Endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal angioplasty : results of a prospective randomized study.

BACKGROUND: Inasmuch as endovascular brachytherapy (BT) has gained recent interest because of its inhibitory effect on mechanisms leading to restenosis after percutaneous transluminal angioplasty (PTA), we performed this randomized study to determine its efficacy for prophylaxis of restenosis after femoropopliteal PTA. METHODS AND RESULTS: One hundred thirteen patients (63 men, 50 women; mean age 71 years) with de novo or recurrent femoropopliteal lesions were included in this randomized trial comparing the restenosis rate after PTA plus BT (57 patients, PTA+BT group) versus PTA (56 patients, PTA group) without stent implantation. The mean treated length was 16.7 cm (PTA+BT group) versus 14.8 cm (PTA group). In patients randomized to PTA plus BT, a dose of 12 Gy was applied by an (192)Ir source 3 mm from the source axis. Follow-up examinations included measurement of the ankle-brachial index, color-flow duplex sonography, and angiography. The primary end point of the study was patency after 6 months. The overall recurrence rate after 6 months was 15 (28.3%) of 53 in the PTA+BT group versus 29 (53.7%) of 54 in the PTA group (chi(2) test, P<0.05). The cumulative patency rates at 12 months of follow-up were 63.6% in the PTA+BT group and 35.3% in the PTA group (log-rank test, P<0.005). CONCLUSIONS: This is the first randomized study to demonstrate the efficacy of endovascular BT for prophylaxis of restenosis after femoropopliteal PTA. The value of this approach should now be improved by modification of the BT procedure and by combination with stent implantation.

Effect of nimodipine on ocular blood flow and colour contrast sensitivity in patients with normal tension glaucoma.

AIM: To investigate the effects of oral nimodipine on ocular haemodynamic parameters and colour contrast sensitivity in patients with normal tension glaucoma (NTG). DESIGN: The study was performed in a randomised, placebo controlled, double masked, crossover design. PARTICIPANTS: Nimodipine (60 mg) or placebo was administered to 14 consecutive NTG patients. METHODS: The effects or oral nimodipine or placebo on ocular and systemic haemodynamic parameters and colour contrast sensitivity along the tritan axis were studied two hours after administration. Optic nerve head blood flow (ONHBF) and choroidal blood flow (CHBF) were assessed with laser Doppler flowmetry. Ocular fundus pulsation amplitude (FPA) was measured with laser interferometry. Colour contrast sensitivity (CCS) was determined along the tritan colour axis. MAIN OUTCOME MEASURES: ONHBF, CHBF, FPA, intraocular pressure and CCS were assessed in patients with NTG. RESULTS: Mean ocular FPA increased by 14% (SD 14%) (p = 0.0008), ONHBF by 18% (SD 16%) (p = 0.0031), and CHBF by 12% (SD 14%) (p<0.001) after administration of nimodipine. Nimodipine also decreased the threshold of colour contrast sensitivity along the tritan colour axis (-14% (SD 12%); p = 0.048). However, individual changes in FPA, ONHBF, or CHBF were not correlated with changes in threshold of CCS along the tritan colour axis. CONCLUSIONS: The results indicate that nimodipine increases ONH and choroidal blood flow in NTG patients and improves CCS. The latter effect does not, however, seem to be a direct consequence of the blood flow improvement.

Elevated lipoprotein(a) and increased incidence of restenosis after femoropopliteal PTA. Rationale for the higher risk of recurrence in females?

It has been shown that the incidence of recurrent stenosis following successful percutaneous transluminal coronary angioplasty (PTCA) is correlated with serum Lipoprotein(a) [Lp(a)] levels. The aim of the present study was to examine the influence of Lp(a) on restenosis after primary successful femoropopliteal PTA. One hundred and thirty nine consecutive patients with peripheral arterial occlusive disease (PAOD) and successful femoropopliteal PTA were studied. Follow-up included clinical examination and non-invasive laboratory testing (pulse volume recordings, ankle-brachial arterial pressure measurement) in every patient before and after 1, 3, 6 and 12 months following intervention. Duplex sonography was performed 1 year after PTA. Suspicion of restenosis (> or = 50% diameter reduction) was verified by angiography. Lp(a) was determined using ELISA technique (mg/dl). Twelve months after successful PTA no restenosis was found in 82 patients (59%: group A). The one-year recurrence rate of 41% (group B) was due to significant restenosis in 35 patients (25%) and reocclusion in 22 patients (16%). The corresponding mean values +/- S.E.M. for Lp(a) were as follows: group A, 28 +/- 5.3; group B 59 +/- 11 (P < 0.01). Women showed a higher frequency of recurrences (55%) versus men (30%, P < 0.01) also corresponding with a high Lp(a) level (51.8 +/- 8 versus 32.7 +/- 5; P < 0.05). Furthermore Lp(a) aggravated the well known increased risk for recurrence in multiple stenoses or occlusions of > or = 5 cm in length. There were no significant differences between groups A and B with respect to age, diabetes, hyperlipidaemia, obesity and cigarette smoking. The results support the view that Lp(a) is an independent risk factor for recurrence after PTA in the femoropopliteal area. It might also be a causal basis for the higher incidence of recurrences in female PAOD patients.

Intraarterial (192)Ir high-dose-rate brachytherapy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty: the prospective randomized Vienna-2-trial radiotherapy parameters and risk factors analysis.

PURPOSE: The aim of the Vienna-2-trial was to compare the restenosis rate of femoropopliteal arteries after percutaneous transluminal angioplasty (PTA) with or without intraarterial high-dose-rate (HDR) brachytherapy (BT) using an (192)Ir source. MATERIALS AND METHODS: A prospective, randomized trial was conducted from 11/96 to 8/98. A total of 113 patients (63 men, 50 women), with a mean age of 71 years (range, 43-89 years) were included. Inclusion criteria were (1) claudication or critical limb ischemia, (2) de-novo stenosis of 5 cm or more, (3) restenosis after former PTA of any length, and (4) no stent implantation. Patients were randomized after successful PTA for BT vs. no further treatment. A well-balanced patient distribution was achieved for the criteria used for stratification, as there were "de-novo stenosis vs. restenosis after former PTA," "stenosis vs. occlusion," "claudication vs. critical limb ischemia" and above these for "diabetes vs. nondiabetes." PTA length was not well balanced between the treatment arms: a PTA length of 4-10 cm was seen in 19 patients in the PTA alone group and in 11 patients in the PTA+BT group, whereas a PTA length of greater than 10 cm was seen in 35 patients and 42 patients, respectively. A dose of 12 Gy was prescribed in 3-mm distance from the source axis. According to AAPM recommendations, the dose was 6.8 Gy in 5-mm distance (vessel radius + 2 mm). Primary endpoint of the study was femoropopliteal patency after 6 months. RESULTS: PTA and additional BT were feasible and well tolerated by all 57 pts in this treatment arm. No acute, subacute, and late adverse side effects related to BT were seen after a mean follow up of 12 months (6-24 months) in 107 patients (PTA n = 54; PTA+ BT n = 53). Crude restenosis rate at 6 months was in the PTA arm 54% vs. 28% in the PTA + BT arm (chi(2) test; p < 0.013). Actuarial estimate of the patency rate was at 6 months 45% vs. 72% (p < 0.004). Comparison of restenosis rates for the different subgroups with risk factors (restenosis after former PTA, occlusion and PTA length >10 cm) showed significant decrease of the restenosis rate, if BT was added. Significant reduction was not achieved in diabetes patients. CONCLUSION: BT after femoropopliteal PTA is feasible and a safe therapeutic option. No BT related morbidity was observed. A significant reduction of the restenosis rate was obtained in the PTA+BT arm. Subgroup analysis showed significant decrease of restenosis rate in the subgroups with restenosis after former PTA, occlusion and PTA length of greater than 10 cm. With dose escalation and reduction of dose variation by a centering device a further significant decrease of restenosis rate can be expected.

Increased serum laminin and angiogenin concentrations in patients with peripheral arterial occlusive disease.

AIM: To measure serum laminin and angiogenin concentrations in patients with peripheral arterial occlusive disease (PAOD) Fontaine stages IIb, III, and IV. METHODS: The study population comprised 38 patients (20 men and 18 women) with stage IV PAOD, 11 patients (six men and five women) with stage III PAOD, 18 patients (10 men and eight women) with stage IIb PAOD, and 23 patients (10 men and 13 women) with deep vein thrombosis. Fifteen normal subjects (matched for risk factors) and 10 patients (five men and five women) without PAOD served as controls. Serum samples were obtained at admission and serum laminin and angiogenin concentrations were measured using an enzyme linked immunosorbent assay. RESULTS: Patients with stage IV PAOD had higher serum laminin (mean +/- SEM; 826 +/- 97 ng/ml) and angiogenin concentrations (467 +/- 26 pg/ml) than normal subjects (laminin: 379 +/- 21 ng/ml; angiogenin: 358 +/- 16 pg/ml) and patients without PAOD (laminin: 277 +/- 34 ng/ml; angiogenin: 406 +/- 25 pg/ml). A significant correlation was found between angiogenin and laminin and between serum laminin and fibrinogen concentrations in patients with stage IV disease. CONCLUSIONS: Raised laminin and angiogenin concentrations may be indicators of endothelial damage caused by reduced vascular perfusion or compensatory revascularisation, or both.

Post-thrombotic syndrome after primary event of deep venous thrombosis 10 to 20 years ago.

AIMS: We investigated the impact of the extent of primary deep venous thrombosis (DVT) and recurrent thrombotic events in accordance to other presumed prognostic factors for long-term clinical outcome after first DVT. PATIENTS AND METHODS: All consecutive in-patients, who were treated following first acute DVT between January 1, 1978 and December 31, 1988 at the Department of Angiology were identified by admission lists. Localisation, extent of primary DVT, etiology and concomitant pulmonary embolism (PE) at the time of initial presentation and occurrence of post-thrombotic syndrome (PTS) at follow-up visits were assessed by chart review. The duration and quality of the compression therapy, as well as the accuracy of the oral anticoagulant (OAC) treatment were documented. Recurrence of thrombosis embolism and/or PE with respect to the intensity of OAC was analyzed. Patients were invited to participate in clinical reinvestigation. Patients' history and clinical stage of PTS were re-evaluated and patients were asked for compliance in wearing compression stockings. A survey concerning restriction in quality of life was conducted. Hemodynamic measurements by strain-gauge plethysmography (SGP) were performed. RESULTS: One hundred and sixty-one patients were eligible for the study. Out of these 132 patients, 82% suffered from the PTS, defined as signs of chronic venous insufficiency (CVI) secondary to DVT of the lower limbs: 74 patients (46%) presented with clinical stage I after Widmer, 47 patients (29%) with clinical stage II and 11 patients (7%) with clinical stage III. No sign of PTS was seen in 29 patients (18%). The mean follow-up period of 6.6 years was statistically not different between the three severity groups of PTS. The severity of clinical symptoms was significantly associated with the recurrence of ipsilateral thrombosis (n = 26/16%). Highest risk for developing severe PTS was seen after four-level DVT and deep vein thrombosis of the lower leg. Patients having had a non-sufficient OAC (Hepatoquick > 25% in more than 50% of measurements) exhibited worse progradient clinical stages. Besides the high rate of bleeding complications after thrombolytic therapy, this strategy did not show more efficiency in prevention of development of severe PTS than heparin therapy alone. CONCLUSION: Our results show that primary four-level DVT, calf vein thrombosis, recurrence of ipsilateral DVT and a non-sufficient oral anticoagulation are of prognostic significance for developing clinically relevant PTS within 10 to 20 years after first DVT.

Effects of transvenous regional guanethidine block in the treatment of critical finger ischemia.

The objective of this study was to determine the effects of transvenous regional guanethidine block in the treatment of patients with critical finger ischemia. Twenty-seven patients (17 collagen vascular disease, four thromboangiitis obliterans, three embolism, three atherothrombosis) presenting with ischemic rest pain and/or ulcerations of the fingers received a single block with 5 mg guanethidine injected in 60 mL into the clinically more affected hand under 30 minutes of arterial arrest. Marked hyperemia was induced in the treated upper limb, increases (p < 0.01) in finger blood flow, finger skin temperature, and laser Doppler flux were higher and longer lasting than in forearm blood flow, persisting for a whole month. Effects in patients with ischemic finger ulcers were less pronounced than in those without, yet statistically significant increases of all evaluated parameters were observed in these patients too. No effects were seen in the contralateral untreated upper limb or in systemic blood pressure. Subjective symptoms (reduction of rest pain, numbness, vasospastic attacks) were improved in 25/27 (92.6%) patients, ischemic rest pain disappeared in 20/27 (74.1%), and complete healing of finger tip ulcerations within 1 month was achieved in 10/12 (83.3%) affected patients. No side effects were observed. This described method combines good clinical efficacy with lack of undesirable side effects and can be repeated easily. Therefore, this technique is recommended for broader clinical use.

A severe case of vascular thoracic outlet syndrome.

We report a 21-year-old patient who presented at the outpatient department of angiology with incipient necroses in the fingertips of the right hand. Colour-coded duplex sonography and angiography demonstrated occlusion of the right brachial, ulnar and radial arteries, obviously resulting from an embolism from the subclavian artery narrowed by a cervical rib. After partly successful local thrombolysis this accessory rib was resected. We review angiologic signs and neurological symptoms of the thoracic outlet syndrome (TOS) and analyse the current literature regarding diagnostic procedures and treatment. This complicated and severe case of TOS in a young patient ending with paresis of the right arm and partial finger amputation emphasises the importance of early diagnosis of this condition.

Low level laser therapy for treatment of primary and secondary Raynaud's phenomenon.

BACKGROUND: We recently performed a pilot study which suggested that clinical and thermographic improvements occurred in patients with primary and secondary Raynaud's phenomenon (RP) following treatment with low level laser irradiation (LLLI). In view of these findings, we have proceeded with a double blind, placebo-controlled study. METHODS: Forty seven patients suffering from primary or secondary RP were randomly assigned in a double-blind manner to receive either 10 sessions of distant LLLI (16 f, 8 m, median age 45 years) or placebo irradiation (21 f, 2 m, median age 46 years) during winter months. The attack frequency of RP was measured by a diary count; its severity was assessed by means of visual analogue scale. Response to cold challenge test before and after LLL or placebo treatment was assessed by infrared thermography. RESULT: Overall a significant reduction of the frequency as well as the severity of RP in patients with either LLLI (frequency p < 0.0001, severity p < 0.0001) or placebo treatment (frequency p < 0.0001, severity p = 0.02) was found, but patients in the LLLI group exhibited a statistically more significant improvement of the frequency at 6 weeks p = 0.007 and 3 months p = 0.02 and the severity p = 0.02, p = 0.04 of RP. Thermographic response to cold challenge improved only in patients treated with LLL but not in those treated with placebo. CONCLUSION: LLLI significantly lowers the frequency and severity of Raynaud's attacks in patients with primary and secondary RP. Since this therapeutic modality is a safe, and non-invasive treatment, it might be considered as an alternative to existing therapeutic regimes.

Temporary vena cava filters do not always protect from fatal pulmonary embolism.

We describe the case of a young woman who developed fatal pulmonary embolism during thrombolytic therapy of a deep pelvic and leg vein thrombosis, despite the insertion of a temporary vena cava filter. So the opinion that the insertion of inferior vena cava filters always prevents lethal pulmonary embolism caused by thrombi of the deep vein system must be revised.

Low level laser treatment of primary and secondary Raynaud's phenomenon.

BACKGROUND: Patients who had been treated with low level laser (LLL) for their digital ulcers reported an impressive improvement of their symptoms of episodic digital ischaemia. Therefore this pilot study was performed to evaluate the efficacy of LLL as a new non-drug non-invasive treatment for patients with primary and secondary Raynaud's phenomenon (RP). PATIENTS AND METHODS: Forty patients (29 female, 11 male, mean age 51 years) with active primary (28%) and secondary (72%) Raynaud's phenomenon received 10 sessions of LLL distant irradiation during winter months. Assessment of subjective and objective parameters was performed at baseline, one week after the last session and three months later. Variations of subjective parameters as number of daily acute episodes and severity of discomfort were assessed by a coloured visual analogue scale. A standardised cold challenge test using computed thermography of continuous temperature recordings by means of infrared telethermography was used to assess the digital blood flow. RESULTS: A significant improvement was noticed clinically and thermographically after 6 weeks and 3 months, respectively (p < 0.0001). CONCLUSIONS: These data suggest that LLL treatment has a good short and medium term effectiveness in patients with Raynaud's phenomenon.

Homocysteine levels in patients with Raynaud's phenomenon.

BACKGROUND: Patients with Raynaud's phenomenon (RP) have vasomotor dysregulation, mainly cause by dysfunction of the endothelium. Since homocysteine has been found to be damaging to endothelial cells, we investigated the concentrations of plasma homocysteine, folate and vitamin B12 in patients with primary or secondary RP compared to healthy individuals. PATIENTS AND METHODS: We measured the concentrations of plasma fasting homocysteine, folate and vitamin B12 in a group of healthy individuals (n = 45) and in patients with primary (n = 26) or secondary RP (n = 42). RESULTS: Median homocysteine levels in healthy controls and in patients with primary RP, secondary RP were 7.9 (IQR 4.1 to 11.8) 9.8 (IQR 5.1 to 14.4), and 10.6 (6.0 to 15.3) mumol/L, respectively. Patients with primary and secondary RP had significantly higher homocysteine concentration compared to healthy controls (Kruskal Wallis p = 0.01). After matching for age and sex, patients with either primary or secondary RP showed significantly higher homocysteine levels (Wilcoxon p < 0.0001). No significant differences between the three groups were found concerning serum levels of vitamin B12 (p = 0.9) and serum folate levels (p = 0.2). CONCLUSION: These data demonstrate that patients with RP have higher plasma levels of homocysteine. No significant differences in folate and vitamin B12 levels were found between patients with primary RP, secondary RP, and healthy individuals. These data suggest that homocysteine may play a role in RP and may provide new clues in understanding of the vasomotor dysregulation.

Serum nitrate concentrations in patients with peripheral arterial occlusive disease.

BACKGROUND: Nitric oxide (NO), an endogenous product of L-arginine oxidation, seems to account for the vasodilatatory effect of the endothelium-derived relaxing factor. It was the aim of the present study to measure serum nitrate concentrations, the degradation product of nitric oxide in patients with peripheral arterial occlusive disease (PAOD). PATIENTS AND METHODS: 20 patients with PAOD in Fontaine stage IIb, 10 patients in stage III and IV respectively were included in the study. Serum samples for determination of nitrate were taken at admission after fasting overnight. Nitrate concentrations were determined using a recently developed high performance liquid chromatography which allows direct measurement of nitrate. The control group comprised 14 age and risk factor matched volunteers. RESULTS: We found significantly increased nitrate concentrations in patients with PAOD compared to the control group [stage IIb: 6.65 +/- 1.58 mumol/l; stage III: 6.94 +/- 1.85 mumol/l, stage IV: 7.05 +/- 1.16 mumol/l; control: 4.41 +/- 1.24 mumol/l], however no significance was calculated within the different PAOD groups. There was no association of either diabetes mellitus, hypertension and smoking behaviour with increased nitrate levels. CONCLUSION: These data might indicate that NO might be involved in adaptive vasodilatation already in the early phase of the disease. The source of nitrate in PAOD patients, however, remains unclear.

Ultrasound guided compression therapy in 134 patients with iatrogenic pseudo-aneurysms: advantage of routine duplex ultrasound control of the puncture site following transfemoral catheterization.

BACKGROUND: The following study was designed to evaluate the effectiveness and safety of ultrasound guided compression therapy (UGCT) of iatrogenic postcatheterization pseudo-aneurysms (PA) on the one hand and to justify the usefulness of the routine colour duplex control of the puncture site following transfemoral catheterization, on the other hand. MATERIAL AND METHODS: During the study period 142 patients with (PA) following transfemoral catheterization were identified by means of colour duplex examination Eighty of these 142 patients were identified during a routine colour duplex control of the puncture site the day after PTA/angiography because of peripheral arterial occlusive disease (PAOD) [group A]; the remaining 62 patients with symptomatic groins were referred from other departments [group B]. RESULTS: In 8 patients of group B UGCT was considered to be contra-indicated, they were primarily treated by surgical repair of the PA. A total of 134 patients (group A 80 patients, group B 54 patients) underwent an UGCT. In total the success rate of UGCT was in group A 100% and in group B 78%. 12/54 patients (all group B) with failure of UGCT underwent a secondary surgical repair of the PA. Within group B there was a negative correlation between delay of diagnosis/UGCT and success (p < 0.04), whereas the size of the sheath did not influence the outcome of the UGCT (p = 0.3). CONCLUSION: Our study confirms the effectiveness and safety of UGCT. Routine colour duplex control of the puncture site the day following the removal of the sheath after percutaneous catheterization and UGCT of PAs without delay can increase the success rate of UGCT and minimize the need for surgical repair of PAs.

Impact of different therapeutic alternatives in treatment of severe limb ischemia: experiences on 190 consecutive patients at a department of medical angiology.

BACKGROUND: Different therapies in consecutive patients (1987-1992) with chronic critical limb ischemia at a department of medical angiology, their short- and long-term outcome were investigated. PATIENTS AND METHODS: 190 patients (112 males, 78 females; age: 67 +/- 12 years); 78 in grade II, 112 in grade III according to Rutherford's classification. Therapeutic regimen: 1. vascular recanalisation by percutaneous transluminal angioplasty [PTA], local or systemic lysis; 2. surgical vascular reconstruction in case of impossibility or failure of catheter procedures; 3. prostanoids and/or antibiotics; 4. local wound treatment including amputations. RESULTS: Vascular recanalisation was attempted in 156/190 (82.1%): PTA in 116/190, surgical vascular reconstruction in 50/190, local in 24/190 and systemic lysis in 8/190 patients. Prostanoids were applied in 89/190 and antibiotics in 73/190 patients. At the time of dismissal 164/190 (86.3%) patients were clinically improved; 11/190 (5.8%) unchanged, 13/190 (6.8%) had undergone major amputations and 2/190 (1.1%) had died. After 2.6 +/- 2.2 years 77 of the 141 patients, who were still alive, were reexamined. Among these 77 patients 84.4% were in grade 0 or 1, 15.6% in chronic critical limb ischemia. Furthermore 13.0% had been amputated since dismissal. Forty-nine of 190 (25.8%) patients had died 3.2 +/- 1.9 years after dismissal from hospital. CONCLUSION: Catheter techniques, mostly PTA, is possible in the majority of patients with chronic critical limb ischemia. Cooperation with vascular surgeons in case of technical impossibility or failure of catheter recanalisation is mandatory. Such a regimen yields satisfactory short- and long-term results and a low rate of complications.

Influence and interaction of diabetes and lipoprotein (a) serum levels on mortality of patients with peripheral artery disease.

BACKGROUND: Diabetes mellitus is a risk factor for early complications and mortality in patients with peripheral artery disease. Lipoprotein (a) [Lp(a)] is also suggested to be a marker of increased cardiovascular risk. We investigated the association and interaction between diabetes mellitus, lipoprotein(a) and mortality in high risk patients with peripheral artery disease (PAD). METHODS: We studied 700 consecutive patients [median age 73 years, interquartile range (IQR) 62-80, 393 male (56%)] with PAD from a registry database. Atherothrombotic risk factors (diabetes, smoking, hyperlipidaemia, arterial hypertension) and Lp(a) serum levels were recorded. We used stratified multivariate Cox proportional hazard analyses to assess the mortality risk at a given patient's age with respect to the presence of diabetes and Lp(a) serum levels (in tertiles). RESULTS: Patients with Lp(a) levels above 36 mg dL(-1) (highest tertile) and insulin-dependent type II diabetes had a 3.01-fold increased adjusted risk for death (95% confidence interval 1.28-6.64, P = 0.011) compared to patients without diabetes or patients with non-insulin-dependent type II diabetes. In patients with Lp(a) serum levels below 36 mg dL(-1) (lower and middle tertile), diabetes mellitus was not associated with an increased risk for death. CONCLUSION: Insulin-dependent type II diabetes mellitus seems to be associated with an increased risk for mortality in PAD patients with Lp(a) serum levels above 36 mg dL(-1). PAD patients with non-insulin-dependent type II diabetes, and patients with diabetes and Lp(a) levels below 36 mg dL(-1) showed survival rates comparable to PAD patients without diabetes.

Fibrinogen predicts mortality in high risk patients with peripheral artery disease.

OBJECTIVE: Fibrinogen plays a key role in the pathogenesis of atherosclerosis and complications of atherothrombotic disease. We investigated the prognostic impact of fibrinogen levels on mortality of high risk patients with peripheral artery disease (PAD). METHODS: We studied 486 patients with PAD and several cardiovascular comorbidities. Atherosclerotic risk factors and fibrinogen levels were determined at initial presentation and patients were followed for median 7 years (IQR 6-10) for all-cause and cardiovascular mortality. Multivariate Cox regression analysis was applied to assess the predictive value of fibrinogen levels (in quartiles) on patients' outcome. RESULTS: Cumulative survival rates at 1, 3, 5 and 10 years were 96, 91, 83 and 67%, respectively. Overall, 138 patients (28%) died, 70% of these patients died of cardiovascular complications (n=96). Patients with fibrinogen levels 10.2-12.2 micromol/l (third quartile) and patients with fibrinogen levels above 12.2 micromol/l (fourth quartile) had a significantly increased adjusted risk for all-cause mortality (hazard ratios [HR] 1.87 and 1.90, p=0.025 and p=0.020, respectively) compared to patients in the lowest quartile (fibrinogen below 8.6 micromol/l). A consistent effect was observed for cardiovascular causes of death. Diabetes mellitus and critical limb ischemia were the only other independent predictor variables (HR 2.08, p<0.001 and 1.88, p=0.001, respectively). CONCLUSION: Elevated fibrinogen levels in high risk patients with PAD indicate an increased risk for poor outcome, particularly for fatal cardiovascular complications.

Monitoring of antiplatelet therapy with the PFA-100 in peripheral angioplasty patients.

BACKGROUND: In patients suffering from peripheral arterial occlusive disease (PAOD) the risk of restenosis after percutaneous transluminal angioplasty (PTA) might be influenced by platelet mediated factors. OBJECTIVE: To look for a correlation between the effect of antiplatelet therapy and recurrence of disease after PTA by monitoring platelet function in 3-month intervals by the platelet function analyzer system, PFA-100, over a period of 1 year. PATIENTS AND METHODS: A group of 98 patients (43 females, 55 males) with PAOD, treated with aspirin (n = 52), thienopyridine (n = 34) or combination therapy of both (n = 12) were followed over a period of 12 months after elective PTA of the lower extremities with regard to occurrence of restenosis or reocclusion at the site of angioplasty, to demonstrate inhibitory effects on platelets, induced by antiplatelet therapy. RESULTS: PFA-100 proved suitable to identify 'non-responders' to antiplatelet therapy, in a 12-month follow-up period. In 'non-responders' to clopidogrel therapy, a higher incidence of restenosis or reocclusion after PTA of the lower limbs was detected compared with 'responders'. CONCLUSION: PFA-100, upon stimulation with ADP, might predict patients under clopidogrel therapy with elevated risk for the development of complications following PTA of the lower limbs. This could offer the chance to switch to an alternative therapy or adapt the dose.

Clinical outcome and prognostic factors for ischaemic ulcers treated with PTA in lower limbs.

OBJECTIVE: To analyse the clinical outcome of patients with ischaemic ulcers (Fontaine stage IV) undergoing percutaneous transluminal angioplasty (PTA). METHODS AND DESIGN: Retrospective cohort study of 40 patients (21 males) treated between January 1998 and December 1998. Cardiovascular risk factors, co-morbid, baseline laboratory, angiographic data and technical success were recorded. Patients were followed for a median of 20 (inter quartile range (IQR) 8-26) months. RESULTS: Cumulative ulcer healing rates at 3, 6, 12, and 24 months were 15, 40, 54 and 81%, respectively. The median time to healing was 5 (IQR 2-7) months. Cumulative restenosis at 1, 3, 6 and 12 months was 3, 10, 29 and 52%, respectively. Nine patients (22%) suffered ulcer reappearance. Lipoprotein (a) serum levels > 30 mg/dl (HR 0.2, 95% CI 0.05-1.0, p = 0.05) and diabetes mellitus (HR 0.2, 95% CI 0.5-0.7, p = 0.01) were associated with delayed ulcer healing. CONCLUSION: PTA leads to ulcer healing in the majority of patients. Elevated lipoprotein (a) levels > 30 mg/dl and diabetes mellitus are independently associated with ulcer persistence.

[Secondary prevention of diabetic retinopathy in type I diabetes mellitus. Dependence on retinopathy status before the intervention]. / Sekundärprävention der diabetischen Retinopathie bei Diabetes mellitus Type I. Abhängigkeit vom Retinopathiestatus vor der Intervention.

OBJECTIVE: To assess prospectively the effect of improving the metabolic state on the course of diabetic retinopathy in relation to the extent of retinal changes before intervention. PATIENTS AND METHODS: 140 patients with type I (insulin-dependent) diabetes mellitus (IDDM) (55 men, 85 women; mean age 30 +/- 11 years; mean duration of illness 11 +/- 8 years), underwent intensified insulin treatment and were then followed for 4 years. At the beginning of the trial fundoscopy was unremarkable in 68 patients (stage 0), a few microaneurysms and (or) punctate bleeding (stage 1) in 21, nonproliferative retinopathy (stage 2) in 27, preproliferative retinopathy (stage 3) in six, proliferative retinopathy (stage 4) in 14, and proliferative retinopathy with complications (stage 5) in four. The average retinopathy stage was 1.2 +/- 1.0, mean HbA1c value 7.0 +/- 1.3%). RESULTS: The retinopathy remained unchanged in 94 patients (group A), it improved in 16 (group B), and deteriorated in 30 (group C). There was no significant change in mean HbA1c value in any of the groups (A: 6.2 +/- 0.9%; B: 6.4 +/- 1.0%; C: 6.3 +/- 6.0%). There were also no differences with respect to blood glucose, M-value according to Schlichtkrull, frequency of hypoglycaemia, serum lipids, blood pressure and renal biopsy parameters. However, significant differences (P < 0.001 C vs. A and B) were found in relation to duration of diabetes (A: 9.3 +/- 7.2 years; B: 8.8 +/- 8.6 years; C: 16.9 +/- 7.8 years) and mean retinopathy stage at beginning of the study (A: 0.8 +/- 0.8; B: 1.2 +/- 0.7; C: 2.4 +/- 1.6). CONCLUSION: Decisive for the course of retinopathy in patients with IDDM of long duration and secondarily optimised metabolic state is the duration of illness and especially the degree of fundal changes when intensified insulin treatment is undertaken.