Galectin-3, Carotid Plaque Vulnerability, and Potential Effects of Statin Therapy.

OBJECTIVES: Galectin-3, a member of galectines, a family of b-galactoside-specific lectins, has been reported to propagate vascular inflammation. The role of galectin-3 in carotid atherosclerosis is controversial. The aim of this study was to investigate the relationship of galectin-3 with plaque vulnerability in patients with high grade carotid stenosis. METHODS: This was a cross sectional study of patients undergoing carotid endarterectomy (CEA). Carotid plaques obtained from 78 consecutive patients (40 symptomatic [SG], 38 asymptomatic [AG]) undergoing CEA were histologically analyzed for galectin-3, macrophages (CD68) and laminin. Pre-operatively the biochemical profile and plaque echogenicity (gray-scale median, GSM) score were determined. RESULTS: There were no significant differences in clinical and demographic parameters between SG and AG(p > .05). The SG had a lower GSM score (44.21 ± 18.24 vs. 68.79 ± 28.79, p < .001) and a smaller positive stained area for galectin-3 (4.89 ± 1.60% vs. 12.01 ± 5.91%, p < .001) and laminin (0.88 ± 0.71% vs. 3.46 ± 2.12%, p < .001) than the AG. On the other hand, intra-plaque macrophage content was increased in SG (p < .001). For the whole cohort, symptomatic status was independently associated with intra-plaque contents of both galectin-3 (OR=0.634, p < .001), and GSM score (OR=0.750, p < .001). Notably, patients on long term statin treatment had elevated galectin-3 and lowered macrophage intra-plaque concentrations compared with those on short term treatment (p < .05). CONCLUSIONS: A low galectin-3 intra-plaque concentration seems to correlate with clinically and ultrasonically defined unstable human carotid plaques. Long term statin treatment may induce increase of intra-plaque galectin-3 concentration mediating plaque stabilization.

Factors Predisposing to Endograft Limb Occlusion after Endovascular Aortic Repair.

OBJECTIVES: The aim of this study was to investigate risk factors for endograft limb occlusion after endovascular abdominal aneurysm repair (EVAR), using a case control design. METHODS: All patients presenting with endograft limb occlusion after elective EVAR between January 2010 and June 2013, along with age, sex, and type of endograft matched controls were included in the study. The impact of atherosclerotic risk factors, anatomic characteristics of the aneurysm, procedural details, and antiplatelet therapy was investigated. Multivariate logistic regression analysis and conditional logistic regression analysis for 1:3 matched pairs deriving adjusted odds ratios (ORs) with 95% confidence intervals (CIs) in order to detect significant risk factors for endograft limb occlusion among cases and controls were modeled. RESULTS: Of the 439 patients treated by EVAR, 18 patients (4.1%) presented with endograft limb occlusion. These patients were compared to 54 matched controls. Limb occlusion was associated with iliac artery angulation ≥ 60° (OR = 5.76, 95% CI =1.24-26.74; p = .03) or perimeter calcification ≥ 50% (OR =5.87, 95% CI = 1.10-31.32; p = .04). Limb occlusion was also associated with ≥ 15% endograft oversizing in the common iliac artery (OR = 5.54, 95% CI = 1.11-27.60; p = .04). No other risk factors for limb occlusion were recognized. CONCLUSIONS: The presence of significant angulation and calcification of the iliac arteries as well as excessive limb oversizing appear to be independent predictors of endograft limb occlusion after EVAR.

The differential anti-inflammatory effects of exercise modalities and their association with early carotid atherosclerosis progression in patients with type 2 diabetes.

OBJECTIVE: Adipokines, visfatin, apelin, vaspin and ghrelin have emerged as novel cardiovascular risk factors. We aimed to evaluate the effects of different exercise modalities on the aforementioned novel adipokines and carotid intima-media thickness in patients with Type 2 diabetes mellitus. METHODS: One hundred patients with Type 2 diabetes were equivalently (n = 25) randomized into four groups: (1) a control group with patients encouraged to perform self-controlled exercise; (2) a supervised aerobic exercise group (exercise four times/week, 60 min/session, 60-75% of maximum heart rate); (3) a resistance training group (60-80% baseline maximum load achieved in one repetition); and (4) a combined aerobic exercise plus resistance training group, as in groups 2 and 3. All participants had HbA(1c) levels ≥ 48 mmol/mol (≥ 6.5%), without overt diabetic vascular complications. Blood samples, clinical characteristics, peak oxygen uptake and carotid intima-media thickness measurements were obtained at baseline and at the end of the study, after 6 months. RESULTS: At baseline, there were non-significant differences between groups. All active groups significantly ameliorated glycaemic profile, insulin sensitivity and triglycerides levels compared with the control group (P < 0.05). Aerobic training further improved lipids, systolic blood pressure and exercise capacity compared with the resistance training and the control groups (P < 0.05). Moreover, high-sensitivity C-reactive protein and visfatin decreased, while vaspin and apelin circulating levels increased within the aerobic exercise group and the aerobic exercise plus resistance training group, and compared with the other groups (P < 0.05). Within- and between-group comparisons showed negligible alterations in ghrelin serum levels and body weight after all exercise modalities. Finally, aerobic training attenuated the carotid intima-media thickness progression (0.017 ± 0.006 mm) compared with the control subjects (0.129 ± 0.042 mm, P < 0.001). That effect was independently associated with visfatin and amelioration of peak oxygen uptake. CONCLUSIONS: In subjects with Type 2 diabetes, all exercise training modalities improved metabolic profile. Importantly, aerobic training predominantly ameliorated adipokines concentrations and carotid intima-media thickness progression.

Critique of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): flaws in CREST and its interpretation.

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) has been used to support the equivalence of carotid artery stenting (CAS) and carotid endarterectomy (CEA) in the treatment of carotid stenosis in both symptomatic and asymptomatic patients. This inclusion of two different forms of the disease decreased the power and significance of the CREST results and weakened the trial. Other flaws in CREST were the equal weighting of mostly minor myocardial infarctions (MIs) with strokes and death in the peri-procedural, composite 'end' point, but not in the 4-year, long-term 'end' point. Although CAS was associated with 50% fewer peri-procedural MIs compared with CEA, there were >2.5-fold more MIs after CAS than CEA at 4 years. The 4-year MI rate, however, was not a component of the primary 'end' point. Additionally, although the initial CREST report indicated that there was no difference in the outcomes of CAS and CEA according to symptomatic status or sex, subsequent subgroup analyses showed that CAS was associated with significantly higher stroke and death rates than CEA in symptomatic patients, in females and in individuals ≥ 65 years of age. The present article will examine these and other flaws and the details of CREST's results derived from the trial's preplanned subanalyses to show why the claims that CREST demonstrates equivalence of the two therapeutic procedures are unjustified.

The European Society for Vascular Surgery guidelines for carotid intervention: an updated independent assessment and literature review.

BACKGROUND AND PURPOSE: Many medical societies now recommend carotid stenting as an alternative to endarterectomy which raises the question of whether the ESVS guidelines are still valid. This review addresses the validity of the ESVS guidelines that refer to carotid stenting based on the evidence available today. METHODS: We conducted a review and meta-analysis based on the original ESVS guidelines paper and articles published over the past 2 years. RESULTS: For symptomatic patients, surgery remains the best option, since stenting is associated with a 61% relative risk increase of periprocedural stroke or death compared to endarterectomy. However, centres of excellence in carotid stenting may achieve comparable results. In asymptomatic patients, there is still no good evidence for any intervention because the stroke risk from an asymptomatic stenosis is very low, especially with the best modern medical treatment. CREST and CAVATAS have verified that mid-term stroke prevention after successful stenting is similar to endarterectomy. EVA-3S, SPACE, ICSS and CREST have provided additional evidence regarding the role of age in choosing therapeutic modality. The role of the cerebral protection devices is challenged by the imaging findings of small randomised trials but supported by large systematic reviews. CONCLUSIONS: The ESVS guidelines that refer to carotid stenting not only remain valid but also have been further strengthened by the latest available clinical data. An update of these guidelines including all of the recent evidence is needed to provide an objective and up-to-date interpretation of the data.

Association between plaque echogenicity and embolic material captured in filter during protected carotid angioplasty and stenting.

OBJECTIVES/DESIGN: The aim of the study was to investigate debris captured in filter embolic protection devices (EPDs) during carotid artery stenting (CAS) and its possible correlation with plaque echogenicity and other risk factors. MATERIALS/METHODS: Between June 2010 and March 2011, 51 consecutive CAS patients (11 females, mean age 71.2 ± 7, 10 symptomatic) who underwent 53 procedures were included in this prospective study. Ultrasonographic Gray-Weale plaque type (I-V, echolucent to echogenic) characterisation was obtained in all cases. The same type of stent and filter EPD was used. Filters were collected and, after macroscopic evaluation, they were examined using the Thin-Prep(®) liquid-based cytology (LBC) technique. RESULTS: Technical success was 100%. Thirty-day stroke and death rates were 1.8% (1/53) and 0%, respectively. Visible debris was detected in eight (15%) filters, whereas LBC revealed the presence of embolic material particles in 30 filters (56.6%). The presence of embolic material into the filter EPD was 2.38-fold increased for every category change from type IV to type I carotid plaques (OR = 2.38, 95%CI = 1.15-4.93). This association remained robust even after adjustment for age, gender and known atherosclerotic disease risk factors (OR = 2.26, 95%CI = 1.02-5.02). In multivariate analysis for risk factors, hypertension was associated with increased presence of embolic material detection in filter EPD (OR = 20.4, 95%CI = 1.28-326.1). The time distance from symptom to CAS was inversely correlated with debris quantity in EPD (Spearman rho -0.716; p = 0.02). CONCLUSIONS: Echolucent plaques, smaller time frame from last symptom and hypertension were associated with increased presence of embolic material.

The chimney graft technique for preserving renal arteries in stent-graft sealing zones.

Patients with juxtarenal aneurysms require complex surgical open repair, which is associated with increased mortality and morbidity. An alternative procedure that can be used is the "chimney graft" technique. Three cases of abdominal aortic aneurysms were successfully treated in our department with this technique. One type-Ia endoleak occurred which was successfully treated with coiling and biological glue infusion. All of the chimney grafts have remained patent for the period of observation. The "chimney" technique has good results as a bail out procedure in complex EVAR or in well planned difficult cases. Long-term data is necessary to determine the efficacy of this technique.

Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies.

BACKGROUND: To compare eversion (ECEA) and conventional (CCEA) carotid endarterectomy from randomised and non-randomised studies. METHODS: Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) and numbers needed to treat (NNTs) were appropriately calculated. A sub-analysis was performed on studies directly comparing ECEA vs. patch CEA (PCEA). Meta-regression analysis was performed to examine the effect of potentially meaningful patient-related, procedure-related and definition-related modifiers. Power calculations were also conducted. RESULTS: A total of 21 studies were deemed eligible (8530 ECEA and 7721 CCEA procedures), seven of which were randomised and 14 non-randomised. ECEA was associated with significant reduction in perioperative stroke (OR = 0.46, 95%CI: 0.35-0.62, NNT = 68, 95%CI: 56-96), death (OR = 0.49, 95%CI: 0.34-0.69, NNT = 100, 95%CI: 85-185) and stroke-related death (OR = 0.40, 95%CI: 0.23-0.67, NNT = 147, 95%CI: 115-270); the results were replicated at the sub-analysis on PCEA. Concerning long-term outcomes, ECEA presented with a significant reduction in late carotid artery occlusion (OR = 0.48, 95%CI: 0.25-0.90, NNT = 143, 95%CI: 100-769) and late mortality (OR = 0.76, 95%CI: 0.61-0.94, NNT = 40, 95%CI: 25-167); the sub-analysis on PCEA replicated only the finding on late mortality. Meta-regression analysis did not point to significant effects mediated by the examined modifiers. Power calculations suggested adequate statistical power. CONCLUSIONS: ECEA compared to CCEA may be associated with a lower incidence in both short-term and long-term outcomes, which does not seem to be hampered by potentially meaningful modifiers.

Open or endovascular repair of aortoenteric fistulas? A multicentre comparative study.

OBJECTIVES: To compare aortoenteric fistula (AEF) outcome after endovascular (EV-AEFR) or open repair (O-AEFR). DESIGN: Multicentre retrospective comparative study. MATERIALS/METHODS: 25 patients with AEF (24 secondary, 23 males, median age 75 years) after aortic surgery (median four years). Preoperative sepsis was evident in 19 cases. Eight patients were managed with EV-AEFR and 17 with O-AEFR. RESULTS: The two groups were comparable in preoperative characteristics. In-hospital mortality after EV-AEFR was lower compared to O-AEFR (0% and 35%, respectively, p = 0.13). Similarly, morbidity after EV-AEFR was lower compared to O-AEFR (25% and 77%, respectively, p = 0.028). There was a trend for worse recurrence-free, sepsis-free, re-operation-free and AEF-related death-free rates after EV-AEFR, while the early survival advantage of EV-AEFR was lost after two years and the overall long-term survival rates (perioperative mortality included) of the two groups were similar. Preoperative sepsis had no effect on recurrence and sepsis-free rates (p = 0.94 and p = 0.92, respectively), but it was associated with worse two year overall survival (24% vs 50%, p = 0.32). On multivariate analysis, the number of symptoms (two vs one) at presentation was the single predictor of worse re-operation rates, AEF-related and overall survival. CONCLUSIONS: EV-AEFR was associated with no postoperative mortality in this study and can achieve satisfactory short and long-term results, comparable to O-AEFR. Further trials should focus on the role of EV-AEFR in patients at high risk for O-AEFR, due to shock or co-morbidities, or as a bridging procedure.

Heparin-induced thrombocytopenia: what a vascular surgeon needs to know.

The use of unfranctioned heparin and low molecular weigh heparins is very common in general medical practice and moreover in angiology and vascular surgery. Heparin-induced thrombocytopenia is a rare, yet catastrophic complication, with an incidence of 1-5% of patients receiving heparin therapy. Clinical presentation may include deep vein thrombosis, pulmonary embolism, arterial thrombosis, and skin lesions. Hemorrhage may also be present as a result of thrombocytopenia. Current diagnostic criteria include clinical scoring systems as well as laboratory tests for the identification of the specific antibodies. Efficient new alternative anticoagulant agents have been developed and are currently indicated for the treatment of such patients. The syndrome curies up to 53% thrombosis risk in untreated patients, and 28% mortality risk in patients complicated with thrombosis. This article aims in a comprehensive review of the literature for newly emerged data in the pathogenesis, diagnosis and management of heparin-induced thrombocytopenia.

Vascular surgery training and its relationship to other surgical specialties.

During the last 50 years vascular surgery has met an enormous evolution, paving the way for the development of modern vascular and endovascular surgery. Although, vascular surgery (VS) has emerged from general (GS) and cardiothoracic surgery (CTS), the need for specialized training has been recognized and gradually practice patterns are shifting towards vascular independence, but yet not in all countries. In these countries VS training is either permitted only after prerequisite GS certification, or as a non accredited surgical specialty, VS might be included in GS or CTS training and certification. Such a policy raises two main issues: the efficiency of vascular training within the GS or CTS curricula and the performance of vascular interventions by general or cardiothoracic surgeons. Meanwhile, the explosion of endovascular procedures has brought new disciplines into play, each one wanting to maintain its stake in the future. Interventional radiologists and a significant number of cardiologists become increasingly involved in the treatment of vascular diseases. The question of which specialist among those qualified should carry out medical treatment, open, and endovascular procedures is still suspended. Under this prism, vascular training issues arise as an important component of the future of vascular surgeons.

An update of the role of endovascular repair in blunt carotid artery trauma.

Blunt carotid injury (BCAI) is an increasingly recognised entity in trauma patients. Without a prompt diagnosis and a proper treatment, they can result in devastating consequences with cerebral ischaemia rate of 40-80% and mortality rate of 25-60%. Several applied screening protocols and continuously improving diagnostic modalities have been developed to identify patients with BCAI. The appropriate treatment of BCAI still remains controversial and strictly individualised. Besides anti-thrombotic/anticoagulation therapy and surgical intervention, continuously evolving endovascular techniques emerge as an additional treatment option for patients with BCAI. We provide an update on blunt carotid trauma, emphasising the role of endovascular approaches.

Beneficial changes of serum calcification markers and contralateral carotid plaques echogenicity after combined carotid artery stenting plus intensive lipid-lowering therapy in patients with bilateral carotid stenosis.

OBJECTIVES/DESIGN: In symptomatic patients treated with ipsilateral carotid artery stenting (CAS) plus intensive lipid lowering, we assessed the changes of osteopontin (OPN), osteoprotegerin (OPG) and the Gray-Scale Median (GSM) score contralateral to symptomatic carotid stenosis. MATERIALS/METHODS: Forty-six symptomatic patients (group A) with significant carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial (NASCET): >70%) underwent ipsilateral CAS. Those patients had simultaneously contralateral low-grade carotid stenosis (NASCET: 30-69%). Group B included 67 symptomatic patients with low-grade bilateral carotid stenosis (NASCET: 30-69%), but without indications for revascularisation. All patients were treated with atorvastatin (10-80mg) to target low-density lipoprotein (LDL)<100mgdl(-1). Blood samples and plaques' GSM score contralateral to brain infarct were assayed at baseline and after 6 months. RESULTS: At baseline, there were no significant differences between groups (p>0.05). Six-month atorvastatin treatment equivalently improved lipid profile in both groups (p<0.05). The parameters hsCRP, OPN and OPG were significantly down-regulated within both groups, but to a greater extent in group A (p<0.05). Besides this, contralateral GSM score was significantly improved from baseline in both groups (p<0.01), but that increment was more pronounced in group A (vs. group B; p=0.041). These changes were inversely correlated with changes in OPN (p=0.014), OPG (p=0.011) and LDL (p=0.041). CONCLUSION: Ipsilateral CAS plus intensive lipid-lowering therapy was associated with enhanced contralateral carotid plaque stability and attenuated inflammatory burden and calcification inhibitors to a greater extent than atorvastatin therapy alone in patients with bilateral carotid stenosis.

Current knowledge on E-vita abdominal endograft.

The field of endovascular abdominal aortic repair has changed remarkably compared to what it was prior to 1993, the year of the first commercial endograft deployment in the United States. Over the years of endovascular aneurysm repair experience, various companies have attempted to construct an ideal stent-graft for exclusion of an abdominal aortic aneurysm (AAA). However, it has become evident that not all abdominal aortic anatomies are amenable to endovascular treatment and that the rationale "one device fits all AAAs" can lead to disastrous results. Different endografts have dissimilar properties and characteristics. Type of graft material, configuration and type of stent structural support, modularity, type of transrenal fixation, are potentially influential factors of endograft behavior. The self-expanding E-vita abdominal stent-graft (JOTEC, Hechingen, Germany) is a relatively new infrarenal, modular stent-graft with suprarenal fixation designed for AAA reconstruction. The present paper analyzes the technical characteristics and properties of this device. We also analyze our experience with the endoprosthesis and review the current literature.

Vascular training and endovascular practice in Europe.

OBJECTIVE: To evaluate the influence of the status of vascular surgery (VS) training paradigms on the actual practice of endovascular therapy among the European countries. METHODS: An email-based survey concerning vascular surgery training models and endovascular practices of different clinical specialties was distributed to a VS educator within 14 European countries. European Vascular and Endovascular Monitor (EVEM) data also were processed to correlate endovascular practice with training models. RESULTS: Fourteen questionnaires were gathered. Vascular training in Europe appears in 3 models: 1. Mono-specialty (independence): 7 countries, 2. Subspecialty: 5 countries, 3. An existing specialty within general surgery: 2 countries. Independent compared to non-independent certification shortens overall training length (5.9 vs 7.9 years, p=0.006), while increasing overall training devoted specifically to VS (3.9 vs 2.7 years, p=0.008). Among countries with independent certification an average of 76% of aortic and 50% of peripheral endovascular procedures are performed by vascular surgeons, while the corresponding values, for countries with a non-independent certification, are 69% and 36% respectively. Countries with independent vascular certification, despite their lower average endovascular index (procedures per 100,000 population), reported a higher growth rate of aortic endovascular procedures (VS independent 132% vs VS non-independent 87%), within a four-year period (2003-2007). Peripheral endovascular procedures, though, have similar growth rates in both country groups (VS independent 62% vs VS non-independent 60%). CONCLUSIONS: In European countries with VS as an independent specialty, vascular surgeons have a shorter total training period but spend more time in VS training, although they may not undertake a greater proportion of the endovascular procedures their countries appear to have adopted endovascular technologies more rapidly compared to the ones with non-independent VS curricula. Whether such differences influence patient outcomes requires investigation in future studies.

ESVS guidelines. Invasive treatment for carotid stenosis: indications, techniques.

The European Society for Vascular Surgery brought together a group of experts in the field of carotid artery disease to produce updated guidelines for the invasive treatment of carotid disease. The recommendations were rated according to the level of evidence. Carotid endarterectomy (CEA) is recommended in symptomatic patients with >50% stenosis if the perioperative stroke/death rate is <6% [A], preferably within 2 weeks of the patient's last symptoms [A]. CEA is also recommended in asymptomatic men <75 years old with 70-99% stenosis if the perioperative stroke/death risk is <3% [A]. The benefit from CEA in asymptomatic women is significantly less than in men [A]. CEA should therefore be considered only in younger, fit women [A]. Carotid patch angioplasty is preferable to primary closure [A]. Aspirin at a dose of 75-325 mg daily and statins should be given before, during and following CEA. [A] Carotid artery stenting (CAS) should be performed only in high-risk for CEA patients, in high-volume centres with documented low peri-operative stroke and death rates or inside a randomized controlled trial [C]. CAS should be performed under dual antiplatelet treatment with aspirin and clopidogrel [A]. Carotid protection devices are probably of benefit [C].

Urgent CAS for patients in high neurologic risk.

Patients with residual carotid stenosis discovered following an acute ischemic insult represent a new subset of patients eligible for early carotid intervention that may decrease the risk of recurrent stroke by new emboli and improve cerebral blood flow. Short-term clinical outcomes of patients undergoing urgent CAS appear favorable, indicating that endovascular management may be a reasonable treatment option, particularly when combined with endovascular interventions for intracranial lesions. Data on indication and complication profiles are still limited. This review focuses on current knowledge, advantages and pitfalls of urgent and/or early (up to 2 weeks) carotid stenting in those presenting with an acute neurologic event or recently symptomatic carotid stenosis.

Beneficial effects of rosiglitazone on novel cardiovascular risk factors in patients with Type 2 diabetes mellitus.

AIM: Impaired exercise capacity, adiponectin, MMPs and TIMPs have all been implicated in the development of cardiovascular disease. The aim of our study was to determine the effects of rosiglitazone on these factors in diabetic patients. METHODS: Seventy individuals with Type 2 diabetes were assigned randomly to either a rosiglitazone group (8 mg/day, RG) or a control group (CG) for 6 months. All participants took gliclazide 160 mg plus metformin 1700 mg in stable dose. None of the individuals had diabetic complications or had previously participated in an exercise programme. Anthropometric parameters, VO2 peak, oxygen pulse, glycaemic indices, lipid profile, adiponectin, insulin resistance, blood pressure and serum MMP-9, TIMP-1, TIMP-2 levels were assessed at baseline and at the end of the study. After Bonferroni adjustment, a P-value < 0.017 was assumed to be statistically significant. RESULTS: Rosiglitazone treatment significantly increased VO2 peak (P < 0.0001), the duration of the exercise test (P < 0.0001), oxygen pulse (P = 0.010) and TIMP-2 levels (P = 0.008) in comparison with CG. Insulin resistance, hyperglycaemia, diastolic blood pressure and MMP-9 levels were also reduced (P < 0.017). Fat mass, lipid profile, TIMP-1 levels and MMP9 : TIMP-1 ratio were unaltered after rosiglitazone treatment. There were no significant changes in these parameters in control subjects. In univariate analysis, the rosiglitazone-induced increment of VO2 peak was associated with alterations in plasma adiponectin (r = 0.691), HOMA-IR (r = -0.782) and HbA(1c) (r = -0.676) (P < 0.017). These relationships retained significance after multiple regression analysis (P = 0.005). CONCLUSIONS: Rosiglitazone treatment increases cardiorespiratory fitness and modulates favourably serum adiponectin, MMP-9 and TIMP-2 levels. Whether these effects produce cardiovascular benefits in the long term requires further investigation.