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Purpose: This study investigated whether recommendations given to the treating vascular specialist and the GP by a multidisciplinary team of vascular specialists concerning the medical treatment of risk factors, based on international guidelines, led to an increased medication use in a high-risk population., Methods: Data were obtained from 618 patients enrolled in the SMART study, an ongoing single-center prospective cohort study of patients referred to the University Medical Center Utrecht for atherosclerotic vascular diseases. All patients underwent a vascular screening and their physicians received recommendations concerning the medical treatment of newly detected or not yet sufficiently treated vascular risk factors. After a median follow-up of 29 months, questionnaires about medication use were sent to 618 patients; 534 (86%) questionnaires were returned. Actual use of medication was compared with medical treatment recommendation given at baseline., Results: The proportion of patients on antihypertensive medication with hypertension (> or =140/90 mmHg) and not diagnosed with coronary heart disease increased from 56% to 68% (95% confidence interval (95% CI) 2 - 23). The frequency of lipid-lowering medication use increased substantially from 47% to 69% (95% CI 17 - 28). The frequency of glucose-lowering medication use increased slightly from 11% to 14% (95% CI 1 - 7). The use of folic acid increased from 2% to 14% (95% CI 9 - 15) in patients with hyperhomocysteinaemia., Conclusions: Medical treatment recommendations, formulated by a multidisciplinary team, led to a significant increase in medication use. The increase is marginal compared with trends in medication use without this intervention in usual care.

Objective: Patch closure after carotid endarterectomy (CEA) improves clinical outcome compared with primary closure. Whether there are differences in outcome between various patch materials is still not clear. The objective of this retrospective study was to investigate whether a relationship exists between the patch type and the number of microemboli as registered during CEA by transcranial Doppler imaging, the clinical outcome (transient ischemic attack and cerebrovascular accident), and the occurrence of restenosis., Methods: We included 319 patients who underwent CEA. Intraoperative microembolus registration was performed in 205 procedures. Microembolization was recorded during four different periods: dissection, shunting, clamp release, and wound closure. The decision to perform primary closure or to use a patch for the closure of the arteriotomy was made by the surgeon, and Dacron patches were used when venous material was insufficient. Cerebral events were recorded within the first month after CEA, and duplex scanning was performed at 3 months (n = 319) and 1 year (n = 166) after CEA. A diameter reduction of more than 70% was defined as restenosis., Results: Primary, venous, and Dacron patch closures were performed in 83 (26.0%), 171 (53.6%), and 65 (20.4%) patients, respectively. Primary closure was significantly related to sex (Dacron patch, 35 men and 30 women; venous patch, 108 men and 63 women; primary closure, 72 men and 11 women; P < .001). The occurrence of microemboli during wound closure was also related to sex (women, 2.5 +/- 0.6; men, 1.0 +/- 0.2; P = .01). Additionally, during clamp release, Dacron patches were associated with significantly more microemboli than venous patches (11.1 +/- 3.4 vs 4.0 +/- 0.9; P < .01), and this difference was also noted during wound closure (3.1 +/- 0.9 vs 1.4 +/- 0.4; P < .05). Transient ischemic attacks and minor strokes after CEA occurred in 5 (2.4%) of 205 and 6 (2.9%) of 205 procedures, respectively, and the degree of microembolization during dissection was related to adverse cerebral events (P = .003). In contrast, the type of closure was not related to immediate clinical adverse events. However, primary closure and Dacron patches were associated with an increase in the restenosis rate compared with venous patches: after 400 days, the restenosis rate for Primary closure was 11%, Dacron patch 16%, and venous patch 7% (P = .05; Kaplan-Meier estimates)., Conclusions: Microemboli are more prevalent during clamp releases and wound closure when Dacron patches are used. Additionally, the observed differences in embolization noted by patch type were mainly evident in women. However, the use of Dacron patches was not related to immediate ischemic cerebral events but was associated with a higher restenosis rate compared with venous patch closure. This suggests that venous patch closure may be preferred for CEA.

Objective: To compare the consequences of occlusion of infrainguinal venous and prosthetic grafts., Methods: In total, 2690 patients were included in the Dutch BOA study, a multicenter randomised trial that compared the effectiveness of oral anticoagulants with aspirin in the prevention of infrainguinal bypass graft occlusion. Two thousand four hundred and four patients received a femoropopliteal or femorodistal bypass with a venous (64%) or prosthetic (36%) graft. The incidence of occlusion and amputation was calculated according to graft material and the incidence of amputation after occlusion was compared with Cox regression to adjust for differences in prognostic factors., Results: The indication for operation was claudication in 51%, rest pain in 20% and tissue loss in 28% of patients. The mean follow up was 21 months. After venous bypass grafting 171 (15%) femoropopliteal and 96 (24%) femorodistal grafts occluded. After prosthetic bypass grafting 234 (30%) femoropopliteal and 25 (38%) femorodistal grafts occluded. Patients with occlusions in the venous group had more severe ischemia, less runoff vessels and were older than the patients with prosthetic grafts. In the venous occlusion group 54 (20%) amputations were performed compared to 42 (16%) in the prosthetic occlusion group; crude hazard ratio 1.17 (95% CI 0.78-1.75). After adjustment for above mentioned differences in patient characteristics the hazard ratio was 0.86 (95% CI 0.56-1.32)., Conclusion: The need for amputation after occlusion is not influenced by graft material in infrainguinal bypass surgery.

Objectives: The beneficial effect of oral anticoagulants after infrainguinal venous bypass surgery is compromised by bleeding complications. We developed a model to identify patients, treated with anticoagulation, at risk of major haemorrhage and estimated whether this complication could have been prevented if patients had received aspirin., Design: Randomised clinical trial., Methods: Data of patients who participated in the Dutch Bypass Oral Anticoagulation or Aspirin Study were reanalysed using Cox regression. After infrainguinal bypass surgery these patients were randomised to oral anticoagulants (n = 1326) or aspirin (n = 1324)., Results: Predictors of major haemorrhage for patients on oral anticoagulants were increased systolic blood pressure (> or = 140 mmHg, hazard ratio [HR] 1.62), age > or = 75 years (HR 2.77) and diabetes mellitus (HR 1.60). If the 345 patients in the highest risk quartile had received aspirin, major haemorrhages would have been reduced from 46 to 22, with no major changes in ischemic events and graft occlusions. In the subgroup with venous bypasses major haemorrhages would have been reduced from 27 to 13, at the cost of seven more ischemic events (mostly fatal) and 17 more graft occlusions., Conclusions: Treating patients at highest risk of major haemorrhage with aspirin instead of oral anticoagulants would have resulted in a reduction of non-fatal haemorrhages, but for venous bypasses this reduction was outweighed by an increase in ischemic events and graft occlusions. We still recommend treatment with oral anticoagulants after peripheral venous bypass surgery.

Purpose: To assess the cost-effectiveness of noninvasive imaging strategies in patients who have had a transient ischemic attack (TIA) or minor stroke and are suspected of having significant carotid artery stenosis., Materials and Methods: From 1997 through 2000, 350 patients were included in a multicenter blinded consecutive cohort study. The sensitivities and specificities of duplex ultrasonography (US), magnetic resonance (MR) angiography, and these two examinations combined were estimated by using digital subtraction angiography (DSA) as the reference standard. The actual costs (from a societal perspective) of performing imaging and endarterectomy were estimated. The survival, quality of life, and costs associated with stroke were based on data reported in the literature. Markov modeling was used to predict long-term outcomes. Subsequently, a decision model was used to calculate costs, quality-adjusted life-years (QALYs), and incremental costs per QALY gained for 62 examination-treatment strategies. Extensive sensitivity analyses were performed., Results: Duplex US had 88% sensitivity and 76% specificity with use of conventional cutoff criteria. MR angiography had comparable values: 92% sensitivity and 76% specificity. Combined concordant duplex US and MR angiography had superior diagnostic performance: 96% sensitivity and 80% specificity. Duplex US alone was the most efficient strategy. Adding MR angiography led to a marginal increase in QALYs gained but at prohibitive costs (cost-effectiveness ratio > 1 500 000 per QALY gained). Performing DSA owing to discordant duplex US and MR angiographic findings and to confirm duplex US and MR angiographic findings led to extra costs and QALY loss owing to complications. Sensitivity analyses revealed that duplex US as a stand-alone examination remained the preferred strategy while estimates and assumptions were varied across plausible ranges., Conclusion: Duplex US performed without additional imaging is cost-effective in the selection of symptomatic patients suitable for endarterectomy. Adding MR angiography increases effectiveness slightly at disproportionately high costs, whereas DSA is inferior because of associated complications., (Copyright RSNA, 2004)

Aim: Seeding venous endothelial cells (EC) onto damaged vascular surfaces attenuates the development of intimal hyperplasia. Unlike venous EC, fat derived microvascular endothelial cells (MVEC) do not require a culture step to increase the yield. The authors investigated whether fat derived MVEC are suitable to reduce intimal hyperplasia after PTA., Methods: Five rabbits were subjected to percutaneous transluminal angioplasty (PTA) of both iliac arteries. One side was seeded transluminally with autologous perirenal fat derived MVEC, using a double balloon catheter. The contralateral side was sham seeded, and served as a control. Follow-up was 4 weeks. Another rabbit was used for a feasibility experiment. This rabbit was subjected to a 1-sided seeding procedure and was sacrificed after 1 week. In a 7th rabbit, a 1-sided PTA was transformed, and autologous labelled cells were injected in the distal aorta instead of seeded, follow-up was 1 week. Histological investigation was per-formed., Results: The MVEC seeded artery of the pilot experiment was patent. All sham seeded arteries (5) except for 1 were patent. The patent ones showed moderate intimal hyperplasia. MVEC seeding (5) resulted in occlusion twice. In the patent MVEC seeded arteries intimal hyperplasia was present in more extended form than in the sham seeded arteries. Both the patent MVEC- and sham-seeded arteries were covered with an EC layer. Injected labelled MVEC were not found again on the de-endothelialized artery., Conclusion: In this study seeding of fat derived MVEC on damaged native arteries results in an increased development of intimal hyperplasia and a decreased patency. One of the reasons may be the presence of non-EC in the seeded cell population.

Background: Microvascular endothelial cells (MVEC) derived from s.c. fat are seeded on vascular grafts to prevent early occlusion. We have demonstrated the presence of contaminating cells contributing to MVEC seeding-related intimal hyperplasia in MVEC isolates from fat tissue. We found that cell isolates additionally purified after the isolation process, were associated with a reduced thrombogenicity and development of intimal hyperplasia in vitro. A combination of 11Fibrau (F11)- and CD14-coated Dynabeads was used to deplete the contaminating cells, fibroblasts, and monocytes/macrophages. Unfortunately, clinical-grade F11 is not available, and thus cannot be used for clinical practice. CD34 selection with clinical-grade products is widely used for the isolation of hematopoietic progenitors, and endothelial cells (EC) express CD34 on their surfaces. The aims of this study were to test the effectiveness of two different CD34-selection techniques for purification of MVEC, and to compare the results with those of the F11/CD14-method., Methods: Liposuction fat was enzymatically digested and centrifuged twice to remove adipocytes and collagenase. CD34 selection was performed using the commercially available methods from Nexell or Miltenyi. Both techniques were modified for our use. The purity after isolation and culture, and recovery were determined by flow-cytometry (CD31-expression) and compared with that of cells purified with the F11/CD14-method., Results: Besides MVEC, the contaminating fibroblasts and macrophages/monocytes weakly expressed the CD34 Ag. Enrichment of MVEC was not successful with the Miltenyi method. Variations in neither the dose of Ab nor the use of direct selection and different separation programs improved the results. With the Nexell method, MVEC were enriched to 86%, a comparable purity to that obtained with the F11/CD14-method. However, a lower recovery was achieved with the Nexell method., Conclusion: Enrichment of MVEC could be achieved with a modified protocol of the clinical grade CD34(+) selection method from Nexell, but not with the CD34 method from Miltenyi.

Objective: Tracing and treating cardiovascular risk factors in patients with arterial vascular disease and in patients with high risk of developing vascular diseases., Design: Descriptive., Method: In September 1996 at the University Medical Center Utrecht, the Netherlands, a vascular screening and prevention programme was started for newly referred patients aged between 18 and 79 years presenting with one or more of the following: coronary artery disease, cerebrovascular disease, peripheral arterial disease, hypertension, diabetes mellitus or lipid disorders. In all patients, risk factors for developing (new) vascular diseases were assessed and non-invasive vascular diagnostics aimed at finding asymptomatic vascular disease were done., Results: Between 1 September 1996 and 31 October 2002, 3075 patients took part in the screening programme. Within the various patient groups and often despite treatment, there was a high prevalence of hypertension, smoking, dyslipidaemia, hyperhomocystemia and overweight. In patients with peripheral artery disease, carotid artery stenosis > or = 50% was detected in 17% and an aneurysm of the abdominal aorta in 5%. In patients presenting with diabetes mellitus, hypertension or lipid disorders the prevalence of asymptomatic arterial disease was 1-5%. Asymptomatic vaso-dilatory disease in particular was uncommon., Conclusion: A hospital-wide vascular screening and prevention programme for a wide range of high-risk vascular patients was shown to be feasible and resulted in the detection of risk factors and asymptomatic arterial disease. It is a reliable starting point for actual risk intervention. More attention should be paid to treating existing risk factors.

Purpose: To assess accuracy of contrast material-enhanced magnetic resonance (MR) angiography as compared with three-dimensional (3D) time-of-flight (TOF) MR angiography and reference digital subtraction angiography (DSA) in diagnosis of carotid artery stenosis., Materials and Methods: Enhanced and 3D TOF MR angiography and DSA were performed in 51 consecutive patients suspected of having carotid artery stenosis at duplex ultrasonography. Stenoses were measured by two independent observers blinded to clinical information and other test results. Pearson correlation coefficients were used, and kappa for interobserver variabilities was estimated. Sensitivity and specificity of enhanced and 3D TOF MR angiography were calculated and compared with those of DSA., Results: Pearson correlation coefficients were 0.94 (P <.01) for enhanced angiography versus DSA, 0.92 (P <.01) for 3D TOF angiography versus DSA, and 0.93 (P <.01) for enhanced versus 3D TOF angiography for observer 1 and 0.94 (P <.01), 0.95 (P <.01), and 0.94 (P <.01), respectively, for observer 2. kappa statistics were 0.81 for enhanced angiography, 0.79 for 3D TOF angiography, and 0.78 for DSA. Stenosis measurements of observer 1 at enhanced MR angiography, with inclusion of carotid arteries on the symptomatic side only, compared with those of DSA yielded a sensitivity of 90% (95% CI: 68%, 99%) and a specificity of 77% (95% CI: 55%, 92%). 3D TOF angiography yielded a sensitivity of 86% (95% CI: 67%, 97%) and a specificity of 73% (95% CI: 50%, 89%) compared with those of DSA. For observer 2, sensitivity and specificity for enhanced angiography were 91% (95% CI: 70%, 99%) and 76% (95% CI: 52%, 91%), respectively, and 90% (95% CI: 68%, 99%) and 77% (95% CI: 51%, 92%), respectively, for 3D TOF angiography., Conclusion: Accuracy of enhanced MR angiography in diagnosis of severe stenosis is similar to that of 3D TOF MR angiography.

Patients with peripheral artery disease suffer from a high incidence of ischemic vascular complications in coronary, cerebral, and peripheral vascular beds. Reduction of atherothrombotic complications with aspirin or clopidogrel has proven to be successful. The role of oral anticoagulants in patients with symptomatic peripheral artery is limited. Randomized controlled trials comparing the effects of aspirin with oral anticoagulants are scarce. Oral anticoagulants (International Normalized Ratio = 2.5 to 4.5) are more effective than aspirin in preventing infrainguinal bypass occlusion only when venous graft material is used and the bypass is considered to be at high risk for occlusion. Whether the use of oral anticoagulants reduces all-cause morbidity and mortality is not unequivocally clear. The risk of ischemic events is reduced at the expense of an increased number of bleeding complications, which is one of the main reasons that therapy has not been widely adopted.

Background and Purpose: In patients with severe obstruction of the internal carotid artery (ICA), it is recognized that the preoperative failure to visualize collaterals of the circle of Willis increases the risk of hemispheric ischemia before, during, and after carotid endarterectomy (CEA). The purpose of the present study was to assess the effect of CEA on the anatomy and function of the circle of Willis., Methods: Time-of-flight and phase-contrast MR angiography were used to study changes in vessel diameter and collateral flow of the circle of Willis in 48 patients with 70% to 99% ICA stenosis before and after CEA., Results: In patients with unilateral ICA stenosis, all preoperative vessel diameters on both sides of the circle of Willis were larger than in control subjects. All demonstrated a significant diameter decrease to reach normal values after CEA. Furthermore, preoperative collateral flow patterns normalized after CEA (P=0.03). In patients with stenosis and contralateral ICA occlusion, CEA resulted in a significant increase in the prevalence of collateral flow via the anterior communicating artery (33% to 83%, P<0.01) and a significant increase in diameter of both A1 segments (P<0.05) in patients in whom collateral flow developed after CEA., Conclusions: CEA reduces the caliber of compensatory collateral channels to normal levels by MR angiography measurements in the presence of severe unilateral stenosis; when the opposite side is occluded and the stenosis is removed ipsilaterally, a greater amount of compensatory collateral circulation can be measured on both the occluded side and the fully opened side.

Purpose: To assess the value of MR angiography (MRA) with automatic table movement in a consecutive series of patients with peripheral arterial disease., Methods: Seventy-two patients underwent both conventional angiography (CA) and MRA for peripheral arterial occlusive disease. Both techniques were scored in a masked way. Consensus scoring for CA was compared with MRA scoring per observer. If there was a discrepancy in scoring of a segment on MRA and CA, the images were reviewed and a consensus arrived at., Results: Observer A found 7.4% and observer B found 6.5% of the segments could not be analyzed on MRA. Observer A scored 11.4% dissimilar on MRA and CA, observer B 15.2%. In the aortoiliac arteries, this was mainly caused by stents and overestimation of stenoses; in the crural arteries it resulted from underestimation of the stenoses on MRA. Overall sensitivity and specificity for the aortoiliac, femoropopliteal and crural vessels were respectively 90% and 91%, 90% and 96%, 59% and 96% for observer A, and 85% and 91%, 84% and 89%, 68% and 85% for observer B., Conclusion: Although MRA of the lower extremities is a promising technique, improvements still need to be made. In particular, MRA below the knee is suboptimal for clinical use.

Background and Purpose: Time-of-flight (TOF) magnetic resonance angiography (MRA) is commonly used to visualize the carotid arteries; however, flow void artifacts can appear. Our purpose was to determine the frequency and diagnostic meaning of flow voids by using real patient data, as part of a larger study of MRA compared with the criterion standard, digital subtraction angiography (DSA)., Methods: In 1997-2000, 390 consecutive patients with sonographic findings suggestive of carotid artery stenosis were included in this study. All patients subsequently underwent three-dimensional (3D) TOF MRA and conventional DSA. The frequency of flow void artifacts on 3D TOF MRA images were compared with stenosis measurements on DSA images., Results: We recorded 107 flow voids (16%) during 3D TOF MRA of 662 carotid arteries. DSA images were available for comparison in 102 cases. The median percentage of stenosis in this subgroup of flow voids on MRA images was 80%, compared with measurements on DSA images according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Stenoses ranged from 36% to 100% (occlusion). Three flow voids (2.9%) were in the 0-49% range; 11 (10.8%), in the 50-69% range; and 86 (84.3%), in the 70-99% range. Two flow voids (2.0%) represented occlusions. The positive predictive value of a flow void artifact for the presence of severe (70-99%) stenosis was 84.3% (95% CI: 77.3%, 91.4%)., Conclusion: Flow void artifacts represented severe stenosis in most of the arteries. According to our data, the assumption that flow voids on 3D TOF MRA images represent severe stenosis is justified.

Objective: In patients with stenosis of the internal carotid artery (ICA), the presence of collateral circulatory pathways may be crucial to maintain cerebral perfusion pressure, metabolism, and function. The purpose of the present study was to determine whether patients with asymptomatic stenosis of the ICA have a better collateral ability of the circle of Willis when compared with patients with symptomatic ICA stenosis., Method: Magnetic resonance angiography consisting of the circle of Willis was performed in 19 patients with severe asymptomatic ICA stenosis and in 21 patients with severe symptomatic ICA stenosis prior to carotid endarterectomy and in 53 control subjects. Between group comparisons were made for function (directional flow) and anatomy (diameter)., Results: In patients with asymptomatic ICA stenosis, the prevalence of collateral flow via the anterior communicating artery was significantly increased (37%, 7 of 19) compared with symptomatic patients (10%, 2 of 21) and control subjects (0%; P <.001). Patients with asymptomatic ICA stenosis demonstrated the largest mean diameter of the anterior communicating artery (1.33 +/- 0.18 mm) compared with patients with symptomatic ICA stenosis (1.22 +/- 0.18 mm) and control subjects (1.06 +/- 0.10 mm, P <.05). No differences in collateral flow pattern or diameter were found for the posterior communicating artery between the groups., Conclusions: The present cross-sectional study demonstrates the importance of an adequate hemodynamic compensation via the circle of Willis in patients with ICA stenosis. Whether differences in collateral compensation can be used to select patients for CEA has yet to be determined.

Background and Purpose: Three-dimensional time-of-flight (3D TOF) magnetic resonance angiography (MRA) is generally considered to overestimate the degree of stenosis in the internal carotid artery (ICA) in comparison with the reference standard intraarterial digital subtraction angiography (DSA). We evaluated whether the degree of stenosis was more accurately assessed with 3D TOF MRA if corresponding projections on MRA and DSA were compared instead of comparison of maximal stenosis at MRA with maximal stenosis at DSA., Methods: From February 1997 to December 1999, we included 186 symptomatic and 17 asymptomatic consecutive patients suspected of having carotid artery stenosis on the basis of clinical presentation and screening with duplex ultrasound scan examination. All patients subsequently underwent DSA and MRA imaging. From each ICA, 12 maximum intensity projections with 3D TOF MRA and two or three projections with DSA were obtained. First, we compared the maximal stenosis at MRA with the maximal stenosis at DSA. Subsequently, we used the stenosis at MRA measured on the projection corresponding with the DSA projection that showed the maximal stenosis. For both strategies, the mean differences in stenosis and sensitivity and specificity for assessment of severe stenosis (70% to 99%) were calculated and compared., Results: The MRA and DSA images of 354 ICAs could be compared. The sensitivity and specificity of MRA with the projection that showed the maximal stenosis were 92.6% (95% CI, 85.3% to 97.0%) and 82.7% (95% CI, 78.1% to 87.3%), respectively. The sensitivity and specificity with the MRA projection, corresponding with the DSA projection showing the maximal stenosis, were 88.3% (95% CI, 81.8% to 94.8%) and 89.6% (95% CI, 85.9% to 93.3%), respectively. The mean difference between maximal stenosis at MRA and DSA was 7.5% (95% CI, 5.2% to 9.9%). The mean difference between stenosis at MRA and DSA in corresponding projections was 0.4% (95% CI, -2.0% to 2.7%)., Conclusion: If corresponding MRA and intraarterial DSA projections are compared, 3D TOF MRA does not overestimate carotid stenosis.

Background: During clinical evaluation of young women with peripheral arterial occlusive disease, we were surprised by the high prevalence of pregnancy loss in women with segmental stenosis confined to the aortoiliac segment. We wondered if increased occurrence of miscarriage is the result of high expression of vascular and obstetrical risk factors in these patients, or if it is related to localization of disease. In a case-control study designed to investigate risk factors for peripheral arterial occlusive disease in young women, we assessed the risk of miscarriage in these patients according to level of obstruction., Methods: A total of 202 female patients, aged 18-49 years and 466 healthy control women from a population based case-control study, donated venous blood samples and filled out a structured questionnaire concerning classical cardiovascular risk factors and obstetrical history. In all patients, diagnosis of peripheral arterial occlusive disease was confirmed by intra-arterial angiography. Patients were classified into two groups: those with and those without stenosis of the aortoiliac segment (aortoiliac disease)., Results: In 77 of the 202 patients (38%) with peripheral arterial occlusive disease, the obstruction was confined to the aortoiliac segment. The occurrence of miscarriage was high (42%) in young women with aortoiliac disease. Compared to healthy controls, the risk of miscarriage increased 3-fold (OR 3.1; 95% CI 1.8-5.6) in these patients. Adjustment for obstetrical and vascular risk factors did not affect the risk estimate., Conclusion: This is the first study that identifies aortoiliac disease as a risk factor for pregnancy loss in young women. The risk of miscarriage is increased 3-fold in women with aortoiliac disease. The presence of vascular and obstetrical risk factors did not affect the strength of the association. Pregnancy loss could be the first sign of insufficient aortic circulation in these patients.

Background and Purpose: Carotid endarterectomy has been shown to be beneficial in symptomatic patients with a severe stenosis (70% to 99%) of the internal carotid artery (ICA). Digital subtraction angiography (DSA) is the standard of reference in the diagnosis of carotid artery stenosis but has a relatively high complication rate. In a diagnostic study we investigated the accuracy of noninvasive testing compared with DSA., Methods: In a prospective diagnostic study we performed duplex ultrasound (DUS), magnetic resonance angiography (MRA), and DSA on 350 consecutive symptomatic patients. Stenoses were measured with the observers blinded for clinical information and other test results. Separate and combined test results of DUS and MRA were compared with the reference standard DSA. Only the stenosis measurements of the arteries on the symptomatic side were included in the analyses., Results: DUS analyzed with previously defined criteria resulted in a sensitivity of 87.5% (95% CI, 82.1% to 92.9%) and a specificity of 75.7% (95% CI, 69.3% to 82.2%) in identifying severe ICA stenosis (70% to 99%). Stenosis measurements on MRA yielded a sensitivity of 92.2% (95% CI, 86.2% to 96.2%) and a specificity of 75.7% (95% CI, 68.6% to 82.5%). When we combined MRA and DUS results, agreement between these 2 modalities (84% of patients) gave a sensitivity of 96.3% (95% CI, 90.8% to 99.0%) and a specificity of 80.2% (95% CI, 73.1% to 87.3%) for identifying severe stenosis., Conclusions: MRA showed a slightly better accuracy than DUS in the diagnosis of carotid artery stenosis. To achieve the best accuracy, however, both tests should be performed subsequently.

Objective: Hyperhomocysteinemia has been identified as a risk factor for (cardio)vascular disease. Whether hyperhomocysteinemia contributes to graft failure after peripheral bypass surgery remains unclear. The present study evaluated the influence of hyperhomocysteinemia on graft patency after infrainguinal bypass surgery., Design: The present study was designed as a nested case-control study., Method: In this study (nested in the Dutch Bypass Oral anticoagulants or Aspirin Study), 150 patients with graft occlusion were each matched with two randomly selected controls with patent grafts (N = 299) from the same trial. Venous blood samples were drawn from cases and controls, and total plasma homocysteine (tHcy) was determined. Mean serum homocysteine levels and the presence of hyperhomocysteinemia (>95th percentile in healthy individuals) were compared between cases and controls., Results: No significant differences were found between serum levels of homocysteine in patients with and without graft occlusion. The mean plasma homocysteine levels were 14.4 micromol/L and 14.9 micromol/L in the case and control groups, respectively. The resulting mean difference was -0.4 (95% confidence interval [CI], -1.8-0.9). The odds ratio of hyperhomocysteinemia was 0.81 (95% CI, 0.49-1.33). Adjustment for risk factors of graft occlusion did not change these results., Conclusions: Postoperative raised serum levels of homocysteine proved not to be a risk factor for graft occlusion after infrainguinal bypass grafting.

The Dutch Society for Vascular Surgery was founded in 1981, as the first daughter of the Association of Surgeons in the Netherlands. Twenty years of vascular surgery show a broad perspective. Aside from the traditional handywork--central vascular reconstruction, bypass surgery (especially in the legs), and carotid surgery--, there have been many developments. Operations are less invasive and vascular surgeons are cooperating more and more intensively with other medical disciplines, especially radiology. Examples are the endovascular treatment of abdominal aortic aneurysm, in which an endoprosthesis is inserted via minute incisions in the groin by the vascular surgeon and an (interventional) radiologist together. In addition, interventions such as percutaneous transluminal angioplasty and stenting as well as new diagnostic possibilities (e.g. MRA) strengthen the cooperation with the radiologists. The multidisciplinary approach is also extremely important in other areas. Vascular surgeons team up with internal-medicine specialists (diabetes, hypertension, lipid metabolism disorders, thrombotic syndromes, etc.), rehabilitation specialists and podotherapists (in cases of diabetic foot and amputation), vascular laboratory technicians (diagnostics and follow-up by means of doppler and duplex techniques), and neurologists (cerebrovascular diseases). In the vascular centres, patients are treated effectively by a multidisciplinary team that draws up a plan for diagnosis and treatment. The two-year postgraduate course in vascular surgery is one of the tools used to guarantee and improve the high standard of quality. To this end, cooperation within Europe in the European Society for Vascular Surgery and the development and organisation of European examinations in vascular surgery are also of the essence.

Introduction: fat derived microvascular endothelial cells (MVEC) seeded on prosthetic vascular grafts, improve patency in animals. Results in humans were disappointing, due to thrombogenicity and progressive intimal hyperplasia. Also in animals intimal hyperplasia was found. We postulate that contaminating cells present in the transplant are involved in the intimal hyperplasia. We developed a method to further purify human MVEC from 40-90%. Here we tested the effects of enrichment upon thrombogenicity and seeding-related intimal hyperplasia., Methods: liposuction fat was enzymatically digested and centrifuged. To enrich MVEC, contaminating macrophages and fibroblasts were removed with dynabeads coated with macrophage- and fibroblast-specific antibodies. Thrombogenicity was assessed by measuring tissue factor and thrombomodulin activity, presence of endothelial nitric oxide synthase and via perfusion of the cells with whole blood. To investigate seeding-related intimal hyperplasia, PTFE grafts were seeded with the cells and cultured for 3 weeks., Results: tissue factor activity of purified cells was reduced compared to nonpurified cells. Purified cells showed thrombomodulin activity and eNOS expression. Fragment 1+2 and Fibrinopeptide A generation after perfusion of purified cells were significantly lower than after perfusion of nonpurified cells, and only nonpurified cells were covered with platelets and fibrin. Prostheses seeded with nonpurified cells showed an EC monolayer above a multilayer of myofibroblasts, prostheses seeded with purified cells only showed a single EC monolayer. Mixing experiments with human umbilical cord EC (HUVEC) and fibroblasts showed that when more than 25% HUVEC were present a confluent EC layer was formed. When the amount of fibroblasts was 25% or less, no development of a subendothelial multilayer of myofibroblasts was found within 3 weeks., Conclusion: reduction of non-endothelial cell contamination of microvascular endothelial cell seeded grafts decreases thrombogenicity and might prevent seeding-related intimal hyperplasia., (Copyright 2002 Harcourt Publishers Limited.)

Objectives: seeding prosthetic grafts with fat-derived microvascular endothelial cells (MVEC) results not only in a non-thrombogenic EC layer, but also in intimal hyperplasia. Here we investigated incidence, composition, progression, and cause of this intimal hyperplasia., Design: EPTFE grafts with MVEC were implanted as carotid interpositions in six dogs with 1 month, and in three dogs with 4, 8 and 12 months follow-up. Grafts seeded without cells, implanted in the contralateral carotid, served as a control. In another three dogs labelled cells were seeded to investigate the contribution of the seeded cells (2-3 weeks)., Materials and Methods: MVEC were isolated from the falciform ligament. Cells were pressure seeded on ePTFE grafts. Labelling was performed using retroviral gene transduction. The grafts were analysed with immunohistochemical techniques., Results: after 1 month, all patent non-seeded grafts (5/6) showed fibrin and platelet deposition, and all patent seeded grafts (5/6) were covered with a confluent endothelial monolayer on top of a multilayer of myofibroblasts, elastin and collagen. After long term follow-up, all non-seeded grafts were occluded, all patent seeded grafts (4 and 12 months) were covered with an EC-layer with intimal hyperplasia underneath. The thickness of the intima did not progress after 1 month. Transduced cells were found in the endothelial monolayer, hyperplastic intima and luminal part of the prosthesis., Conclusions: MVEC seeding in dogs results in intimal hyperplasia in all patent grafts, which contains myofibroblasts. Contaminants from the transplant contribute to this intimal hyperplasia., (Copyright 2002 Harcourt Publishers Limited.)

Objective: Several studies have reported an association between abdominal aortic dilatation and peripheral arterial occlusive disease. Narrowing of aortic diameter, also called abdominal aortic hypoplasia, and peripheral arterial occlusive disease have received insufficient attention. Precise estimates of the relationship between aortic hypoplasia and peripheral arterial occlusive disease are lacking. In this study, we assessed the relationship between abdominal aortic diameter and peripheral arterial occlusive disease., Methods: In this cross-sectional study, we analyzed 1572 patients 18 to 79 years of age, newly referred to the vascular center of our hospital with clinically manifest atherosclerotic arterial disease or for treatment of cardiovascular risk factors. Diameter measurements were used to subdivide patients according to tertiles of abdominal aortic diameter. Peripheral arterial occlusive disease was assessed by adjusted Rose questionnaire, ankle-brachial pressure index, and the presence of gangrene or leg ulcers., Results: Compared with patients with normal aortic diameter, peripheral arterial occlusive disease was twice as prevalent in patients at both ends of the aortic diameter spectrum. When the lowest tertile was compared with the middle tertile in male patients, the adjusted odds ratio was 1.7 (95% CI, 1.0-3.1). When the highest tertile was compared with the middle tertile, the adjusted odds ratio was 2.1 (95% CI, 1.2-3.4). Similar results were found in female patients. The adjusted odds ratio of lowest versus middle tertile was 2.4 (95% CI, 1.1-5.0) and 1.8 (95% CI, 0.8-4.0) when the highest tertile was compared with the middle tertile., Conclusion: The risk of peripheral arterial occlusive disease was increased in the lower and upper distribution of aortic diameter. Apparently, both patients with an aortic diameter too large and patients with an aortic diameter too small are prone to peripheral arterial occlusive disease. This is the first large study that shows that small aortic diameter is associated with peripheral arterial occlusive disease.

Purpose: Several antithrombotic therapies are available for the treatment of patients with peripheral vascular diseases. It is unknown how quality of life and costs of treatment are influenced by different therapies. This study assessed the cost-effectiveness of oral anticoagulants versus aspirin in patients after infrainguinal bypass grafting surgery., Methods: Clinical outcome events and event-free survival were collected from 2650 patients in 77 centers who participated in the Dutch Bypass Oral anticoagulants or Aspirin trial. Approximately half the patients had critical ischemia; 60% received vein grafts, and 20% had femorocrural bypass grafts. A model that was primarily driven by clinical outcome events was used as a means of determining quality of life (EuroQol EQ-5D) and costs for each patient. The main outcome measure was the incremental health care costs in relation to the additional number of quality-adjusted life years and the additional number of event-free years., Results: The mean costs during the 21 months of follow-up were epsilon 6875 per patient in the oral anticoagulants group versus epsilon 7072 in the aspirin group (difference, 197; 95% CI, -746 to 343). The event-free survival was 1.10 years in the group treated with oral anticoagulants versus 1.09 years in the group treated with aspirin (difference, 0.01; 95% CI, -0.07 to 0.08), whereas the corresponding quality-adjusted life years were 1.06 and 1.05, respectively (difference, 0.01; 95% CI, -0.03 to 0.06)., Conclusion: Health care costs, event-free survival, and quality-adjusted life years in patients after infrainguinal bypass surgery were not different in patients treated with aspirin and patients treated with oral anticoagulants. The extra costs of monitoring patients treated with oral anticoagulants were limited and play no role in the decision for treatment.

Until recently, intra-arterial angiography was the diagnostic method of first choice when pathology of the aorta or its branches was suspected. A disadvantage of this technique is that only the lumen of spaces with blood flow can be visualised and that the soft tissue surroundings remain (partly) invisible. Spiral computer tomographic angiography (CTA) has some major advantages compared with conventional angiography. The technique is less invasive and faster. Also, the soft tissue is imaged by CTA. In addition, computer reconstructions allow viewing from all directions without the limitations of overprojection. Spiral CTA is a suitable technique for imaging the thoracic part of the aorta: in case of dissection if transoesophageal echography is not available, in case of an aneurysm to determine the diameter and in case of rupture as a highly sensitive but not very specific examination technique. For imaging of the abdominal part of the aorta, spiral CTA may be considered. In case of an aneurysm or a possible rupture of this part of the aorta it is then possible to visualize the operation area and to choose the optimal approach. For the exclusion of stenoses in mesenteric arteries or in renal arteries, spiral CTA offers the advantage of non-invasivity. The technique is less suitable for demonstration of these stenoses and does not allow immediate intervention.

Objective: to describe redistribution of cerebral blood flow in patients with severe internal carotid artery (ICA) stenoses in relation to contralateral ICA disease., Methods: sixty-six patients scheduled for carotid endarterectomy (CEA) were grouped according to severity of contralateral stenosis (<30% [group I]; 30-69% [group II]; 70-99% [group III]; occlusion [group IV]. Transcranial Doppler (TCD) and magnetic resonance angiography (MRA) investigations were performed preoperatively., Results: TCD demonstrated a reversed flow in the contralateral anterior cerebral artery (A(1)segment) and ophthalmic artery in three-quarters of group IV patients (p <0.0001). Group IV patients also exhibited decreased blood flow velocity in the contralateral middle cerebral artery (p =0.001). MRA showed increased ipsilateral ICA and basilar artery (BA) blood flow volumes (Q-flows) in group IV patients when compared to the other groups (p <0.001). No changes in total Q-flow (ICAs+BA) were found., Conclusions: in patients considered for CEA, the severity of the contralateral ICA disease is an important determinant of the pattern of blood flow redistribution through the anterior communicating pathway and ophthalmic artery. Significant flow redistribution through the posterior communicating pathway occurs especially in patients with contralateral ICA occlusion., (Copyright 2001 Harcourt Publishers Limited.)

Objectives: The purpose of this study was to determine the optimal intensity of oral anticoagulation in patients who participated in a randomized trial of oral anticoagulants or aspirin after infrainguinal bypass graft surgery., Methods: The distribution of patient-time spent in international normalized ratio (INR) classes of 0.5 INR unit was calculated assuming a linear change between successive measurements. INR-specific incidence rates of ischemic and hemorrhagic events were calculated as the ratio of the number of events at a certain INR category and the total patient-time spent in that class. The relationship between INR class and event rates was quantified by rate ratios calculated in a Poisson regression model., Results: In 1326 patients (mean age, 69 years) 41,928 INR measurements were recorded in 1698 patient-years. Patients spent 50% of the total time within the target range of 3.0 to 4.5 INR. Most of the patient-time (60%) was spent between 2.5 and 3.5 INR. For each increasing class of 0.5 INR, the incidence of ischemic events (n = 154, INR data on event available in 49%) decreased by a factor of 0.97 (95% CI, 0.87-1.08). The incidence of major bleeding (n = 123, INR data on event available in 65%) increased significantly by a factor of 1.27 (95% CI, 1.19-1.34) for each increasing 0.5 INR category. The optimal target range was 3.0 to 4.0 INR, with an incidence of 3.8 events (0.9 ischemic and 2.9 hemorrhagic) per 100 patient-years., Conclusions: The target range of 3.0 to 4.0 INR is the optimal range of achieved anticoagulation intensity and is safe for the prevention of ischemic events in patients after infrainguinal bypass graft surgery.

Background and Purpose: We sought to investigate whether in patients with a symptomatic internal carotid artery (ICA) occlusion, endarterectomy of a severe stenosis of the contralateral carotid artery can establish long-term cerebral hemodynamic improvement., Methods: Nineteen patients were studied on average 1 month before and 6 months after contralateral carotid endarterectomy (CEA). Volume flow in the main extracranial and intracranial arteries was measured with MR angiography. Collateral flow via the circle of Willis and the ophthalmic arteries was studied with MR angiography and transcranial Doppler sonography, respectively. Cerebral metabolism and CO(2) vasoreactivity were investigated with MR spectroscopy and transcranial Doppler sonography, respectively. Twelve nonoperated patients with a symptomatic ICA occlusion and contralateral ICA stenosis, who were matched for age and sex, served as control patients., Results: In patients who underwent surgery, flow in the operated ICA increased significantly (P:<0.05) and flow in the basilar artery decreased significantly (P:<0.01) after CEA. On the occlusion side, mean flow in the middle cerebral artery increased significantly from 71 to 85 mL/min (P:<0.05) after CEA. The prevalence of collateral flow via the anterior communicating artery to the occlusion side increased significantly (47% before and 84% after CEA; P:<0.05), while the prevalence of reversed ophthalmic artery flow on the operation side decreased significantly (42% before and 5% after CEA; P:<0.05). In the hemisphere on the side of the ICA occlusion, lactate was no longer detected after CEA in 80% of operated patients, whereas it was no longer detected over time in 14% of nonoperated patients (P:<0.05). CO(2) reactivity increased significantly in operated patients in both hemispheres (P:<0.01)., Conclusions: Contralateral CEA in patients with a symptomatic ICA occlusion induces cerebral hemodynamic improvement not only on the side of surgery but also on the side of the ICA occlusion.

Objective: To provide a long-term perspective on the durability of the proximal abdominal aortic aneurysm endograft fixation from a single device series with perpendicular neck measurements in two groups of patients with complete 2- and 3-year follow-up., Design: This was a prospective study of postoperative, radiologic images., Setting: The study used a referral center, institutional practice, and ambulatory patients., Subjects: From January 1994 until May 1998, 37 endografts were implanted for abdominal aortic aneurysm. In the first postoperative year, there were four unrelated deaths and six conversions, leaving 27 patients with complete 24-month data and 13 with complete 36-month data., Main Outcome Measure: Computed tomography angiograms were processed on a work station to measure the neck perpendicular to the central lumen line of the aorta. The surface area at the proximal endovascular anastomosis was recorded at each follow-up interval and related to the postoperative size at the same level., Results: Significant dilatation of the surface area was found: 20% (16% to 27%) at 24 months (c2 = 30; P < .001, Friedman) and 23% (18% to 28%) at 36 months (c2 = 27; P < .001, Friedman). This increase in neck size was continuous and linear, with a yearly rate of approximately 10% surface area; translated into diameter, this approximates 1 mm/y., Conclusion: A continuous aortic enlargement of approximately 1 mm/y at the level of the proximal endovascular anastomosis was found. Because of the practice of oversizing the endograft relative to the infrarenal aortic neck, a loss of the endovascular seal may not become apparent until several years after endovascular abdominal aortic aneurysm repair is performed.

Purpose: This open single-center prospective study aimed to determine the redistribution of blood flow within the circle of Willis and through collateral pathways after carotid endarterectomy. Blood flow velocity and flow direction in the major cerebral arteries were determined, both at rest and during CO(2) inhalation., Methods: Carotid endarterectomy was performed in 148 patients with a 70% or greater diameter stenosis of the internal carotid artery while patients were under general anesthesia. Arteriotomy closure was done with a venous patch. Selective shunting was performed with an electroencephalogram. Baseline blood flow velocity of the basal cerebral arteries was measured by means of transcranial Doppler sonography preoperatively (within 1 week before surgery) and 3 months postoperatively. At the same times, cerebrovascular reactivity was calculated during CO(2) inhalation insonating both middle cerebral arteries., Results: Baseline blood flow velocity in the ipsilateral middle cerebral artery hardly changed 3 months postoperatively, but there was a considerable redistribution of flow in the circle of Willis. This was characterized by a decrease in contribution from the contralateral hemisphere through the anterior communicating artery, reduced cerebropetal flow rates in the ophthalmic artery, and smaller contribution of the posterior collateral sources. The CO(2) reactivity on the side of surgery increased in all patients. In patients with a contralateral occlusion, CO(2) reactivity increased on both sides. The redistribution of flow was most pronounced in patients who needed intraoperative shunting and in patients with a contralateral internal carotid artery occlusion., Conclusion: After carotid endarterectomy, flow redistribution, as expressed by changes in blood flow velocity values, occurs in the circle of Willis. The contribution of collateral sources is diminished, and the CO(2) reactivity increases, both of which reflect improvement of the hemodynamic condition. The most improvement occurs in patients with contralateral occlusion.

Objectives: To study the effect of the severity of internal carotid artery (ICA) lesions on cerebral haemodynamics., Design: Cross-sectional study., Materials and Methods: Magnetic resonance (MR) imaging, angiography (MRA) and spectroscopy (MRS) were used to study the prevalence of (border-zone) infarctions, volume flow in the main cerebropetal and middle cerebral arteries (MCA) and metabolic changes in the MCA territories in 170 patients with symptomatic ICA stenoses or occlusions and 25 control subjects., Results: No significant correlation was found between severity of the carotid lesion and the prevalence of border-zone infarctions. Also, no significant correlation was found with changes in the N -acetyl-aspartate/choline ratio nor with the prevalence of cerebral lactate. In patients with at least one severe ICA lesion, flow in the basilar artery was increased. Flow in the MCA on the symptomatic and asymptomatic side was decreased when at least one ICA was occluded. Total cerebropetal flow (flow through the ICAs plus basilar artery) was decreased when at least one ICA was occluded. No significant correlation was found between changes in cerebropetal flow and the N -acetyl-aspartate/choline ratio nor with the prevalence of border-zone infarctions., Conclusion: Border-zone infarctions and ischaemic metabolic changes are not directly the result of cerebral hypoperfusion caused by severe ICA lesions.