Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial.

OBJECTIVE: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is superior to ASA alone in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. We sought to determine whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in patients undergoing below-knee bypass grafting. METHODS: Patients undergoing unilateral, below-knee bypass graft for atherosclerotic peripheral arterial disease (PAD) were enrolled 2 to 4 days after surgery and were randomly assigned to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100 mg/day for 6 to 24 months. The primary efficacy endpoint was a composite of index-graft occlusion or revascularization, above-ankle amputation of the affected limb, or death. The primary safety endpoint was severe bleeding (Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries [GUSTO] classification). RESULTS: In the overall population, the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs 151 of 426 patients in the placebo (plus ASA) group (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.78-1.23). In a prespecified subgroup analysis, the primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients (HR, 0.65; 95% CI, 0.45-0.95; P = .025) but not in venous graft patients (HR, 1.25; 95% CI, 0.94-1.67, not significant [NS]). A significant statistical interaction between treatment effect and graft type was observed (P(interaction) = .008). Although total bleeds were more frequent with clopidogrel, there was no significant difference between the rates of severe bleeding in the clopidogrel and placebo (plus ASA) groups (2.1% vs 1.2%). CONCLUSION: The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting. Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk.

Outcome after occlusion of infrainguinal bypasses in the Dutch BOA Study: comparison of amputation rate in venous and prosthetic grafts.

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.

Risk of major haemorrhage in patients after infrainguinal venous bypass surgery: therapeutic consequences? The Dutch BOA (Bypass Oral Anticoagulants or Aspirin) Study.

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.

Multidisciplinary vascular screening program modestly improves the medical treatment of vascular risk factors.

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.

In vivo transluminal microvascular endothelial cell seeding on balloon injured rabbit arteries.

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.

Application of a clinical grade CD34-mediated method for the enrichment of microvascular endothelial cells from fat tissue.

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.

[Hospital-wide vascular screening program at the University Medical Center, Utrecht: prevalence of risk factors and asymptomatic vascular disease from 1996 to 2002]. / Ziekenhuisbreed vasculair screeningsprogramma in het Universitair Medisch Centrum Utrecht: prevalentie van risicofactoren en asymptomatisch vaatlijden in 1996/'02.

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.

Screening for asymptomatic internal carotid artery stenosis and aneurysm of the abdominal aorta: comparing the yield between patients with manifest atherosclerosis and patients with risk factors for atherosclerosis only.

OBJECTIVE: The purpose of this study was to investigate whether screening for internal carotid artery stenosis (ICAS) and aneurysm of the abdominal aorta (AAA) is indicated in patients with either manifest atherosclerotic disease or with only risk factors for atherosclerosis. STUDY DESIGN: Data were obtained for 2274 patients enrolled in the SMART study, an ongoing single-center, prospective cohort study of patients referred to our vascular center with manifest atherosclerotic disease (peripheral atherosclerotic disease [PAD]; transient ischemic attack [TIA], stroke, or ICAS; AAA; angina pectoris; or myocardial infarction [MI]) or with only risk factors for atherosclerosis (diabetes mellitus, hypertension, hyperlipidemia). The presence of ICAS or AAA was determined with duplex scanning and ultrasonography. RESULTS: The prevalence of ICAS 70% or greater is low in patients with risk factors for atherosclerosis only (1.8%-2.3%), intermediate in patients with angina pectoris or MI (3.1%), and highest in patients with PAD (12.5%) or AAA (8.8%). The prevalence of AAA 3 cm or larger is low in patients with risk factors for atherosclerosis only (0.4-1.6%), intermediate in patients with angina pectoris or MI (2.6%), and highest in patients with PAD (6.5%) or TIA, stroke, or ICAS (6.5%). The prevalence of AAA larger than 5 cm is low in all of the considered patient groups. The yield of screening can be optimized through selection on the basis of simple patient characteristics. In patients with PAD, selecting those with advanced age (>54 years) increased the prevalence of ICAS to 21.8%. Selecting patients with lower diastolic blood pressure (<83 mm Hg) increased the prevalence of ICAS to 17.9%. In patients with both advanced age and lower diastolic blood pressure, the prevalence of ICAS increased to 34.7%. Selecting patients with advanced age increased the prevalence of AAA 3 cm or larger to 9.6%. In patients with TIA, stroke, or ICAS, selecting those with advanced age increased the prevalence of AAA 3 cm or larger to 8.2%. Selecting patients with taller stature (>169 cm) increased the prevalence of AAA 3 cm or larger to 9.3%. In patients with advanced age and taller stature, the prevalence of AAA 3 cm or larger increased to 13.1%. CONCLUSIONS: Screening for ICAS should be limited to patients referred with PAD or AAA, especially those with advanced age or with low diastolic blood pressure. Screening for AAA should be limited to patients referred with PAD or with TIA, stroke, or ICAS, particularly those with advanced age or tall stature. In patients referred with angina pectoris or MI and those referred with only risk factors for atherosclerosis, screening cannot be endorsed.

MR angiography of the lower extremities with a moving-bed infusion-tracking technique.

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.

Oral anticoagulant therapy in patients with peripheral artery disease.

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.

The influence of hyperhomocysteinemia on graft patency after infrainguinal bypass surgery in the Dutch BOA Study.

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.

[One hundred years of the Association of Surgeons in the Netherlands. VII. Vascular surgery]. / Honderd jaar Nederlandse Vereniging voor Heelkunde. VII. Vaatchirurgie.

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.

Reduction of non-endothelial cell contamination of microvascular endothelial cell seeded grafts decreases thrombogenicity and intimal hyperplasia.

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.

Detection and treatment of claudication due to functional iliac obstruction in top endurance athletes: a prospective study.

BACKGROUND: Endurance athletes often have restrictions in flow in their iliac arteries during exercise. Such restrictions have previously been ascribed solely to intravascular lesions. We postulate that flow could also be restricted by functional kinking in the arteries, and that surgical release of these kinks might be an effective treatment. METHODS: We prospectively studied 80 endurance athletes who had complaints suggestive of flow restriction in the iliac arteries of one (n=74) or both (6) legs (total 92 legs). Using vascular diagnostic tools, we examined athletes while they were doing activities that often provoke flow restrictions. Restrictions were determined by measurement of systolic pressure in the ankle after exercise; peak systolic velocities were measured with echo-doppler. Kinks were detected with echo-doppler and magnetic-resonance angiography. When functional kinking was diagnosed as the cause of the restriction, the athlete was offered surgery to release the iliac arteries, as part of our prospective study. FINDINGS: We recorded flow restrictions in the iliac arteries of 58 of 92 (63%) legs. In 40 of these legs (69%), kinks were the most important cause of the restriction, making these legs suitable for surgical release. We operated on 23 of 58 (40%) legs. All athletes who had an operation subjectively improved. Maximum workload in a cycling test and ankle pressure significantly improved after the operation. 20 (87%) athletes were able to successfully return to their desired high level of competition. INTERPRETATION: Our sports-specific protocol is effective in detecting kinking of the iliac arteries as a cause for flow restriction in athletes who have few intravascular abnormalities when investigated with conventional vascular diagnostic tools. Surgical treatment directed at the kinking was less invasive and therefore a better alternative to vascular reconstruction in these athletes.

Contaminants from the transplant contribute to intimal hyperplasia associated with microvascular endothelial cell seeding.

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.

Distal aortic diameter and peripheral arterial occlusive disease.

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.

Cost-effectiveness of oral anticoagulants versus aspirin in patients after infrainguinal bypass grafting surgery.

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.

[Spiral computed tomographic angiography as a substitute for intra-arterial angiography of aorta and its branches]. / Spiraaltomografische angiografie als vervanger van intra-arteriële angiografie van aorta en zijtakken.

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.