery again if they would have a ruptured abdominal aortic aneurysm. Conclusions Survivors of ruptured abdominal aortic aneurysm have similar long-term quality of life scores compared to the age-matched general population. The majority of all survivors would choose to undergo acute abdominal aortic aneurysm repair again.

Background and Aims: Previously, we showed that patients undergoing carotid endarterectomy have an increased risk for major atherosclerotic events in the presence of moderate or poor kidney function. Acceleration of vascular inflammatory responses is considered to be causally involved in progression of atherogenesis and poor outcome in chronic kidney disease patients. The association between kidney function and plaque composition has not been thoroughly investigated yet. The aim of this study was to investigate the association between kidney function and atherosclerotic plaque composition in patients undergoing carotid endarterectomy., Methods: Atherosclerotic plaques, harvested from 1796 patients who underwent carotid endarterectomy, were immunohistochemically stained for macrophages, smooth muscle cells, calcifications, collagen, microvessels, lipid core size and intraplaque hemorrhage. Cytokines were measured in plaque and plasma and associated with kidney function. Quantitative proteomics were performed on 40 carotid plaques and associated with kidney function., Results: Decreased kidney function was associated with increased odds ratio of intraplaque hemorrhage, OR 1.15 (95% CI; 1.02-1.29 (p = 0.024)) and increased odds ratio of fibrous-atheromatous plaques (plaques with lipid core presenting more than 10% of total plaque surface) OR 1.21 (95% CI; 1.07-1.38 (p = 0.003)) per decrease of 20 points in eGFR. Proteomics revealed that decreased kidney function was associated with upregulation of the classical pathway of the complement system and the intrinsic pathway of the coagulation system., Conclusions: Decreased kidney function was associated with plaque hemorrhage but not with inflammatory plaque characteristics. Our data suggests that other pathways than the inflammation-pathway are involved in plaque vulnerability and poor outcome in patients with decreased kidney function., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives Endovascular treatment of pararenal abdominal aortic aneurysm has gained terrain over the past decade, despite the substantial need for reinterventions during follow-up. However, open repair is still a well-established treatment option. With the current study we report the results of a consecutive series of elective primary open pararenal abdominal aortic aneurysm repair in a tertiary vascular referral centre, combined with an overview of current literature and pooled data analysis of perioperative mortality of open and endovascular pararenal abdominal aortic aneurysm repair. Methods A retrospective analysis of a prospective database of all elective open pararenal abdominal aortic aneurysm repairs in the St. Antonius Hospital between 2005 and 2014 was performed. Primary endpoint was 30-day mortality. Secondary endpoints were 30-day morbidity, new onset dialysis, reintervention free survival, and overall survival during follow-up. Results Between 2005 and 2014, 214 consecutive patients underwent elective open pararenal abdominal aortic aneurysm repair. Mean age was 69.8 (±7.1) years, 82.7% (177/214) were men, and mean abdominal aortic aneurysm diameter was 62 (±11) mm. Thirty-day mortality was 3.4%. Thirty-day morbidity was 27.1%, which predominantly consisted of pneumonia (18.7% (40/214)), cardiac events (3.3% (7/214)), and new onset dialysis (2.8% (6/214)). Estimated five-year overall survival rate was 74.2%. 0.9% (2/214) of patients required abdominal aortic aneurysm-related reintervention, and an additional 2.3% (5/214) required surgical repair of an incisional hernia. Pooled analysis of literature revealed a 30-day mortality of 3.0% for open pararenal repair and 1.9% for fenestrated endovascular repair. Conclusion Open pararenal abdominal aortic aneurysm repair in the era of increasing endovascular options results in acceptable perioperative morbidity and mortality rates. Mid-term reintervention rate is low compared to fenestrated endovascular aneurysm repair. Expertise with open repair still remains essential for treatment of pararenal abdominal aortic aneurysms in the near future, especially for those patients that are declined for endovascular treatment.

More challenging abdominal aortic aneurysms with unfavorable proximal aortic neck anatomy are treated with endovascular means. As a consequence, proximal inadequate sealing may result in type IA endoleak, which in turn can lead to abdominal aortic aneurysm progression or rupture. The presence of type IA endoleak is an indication for secondary interventions. External aortic banding can be a good option to solve a type IA endoleak, but is underreported in literature; we present two cases and review literature., (© The Author(s) 2015.)

Background: The optimal post-operative care regimen after surgically fixed Lauge Hansen supination exorotation injuries remains to be established. This study compares whether unprotected weight bearing as tolerated is superior to protected weight bearing and unprotected non-weight bearing in terms of functional outcome and safety., Methods/design: The WOW! Study is a prospective multicenter clinical trial. Patients between 18 and 65 years of age with a Lauge Hansen supination exorotation type 2, 3 or 4 ankle fractures requiring surgical treatment are eligible for inclusion. An expert panel validates the classification and inclusion eligibility. After surgery, patients are randomized to either the 1) unprotected non-weight-bearing, 2) protected weight-bearing, or 3) unprotected weight-bearing group. The primary outcome measure is ankle-specific disability measured by the Olerud-Molander ankle score. Secondary outcomes are 1) quality of life (e.g., return to work and resumption of sport), 2) complications, 3) range of motion, 4) calf wasting, and 5) maximum pressure load after 3 months and 1 year., Discussion: This trial is designed to compare the effectiveness and safety of unprotected weight bearing with two commonly used post-operative treatment regimens after internal fixation of specified, intrinsically stable but displaced ankle fractures. An expert panel has been established to evaluate every potential subject, which ensures that every patient is strictly screened according to the inclusion and exclusion criteria and that there is a clear indication for surgical fixation., Trial Registration: The WOW! Study is registered in the Dutch Trial Register ( NTR3727 ). Date of registration: 28-11-2012.

Introduction: Elderly patients with a hip fracture represent a large proportion of the trauma population; however, little is known about outcome differences between different levels of trauma care for these patients. The aim of this study is to analyse the outcome of trauma care in patients with a hip fracture within our inclusive trauma system., Materials and Methods: Retrospective cohort study. Data were collected from the electronic patient documentation of patients, with an isolated hip fracture (aged ≥ 60), admitted to a level I or level II trauma centre between January 2008 and December 2012. Main outcomes were time to operative treatment, complications, mortality, and secondary surgical intervention rate., Results: A total of 204 (level I) and 1425 (level II) patients were admitted. Significantly more ASA4 patients, by the American Society of Anesthesiologists (ASA) classification, were treated at the level I trauma centre. At the level II trauma centre, median time to surgical treatment was shorter (0 days; IQR 0-1 vs 1 day; IQR 1-2; P < 0.001), which was mainly influenced by postponement due to lack of operation room availability (14%, n = 28) and co-morbidities (13%, n = 26) present at the level I trauma centre. At the level II trauma centre, hospital stay was shorter (9 vs 11 days; P < 0.001) and the complication rate was lower (41%; n = 590 vs 53%; n = 108; P = 0.002), as was mortality (4%; n = 54 vs 7%; n = 15; P = 0.018). Secondary surgical intervention was performed less often at the level II trauma centre (6%; n = 91 vs 12%; n = 24; P = 0.005). However, no differences in secondary surgical procedures due to inadequate postoperative outcome or implant failure were observed., Conclusion and Relevance: The clinical pathway and the large volume of patients at the level II centre resulted in earlier surgical intervention, lower overall complication and mortality rate, and a shorter length of stay. Therefore, the elderly patient with a hip fracture should ideally be treated in the large-volume level II hospital with a pre-established clinical pathway. However, complex patients requiring specific care that can only be provided at the level I trauma centre may be treated there with similar operative results., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Purpose: For symptomatic patients with carotid artery stenosis, the risk benefit for surgical intervention may vary among patient groups. Various modalities of plaque imaging have been promoted as potential tools for additional risk stratification, particularly in patients with moderate stenosis. However, it remains uncertain to what extent carotid plaque components predict risk of future ipsilateral ischemic stroke., Methods: In 2 large atherosclerotic carotid plaque biobank studies, we related histological characteristics of 1640 carotid plaques with a validated risk model for the prediction of individual 1- and 5-year stroke risk., Results: No significant heterogeneity between the studies was found. Predicted 5-year stroke risk (top versus bottom quartile) was related to plaque thrombus (odds ratio, 1.42; 95% confidence interval, 1.11-1.89; P=0.02), fibrous content (0.65; 0.49-0.87; P=0.004), macrophage infiltration (1.41; 1.05-1.90; P=0.02), high microvessel density (1.49; 1.05-2.11; P=0.03), and overall plaque instability (1.40; 1.05-1.87; P=0.02). This association was not observed for cap thickness, calcification, intraplaque hemorrhage, or lymphocyte infiltration. Plaques removed within 30 days of most recent symptomatic event were most strongly correlated with predicted stroke risk., Conclusions: Features of the vulnerable carotid plaque, including plaque thrombus, low fibrous content, macrophage infiltration, and microvessel density, correlate with predicted stroke risk. This study provides a basis for plaque imaging studies focused on stroke risk stratification., (© 2014 American Heart Association, Inc.)

Aim: The aim of this paper was to review technical success and clinical outcome of reinterventions to treat complications after endovascular abdominal aortic aneurysm (AAA) repair (EVAR) in a tertiary vascular center., Methods: The study enrolled 107 patients treated for post-EVAR complications between January 2005 and March 2014. Details of reinterventions, technical success, and midterm clinical outcome were analyzed for reinterventions. Radiologic follow-up after reinterventions was performed by computed tomography scans and duplex ultrasonography., Results: Indications for reinterventions in the 107 patients were predominantly endoleaks type Ia, Ib, II, and III (55.1%). Endograft obstructions were observed in 39 patients (36.4%). The initial technical success rate for the 107 reinterventions was 93.5% (N.=100). Median follow-up postreintervention was 20 months (range, 1-107 months). During follow-up, 34 of 107 patients (31.8%) needed at least one renewed reintervention. Kaplan-Meier analysis of overall survival after the primary reinterventions was 85% at 1 year, and 78% at 3 years of follow-up. AAA/EVAR-associated mortality was 4% at 3 years. Kaplan-Meier survival estimation of freedom of recurrence was 88% at 1 year post-reintervention and 78% at 3 years. Renewed reintervention-free survival dropped to 78% at 1 year and 58% at 3 years., Conclusion: In this series of patients, the technical success rate of reinterventions to treat post-EVAR complications was high. During a median follow-up of 20 months, AAA-associated mortality is low, but the need for renewed (endovascular) reinterventions is substantial.

Aims: Diabetes accelerates progression of atherosclerotic disease, but data on associations between diabetes and advanced atherosclerotic plaque composition are scarce., Methods and Results: We used one of the largest biobanks, the Athero-Express study (n=1455) at carotid endarterectomy (CEA). All plaques were subjected to histological analysis to assess lipid core size, collagen, macrophages, smooth muscle cells, micro-vessel density and calcifications. In addition, within a subset of patients cytokines and chemokines were assessed. The 295 patients (20%) with type-2 diabetes showed a higher proportion of previous cardiovascular interventions and more stringent treatment for hypertension and hypercholesterolaemia compared with patients without type-2 diabetes. Surprisingly, no associations between diabetes and histological plaque characteristics were observed. In addition, no differences were observed in the expression of inflammatory chemokines, cytokines or advanced glycation end products in plaques of diabetic and non-diabetic patients., Conclusion: In patients suffering from significant carotid artery disease, diabetes does not appear to be associated with specific atherosclerotic plaque characteristics., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Time-dependent trends in the incidence of cardiovascular disease have been reported in high-income countries. Because atherosclerosis underlies the majority of cardiovascular diseases, we investigated temporal changes in the composition of atherosclerotic plaques removed from patients undergoing carotid endarterectomy., Methods and Results: The Athero-Express study is an ongoing, longitudinal, vascular biobank study that includes the collection of atherosclerotic plaques of patients undergoing primary carotid endarterectomy in the province of Utrecht from 2002 to 2011. Histopathologic features of plaques of 1583 patients were analyzed in intervals of 2 years. The analysis included quantification of collagen, calcifications, lipid cores, plaque thrombosis, macrophages, smooth muscle cells, and microvessels. Large atheroma, plaque thrombosis, macrophages, and calcifications were less frequently observed over time, with adjusted odds ratios of 0.72 (95% confidence interval, 0.650-0.789), 0.62 (95% confidence interval, 0.569-0.679), 0.87 (95% confidence interval, 0.800-0.940), and 0.75 (95% confidence interval, 0.692-0.816) per 2-year increase in time, respectively. These changes in plaque characteristics were consistently observed in patient subgroups presenting with stroke, transient ischemic attack, ocular symptoms, and asymptomatic patients. Concomitantly, risk factor management and secondary prevention strategies among vascular patients scheduled for carotid endarterectomy significantly improved over the past decade., Conclusions: In conclusion, over the past decade, atherosclerotic plaques harvested during carotid endarterectomy show a time-dependent change in plaque composition characterized by a decrease in features currently believed to be causal for plaque instability. This appears to go hand in hand with improvements in risk factor management., (© 2014 American Heart Association, Inc.)

Aim: Carotid plaque composition is associated with ipsilateral cerebrovascular events. Among patients with carotid artery stenosis, presence of microembolic signals (MES) detected with transcranial Doppler (TCD) is associated with increased stroke risk. We aimed to investigate whether MES detected with TCD in the outpatient clinic among patients scheduled for carotid endarterectomy, was associated with underlying carotid plaque composition., Methods: TCD was used to detect MES among 38 symptomatic patients scheduled for carotid endarterectomy. Measurements were performed for 30 minutes. Carotid plaques harvested during CEA were subjected to histopathological examination. Plaques from patients without spontaneous MES were compared with plaques from patients with ≥1 MES., Results: Median time between TCD and surgery was 4 days. At least 1 MES was detected in 10/38 (26%) patients. Five of ten (50%) patients with spontaneous MES had lipid-rich plaques, compared with 5/28 (17.2%) plaques from patients without MES (P=0.048). Luminal thrombus was observed in 6/10 (60.0%) of plaques from patients with MES compared with 7/28 (25.0%) of plaques from patients without MES (P=0.045)., Conclusion: Spontaneous MES were detected in 26% of symptomatic patients scheduled for CEA and were associated with unstable carotid plaque characteristics. TCD might be a useful tool to help identify patients with vulnerable plaques.

Background and Purpose: Patients with carotid artery stenosis and ocular ischemic events have a much lower risk of future ipsilateral ischemic stroke on medical treatment and lower procedural risks for endarterectomy and stenting than patients with cerebral ischemic events, and are closer in risk to patients with asymptomatic stenosis. The reasons for this difference in prognosis are not fully understood, but may reflect differences in carotid plaque pathology., Methods: In consecutive patients undergoing carotid endarterectomy for recently symptomatic stenosis (Oxford Plaque Study, Athero-Express Study), we compared carotid plaque histology (using validated semiquantitative scales) in those who had cerebral events within the last 6 months (n=1317) versus those with ocular events only (n=323)., Results: Compared with plaques from patients with ocular events only, those from patients with cerebral events had significantly more large lipid core (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.05-1.82; P=0.02), inflammation (OR, 1.32; 95% CI, 1.02-1.72; P=0.04) and overall plaque instability (OR, 1.37; 95% CI, 1.05-1.80; P=0.02), and less fibrous content (OR, 0.71; 95% CI, 0.54-0.92; P=0.01), and calcification (OR, 0.70; 95% CI, 0.54-0.91; P=0.008). The overall number of histological features known to be associated with vulnerable plaque was greater in patients with cerebral events than in those with ocular events (P=0.002)., Conclusions: Carotid plaques from patients undergoing endarterectomy for previous ocular ischemic events have fewer vulnerable plaque features than those from patients with recent cerebral ischemic events, possibly explaining some of the differences in risk of stroke between these groups.

Objectives: Optimal surgical treatment of patients with asymptomatic carotid artery stenosis (ACAS) remains a matter of debate. Established definitions of ACAS include: (1) patients who never suffered from ipsilateral cerebrovascular events (group 1) or (2) patients who suffered from ipsilateral cerebrovascular events more than 6 months prior to revascularisation (group 2). Cerebrovascular symptoms are closely related to underlying carotid plaque composition and therefore we investigated potential plaque differences between these definition-based subgroups., Design: Cross-sectional analysis of a longitudinal prospective biobank study., Material and Methods: Carotid atherosclerotic plaques from 264 asymptomatic patients were harvested during endarterectomy, and subjected to histopathological examination. Patients were divided into two groups: group 1: truly asymptomatic (n = 182), and group 2: patients with ipsilateral events more than 6 months before carotid endarterectomy (CEA) (n = 82)., Results: Patients in group 1 had relatively more stable plaque characteristics as compared with patients in group 2, with a higher median plaque smooth muscle cell content (2.1 (0.0-18.7) vs. 1.6 (0.0-14.4); P = 0.036), a higher proportion of heavily calcified plaques (67.7% (123/182) vs. 48.8% (40/82); P = 0.005) and less frequently intraplaque haemorrhages (11.5% (21/182) vs. 30.5% (25/82); P = 0.001)., Conclusion: Different plaque characteristics within subgroups of ACAS patients can be identified based on reported past ipsilateral events, which might result in adjusted future treatment strategies., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: To identify plaque characteristics of carotid artery radiation-induced stenosis., Materials and Methods: Nineteen carotid plaques were obtained during carotid endarterectomy (CEA) in 17 consecutive patients with prior cervical radiation therapy (XRT) (median interval 10 years) and compared with 95 matched control carotid plaques of patients without a history of XRT. The following histopathological factors were assessed: calcification, collagen, macrophages, smooth muscle cells, atheroma, microvessels and intraplaque haemorrhage. Association of individual histological parameters with XRT plaque was analysed through a multivariable regression model., Results: Less infiltration of macrophages (6/19 versus 60/95, adjusted p = 0.003) and a smaller lipid core size (Atheroma >10%: 10/19 versus 80/95, adjusted p = 0.006) were independently associated with XRT plaque, compared to non-XRT plaques., Conclusions: Carotid stenotic lesions in patients with previous cervical radiation are less inflammatory and more fibrotic than carotid atherosclerotic lesions in non-radiated patients., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Platelets foster an inflammatory environment that influences atherosclerotic lesion progression and facilitates plaque rupture, in addition to their role in acute thrombus formation. The route of entry of platelets into the atherosclerotic plaque and their exact location inside the plaque are however not completely understood., Methods and Results: 188 carotid plaques were examined for the presence of platelets using immunohistochemistry (CD42b), and 76/188 (40.4%) were platelet positive. Platelets were observed in intraplaque hemorrhages, around plaque microvessels, mostly without leakage of erythrocytes; and in mural thrombi. Platelet positive staining was associated with a higher plaque microvessel density, and elevated plaque-levels of interleukin-8., Conclusion: Due to their short life span, platelets reflect recent bleeding. It can be hypothesized that platelets might serve as a marker for leaky microvessels inside atherosclerotic plaques that are at risk for development, or progression of plaque hemorrhage., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: Exogenous insulin use in patients with type 2 diabetes (DM2) has been associated with an increased risk of cardiovascular events. Through which mechanisms insulin may increase atherosclerotic plaque vulnerability is currently unclear. Because insulin has been suggested to promote angiogenesis in diabetic retinopathy and tumors, we hypothesized that insulin enhances intra-plaque angiogenesis., Methods: An in vitro model of pathological angiogenesis was used to assess the potential of insulin to enhance capillary-like tube formation of human microvascular endothelial cells (hMVEC) into a three dimensional fibrin matrix. In addition, insulin receptor expression within atherosclerotic plaques was visualized in carotid endarterectomy specimens of 20 patients with carotid artery stenosis, using immunohistochemical techniques. Furthermore, microvessel density within atherosclerotic plaques was compared between 68 DM2 patients who received insulin therapy and 97 DM2 patients who had been treated with oral glucose lowering agents only., Results: Insulin, at a concentration of 10(-8)M, increased capillary-like tube formation of hMVEC 1.7-fold (p<0.01). Within human atherosclerotic plaques, we observed a specific distribution pattern for the insulin receptor: insulin receptor expression was consistently higher on the endothelial lining of small nascent microvessels compared to more mature microvessels. There was a trend towards an increased microvessel density by 20% in atherosclerotic plaques derived from patients using insulin compared to plaques derived from patients using oral glucose lowering agents only (p=0.05)., Conclusion: Exogenous insulin use in DM2 patients may contribute to increased plaque vulnerability by stimulating local angiogenesis within atherosclerotic plaques., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: Prognosis after carotid endarterectomy is mainly determined by the occurrence of major adverse cardiovascular events (MACEs). Optimal medical treatment to reduce risk is the mainstay of MACE prevention. The level of risk of MACE may determine the initiation and aggressiveness of medical treatment, yet a prediction rule to assess that absolute MACE risk after carotid endarterectomy is currently unavailable., Methods: The prediction model was developed in a consecutive cohort of 1138 patients who underwent carotid endarterectomy between 2002 and 2009. Primary end point was MACE and encompassed myocardial infarction, stroke, and cardiovascular death. Fourteen potential clinical predictors were entered into a Cox proportional hazard model. After backward stepwise regression, internal validation was conducted with bootstrapping techniques to correct for overfitting. To provide an easily applicable clinical tool, a score chart was constructed, dividing patients into 4 risk groups. Model performance was assessed in terms of discrimination, calibration, and risk stratification., Results: During a mean follow-up of 2.28 (± 0.95) years, 148 events occurred, corresponding to a cumulative incidence of 13%. Clinical predictors in the final model were age, history of coronary or peripheral artery disease, smoking, systolic blood pressure, use of antihypertensive drugs, clinical presentation, presence of contralateral carotid stenosis, and serum creatinine levels. Discrimination of the final model, in terms of a C statistic, was 0.69 (0.64-0.73) and calibration showed a good overall fit (Gronnesby and Borgan, P=0.39). The observed incidence of MACE in the 4 risk groups was 6%, 9%, 19%, and 35%, respectively, indicating good overall risk stratification., Conclusions: The clinical prediction model for MACE in the first 3 years after carotid endarterectomy may be used to identify high-risk patients to help optimize medical treatment and risk factor management as part of secondary prevention to increase life expectancy free from MACE. Despite our success in stratifying risk among these patients, even the lowest stratum remains at high risk and all of these patients should receive maximal secondary preventive measures.

Background and Purpose: Intraplaque hemorrhage (IPH) is an important determinant of progression and destabilization of atherosclerotic plaque. We recently demonstrated that IPH is an independent predictor of cardiovascular events. IPH has become more clinically relevant since magnetic resonance imaging (MRI) technique is able to visualize IPH in vivo. Different stages of IPH have been described. However, etiology of the different stages is not known and it is unclear if these detected different stages are all associated with the vulnerable plaque phenotype., Methods and Results: 1070 patients who underwent a carotid (n=794) or femoral (n=276) endarterectomy were included. Histopathological presence of IPH was determined and divided into 3 types: recent, organized and amorphous IPH. Carotid IPH was observed in 644/794 (81%) plaques, divided into 14 (2%) recent, 70 (11%) organized and 560 (87%) amorphous. Femoral IPH was observed in 175/276 (63%) plaques, divided into 2 (1%) recent, 89 (51%) organized and 84 amorphous (48%). Overall presence of carotid IPH was associated with a large lipid core, no or minor staining of smooth muscle cells, no or minor calcification and high microvessel density. Overall presence of femoral IPH was associated with moderate to heavy staining of macrophages. Plaques with organized IPHs revealed more macrophages, a larger lipid core, less smooth muscle cells, less calcification and higher microvessel density than plaques with amorphous IPHs., Conclusions: IPH is a significant characteristic of carotid and femoral atherosclerotic plaque and can be classified into different types. Organized IPH is associated with unstable and amorphous IPH with stable plaque characteristics., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: Recent randomized trials showed an increased periprocedural risk for stroke with increasing age in patients undergoing carotid artery stenting. Manipulation of atherosclerotic plaques during carotid artery stenting can result in plaque rupture with subsequent superimposed thrombus formation, embolization, and cerebrovascular events. We hypothesized that atherosclerotic plaques become more unstable with increasing age and thereby might provide insight into the age-related increased risk of cerebrovascular events during carotid artery stenting., Methods: Carotid atherosclerotic plaques were harvested from 1385 consecutive patients undergoing carotid endarterectomy between 2002 and 2010. Carotid plaques were quantitatively analyzed for macrophages, smooth muscle cells, and microvessels; and semiquantitatively analyzed for collagen, calcifications lipid cores, and intraplaque hemorrhages. Patients were divided in 4 groups by age: <60, 60 to 69, 70 to 79, and ≥80 years. Measures of association between age as a continuous variable and histological characteristics were also calculated., Results: Increasing age was associated with a decrease in the amount of smooth muscle cells in the carotid plaque. More plaques with large atheroma and heavy plaque calcifications were observed among elderly patients. After correction for baseline differences, risk factors, and medication use, age was independently associated with a more vulnerable carotid plaque composition., Conclusions: Plaque stability decreases gradually with age. Older patients with carotid stenosis have relatively unstable plaques with low smooth muscle cell content, a high amount of large lipid cores, and more calcified plaques as compared with younger patients. The underlying vulnerable plaque composition in the elderly might be an important contributing factor to the increased risk of stroke for older patients undergoing carotid artery stenting.

Background and Purpose: Carotid endarterectomy (CEA) of stable atherosclerotic plaques is associated with an increased risk for restenosis. Patients with transient ischemic attack and patients with and stroke have relatively unstable atherosclerotic plaques. However, carotid plaques stabilize over time after a cerebrovascular event due to plaque repair after rupture. These findings raised 2 questions: (1) Is preoperative clinical presentation related to restenosis after CEA? (2) Does delayed revascularization result in a higher risk for restenosis compared with CEA in the short term after a cerebrovascular event?, Methods: Between 2002 and 2009, 1203 patients undergoing CEA were included. The impact of clinical presentation on the occurrence of restenosis 1 year after CEA was investigated and corrected for cardiovascular risk factors, medication use, and type of arteriotomy closure. Patency was assessed with standardized duplex ultrasound imaging at 1 year after CEA. Restenosis was defined as recurrent luminal narrowing ≥50% at the endarterectomy site., Results: At 1 year of follow-up, restenosis was observed more frequently in asymptomatic patients than in patients with transient ischemic attack and patients with stroke. The adjusted odds ratio (95% CI) for restenosis was 0.56 (0.35 to 0.89) for patients with transient ischemic attack and 0.49 (0.27 to 0.87) for patients with stroke compared with asymptomatic patients. Subgroup analysis showed an increased risk for restenosis if CEA was performed >30 days after stroke (adjusted OR, 2.23; 1.02 to 5.73)., Conclusions: Asymptomatic patients have an increased risk for restenosis at 1 year after CEA compared with patients with transient ischemic stroke and patients with stroke. CEA within 30 days after stroke is associated with a decreased risk of restenosis, which supports the current strategy for early surgical intervention after stroke.

Background and Purpose: Carotid Angioplasty and Stenting (CAS) has emerged as an alternative to Carotid Endarterectomy (CEA) in treatment of carotid stenotic disease. With increasing life expectancy clinicians are more often confronted with patients of higher age. Octogenarians were often excluded from randomized trials comparing CAS to CEA because they were considered high-risk for revascularization. Conflicting results on the peri-procedural outcome of carotid revascularization in these patients have been reported. In order to objectively evaluate whether age above 80 years should be an upper limit for indicating carotid revascularization we systematically reviewed the currently available literature., Methods: Literature was systematically reviewed between January 2000 and June 2010 using Pubmed and Embase, to identify all relevant studies concerning CAS and CEA in octogenarians. Inclusion criteria were 1) reporting outcome on either CEA or CAS; and 2) data subanalysis on treatment outcome by age. The 30-day Major Adverse Event (MAE) rate (disabling stroke, myocardial infarction or death) was extracted as well as demographic features of included patients., Results: After exclusion of 23 articles, 46 studies were included in this review, 18 involving CAS and 28 involving CEA. A total of 2.963 CAS patients and 14.365 CEA patients with an age >80 years were reviewed. The MAE rate was 6.9% (range 1.6 - 24.0%) following CAS and 4.2% (range 0 - 8.8%) following CEA. A separate analysis in this review included the results of one major registry 140.376 patients) analyzing CEA in octogenarians only reporting on 30-day mortality and not on neurological or cardiac adverse events. When these data were included the MAE following CEA is 2.4% (range 0 - 8.8%), Conclusions: MAE rates after CEA in octogenarians are comparable with the results of large randomized trials in younger patients. Higher complication rates are described for CAS in octogenarians. In general, age > 80 years is not an absolute cut off point to exclude patients from carotid surgery. In our opinion, CEA should remain the golden standard in the treatment of significant carotid artery stenoses, even in the very elderly.

Statins have an established role in the treatment of hypercholesterolemia and the prophylactic treatment of patients with atherosclerotic disease, and have been found to prevent secondary cardiovascular events and thereby reduce morbidity and mortality. Nevertheless, the pathophysiologic effect of statins on inflammatory responses and local atherosclerotic plaque morphology in humans remains a matter of debate. In particular the question is unanswered whether statin-induced alterations in plaque composition can be ascribed to LDL lowering or an anti-inflammatory pleiotropic effect. We will discuss the results of a recent study by Puato et al. concerning the effect of two different atorvastatin dosages and a nonstatin lipid-lowering drug on atherosclerotic plaque morphology.

With the aging population and the increasing number of patients suffering from diabetes, the incidence of clinical manifestations of atherosclerotic disease is rising. Risk factors for development of atherosclerosis have been described and it is a challenge to develop risk scores that can be applied for individual patients. Specific predictors for progression of atherosclerosis and secondary manifestations of the disease are lacking. The search for new serological and genetic markers predictive for cardiovascular events is an emerging research field. Local plaque instability can give rise to thromboembolic cardiovascular events, which suggests that certain information might be enclosed in local atherosclerotic tissue. Because of the systemic character of atherosclerosis, it can be hypothesized that local plaque characteristics encompass information of other atherosclerotic lesions throughout the vascular tree. Biobank studies with a longitudinal design have been initiated to investigate the link between characteristics of local atherosclerotic tissue and outcome during follow up. These studies might reveal new insights in predictors for cardiovascular outcome for vascular patients at an individual level.

Purpose: To evaluate initial and long-term results of secondary interventions after endovascular aneurysm repair (EVAR) with an AneuRx endoprosthesis., Methods: Between 1996 and 2003, an AneuRx device was used primarily in 212 patients (197 men; mean age 71+/-7.0 years). Sixty-two (29%) patients (58 men; mean age 73+/-7.2 years) required a secondary intervention (percutaneous, endovascular, or open repair) after EVAR and were prospectively followed after their secondary interventions. Data were analyzed retrospectively., Results: Of the 212 AneuRx patients, 59 (28%) required secondary interventions for endoleaks (28 type Ia, 6 type Ib, 8 type II, and 17 type III) and 3 (1%) for obstruction of the endoprosthesis. The mean interval between primary EVAR and secondary intervention was 39+/-30 months. The yearly risk of requiring a secondary intervention after receiving a primary AneuRx graft was 3.7%. Overall 30-day morbidity after a secondary intervention was 18% (11/62); the 30-day mortality was 5% (3/62). Short endovascular extender cuffs were used for type Ia endoleaks in 23 of 28 patients. Over a mean follow-up of 81+/-34 months after the secondary intervention, the success of short endovascular cuffs for treatment of type Ia endoleak was 52% (12/23); the remaining 11 (48%) patients required additional reinterventions for recurrent endoleak or persistent aneurysm growth., Conclusion: Patients with a primary AneuRx stent-graft had an acceptable yearly risk of requiring a secondary intervention following EVAR, but 30-day morbidity and mortality rates were significant and must be taken into account during primary decision making for endovascular or open repair. Proximal extender cuffs may not be a durable treatment for type Ia endoleak.