[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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%).
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.
Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 10/2010; 52(4):825-33, 833.e1-2. DOI:10.1016/j.jvs.2010.04.027 · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND.
If carotid artery narrowing remains asymptomatic (ie, has caused no recent stroke or other neurological symptoms), successful carotid endarterectomy (CEA) reduces stroke incidence for some years. We assessed the long-term effects of successful CEA.
Between 1993 and 2003, 3120 asymptomatic patients from 126 centres in 30 countries were allocated equally, by blinded minimised randomisation, to immediate CEA (median delay 1 month, IQR 0·3-2·5) or to indefinite deferral of any carotid procedure, and were followed up until death or for a median among survivors of 9 years (IQR 6-11). The primary outcomes were perioperative mortality and morbidity (death or stroke within 30 days) and non-perioperative stroke. Kaplan-Meier percentages and logrank p values are from intention-to-treat analyses. This study is registered, number ISRCTN26156392.
1560 patients were allocated immediate CEA versus 1560 allocated deferral of any carotid procedure. The proportions operated on while still asymptomatic were 89·7% versus 4·8% at 1 year (and 92·1%vs 16·5% at 5 years). Perioperative risk of stroke or death within 30 days was 3·0% (95% CI 2·4-3·9; 26 non-disabling strokes plus 34 disabling or fatal perioperative events in 1979 CEAs). Excluding perioperative events and non-stroke mortality, stroke risks (immediate vs deferred CEA) were 4·1% versus 10·0% at 5 years (gain 5·9%, 95% CI 4·0-7·8) and 10·8% versus 16·9% at 10 years (gain 6·1%, 2·7-9·4); ratio of stroke incidence rates 0·54, 95% CI 0·43-0·68, p<0·0001. 62 versus 104 had a disabling or fatal stroke, and 37 versus 84 others had a non-disabling stroke. Combining perioperative events and strokes, net risks were 6·9% versus 10·9% at 5 years (gain 4·1%, 2·0-6·2) and 13·4% versus 17·9% at 10 years (gain 4·6%, 1·2-7·9). Medication was similar in both groups; throughout the study, most were on antithrombotic and antihypertensive therapy. Net benefits were significant both for those on lipid-lowering therapy and for those not, and both for men and for women up to 75 years of age at entry (although not for older patients).
Successful CEA for asymptomatic patients younger than 75 years of age reduces 10-year stroke risks. Half this reduction is in disabling or fatal strokes. Net benefit in future patients will depend on their risks from unoperated carotid lesions (which will be reduced by medication), on future surgical risks (which might differ from those in trials), and on whether life expectancy exceeds 10 years.
The Lancet 01/2010; 2010(376):1074-1084. · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis. Methods: This was a prospective, multicenter, cohort study of patients undergoing medical intervention for vascular disease. Hazard ratios for ICA stenosis, clinical features, and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic (CORI) events were calculated using proportional hazards models. Results: A total of 1121 patients with 50% to 99% asymptomatic ICA stenosis in relation to the bulb (European Carotid Surgery Trial [ECST] method) were followed-up for 6 to 96 months (mean, 48). A total of 130 ipsilateral CORI events occurred. Severity of stenosis, age, systolic blood pressure, increased serum creatinine, smoking history of more than 10 pack-years, history of contralateral transient ischemic attacks (TIAs) or stroke, low grayscale median (GSM), increased plaque area, plaque types 1, 2, and 3, and the presence of discrete white areas (DWAs) without acoustic shadowing were associated with increased risk. Receiver operating characteristic (ROC) curves were constructed for predicted risk versus observed CORI events as a measure of model validity. The areas under the ROC curves for a model of stenosis alone, a model of stenosis combined with clinical features and a model of stenosis combined with clinical, and plaque features were 0.59 (95% confidence interval [CI] 0.54-0.64), 0.66 (0.62-0.72), and 0.82 (0.78-0.86), respectively. In the last model, stenosis, history of contralateral TIAs or stroke, GSM, plaque area, and DWAs were independent predictors of ipsilateral CORI events. Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke, with predicted risk close to observed risk. Of the 923 patients with <70% stenosis, the predicted cumulative 5-year stroke rate was <5% in 495, 5% to 9.9% in 202, 10% to 19.9% in 142, and <20% in 84 patients. Conclusion: Cerebrovascular risk stratification is possible using a combination of clinical and ultrasonic plaque features. These findings need to be validated in additional prospective studies of patients receiving optimal medical intervention alone.
Journal of Vascular Surgery 01/2010; 52(6):1486-1496. · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with peripheral arterial disease are at high risk of ischemic events and therefore are treated with antithrombotics. In patients with coronary artery disease or cerebrovascular disease, bleeding is related to the subsequent occurrence of ischemic events. Our objective was to assess whether this is also the case in patients with peripheral arterial disease.
All patients from the Dutch Bypass and Oral Anticoagulants or Aspirin (BOA) Study, a multicenter randomized trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery, were included. The primary outcome event was the composite of nonfatal myocardial infarction, nonfatal ischemic stroke, major amputation, and cardiovascular death. To identify major bleeding as an independent predictor for ischemic events, crude and adjusted hazard ratios with 95% confidence intervals were calculated with multivariable Cox regression models. From 1995 until 1998, 2650 patients were included with 101 nonfatal major bleedings. During a mean follow-up of 14 months, the primary outcome event occurred in 218 patients; 22 events were preceded by a major bleeding. The mean time between major bleeding and the primary outcome event was 4 months. Major bleeding was associated with a 3-fold increased risk of subsequent ischemic events (crude hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.6; adjusted hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.7).
In patients with peripheral arterial disease, as in patients with coronary artery disease or cerebrovascular disease, major bleeding was independently associated with major ischemic complications. Without compromising the benefits of antithrombotics, these findings call for caution relative to the risks of major bleeding.
[Show abstract][Hide abstract] ABSTRACT: Objectives: This study tested the hypothesis that silerit embolic infarcts on computed tomography (CT) brain scans can predict ipsilateral neurologic hemispheric events and stroke in patients with asymptomatic internal carotid artery stenosis. Methods: In a prospective multicenter natural history study, 821 patients with asymptomatic carotid stenosis graded with duplex scanning who had CT brain scans were monitored every 6 months for a maximum of 8 years. Duplex scans were reported centrally, and stenosis was expressed as a percentage in relation to the normal distal internal carotid criteria used by the North American Symptomatic Carotid Endarterectomy Trialists. CT brain scans were reported centrally by a neuroradiologist. In 146 patients (17.8%), 8 large cortical, 15 small cortical, 72 discrete subcortical, and 51 basal ganglia ipsilateral infarcts were present; these were considered likely to be embolic and were classified as such. Other infarct types, lacunes (n = 15), watershed (n = 9), and the presence of diffuse white matter changes (n = 95) were not considered to be embolic. Results: During a mean follow-up of 44.6 months (range, 6 months-8 years), 102 ipsilateral hemispheric neurologic events (amaurosis fugax in 16, 38 transient ischemic attacks [TIAs], and 47 strokes) occurred, 138 patients died, and 24 were lost to follow-up. In 462 patients with 60% to 99% stenosis, the cumulative event-free rate at 8 years was 0.81 (2.4% annual event rate) when embolic infarcts were absent and 0.63 (4.6% annual event rate) when present (log-rank P = .032). In 359 patients with <60% stenosis, embolic infarcts were not associated with increased risk (log-rank P = .65). In patients with 60% to 99% stenosis, the cumulative stroke-free rate was 0.92 (1.0% annual stroke rate) when embolic infarcts were absent and 0.71 (3.6% annual stroke rate) when present (log-rank P = .002). In the subgroup of 216 with moderate 60% to 79% stenosis, the cumulative TIA or stroke-free rate in the absence and presence of embolic infarcts was 0.90 (1.3% annual rate) and 0.65 (4.4% annual rate), respectively (log-rank P = .005). Conclusion: The presence of silent embolic infarcts can identify a high-risk group for ipsilateral hemispheric neurologic events and stroke and may prove useful in the management of patients with moderate asymptomatic carotid stenosis.
Journal of Vascular Surgery 01/2009; 49(4):902-909. · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This article investigates the results of endovascular aneurysm repair with the Endovascular Technologies Tube and Bifurcated Endograft. During a three year period, 30 patients were operated on as part of an FDA-supervised international trial. A tube graft was inserted in 17 cases and a bifurcated graft in 13. All patients were treated in the operating theater, using a mobile fluoroscopy arm. Successful cases were subjected to a follow-up regime of repeated physical and radiological exams. The endograft could be inserted in 27 patients (90%). In two cases the graft could not be advanced due to severe calcification of the iliac arteries. In one patient, inadequate distal positioning of a tube graft could not be corrected by endovascular techniques. One patient died (3%) due to a proximal aortic tear. Except abdominal wound dehiscence in a converted patient, no serious postoperative complications were seen. Endoleak was encountered in 11 patients (37%), resulting in conversion in five (17%). The success rate at a median follow- up of 12 months was 70%; however, 6 out of 8 technical failures occurred in the first 15 patients. This study demonstrated a learning curve in endovascular aneurysm repair. Arrest of growth or shrinkage of the aneurysm was seen in all patients with a completely thrombosed aneurysm sac. No evidence of graft migration, infection, or thrombosis was found in this series during follow-up.
Seminars in Interventional Radiology 03/2008; 15(01):81-88. DOI:10.1055/s-2008-1057061
[Show abstract][Hide abstract] ABSTRACT: We investigated whether total cerebral blood flow (CBF) was associated with brain atrophy, and whether this relation was modified by white matter lesions (WML). Within the Second Manifestations of ARTerial disease-magnetic resonance (SMART-MR) study, a prospective cohort study among patients with arterial disease, cross-sectional analyses were performed in 828 patients (mean age 58±10 years, 81% male) with quantitative flow, atrophy, and WML measurements on magnetic resonance imaging (MRI). Total CBF was measured with MR angiography and was expressed per 100 mL brain volume. Total brain volume and ventricular volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF) and ventricular fraction (VF). Lower BPF indicates more global brain atrophy, whereas higher VF indicates more subcortical brain atrophy. Mean CBF was 52.0±10.2 mL/min per 100 mL, mean BPF was 79.2±2.9%, and mean VF was 2.03±0.96%. Linear regression analyses showed that lower CBF was associated with more subcortical brain atrophy, after adjusting for age, sex, vascular risk factors, intima-media thickness, and lacunar infarcts, but only in patients with moderate to severe WML (upper quartile of WML): Change in VF per s.d. decrease in CBF 0.18%, 95% CI: 0.02 to 0.34%. Our findings suggest that cerebral hypoperfusion in the presence of WML may be associated with subcortical brain atrophy.
[Show abstract][Hide abstract] ABSTRACT: To compare the consequences of occlusion of infrainguinal venous and prosthetic grafts.
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.
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).
The need for amputation after occlusion is not influenced by graft material in infrainguinal bypass surgery.
European Journal of Vascular and Endovascular Surgery 01/2006; 30(6):604-9. DOI:10.1016/j.ejvs.2005.06.023 · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study is part of ATHERO-EXPRESS, which is an ongoing prospective longitudinal study with the objective of investigating the etiologic value of plaque characteristics in long-term outcome in patients with carotid atherosclerosis. The design of the study has been described previously,13 and ATHERO-EXPRESS is currently being executed in two Dutch hospitals. Recruitment of patients started in April 2002 and will continue until at least 1000 patients have been included. All patients receiving operative treatment for carotid stenosis in the vascular surgery departments of the participating centers are enrolled. Patients can be symptomatic or asymptomatic, and surgery is indicated when color Doppler–assisted duplex ultrasound investigation, magnetic resonance angiography, computed tomographic angiography, or angiography reveals a diameter reduction of more than 70% on at least one side. In asymptomatic patients with stenosis greater than 70%, the indication for surgery is also based on recommendations published by the Asymptomatic Carotid Surgery Trial.14 At baseline, clinical data from patients’ records, a questionnaire about medical history, blood samples, and atherosclerotic tissue harvested during CEA are collected. In this study, we analyzed 319 patients with 3 months and 1 year (n = 166) of follow-up after CEA.
Journal of Vascular Surgery 01/2006; 42(6):1082-8. DOI:10.1016/j.jvs.2005.08.011 · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Aim. This study determines the factors associated with mortality in patients with asymptomatic carotid stenosis. Methods. Patients (n=1 101) with asymptomatic internal carotid artery stenosis greater than 50% in relation to the bulb diameter were followed up for a period of 6 to 84 (median 38) months. Stenosis was graded using duplex scanning and expressed as a percentage of the carotid bulb diameter. Clinical and biochemical risk factors were recorded. The end-points were ipsilateral ischemic stroke, cardiovascular death and all cause mortality. Results. In a Cox multivariate analysis 6 factors emerged as independent predictors of risk. Age, male gender, cardiac failure, left ventricular hypertrophy on electrocardiogram (ECG) and myocardial ischemia on ECG were associated with increased risk. Antiplatelet therapy was associated with decreased risk. Based on these risk factors a high-risk group consisting of one third of the population with a 40% cumulative cardiovascular death rate and a 66% all cause death rate at 7 years could be identified. The remaining 2/3 consisted of a low-risk group with a 10% cumulative cardiovascular death rate and a 21% all cause death rate at 7 years (P<0.0001 compared to the high risk group). There was not any significant difference in the cumulative ipsilateral stroke rate, which was 12% in the low and 13% in the high cardiovascular risk group (Log Rank P>0.05). Conclusion. The methodology and findings from the ACSRS natural history study need to be applied to randomized controlled trials on the value of carotid endarterectomy or stenting in patients with asymptomatic carotid stenosis. They may help refine the indications for intervention in patients with carotid endarterectomy.
[Show abstract][Hide abstract] ABSTRACT: 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.
Randomised clinical trial.
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).
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.
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.
European Journal of Vascular and Endovascular Surgery 08/2005; 30(2):154-9. DOI:10.1016/j.ejvs.2005.03.005 · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
The Journal of cardiovascular surgery 05/2004; 45(2):129-37. · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Tracing and treating cardiovascular risk factors in patients with arterial vascular disease and in patients with high risk of developing vascular diseases.
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.
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.
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.
Nederlands tijdschrift voor geneeskunde 11/2003; 147(48):2376-82.