Aspirin in peripheral arterial disease: breakthrough or pitfall?

BACKGROUND: This paper introduces a proof-of-concept trial in progress, supposedly providing new important information on anti-platelet drugs used in patients with peripheral arterial disease (PAD). The Arteriogenesis Competence Network (Art.Net.) of the Universities of Basel, Berlin, and Freiburg could show in animal models that Aspirin (ASA), in contrast to Clopidogrel, inhibits the formation of an appropriate collateral network (arteriogenesis). This trial is supposed to reproduce the animal data in man. MATERIALS AND METHODS: In a prospective, double-blind, parallel-group, bi-national (D, CH), multicentre trial, 250 patients will be randomised to either 100 mg ASA or 75 mg Clopidogrel once daily. Patients will then enter a three months structured rehabilitation programme with daily physical training supposed to induce arteriogenesis. The claudication distances will be tested as the primary endpoint at baseline, 6 weeks, and at 3 months. Also, the 24h physical activity profile of all patients will be electronically documented. CONCLUSIONS: This trial will provide information on potential disadvantages when using ASA in PAD patients. If data emerging from animal pharmacology can be reproduced in man, the present standard scheme of anti-aggregant treatment in PAD patients has to be reconsidered.

Quality of life improvement after hospital- based rehabilitation or home-based physical training in intermittent claudication.

BACKGROUND: The magnitude of potential changes in Quality-of-Life (QoL) after structured institution-based or home-based peripheral arterial disease (PAD) rehabilitation programs are largely unknown at present. This pilot study provides first QoL data after PAD rehabilitation or a home-based PAD training. PATIENTS AND METHODS: In a non-randomized, open-label pilot study three groups of out-patients were compared: group 1 (n = 18) PAD rehabilitation; group 2 (n = 17) PAD rehabilitation + clopidogrel 75 mg once daily; group 3 (n = 20) home-based training. The training period was 3 months, which was followed by a 3-month observation phase (without prescribed training). The institution-based rehabilitation program consisted of 3 training hours per week whereas patients training at home were instructed to walk for 1 hour per day on an outdoor track. QoL assessment was performed using MOS SF-36, PAVK-86 and PAD-WIQ questionnaires. RESULTS: At baseline background variables, demographics and claudication distances were comparable between groups. After three months of training the percentage changes for the initial and the absolute claudication distance (ICD, ACD) for groups 1, 2, and 3 amounted to 164%, 201%, 44% (ICD) and 83%, 131%, 5% (ACD), respectively. Statistically significant QoL improvements were recorded for physical functions, pain and disease related anxiety in all three study groups; statistically significant inter-group differences were not found. CONCLUSIONS: In sharp contrast to the development of the claudication distances the improvement in QoL, found after 3 months of training, was comparable and not consistently different between the groups.

Unusual cause of intermittent claudication.

Spontaneous dissection of a peripheral artery is a rare event. We report a case of a spontaneous, non-atherosclerotic and non-aneurysmal dissection limited to the external iliac artery in a 60-year-old woman who was admitted with a left calf claudication. Non-invasive examination documented signs of leg ischemia due to a floating wall dissection of the external iliac artery. After medical treatment over eight weeks the dissection membrane had been adapted to the vessel wall. A similar case of a spontaneous dissection limited to the external iliac artery, followed by a spontaneous healing has not been reported in the literature.

Symptomatic vascular complications after vascular closure device use following diagnostic and interventional catheterisation.

BACKGROUND: Haemostatic puncture closure devices for rapid and effective hemostasis after arterial catheterisation are a comfortable alternative to manual compression. Implanting a collagen plug against the vessel wall may become responsible for other kind of vascular injuries i.e. thrombotic or stenotic lesions and peripheral embolisation. The aim of this paper is to report our clinically relevant vascular complications after Angio-Seal and to discuss the results in the light of the current literature. PATIENTS AND METHODS: We report the symptomatic vascular complications in 17 of 7376 patients undergoing diagnostic or therapeutic catheterisation between May 2000 and March 2003 at the University Hospital Basel. RESULTS: Most patients presented with ischaemic symptoms, arterial stenoses or occlusions and thrombotic lesions (n = 14), whereas pseudoaneurysms were extremely rare (n = 3). Most patients with ischaemic lesions underwent vascular surgery and all patients with a pseudoaneurysm were successfully treated by ultrasound-guided compression. CONCLUSIONS: Severe vascular complications after Angio-Seal are rare, consistent with the current literature. There may be a shift from pseudoaneurysms to ischaemic lesions.

Acute deep vein thrombosis: early mobilization does not increase the frequency of pulmonary embolism.

Outpatient treatment for acute symptomatic deep vein thrombosis (DVT) was shown to be safe for most patients. However, little is known whether patients treated on an outpatient basis were ambulating or predominantly resting, a factor which may be decisive for the outcome. In the present study 129 DVT patients were randomized to either strict immobilization for 4 days or to ambulate for > or = 4 hours per day under supervision in order to show, whether the old concept of temporary immobilization is superior to early mobilization or not. The DVT diagnosis was based on duplex sonography; all patients were screened for PE at baseline and at day 4 by pulmonary ventilation-perfusion scanning, and were followed up for a total of 3 months. Clinically, changes in leg circumferences and leg pain were evaluated. The frequency of PE at baseline was 53.0% and 44.9% in the immobile and the mobile groups, respectively. During the 4 days observation period new PEs were found in 10.0% and in 14.4% of the immobilized and the ambulating patients (delta 4.4%; 95% CI -0.5 to 13.8; chi2 = 0.596, p = 0.44). The occurrence of new PE was related to the presence of PE at baseline but not to other potential predictors. The magnitude of a decrease in leg circumferences and leg pain was comparable in both groups. No patient died during the 4 day observation period. The total 3 month mortality rate was 3.9% (5 patients; 2 from the immobile, 3 from the ambulating group). All 5 patient suffered from malignancies. The results of this study show in accordance with the trial hypothesis that, regarding the frequency of PE, immobilization is not superior to early mobilization, suggesting that early mobilization is safe.

[The value of walking exercise in treatment of intermittent claudication]. / Der Stellenwert des Gehtrainings in der Behandlung der Claudicatio intermittens.

Physical training is one of the basic measures for all patients suffering from a generalized atherosclerosis. Specific training forms for PAD patients include home-based and structured, organized physical training programs; these are discussed and the results of meta-analyses presented. Whereas the published materials available for a home-based training is non-conclusive, structured training programs will lead to a statistically significant and clinically relevant improvement of a PAD patients' functional capacity.

The reliability of leg circumference assessment: a comparison of spring tape measurements and optoelectronic volumetry.

The purpose of this study was to compare the reliability of repeated spring tape measurements with optoelectronic volumeter measurements for the assessment of lower leg circumferences. The limb circumferences at mid-calf and ankle level of both legs were measured three times using a spring tape measure as well as an optoelectronic volumeter. In all, 30 healthy volunteers participated in the study. Test reliability and repeatability were described through the process-related and between-subject variances and variance-derived parameters such as the reliability coefficient (intraclass correlation coefficient, RC), the relative precision (RP), and the coefficient of repeatability (CR). A higher value for the RC and a lower value for the RP indicate that the test variability is predominantly due to between-subject variance and not to test process-related variance. RCs for both methods, independent of whether measurements were taken at calf or at ankle level, always exceeded 0.95. RPs were in the same order of magnitude for both methods but lower for measurements at calf than at ankle level (range: RPcalf 6.36-8.74%; range: RPankle 12.49-18.56%). CRs for both methods were low and of comparable magnitude (CR range: 4.8-7.7), although slightly smaller for the spring tape. When measurement results from the spring tape and the volumeter were compared, results achieved with the volumeter were significantly longer than those from the spring tape (p<0.05). Results from both methods were linearly in good agreement and there was no proportional bias; differences shown were due to a significant constant bias regarding the volumeter. Circumference measurements taken by spring tape and by optoelectronic volumetry are both characterized by a comparably high reliability. However, these methods cannot be used in an interchangeable way because a constant bias exists for volumetry, resulting in significantly larger circumferences compared with those measured using the spring tape.

Assessment of collateral perfusion: a pharmacodynamic study with buflomedil hydrochloride.

The aim of the study was to assess the influence of Buflomedil hydrochloride on collateral function. Ten patients with isolated superficial femoral occlusions were investigated twice by duplex sonography with measurement sites at the common femoral artery (CF) and the popliteal artery (PA). After the second scan 200 mg of Buflomedil hydrochloride were infused; the infusion was followed by a third duplex examination. Endpoints assessed included the arterial diameter (D(CF), D(PA)), the systolic peak velocity (Vmax), the mean velocity of the maximum envelope (Vmean m.e.), the intensity weighted time average mean velocity (Vmean i.w.), the maximum reverse flow velocity (Vrev), the end-diastolic velocity (Venddiast), the calculated volume flow (Q), the pulsatility and the resistance indices (PI, RI), and PI and RI based segmental damping factors (DF(PI), DF(RI)). For the CF measurement site the infusion of Buflomedil hydrochloride resulted in a significant reduction in Vrev and PI (p<0.05), whereas trends in the opposite direction (increase) were observed for both measures of Vmean and for Q (0.1

Platelets and cytokines in concert with endothelial activation in patients with peripheral arterial occlusive disease.

We tested the hypothesis whether circulating oncostatin-M (OSM), a cytokine that in vitro promotes fibrinogen biosynthesis and smooth muscle cell proliferation, or soluble CD40 ligand (CD40L; CD154), a leukocyte and platelet surface marker that stimulates endothelial cells, were associated: (a) with fibrinogen and other soluble cell adhesion molecules, such as P-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 and platelet-endothelial cell adhesion molecule-1; or (b) with restenosis and platelet activation in 71 patients with peripheral arterial occlusive disease undergoing peripheral angioplasty (PTA). Platelet membrane activation markers (CD62P, CD63, activated GPIIb/IIIa) were immunologically measured at 0, 1, 24 and 48 h, and 3 and 6 months after PTA. Soluble cell adhesion molecules, endothelial markers and various hemostatic variables were measured before PTA. Of the patients, 42.3% developed restenosis within 6 months, defined as a >50% reduction of the lumen at the site of balloon dilatation. Soluble CD40L was not higher in the restenosis group. Interestingly, patients with high CD40L showed significantly higher soluble VCAM-1 (P < 0.01) and thrombomodulin (P < 0.01), as well as trends for higher soluble P- and E-selectin. Platelet activation was found uniformly increased mostly at 1 and 24 h, as well as at 3 and 6 months. OSM was measurable in 53.5% (6.9 +/- 9.4 pg/ml) of the patients and undetectable in the others. No differences in the rate of restenosis was found in these two groups, which did not differ with respect to fibrinogen (3.14 +/- 1.00 versus 3.21 +/- 0.70 g/l), or the other parameters. In conclusion, soluble CD40L is associated with higher endothelial biological markers that might implicate its involvement in endothelial activation. Platelet activation, probably intermittent, might play a significant role through the expression of CD40L as a source of activation signals to the endothelial cells. Free circulating OSM does not seem to correlate directly with fibrinogen or with other acute phase reaction proteins, the synthesis of which it could influence in vitro. This might well not mean, however, that OSM lacks this activity in vivo.

[Venous cross-sectional area: measured or calculated?]. / Venenquerschnittsfläche: messen oder berechnen?

AIM: The aim of this study was to compare measured versus calculated venous cross-sectional area in healthy subjects in a standing and a lying position with normal breath-ing and during Valsalva manoeuvre. METHOD: Measurements were carried out in 30 venous segments (the common femoral vein CFV, the superficial femoral vein SFV, the greater saphenous vein GSV) of 5 healthy volunteers (4 female, 1 male) with a median age of 28.7 years (range 23.4-46.7 years) in supine and standing position, while normally breathing and during a standardised Valsalva manoeuvre. Venous diameters were measured from B-mode in longitudinal view while cross-sectional areas were planimetrically assessed from transverse B-mode as recorded on video (S-VHS). The mathematical calculation of areas followed the formula (0.5 diameter)2 x pi. All investigations were performed 3 times; mean values from these 3 measurements were used for further computation. Measurements were performed using the NIH Image 1.6 program. RESULTS: Correlation coefficients r of the calculated versus the measured venous area while normal breathing in standing and in lying subjects were: 0.92 and 0.82 in the CFV, 0.92 and 0.84 in the SFV as well as 0.98 and 0.97 in the GSV, respectively. During Valsalva manoeuvre in standing and lying subjects the correlation coefficients r amounted to: 0.94 and 0.93 in the CFV, 0.92 and 0.94 in the SFV as well as 0.99 and 0.98 in the GSV, respectively. CONCLUSIONS: In healthy volunteers measured and calculated venous cross-sectional area at rest and during Valsalva manoeuvre correlate well. Correlation is numerically better in standing compared to lying subjects while normal breathing. Calculated venous area is accurate and can be used for further calculations.

Reliability of treadmill testing in peripheral arterial disease: a comparison of a constant load with a graded load treadmill protocol.

This study aims to evaluate the reliability of repeated graded workload treadmill testing (G-test; 2 mph; 0% grade, increasing 2% every 2 min) and to compare the reliability of a constant workload treadmill protocol (C-test; 2 mph; 12% grade) versus the graded workload treadmill protocol in patients with intermittent claudication, studied longitudinally. A clinical trial investigating an orally stable prostacycline derivative that included 330 patients with intermittent claudication was performed. The trial employed three active treatment groups and one placebo group. Because there were no significant inter-group differences at baseline or after treatment, data from all groups were pooled for the evaluation of treadmill test reliability. Treadmill data were obtained from a 2-week run-in phase where three G-tests were performed, as well as from the beginning and the end of a 3-month double-blind phase where a G-test and a C-test were performed in random order. Treadmill test reliability was described through test process-related and between-subject variances and also using variance-derived parameters such as the reliability coefficient (RC) and the relative precision (RP). A higher value for the RC and a lower value for the RP indicate that the test variability is predominantly due to between-subject variance and not to test process-related variance. Estimates of variance were described for both the maximal or absolute claudication distance (ACD) and the initial claudication distance (ICD) with each treadmill test. Reliability estimates are reported for the total study sample and for patients with baseline claudication distances < or =300 feet and >300 feet (approximately < or =100 m; >100 m), as measured with the C-test. The cut-off value was empirically chosen to separate severely diseased from mild to moderately diseased claudicants. Theoretical considerations suggest that reliability measures may differ in these subgroups. With repeated testing during the run-in phase for the measure of ACD, the G-test had an RC of 0.952 and an RP of 21.9%. With the comparison of both test protocols in the entire study population for the measurement of ACD, the G-test had an RC of 0.902 and an RP of 31.3%, while the C-test had an RC of 0.876 and an RP of 35.2%. The results for ICD on the G-test were an RC of 0.809 and an RP of 43.7%, while the C-test had an RC of 0.737 and an RP of 51.3%. The reliability of the ACD measurement for RC and RP was numerically superior to those for the ICD for both protocols. In patients with a baseline ACD < or =300 feet, the RC for ACD on the G-test was 0.827 and the RP was 41.4%. In contrast, on the C-test the RC decreased to 0.250 and the RP increased to 86.6%. These changes in RC and RP were due to a marked decrease in the between-subject variance, demonstrating the inability of the C-test to separate appropriately the different claudication distances in populations with highly limited baseline claudication distances. During a run-in phase, the G-test has excellent test characteristics. During the longitudinal phase of a trial, the reliability of G-tests and C-tests are comparable in the entire study population. However, in patients with low claudication distances, the G-test should be given preference over the C-test.

The value of rapid D-dimer testing combined with structured clinical evaluation for the diagnosis of deep vein thrombosis.

PURPOSE: Large studies have shown that most cases referred for duplex sonography for suspected deep vein thrombosis (DVT) have normal scan results. For medical and economic reasons, a preselection procedure, which allows the detection of true-negative cases before duplex scanning, is required; this procedure should be characterized by a high sensitivity and a high negative predictive value. METHODS: In 343 patients (398 lower extremities) with suspected DVT, the DVT probability was clinically assessed, and a whole blood D-dimer agglutination test and a duplex scan were performed. The diagnostic sensitivities of the D-dimer test alone, a high clinical DVT probability alone, and the combination of both were evaluated. RESULTS: The sensitivity values for the D-dimer test to diagnose proximal and distal DVTs were 88.7% and 80.9%, the negative predictive values (NPV) were 96.3% and 97.9%, and the specificity and the positive predictive value (PPV) were 54.8% and 49.6% and 26.6% and 8.2%, respectively. The sensitivities of the clinical DVT probability assessment for the diagnosis of proximal and distal DVTs were 83.9% and 66.7%, respectively; the corresponding NPVs were 94.9% and 96.5%, respectively. The specificity was 56.1% and 50.8%, and the PPVs were 26.1% and 7.0%, respectively. The combined use of the results of the clinical probability assessment and the D-dimer test resulted in sensitivities for proximal and distal DVTs of 98.4% and 90.5%, NPVs of 99.3% and 98.6%, a specificity of 43.4% and 38.4%, and PPVs of 24. 3% and 7.6%, respectively. CONCLUSION: The combined use of a clinical DVT probability assessment scheme and the D-dimer test largely avoids false negative results, has a high sensitivity and NPV, helps to reduce the costs of DVT diagnosis, and may, in the future, be useful as a preselection procedure before duplex sonography.

A new rotational thrombectomy catheter: system design and first clinical experiences.

PURPOSE: To describe a new catheter for the percutaneous mechanical removal of fresh and organized thrombi, and to assess its efficacy and safety in vitro and in vivo. METHODS: The catheter consists of a coated stainless steel spiral that rotates at 40,000 rpm over a guidewire inside the whole length of an 8 Fr, single-lumen, polyurethane catheter, driving a dual-blade cutting crown. Abraded occlusion material is sucked into the catheter head through distal side holes and transported by the spiral into a reservoir at the proximal end. The efficacy of the device was tested in arterial models and fresh bovine carotid arteries (n = 72). In a clinical pilot study 10 patients (8 women, 2 men; mean age 70.6 +/- 10.1 years) with occlusions of the superficial femoral artery (2-12 cm, mean 5.8 cm), not older than 4 weeks, underwent thrombectomy with the new catheter. RESULTS: In arterial models and bovine cadaver arteries the catheter completely removed fresh thrombi. Occlusion material of higher consistency was cut into particles of 100-500 micron and transported outside. Thrombectomy was successful and vessel patency restored in all 10 patients. The ankle/brachial pressure index significantly (p < 0.0005) increased from 0.41 +/- 0. 18 before intervention to 0.88 +/- 0.15 after 48 hr and to 0.84 +/- 0.20 after 3 months. Two reocclusions occurred within 14 days after the intervention. CONCLUSION: Thrombectomy with the new device appears to be feasible and safe in patients with acute and subacute occlusions of the femoropopliteal artery.

Transatlantic Conference on Clinical Trial Guidelines in Peripheral Arterial Disease: clinical trial methodology. Basel PAD Clinical Trial Methodology Group.

Guidelines for the clinical development of drugs in peripheral arterial disease (PAD) have been issued by the Food and Drug Administration for the United States and by the regulatory agency of the European Union for Europe. With increasing globalization, transatlantic cooperation in drug research and development is essential for the future and would be substantially facilitated by the existence of transatlantic guidelines. A conference was held in Basel, Switzerland, in November 1997 to discuss the scientific background of the existing guidelines on the basis of published evidence and the extensive knowledge of clinical investigators and experienced regulators. The meeting was attended by 52 invited experts from the United States and Europe, as well as by representatives from the 2 regulatory authorities. The main conclusions from the meeting are presented and may serve as a reference for the future development of transatlantic guidelines for the evaluation of pharmacotherapy in PAD.

Physiological reflux and venous diameter change in the proximal lower limb veins during a standardised Valsalva manoeuvre.

OBJECTIVES: the aim of this study was to provide normal values for venous diameter at rest, and venous diameter and physiologic venous reflux during a standardised Valsalva manoeuvre. The impact of the patient's sex, body mass index (BMI), and family history was investigated. MATERIAL AND METHODS: eighty legs of 40 healthy volunteers were investigated in a supine position. The median age was 28 years (range 20-66 years). The common femoral vein (CFV), the proximal superficial femoral vein (SFV) and the proximal long saphenous vein (LSV) were investigated by duplex sonography. The following parameters were assessed: resting diameter (VDrest) and maximum diameter (VDmax) as well as reflux time (tr) during the Valsalva manoeuvre. The Valsalva manoeuvre was elicited by a forceful expiration into a tube system. The standard values used were a pressure of 30 mmHg, established within 0.5 seconds (s) and maintained over a time period of at least 3 s. RESULTS: mean VDrest and VDmax were 8.3+/-2.2 and 11.1+/-2.8 mm in the CFV, 5.9+/-1. 3 and 7.2+/-1.6 mm in the SFV and 3.5+/-0.9 and 4.3+/-1.4 mm in the LSV. Mean values for tr were 0.61+/-0.63 s in the CFV, 0.25+/-0.26 s in the SFV and 0.28+/-0.40 s in the LSV. A BMI >22.5 kg/m2 was associated with statistically significant larger values for VDrest and tr. If adjusted for BMI, tr in the SFV and the LSV did not differ by sex. For healthy subjects with first-degree relatives suffering from varicose veins (n=19), mean VDrest in the SFV as well as VD in the LSV was significantly larger (p=0.02, 0.05, respectively). Coefficients of variation for repeated measurements (VDrest, VDmax, tr) in the same segment varied between 3.3% and 16. 4% for the three investigated sites. CONCLUSIONS: normal values for VDrest and VDmax as well as reflux time during a standardised Valsalva manouevre were assessed in the proximal lower limb veins. The influences of BMI, sex and family history were investigated. The described standardised Valsalva manoeuvre led to highly reproducible results and can be recommended for further research projects or as a routine procedure for the assessment of venous reflux.

Doppler-based diagnosis of restenosis after femoropopliteal percutaneous transluminal angioplasty: sensitivity and specificity of the ankle/brachial pressure index versus changes in absolute pressure values.

The aim of this study was to investigate the sensitivity and specificity of changes of the ankle/brachial pressure index (ABI) and changes in absolute ankle pressure values to detect restenosis in patients who underwent femoropopliteal percutaneous transluminal angioplasty (PTA). In total, 171 patients were followed up prospectively for 12 months; sensitivity and specificity of Doppler-based diagnosis were calculated with duplex scanning as the gold standard. The criteria for restenosis were: (1) a loss of 50% of the ABI increase or (2) loss of 50% of the absolute ankle systolic pressure, gained by PTA. For both criteria, different cut-off points (minimum increase of ABI or ankle pressure gained by PTA) were evaluated. The overall sensitivity and specificity of the ABI criterion was 67% and 80%, respectively. The introduction of cut-off points (the minimum ABI increase gained by PTA), ranging between > or = 0.13 and > or = 0.35, did not markedly improve the results. The overall sensitivity and specificity of the absolute ankle pressure criterion again was poor (59% and 81%). With the introduction of cut-off points (the minimum increase of absolute ankle pressure gained by PTA) ranging between > or = 15 mm Hg and > or = 20 mm Hg, the sensitivity and specificity of the criterion improved to acceptable 92% and 96%, respectively. It is concluded, that in the long-term follow-up of PTA patients, the "loss of 50% ankle pressure" criterion will detect restenosis with reasonable accuracy in those patients, in whom an increase in systolic ankle pressure > or = 20 mm Hg is warranted.

[Unilateral swelling of the leg]. / Die einseitige Beinschwellung.

Unilateral swelling of the leg is a common problem in general practice. The spectrum of underlying diseases is broad and does include venous and lymphatic disorders but also less frequent diseases such as Baker cysts and Sudeck's dystrophia. In the majority of cases a diagnosis can be made based on the patients history, the clinical findings and some specific laboratory and/or instrumental investigations. Selected cases however, require the attention of the vascular specialist.

Role of hemostatic risk factors for restenosis in peripheral arterial occlusive disease after transluminal angioplasty.

In a prospective study, the role of various hemostatic factors known to be associated with thrombotic risk was investigated in 71 patients with peripheral arterial occlusive disease (PAOD, stages II through IV, Fontaine; aged 68 +/- 13 years). Laboratory investigations were done before; 1, 24, and 48 hours after; and 3 and 6 months after percutaneous transluminal angioplasty (PTA). Thirty of 71 (42.3%) patients developed restenosis (> 50% reduction of the lumen diameter) at the site of PTA within 6 months, verified by color-coded duplex sonography. Significantly increased levels of thrombin-antithrombin III complexes (P < .01), prothrombin fragments 1 + 2 (P < .01), and D-dimers (P < .01) were found 1 hour, as well as 24 to 48 hours, after PTA. Fibrinogen (P < .01) and von Willebrand factor (P < .01) were significantly higher 48 hours after PTA. Restenotic patients as a whole had higher plasma fibrinogen (3.46 +/- 1.12 versus 2.95 +/- 0.62 g/L, P < .01) and C-reactive protein (25.4 +/- 46.7 versus 7.9 +/- 6.9 mg/L, P < .05) at baseline, as well as higher fibrinogen (P < .05) and prothrombin fragments 1 + 2 (P < .01) during months 3 to 6 after PTA. There was a nonsignificant tendency for higher values of von Willebrand factor (206 +/- 98% versus 184 +/- 100%, P = .2) at baseline in patients with restenosis, whereas tissue plasminogen activator, plasminogen activator inhibitor, coagulation screening tests, blood cell counts, and serum lipids showed no significant difference between the two groups. The relative risk for developing restenosis within 6 months while having high fibrinogen (> 2.8 g/L) or C-reactive protein at baseline was 2.80 (95% CI: 1.30-6.02, P < .01) and 1.96 (95% CI: 1.07-3.58, P < .05), respectively. Patients with critical limb ischemia (stage III/IV, Fontaine) had significantly higher fibrinogen and von Willebrand factor at repeated points of time, as well as significantly higher C-reactive protein and lower creatinine clearance at entry. In the logistic regression risk factor analysis, baseline plasma fibrinogen, C-reactive protein concentration, and the severity of the arterial disease were significantly predictive of restenosis. Our results indicate that high procoagulant factors and persistent thrombin generation of the hemostatic system might promote restenosis, particularly in patients with extended atherosclerosis. This finding suggests that new treatment strategies should be taken under consideration for patients with PAOD and PTA.