Wolfgang Mlekusch

Abstract: Atherosclerosis is a chronic inflammatory disease. Ongoing inflammation is associated with elevated levels of beta 2 microglobulin (B2M). We investigated B2M levels in a large cohort of patients with carotid atherosclerosis for the occurrence of major adverse cardiovascular events.

Abstract: Dental status and oral hygiene are associated with progression of atherosclerosis in patients with carotid stenosis. It remains unclear whether dental disease is a risk factor for mortality in these patients. We evaluated the bearing of dental disease on mortality among patients with asymptomatic carotid atherosclerosis.

Abstract: Glioblastoma multiforme (GBM), the most common primary tumor of the central nervous system, is associated with a state of hypercoagulability. We hypothesized that tumor activity is displayed by elevated d-dimer plasma levels and that d-dimer might be used as a predictor of survival in patients with glioblastoma multiforme. We studied effects on clinical outcomes of d-dimer levels obtained two to three weeks following histologic confirmation of the diagnosis of GBM at surgery or needle biopsy, but prior to chemotherapy or radiation therapy, in 23 patients. During a median follow-up of 7.3 months (interquartile range 3.5 to 22 months), we observed a total of 21 deaths (91.3%). Elevated d-dimer levels were significantly associated with mortality compared to normal values (log rank p = 0.002). The adjusted hazard ratio for death in patients with elevated d-dimer levels was 10.8 (95% confidence interval, 1.3 to 93.1; p = 0.03), compared to controls. Similar effect sizes were revealed when analyzing the association between progression-free survival and d-dimer levels (log rank p = 0.002). Additionally, patients with elevated d-dimer levels were more likely to suffer from venous thromboembolism compared to patients with normal values (log rank p = 0.025). Our data support the assumption that d-dimer levels are related to adverse outcome in patients with GBM. However, our results need to be confirmed by a large, prospective cohort study.

Abstract: A single-nucleotide polymorphism (SNP) in the palladin gene (PALLD, rs7439293) has recently been reported to be associated with coronary heart disease (CHD) in two case-control studies as well as in a large population-based cohort (Atherosclerosis Risk in Communities study, ARIC). Its clinical relevance, however, has not been evaluated prospectively. We investigated whether the risk allele (A) of PALLD rs7439293 (G>A) is associated with the occurrence of future major cardiovascular events (MACE) in a cohort of patients with prevalent carotid atherosclerosis.

Abstract: BACKGROUND: Acupuncture has been shown to influence skin perfusion and the subjective cold perception threshold. Therefore, we hypothesized that auricular electroacupuncture (EA) might reduce symptoms in primary Raynaud's phenomenon (PRP). METHODS: Twenty-six patients with PRP received 6 cycles of auricular EA. After 3, 6 and 24 weeks attack frequency and severity were reevaluated using standardized questionnaires and a visual analogue scale (VAS). Skin temperature was assessed by infrared thermography and laser Doppler perfusion imaging was used to determine skin perfusion. RESULTS: Compared to baseline we found a significant reduction of attack frequency after 3 (p = 0.001) and 6 weeks (p < 0.001) of auricular EA. This improvement sustained following cessation of EA, after 24 weeks (p < 0.001). Furthermore, attack associated pain was reduced after 3 (p = 0.003), 6 (p = 0.003) and 24 weeks (p = 0.001) of treatment, while skin temperature and skin perfusion did not change significantly throughout the study period. CONCLUSIONS: Auricular EA reduces symptoms by means of frequency and severity of attacks in PRP but has no influence on skin perfusion and skin temperature.

Abstract: Markers of apoptosis are associated with cardiovascular disease. The soluble apoptosis-stimulating fragment (sFAS) was found to be a predictor for outcome in patients with heart failure, but its importance in patients with atherosclerotic disease has not been fully understood as yet. The aim of the present study was to investigate the impact of sFAS on all-cause and cardiovascular mortality in patients with atherosclerosis in the carotid arteries.

Abstract: Sufficient control of blood glucose levels has been demonstrated to be associated with improved long-term outcome in patients with diabetes. Recent advances in interface technology allow transfer of measurement data to mobile devices, which enables control, multiple access, and storage of these data and virtually links patients and care-giving physicians. The possibility of alerting predefined addressee in case of measurements below or above certain limits offers some sort of security that cannot be obtained by simply penning a single value to a scratchpad. Therefore, treating physicians are able to follow the therapeutic course in an easy and finally time-independent manner. Furthermore, physical contact is not necessary, which may be favorable especially for elderly, sometimes immobile patients.

Abstract: We aimed to investigate the correlation of infrared thermography (IT) with laser Doppler perfusion imager (LDPI) among patients with primary Raynaud's phenomenon and healthy controls.

Abstract: Evidence of carotid atherosclerosis can be detected in 3 to 5% of orthopantomogram (OPG) investigations. The clinical impact of these findings is unknown. We investigated the association of OPG findings of carotid atherosclerosis with the occurrence of future cardiovascular adverse events.

Abstract: BACKGROUND AND PURPOSE: Renal dysfunction is a risk factor for cardiovascular events in patients with atherosclerosis. Unlike serum creatinine or estimated glomerular filtration rate, cystatin C reflects renal dysfunction independent of factors such as sex, weight, and race. We investigated whether baseline serum levels of cystatin C predict major cardiovascular events in patients with asymptomatic carotid atherosclerosis and compared the predictive value of cystatin C to these established markers of renal function. METHODS: We prospectively studied 1004 of 1286 consecutive patients with carotid ultrasound scanning. Patients were followed for the occurrence of major cardiovascular events, a composite of myocardial infarction, percutaneous coronary intervention, coronary bypass graft, stroke, and death. RESULTS: During a median of 3 years of follow-up, we recorded 346 major cardiovascular events in 311 patients. The risk for a first major cardiovascular event increased significantly with increasing quintiles of cystatin C; hazard ratios ranged from 1.18 to 1.94 for the highest versus the lowest quintile (P<0.001 for trend). Creatinine levels showed no significant association with major cardiovascular events, and for glomerular filtration rate, only the lowest quintile was moderately associated with adverse cardiovascular outcome. CONCLUSIONS: Cystatin C was significantly and gradually associated with future cardiovascular events in patients with carotid atherosclerosis. In contrast, neither serum creatinine nor estimated glomerular filtration rate were significant predictors of adverse cardiovascular outcomes.

Abstract: OBJECTIVE: Pseudoaneurysms are characterized by extravascular circulation and therefore may lead to an activation of the coagulation cascade. We investigated d-dimer levels in patients with and without postcatheterization femoral pseudoaneurysms and hypothesized that d-dimer levels correlate with the presence of pseudoaneurysms at the vascular access site. METHODS: Patients with clinical suspected groin pseudoaneurysms after transluminal procedures were eligible. We compared prospectively-collected laboratory values of quantitative d-dimer testing in patients with and without pseudoaneurysms as assessed by color-coded duplex sonography. Furthermore, we measured the peak systolic velocity at the arterial fistula of each pseudoaneurysm. RESULTS: In 48 (40%) of 120 consecutive patients, a pseudoaneurysm was found. The level of d-dimer values was significantly higher in patients with postcatheterization femoral pseudoaneurysms compared with controls (1.9 mug/mL [interquartile range (IQR), 1.34-2.78 mug/mL] vs 0.8 mug/mL [IQR, 0.53-1.14 mug/mL]; P < .001). Values of d-dimer below 0.67 mug/mL have been calculated with a sensitivity of 94% (87%-100%), a specificity of 38% (27%-50%), a positive predictive value of 50% (40%-60%), a negative predictive value of 90% (82%-99%), and a likelihood ratio of 1.52 (1.25-1.85) with regard to the presence of pseudoaneurysms. We also found a significant correlation of the peak systolic velocity at the arterial fistula and increasing d-dimer levels (r = 0.98, P < .0001). CONCLUSION: We found a significantly higher level of d-dimer values in patients with femoral pseudoaneurysms at the vascular access site. Therefore, d-dimer levels could be a potential serological marker in the diagnosis of pseudoaneurysms. A confirmation is warranted in a larger patient sample.

Abstract: Eur J Clin Invest 2009Abstract Background Patients with symptomatic peripheral artery disease (PAD) are considered cardiovascular high-risk patients. Our aim was to investigate whether incidental renal artery stenosis (RAS) increases the risk for adverse cardiovascular and renal outcomes in these patients. Materials and methods We prospectively enrolled 487 consecutive patients admitted for revascularization of symptomatic PAD and performed a renal overview angiogram categorizing RAS as absent (0-29%), moderate (30-59%) and severe (>/= 60%) respectively. Clinical follow-up was for median 15 months (IQR 12-22) for the occurrence of major adverse events [MAE: composite of death, myocardial infarction (MI), stroke, percutaneous coronary intervention, coronary bypass surgery, amputation and kidney failure]. Glomerular filtration rates (GFR) were obtained at 12 months to quantify the course of renal function. Results A severe RAS was found in 76 patients (15.6%). Overall MAE occurred in 121 patients (24.8%), the composite endpoint of MI, stroke, amputation and death occurred in 101 patients (20.7%). Patients with a severe RAS had a 1.87-fold increased adjusted risk for MAE (95% CI 1.12-3.12, P = 0.017), a 2.51-fold increased adjusted risk for occurrence of the composite endpoint of MI, stroke, amputation and death (95% CI 1.45-4.34, P = 0.001) and a 2.93-fold increased risk for death (95% CI 1.41-6.08, P = 0.004), compared to those of patients without RAS respectively. We observed a significant association between the decrease of GFR over the 12-month follow-up period and the severity of RAS by multivariable analysis (P = 0.044). Conclusion Severe RAS in patients with symptomatic PAD is an independent predictor of major adverse cardiovascular events, adverse renal outcome and mortality.

Abstract: BACKGROUND: Recent randomized trials investigating stent implantation compared with balloon angioplasty for treatment of superficial femoral artery (SFA) disease have given divergent results in short (mean 5 cm) and intermediate (mean 10 cm) lesions. We reinvestigated whether primary nitinol stenting is associated with a morphologic and clinical benefit when compared with percutaneous transluminal angioplasty with optional stenting (PTA) in intermediate-length lesions. METHODS: We randomly assigned 73 patients with severe claudication or chronic limb ischemia and average 8 cm long (range 3-20 cm) SFA stenosis or occlusion to primary stent implantation (n = 34) or PTA (n = 39). Restenosis >50% and clinical outcome were assessed at 3, 6, and 12 months postintervention. RESULTS: Average length of the treated segments was 98 + or - 54 mm and 71 + or - 43 mm in the stent and PTA groups (P = 0.011), respectively. In the PTA group, secondary stenting was performed in 10 of 39 patients (26%) due to a suboptimal result after balloon dilation. Restenosis rates in the stent and PTA groups were 21.9% versus 55.6% (P = 0.005) at 6 months by CT-angiography, and 2.9% versus 18.9% (P = 0.033), 18.2% versus 50.0% (P = 0.006), and 34.4% versus 61.1% (P = 0.028) at 3, 6, and 12 months by sonography, respectively. Clinically, patients in the stent group reported a significantly higher maximum walking capacity compared with the PTA group at 6 and 12 months. CONCLUSION: In this randomized multicenter trial, primary stenting with a self-expanding nitinol stent for treatment of intermediate length SFA disease resulted morphologically and clinically superior midterm results compared with balloon angioplasty with optional secondary stenting.

Abstract: OBJECTIVES: We hypothesized that high sensitivity C-reactive protein (hs-CRP) and the presence of renal artery stenosis (RAS) might conjointly predict future major adverse cardiovascular events (MACE) in patients with peripheral artery disease (PAD). BACKGROUND: Clinical outcome in PAD is determined by the extent of atherosclerosis affecting additional vascular beds and the activity of the atherosclerotic process reflected by inflammatory serum markers. Data on the predictive value of hs-CRP on outcome in PAD patients with RAS is limited. METHODS: We prospectively enrolled 447 PAD patients who were admitted to our institution for angioplasty. Preintervention hs-CRP was assessed and renal angiograms were obtained. Patients were then followed clinically for the occurrence of MACE for median 15.6 months. Serum creatinine was obtained in all patients at 12 months. RESULTS: Incidental RAS >or=60% at baseline was found in 68 patients (15.2%), MACE were recorded in 111 patients during follow-up. Hs-CRP was significantly associated with the occurrence of MACE (p<0.001) and with 12 months creatinine levels (p=0.005). Adjusted hazard ratios for MACE for increasing quartiles of hs-CRP as compared to the lowest quartile were 1.11 (95% CI 0.53-2.35), 1.06 (95% CI 0.50-2.26) and 2.79 (95% CI 1.47-5.28). Analyzing joint effects of hs-CRP and RAS, we observed no significant interaction. CONCLUSION: Hs-CRP predicts cardiovascular and renal outcome in PAD patients irrespective of the presence of RAS. Patients with hs-CRP levels above 0.88 mg/dL were at particularly high risk for MACE.

Abstract: PURPOSE: To prospectively determine whether cutting balloon angioplasty, when compared with conventional balloon angioplasty (CBA), improves morphologic and clinical outcome in patients with femoropopliteal in-stent restenosis. MATERIALS AND METHODS: Patients with symptomatic femoropopliteal in-stent restenosis were randomly assigned to undergo CBA or peripheral cutting balloon angioplasty (PCBA) for treatment of lesions up to 20 cm in length. Patients were followed up clinically and with duplex ultrasonography (US) at 1, 3, and 6 months for occurrence of a restenosis of 50% or higher. The Fisher exact test and Mann Whitney U test were used for statistical analyses. RESULTS: Forty patients were enrolled; one patient was lost to follow-up. In the remaining patients, CBA was performed in 22 patients; PCBA was used in 17 patients. Average lesion length was 80 mm +/- 68 (standard deviation). Restenosis rates at 6 months were 65% (11 of 17; 95% confidence interval: 42%, 88%) after PCBA versus 73% (16 of 22; 95% confidence interval: 54%, 92%) after CBA (P = .73). Ankle brachial index (0.83 vs 0.75, P = .26) and maximum walking capacity on the treadmill (117 m vs 103 m, P = .97) at 6 months were also not significantly different between the two groups. CONCLUSION: PCBA failed to prove superiority compared with CBA for treatment of femoropopliteal in-stent restenosis in this pilot study. In restenotic lesions with an average length of approximately 8 cm, both treatment modalities yielded disappointing 6-month patency rates.

Abstract: PURPOSE: To prospectively determine, in a randomized controlled trial, whether cutting balloon angioplasty (CBA) yields superior morphologic and clinical outcomes at 6 months compared with the 6-month outcomes after conventional percutaneous transluminal angioplasty (PTA) in patients with short de novo superficial femoropopliteal artery (SFA) lesions. MATERIALS AND METHODS: This study was approved by the ethics committees of the two participating centers, and informed consent was obtained from all patients. The authors randomly assigned 43 patients (26 men, 17 women; median age, 69 years) who had 5 cm or shorter de novo SFA lesions in association with intermittent claudication or chronic limb ischemia to undergo CBA or PTA. The patients were followed up clinically, and restenosis was assessed with duplex ultrasonography (US) at 6 months. chi(2) and Mann-Whitney U tests were used to compare data between the two treatment groups. RESULTS: The US-determined 6-month restenosis rate was 32% (seven patients) in the PTA group versus 62% (13 patients) in the CBA group (P = .048). Sixteen (73%) PTA group patients versus eight (38%) CBA group patients were asymptomatic at follow-up (P = .059). There was no significant difference in ankle-brachial index (median, 0.83 vs 0.77 for PTA vs CBA group, respectively; P = .56) or pain-free walking distance (median, >1000 m vs 600 m for PTA vs CBA group, respectively; P = .17) between the two groups. CONCLUSION: CBA did not prove to be superior to conventional PTA for treatment of short de novo SFA lesions and yielded increased restenosis rates at 6 months.

Abstract: The authors investigated the incidence of critical limb ischemia (CLI) in 187 patients with intra-aortic balloon pump (IABP) support during a 6-year study period and determined risk factors and long-term outcome (median 5 years) after discharge from a cardiac intensive care unit. Cardiogenic shock following acute myocardial infarction was the predominant cause of IABP support. CLI occurred in 10% of the patients after IABP implantation. Nevertheless, in light of the overall high mortality in this patient population, CLI seems not a primary concern. Furthermore, its incidence significantly decreased during recent years. Duration of IABP support was a significant predictor for CLI.

Abstract: Purpose: To investigate the safety and efficacy of the procoagulant wound dressing Neptune Pad (Biotronik, Berlin, Germany) compared with those of conventional manual compression for access site management after peripheral percutaneous interventions. Materials and Methods: The study was approved by the institutional ethics committee, and all patients gave written informed consent. Two hundred one consecutive patients were enrolled and were randomly assigned to be treated with the Neptune Pad (n = 100) or conventional manual compression (n = 101). Patients were followed up clinically until hospital discharge and with duplex ultrasonography at 24 hours after the procedure to evaluate occurrence of access site complications. Time to hemostasis and time to ambulation were recorded, and patient and physician discomfort were measured by using a visual analogue scale. Results: The risk for access site complications was not significantly different between the Neptune Pad group and the conventional compression group (adjusted odds ratio, 1.15; 95% confidence interval: 0.47, 2.84; P = .76). Time to hemostasis was marginally reduced in the Neptune Pad group. Patient and physician discomfort were lessened with use of the device. Conclusion: The hemostatic device Neptune Pad does not improve the safety of access site management after peripheral percutaneous procedures. Markedly improved comfort was noted among patients in the Neptune Pad group and by the physicians obtaining hemostasis. (c) RSNA, 2008.

Abstract: PURPOSE: To investigate the incidence of complications after peripheral vascular interventions in patients aged 80 years and older compared to patients below the age of 80. METHODS: During a 20-month period, 619 consecutive patients (354 men; mean age 67 years, range 59-87) undergoing balloon angioplasty and stenting for lower limb revascularization were enrolled in the study. The incidence of procedure-related, access-site, and major complications within 30 days post intervention were recorded and compared between patients aged 80 years and older (n=72, 11.6%) and those under 80 years of age. RESULTS: Complication rates were significantly higher in octogenarians compared to patients below 80 years, including the rates of overall complications (18.1% versus 8.5%, p=0.010), major complications (11.1% versus 1.8%, p<0.001), all access site complications (12.5% versus 4.9%, p=0.009), and access site bleeding complications (12.5% versus 2.2%, p<0.001). By multivariable analysis, octogenarians had a 2.49-fold increased adjusted risk (95% CI 1.10 to 5.65, p=0.029) for any postintervention complication and a 10.99-fold increased adjusted risk (95% CI 2.76 to 45.74, p=0.001) for major complications compared to patients below 80 years. No specific risk factor for complications or major complications within the octogenarian population could be identified. CONCLUSION: Patients aged 80 years and older have a dramatically increased risk, particularly for major complications, after peripheral vascular interventions. Identification of risk factors and development of preventive strategies are urgently needed to improve procedure safety in this extremely vulnerable population.

Abstract: OBJECTIVE: To investigate the effect of protected carotid artery stenting on neurocognitive function with particular consideration of the angiographic filling of the ipsilateral anterior cerebral artery (ACA). BACKGROUND: An improved inflow to the supply area of the anterior cerebral artery after revascularisation of severe carotid artery stenosis may beneficially affect frontal lobe cognitive functions. METHODS: We prospectively included 71 consecutive patients who underwent carotid artery stenting (CAS) due to high grade carotid artery stenosis. Intracranial angiograms and filling status of the ACA pre- and post-stenting were analyzed and a battery of 5 selected neuropsychological tests for frontal lobe function were applied prior to and 6 months after CAS. Patients with improvement in at least two tests were defined as having improved neurocognitive function. RESULTS: Compared to baseline, we found a significant improvement of the Trail-Making Test A (median 6% improved change-score; P = 0.01), the test of supermarket items showed a trend towards significant improvement (median 3.7% improved change-score; P = 0.09). In 32 patients (45%) an improvement of at least 2 neurocognitive tests was observed. Neuropsychological improvement was found more frequently in patients with a contrasted ipsilateral ACA after CAS (88%, 95% CI 77 to 99) compared to patients without angiographic filling of the ipsilateral ACA post CAS (13%, 95% CI 1 to 25), respectively (P < 0.01). CONCLUSION: Carotid artery stenting improves neurocognitive function in a considerable proportion of patients. A contrasted ipsilateral anterior cerebral artery after CAS is associated with improved neurocognitive function, presumably due to amelioration of frontal lobe perfusion.

Abstract: PURPOSE: Carotid plaque echolucency seen at ultrasonography (US) is a potential indicator of plaque instability and may help identify patients at risk for major adverse cardiovascular events (MACEs). The authors performed this study to determine whether decreasing gray-scale median (GSM) levels at repeat carotid US examinations are associated with future MACEs. MATERIALS AND METHODS: The study was approved by the institutional ethics committee and all patients provided informed consent. The authors prospectively studied 574 patients with carotid plaques of at least 30% from a group of 1268 consecutive patients who were initially asymptomatic with respect to carotid disease. GSM levels were determined with carotid US at baseline and after a median of 7.5 months (range, 6-9 months), and the mean change of the GSM was calculated. Patients were then followed up clinically for a median of 3.2 years for the occurrence of composite MACE. RESULTS: During the initial period, the median change in carotid GSM was 2.9 (interquartile range [IQR], -6.9 to 11.0). Of 574 study participants, 230 (40%) showed a reduction of GSM levels and 344 (60%) showed an increase. MACEs were observed in 177 (31%) of the 574 patients. Adjusted hazard ratios for the lowest quartile (GSM change less than -6.9), the second quartile (GSM change between -6.9 and 2.9), and the third quartile (GSM change between 3.0 and 11.0) were 1.71 (95% confidence interval [CI]: 1.09, 2.66), 1.36 (95% CI: 0.86, 2.16), and 1.22 (95% CI: 0.77, 1.95), respectively, compared with the highest quartile (GSM change greater than 11.0) (P = .018). CONCLUSION: Increasing echolucency of carotid artery plaques within a 6- to 9-month interval is predictive of midterm clinical adverse events of atherosclerosis.

Abstract: PURPOSE: To evaluate the agreement of duplex ultrasound (DUS) versus digital subtraction angiography (DSA) for assessment of femoropopliteal arterial disease in a real-world clinical setting. METHODS: Consecutive patients with peripheral artery disease who were scheduled for a percutaneous intervention were included in this retrospective study. During an 18-month period, 491 patients (276 men; median age 73 years, interquartile range 64-81) were enrolled. A peak systolic velocity ratio (PSVR)>2.4 was the optimal cutoff for detecting a >50% stenosis by DSA. Findings of preprocedural DUS in the proximal, middle, and distal ipsilateral superficial femoral artery and in the popliteal segment were analyzed for agreement with preprocedural femoropopliteal DSA using kappa statistics. Only the target limb in each patient was analyzed, for a total of 1964 vascular segments. RESULTS: Agreement for the degree of stenosis in 10% increments was only moderate (weighted kappa 0.67, 95% CI 0.65 to 0.69). Using the PSVR>2.4 cutoff, agreement between DUS and DSA for a >50% stenosis was good (kappa 0.79, 95% CI 0.77 to 0.81). Sensitivity, specificity, positive predictive value, and negative predictive value for correctly detecting a >50% stenosis by DUS were 0.81 (0.78 to 0.84), 0.93 (0.91 to 0.94), 0.84 (0.81 to 0.87), and 0.91 (0.87 to 0.95), respectively. Comparable findings were observed within different patient subgroups. CONCLUSION: Agreement between DUS and DSA in the femoropopliteal segment is only moderate with respect to the absolute degree of stenosis. However, detection of a >50% stenosis can be done with acceptable precision in routine clinical practice using PSVR>2.4 as a threshold.

Abstract: PURPOSE: To investigate whether primary nitinol stenting in the superficial femoral artery (SFA) is beneficial to patients' quality of life (QoL). METHODS: One hundred four patients (55 men; mean age 66+/-19 years) with chronic limb ischemia and SFA disease were randomly assigned to primary stent implantation (n=51) or balloon angioplasty (n=53) with optional stenting for a suboptimal angioplasty result (17 of 53). QoL was measured by the SF-36 questionnaire at baseline and at 3, 6, and 12 months post intervention. RESULTS: QoL was significantly improved post intervention and up to 12 months in both treatment groups. Significant inverse associations were observed between QoL parameters and restenosis. Comparing primary stenting (n=51) versus balloon angioplasty with optional stenting (n=53) by the intention to treat, no significant differences in QoL were observed. Analyses of stented patients (n=68) versus balloon angioplasty (n=36) patients, however, demonstrated significantly improved measures of QoL after stenting. CONCLUSION: Endovascular revascularization of SFA disease improves QoL, and restenosis negatively affects QoL outcomes. After stent implantation, whether primary or secondary, QoL was significantly ameliorated compared to balloon angioplasty alone. However, it remains to be proven in larger cohorts whether primary stenting yields a QoL benefit compared to balloon angioplasty with optional secondary stenting.

Abstract: BACKGROUND AND PURPOSE: Atherosclerosis is a systemic inflammatory disease. We demonstrated previously that high-sensitivity C-reactive protein (hs-CRP) is associated with short-term progression of carotid atherosclerosis. We now investigated whether baseline levels of hs-CRP predict midterm clinical outcome in these patients. METHODS: We prospectively studied 1065 of 1268 consecutive patients who were initially asymptomatic with respect to carotid artery disease and were investigated with serial carotid ultrasound examinations at baseline and after a 6- to 9-month interval. Patients were followed-up clinically for the occurrence of cardiovascular events, a composite of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, and death. RESULTS: We recorded progression of carotid stenosis in 93 patients (9%) after 6 to 9 months, and 381 cardiovascular events in 337 patients (27%) during a median of 3 years of clinical follow-up (interquartile range, 2.5 to 3.5 years). The hs-CRP levels were significantly elevated in patients with progressive carotid stenosis (P<0.001), and hs-CRP was significantly associated with the occurrence of a first future cardiovascular event (P<0.001). Adjusted hazard ratios for a first cardiovascular event for increasing quintiles of hs-CRP were 1.41 (95% confidence interval, 0.92 to 2.17), 1.76 (95% confidence interval, 1.17 to 2.66), 2.22 (95% confidence interval, 1.48 to 3.32), and 2.41 (95% confidence interval, 1.61 to 3.60) as compared with the lowest quintile, respectively. This association was independent of traditional cardiovascular risk factors and the baseline degree of carotid stenosis. CONCLUSIONS: Inflammation was associated with morphological and clinical progression of atherosclerotic disease. Patients with elevated levels of hs-CRP exhibit an increased risk for adverse cardiovascular outcome attributable to clinical adverse events of progressive atherosclerotic disease.

Abstract: BACKGROUND AND PURPOSE: The progression of carotid stenosis reflects the activity of atherosclerotic disease and may indicate a risk for systemic atherothrombotic complications. We investigated whether progressive carotid stenosis determined by duplex ultrasonography predicts adverse outcomes in cardiovascular high-risk patients. METHODS: We prospectively studied 1065 of 1268 consecutive patients initially asymptomatic with respect to carotid disease. Carotid ultrasound investigations at baseline and after a median of 7.5 months (range, 6 to 9 months) were performed to identify patients with progressive stenosis as defined by Doppler velocity criteria. Patients were then followed up clinically for a median of 3.2 years for the occurrence of major adverse cardiovascular events (composite MACEs: myocardial infarction, percutaneous coronary or peripheral interventions, coronary or vascular surgery, amputation, stroke, and all-cause mortality). RESULTS: We found progressive carotid stenosis in 93 patients (9%) by ultrasound and thereafter recorded 495 MACEs in 421 patients (40%) during clinical follow-up. Patients with progressive carotid stenosis had a significantly increased risk for cardiovascular events compared with patients with nonprogressive disease: adjusted hazard ratios and confidence intervals were 2.01 for composite MACEs (95% CI, 1.48 to 2.67, P<0.001), 2.38 for myocardial infarction (95% CI, 1.07 to 5.35, P=0.044), 1.59 for any coronary event (95% CI, 1.10 to 2.28, P=0.011), 2.00 for stroke (95% CI, 1.02 to 4.11, P=0.035), 2.42 for any peripheral vascular event (95% CI, 1.61 to 3.62, P<0.001), and 1.75 for cardiovascular death (95% CI, 1.03 to 2.97, P=0.039). CONCLUSIONS: Progression of carotid stenosis within a 6- to 9-month interval detected by duplex ultrasound predicts midterm clinical adverse events of atherosclerosis in high-risk patients affecting the coronary, cerebrovascular, and peripheral circulations.

Abstract: BACKGROUND: Primary stenting with self-expanding nitinol stents of the superficial femoral artery yielded improved morphological and clinical results compared with balloon angioplasty with optional stenting until 12 months in a randomized controlled trial. We now report 2-year data on restenosis and clinical outcomes of these patients. METHODS AND RESULTS: Of 104 patients with chronic limb ischemia and superficial femoral artery obstructions, 98 (94%) could be followed up until 2 years after intervention for occurrence of restenosis (>50%) by duplex ultrasound and for clinical and hemodynamic outcome by treadmill walking distance and ankle brachial index. Restenosis rates at 2 years were 45.7% (21 of 46) versus 69.2% (36 of 52) in favor of primary stenting compared with balloon angioplasty with optional secondary stenting by an intention-to-treat analysis (P=0.031). Consistently, stenting (whether primary or secondary; n=63) was superior to plain balloon angioplasty (n=35) with respect to the occurrence of restenosis (49.2% versus 74.3%; P=0.028) by a treatment-received analysis. Clinically, patients in the primary stent group showed a trend toward better treadmill walking capacity (average, 302 versus 196 m; P=0.12) and better ankle brachial index values (average, 0.88 versus 0.78; P=0.09) at 2 years, respectively. Reintervention rates tended to be lower after primary stenting (17 of 46 [37.0%] versus 28 of 52 [53.8%]; P=0.14). CONCLUSIONS: At 2 years, primary stenting with self-expanding nitinol stents for the treatment of superficial femoral artery obstructions yields a sustained morphological benefit and a trend toward clinical benefit compared with balloon angioplasty with optional stenting.

Abstract: PURPOSE: To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS: C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS: Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION: Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The complement component C5a exerts strong chemotactic and proinflammatory effects. Enhanced complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of complement inhibition thus may be worth investigating with respect to improving patency rates.

Abstract: 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.

Abstract: BACKGROUND: Because stent implantation for disease of the superficial femoral artery has been associated with high rates of late clinical failure, percutaneous transluminal angioplasty is preferred for endovascular treatment, and stenting is recommended only in the event of suboptimal technical results. We evaluated whether primary implantation of a self-expanding nitinol (nickel-titanium) stent yielded anatomical and clinical benefits superior to those afforded by percutaneous transluminal angioplasty with optional secondary stenting. METHODS: We randomly assigned 104 patients who had severe claudication or chronic limb ischemia due to stenosis or occlusion of the superficial femoral artery to undergo primary stent implantation (51 patients) or angioplasty (53 patients). Restenosis and clinical outcomes were assessed at 6 and 12 months. RESULTS: The mean (+/-SD) length of the treated segment was 132+/-71 mm in the stent group and 127+/-55 mm in the angioplasty group. Secondary stenting was performed in 17 of 53 patients (32 percent) in the angioplasty group, in most cases because of a suboptimal result after angioplasty. At 6 months, the rate of restenosis on angiography was 24 percent in the stent group and 43 percent in the angioplasty group (P=0.05); at 12 months the rates on duplex ultrasonography were 37 percent and 63 percent, respectively (P=0.01). Patients in the stent group were able to walk significantly farther on a treadmill at 6 and 12 months than those in the angioplasty group. CONCLUSIONS: In the intermediate term, treatment of superficial-femoral-artery disease by primary implantation of a self-expanding nitinol stent yielded results that were superior to those with the currently recommended approach of balloon angioplasty with optional secondary stenting. (ClinicalTrials.gov number, NCT00281060.).

Abstract: PURPOSE: To evaluate immediate and midterm clinical outcomes after percutaneous transluminal angioplasty (PTA) of deep femoral artery stenosis in patients with chronically occluded superficial femoral arteries (SFA) and to report the results of a systematic review of the literature in this field. METHODS: A retrospective analysis was conducted of 55 consecutive patients (42 men; median age 72 years, interquartile range [IQR] 63-79) with severe intermittent claudication (n = 38) or critical limb ischemia (n = 17) who underwent balloon angioplasty of deep femoral artery stenosis. Patients were followed with ankle-brachial index (ABI) measurement, estimation of maximum walking capacity, clinical staging of peripheral artery disease (PAD), and duplex ultrasound imaging for restenosis. A systematic review of the literature using MEDLINE, EMBASE, and a hand search was done. RESULTS: Technical success (residual stenosis < 30%) was achieved in 85% (47/55), with 1 (2%) minor complication. The median ABI marginally increased from 0.48 at baseline to 0.53 post intervention without significant difference in the change of ABI between patients with supra- or infragenicular reconstitution of the femoropopliteal runoff. During a median 13-month (IQR 3-42) follow-up, no significant improvement in ABI or walking distance was maintained, and only 16 (29%) patients reported a sustained clinical improvement by 1 PAD stage. Cumulative patency and reintervention-free survival rates were, respectively, 71% and 61% at 1 year and 49% and 48% at 3 years. In the literature, only case series were found, but no randomized trial evaluating the efficacy of deep femoral artery PTA. CONCLUSION: PTA of the deep femoral artery can be performed with high technical success rates at a low interventional risk. However, in the majority of patients, this technique yields no sustained hemodynamic or clinical benefit. Due to a high rate of late failures, it should be reserved for limb salvage in patients without a surgical alternative.

Abstract: OBJECTIVES: We investigated the effect of myeloperoxidase (MPO) on progression of carotid stenosis in states of high and low high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) levels. BACKGROUND: Myeloperoxidase is pivotally involved in the pathogenesis of atherosclerosis. In vitro data suggest that MPO exerts deleterious effects via oxidative modulation of lipoproteins. METHODS: We prospectively studied 1,019 of 1,268 consecutive patients who were asymptomatic with respect to carotid artery disease. Patients underwent serial carotid ultrasound investigations at baseline and after a follow-up interval of median 7.5 months (range 6 to 9 months), categorizing carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed or occluded. The MPO, HDL-C, and LDL-C levels were measured at baseline, grouped by medians, and correlated with progression of carotid atherosclerosis. RESULTS: Progression of carotid atherosclerosis was found in 100 of 1,019 patients (9.8%). Myeloperoxidase (p = 0.014) but not HDL-C (p = 0.95) or LDL-C (p = 0.30) were associated with progressive disease. However, MPO > or =310 ng/ml was significantly associated with progressive disease (adjusted odds ratio [OR] 2.57, 95% confidence interval [CI] 1.39 to 4.75) only in patients with HDL-C levels <49 mg/dl. Otherwise, in patients with higher HDL-C levels (> or =49 mg/dl), MPO > or =310 ng/ml did not predict disease progression (adjusted OR 1.42, 95% CI 0.72 to 2.78). No interaction of MPO with LDL-C was observed. CONCLUSIONS: Myeloperoxidase was associated with progression of carotid atherosclerosis in patients with HDL cholesterol levels below 49 mg/dl.

Abstract: PURPOSE: To prospectively evaluate the accuracy of using physical examination to identify puncture-related groin pseudoaneurysms, as assessed by using duplex ultrasonography (US), after percutaneous transluminal procedures and to prospectively evaluate the association between preinterventional platelet count, antiplatelet medication, and the occurrence of pseudoaneurysms. MATERIALS AND METHODS: This study was approved by the local ethics committee, and informed consent was obtained from all patients. The study prospectively included 273 consecutive patients (161 men, 112 women; age range, 34-90 years) who were referred for duplex US evaluation of the inguinal arterial puncture site 1 day after endovascular procedures. Prior to duplex US, all patients underwent physical examination of the groin. In addition, clinical characteristics and preinterventional laboratory parameters were assessed. Statistical significance was determined by using chi2 tests, the Fischer exact test, and unpaired t tests. RESULTS: Twenty-three pseudoaneurysms were found in 273 patients by using duplex US. Pulsatile groin masses that were detected at physical examination were used to correctly identify all pseudoaneurysms (positive predictive value, 100%; negative predictive value, 100%). Painful pulse palpation had a slightly lower predictive power (positive predictive value, 92% [95% confidence interval: 81%, 100%]; negative predictive value, 100% [95% confidence interval: 100%, 100%]). Other clinical parameters, such as the presence of superficial hematomas, systolic bruits, or nonpulsatile groin masses, had no adequate predictive properties. Interobserver agreement was excellent between observers (97% agreement [95% confidence interval: 92%, 100%]). All patients with pseudoaneurysms had a preprocedural platelet count of less than 200 x 10(9)/L. No subacute complications were observed at the access site in patients with a platelet count of more than 200 x 10(9)/L. CONCLUSION: Physical examination revealed sufficient predictive capability in facilitating the identification of iatrogenic pseudoaneurysms after percutaneous vascular procedures. A platelet count of less than 200 x 10(9)/L was associated with high predictive capability, thereby warranting further assessment in a larger series of patient.

Abstract: BACKGROUND AND PURPOSE: Dental and periodontal disease are potentially involved in the pathogenesis of atherosclerosis. We investigated whether dental and periodontal status is associated with the presence and future progression of carotid stenosis. METHODS: We randomly selected 411 of 1268 participants from the prospective Inflammation and Carotid Artery Risk for Atherosclerosis Study and evaluated dental and periodontal status and oral hygiene at baseline measuring three World Health Organization-validated indices: DMFT (decayed, missing, filled teeth), SLI (Silness-Löe Index), and CPITN (community periodontal index for treatment needs), respectively. The degree of carotid stenosis was measured by duplex ultrasound at baseline and after median 7.5 months (range=6 to 9 months) to identify patients with progressive carotid stenosis. RESULTS: DMFT (P<0.01), SLI (P=0.048), CPITN (P=0.007), and edentulousness (P=0.007) were associated with the baseline degree of carotid stenosis. Atherosclerosis progression was observed in 48 of 411 patients (11.7%). DMFT (adjusted odds ratio [OR]=1.11, 95% CI=1.01 to 1.22, P=0.032) and SLI (adjusted OR=1.77, 95% CI=1.09 to 2.79, P=0.021), but not CPITN (adjusted OR=1.51, 95% CI=0.89 to 2.45, P=0.16) were significant predictors of disease progression, irrespective of traditional cardiovascular risk factors and the baseline degree of stenosis. Edentulous patients had a significantly increased risk for disease progression as compared with patients with teeth (adjusted OR=2.10, 95% CI=1.06 to 4.16, P=0.33). CONCLUSIONS: Dental status, oral hygiene, and particularly tooth loss are associated with the degree of carotid stenosis and predict future progression of the disease.

Abstract: PURPOSE: To prospectively evaluate if high-grade (> or = 80% luminal narrowing) internal carotid artery stenosis is associated with depressive symptoms and if carotid artery stent placement (CAS) potentially improves depressive symptoms. MATERIALS AND METHODS: The study was approved by the local ethics committee, and informed consent was obtained from all subjects. One hundred forty-three patients (91 men, 52 women; interquartile range, 63-76 years) undergoing CAS because of asymptomatic high-grade (> or = 80% luminal narrowing) carotid artery stenosis and 102 control subjects (64 men, 38 women; interquartile range, 63-73 years) with advanced peripheral artery disease and without carotid artery stenosis undergoing lower-limb percutaneous transluminal angioplasty were included. Substantial depressive symptoms (defined as a Beck Depression Inventory score of 10 or higher) were recorded at baseline and at 4 weeks (follow-up) after the percutaneous procedures. The chi2 test, Mann-Whitney U test, McNemar test, Wilcoxon rank sum test, and two-group t test were used to check for statistical significance. RESULTS: A significantly higher prevalence of depressive symptoms was found in patients with carotid artery stenosis than in control subjects with peripheral artery disease at baseline (33.6% vs 16.7%, P = .003). At follow-up, a significant reduction of depressive symptoms was found in patients who underwent CAS (33.6% vs 9.8%, P < .001). The frequency of depressive symptoms remained unaffected in control subjects (16.7% vs 13.0%, P = .1). CONCLUSION: High-grade carotid artery stenosis is associated with depressive symptoms in patients with atherosclerosis. CAS seems to exert beneficial effects on the course of depressive symptoms in these patients.

Abstract: PURPOSE: To investigate the efficacy and safety of a novel hemostatic wound dressing designed for rapid hemostasis at arterial puncture sites. METHODS: Over a 15-month period, 209 consecutive patients were randomized to conventional manual compression (n=105) or the use of the Clo-Sur P.A.D. hemostatic device (n=104) after removal of the sheath. Puncture-related and device-related complications, time to hemostasis, time to ambulation, and patient and physician discomfort were recorded. RESULTS: In 209 patients, 21 (10.0%) puncture-related complications were observed, including 11 (5.3%) pseudoaneurysms, 9 (4.3%) hematomas, and 1 (0.5%) major bleeding complication. There was no significant difference (p=0.36) in complications between the hemostatic device (9/104, 8.7%) and the conventional group (12/105, 11.4%). In the hemostatic device group compared to the conventional group, respectively, the average time to hemostasis (13.6 versus 20.3 minutes; p<0.001), time to ambulation (6.5 versus 17.4 hours, p<0.001), patient discomfort (VAS 2.1 versus 4.7, p<0.001), and physician discomfort (VAS 3.8 versus 5.2, p<0.001) were significantly lower. Twenty (19%) sheath removals in the hemostatic device group were classified as a technical failure of the device. CONCLUSION: The use of this hemostatic wound dressing for arterial access site management after percutaneous vascular procedures significantly reduced the time to hemostasis, enabled early mobilization, and reduced patient discomfort without increasing the risk for complications compared to conventional manual compression. A high rate of technical failures, however, warrants further improvement before routine use can be recommended.

Abstract: OBJECTIVE: Circulating concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, are elevated in conditions associated with increased cardiovascular risk. We investigated whether elevated ADMA concentrations predict major adverse cardiovascular events (MACE) in patients with advanced peripheral artery disease (PAD). METHODS AND RESULTS: We prospectively enrolled 496 of 533 consecutive patients with PAD (median age 70 years, 279 males). ADMA and L-arginine were assessed at baseline by high performance liquid chromatography. The occurrence of MACE (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, carotid revascularization, death) was evaluated during a follow-up of median 19 months (interquartile range 11 to 25). One hundred eighty-two MACE were observed in 141 patients (28%). MACE occurred in 39% of the patients in the highest quartile and 26% of those in the lowest quartile of ADMA (P=0.016, log-rank test for all quartiles). Adjusted hazard ratios for occurrence of MACE for increasing quartiles of ADMA compared with the lowest quartile were 0.87 (95% confidence interval [CI], 0.51 to 1.48), 1.12 (95% CI, 0.62 to 1.90), and 1.70 (95% CI, 1.02 to 2.88), respectively. We observed no association between cardiovascular outcome and L-arginine. CONCLUSIONS: High ADMA plasma concentrations independently predict MACE in patients with advanced PAD. This indicates that ADMA may be a new cardiovascular risk marker in these patients.

Abstract:

Abstract: BACKGROUND: A functional GT dinucleotide length polymorphism in the haem oxygenase-1 (HO-1) gene promoter is thought to be involved in the pathogenesis of cardiovascular disease. Short (< 25) (GT)n repeats are suggested to facilitate enhanced HO-1 up-regulation in response to injury and confer potent anti-inflammatory and antioxidative effects. MATERIALS AND METHODS: We investigated the association between the HO-1 GT-polymorphism and cardiovascular outcome in 472 patients with advanced peripheral artery disease. Cardiovascular risk profile and DNA samples for determination of the HO-1 genotype (carrier vs. noncarrier of a short (GT)n repeat allele) were obtained at baseline, and patients were followed for median 21 months for the occurrence of coronary events (myocardial infarction, percutaneous coronary interventions and coronary artery bypass graft), cerebrovascular events (stroke or carotid revascularization) and all-cause mortality. RESULTS: Coronary events occurred in 48 patients (9%), cerebrovascular events in 40 patients (9%) and 59 patients (13%) died. In total, 173 major adverse cardiovascular events (MACE) occurred in 133 patients (28%). Carriers of the short (GT)n repeat allele had a 0.46-fold reduced adjusted hazard ratio for coronary events (P = 0.016) as compared to noncarriers. No significant difference was found for cerebrovascular events, mortality and overall MACE. CONCLUSION: Apparently, the HO-1 genotype exerts potentially protective effects against coronary adverse events in patients with peripheral artery disease. Homozygous and heterozygous carriers of < 25 (GT)n repeats had lower rates of myocardial infarction, percutaneous coronary interventions and coronary bypass operations compared to patients with longer (GT)n repeats.

Abstract: BACKGROUND: Compelling evidence suggests that inflammation is fundamentally involved in the pathogenesis of atherosclerosis; however, temporal correlation between inflammation and morphological features of atherosclerosis progression has not been demonstrated unequivocally. METHODS AND RESULTS: We prospectively studied 1268 consecutive patients who were initially asymptomatic with respect to carotid artery disease. Patients underwent serial carotid ultrasound investigations at baseline and after a follow-up interval of a median of 7.5 months (range 6 to 9 months), with measurement of carotid flow velocities and categorization of carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed or occluded. High-sensitivity C-reactive protein (hs-CRP) and serum amyloid A (SAA) were measured at baseline and follow-up. Progression of carotid atherosclerosis was found in 103 (8.1%) of 1268 patients. Hs-CRP and SAA, respectively, at baseline (P=0.004 and P=0.014) and follow-up (P<0.001 and P<0.001) and the change from baseline to follow-up (P<0.001 and P<0.001) were significantly associated with progressive atherosclerosis. Adjusted ORs (95% CI) for atherosclerosis progression with increasing quintiles of baseline hs-CRP were 1.65 (0.71 to 3.84), 1.87 (0.8 to 4.37), 3.32 (1.49 to 7.39), and 3.65 (1.65 to 8.08), and with increasing quintiles of baseline SAA, they were 0.86 (0.38 to 1.92), 0.99 (0.49 to 1.99), 1.72 (0.91 to 3.28), and 2.28 (1.24 to 4.20), respectively, compared with the lowest quintiles. CONCLUSIONS: These findings supply evidence for a close temporal correlation between inflammation and morphological features of rapidly progressive carotid atherosclerosis, which suggests that elevation or increase of the inflammatory biomarkers hs-CRP and SAA identifies the presence of active atherosclerotic disease.

Abstract: OBJECTIVE: We hypothesized that higher neutrophil counts are associated with an increased incidence of major adverse cardiovascular events (MACE) in patients with clinically advanced atherosclerosis. METHODS: We prospectively studied 398 patients (233 men; median age, 69 years) with symptomatic peripheral artery disease who were admitted to the inpatient ward of the angiology department of a tertiary care university hospital in a cohort study. Total and differential white blood cell (WBC) counts were obtained, and patients were followed for MACE, defined as myocardial infarction, percutaneous coronary interventions, coronary artery bypass grafting, stroke, carotid revascularization, and death. RESULTS: During a median follow-up of 20 months, 140 MACE occurred in 105 patients (26%). Multivariate Cox proportional hazards analysis was used to assess the association of differential WBC count parameters (in tertiles) with MACE and their interrelation with traditional cardiovascular risk factors and other parameters of inflammation. Patients with neutrophil counts >5.8 G/L (upper tertile) exhibited an increased adjusted risk for all MACE (hazards ratio [HR], 1.83; P = .017), death (HR, 3.39; P = .010), and the composite of myocardial infarction, stroke, and death (HR, 2.20; P = . 012) compared with patients in the lower tertile (<4.4 G/L), independently of traditional cardiovascular risk factors and levels of high-sensitivity C-reactive protein. Only neutrophils, but not eosinophils, basophils, monocytes, lymphocytes, or the total WBC count showed a significant association with cardiovascular outcome. CONCLUSION: In patients with peripheral artery disease, neutrophil counts in the upper tertile (>5.8 G/L) indicate a substantially increased risk for major adverse cardiovascular events, adding to the prognostic information of traditional atherothrombotic risk factors and other parameters of inflammation.

Abstract: BACKGROUND: Fibrinogen is a key factor in the coagulation cascade, it exhibits proinflammatory properties, and it is suggested to play a pivotal role in atherogenesis. We investigated whether fibrinogen predicts future progression of carotid atherosclerosis, analyzing whether fibrinogen levels add to the prognostic information of other inflammatory parameters. METHODS: We prospectively studied 1268 consecutive patients without recent (12 months) symptoms from cerebrovascular disease. Patients underwent serial ultrasound investigations in 6- to 9-month intervals, categorizing carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed, or occluded. Fibrinogen levels were determined at baseline and follow-up. The risk for progressive carotid atherosclerosis according to fibrinogen levels was calculated, adjusting for traditional risk factors and other inflammatory parameters (C-reactive protein and serum amyloid A). RESULTS: Progression of carotid atherosclerosis was found in 117 of 1268 patients (9.2%) after a median of 8 months (range 6 to 18). Adjusted hazard ratios for atherosclerosis progression with increasing quartiles of baseline fibrinogen were 1.83 (P=0.037), 2.09 (P=0.008), and 2.45 (P=0.002), respectively, compared with the lowest quartile. Fibrinogen at follow-up also was associated with progressive disease (P=0.004). However, additionally adjusting for other inflammatory parameters diminished these associations to a nonsignificant level. CONCLUSIONS: Elevated fibrinogen, reflecting the level of inflammatory activity, is associated with progression of carotid atherosclerosis, as it was demonstrated previously for other inflammatory parameters. However, this association seems to be nonspecifically related to the extent of the inflammatory process in atherosclerotic disease rather than to specific properties of fibrinogen.

Abstract: PURPOSE: To report a propensity score-adjusted analysis of the long-term risks for stroke after carotid artery stenting (CAS) compared to medical therapy in patients with asymptomatic high-grade carotid artery stenosis. METHODS: A total of 946 consecutive patients (605 men; median age 73 years) with asymptomatic high-grade carotid artery stenoses (> or =70%) identified in a single center registry were treated either medically (n=525) or with CAS (n=421). A propensity score-adjusted analysis was performed to test the hypothesis that long-term neurological outcome might be better after CAS than after medical treatment, depending on the baseline degree of carotid stenosis and the patient's medical status. Baseline degree of stenosis was classified as 70% to 79% (n=307), 80% to 89% (n=366), and 90% to 99% (n=272) by duplex ultrasound. Surgical risk was estimated by the American Society of Anesthesiologists (ASA) score (I to IV). RESULTS: Stroke-free survival rates at 1, 3, and 5 years were 97%, 93%, and 89% after conservative treatment versus 94%, 93%, and 91% after CAS (p=0.56), respectively. Compared to conservatively treated patients with 70% to 79% stenoses, the adjusted hazard ratios for stroke were 2.36 (p=0.044) for conservatively treated patients with 80% to 89% and 3.17 (p=0.026) for those with 90% to 99% stenoses. For CAS patients with 70% to 79%, 80% to 89%, and 90% to 99% stenoses, the adjusted hazard ratios for stroke were 1.32 (p=0.63), 0.91 (p=0.84), and 0.98 (p=0.98) irrespective of the ASA score, the propensity to undergo CAS, and other potential confounders. Thus, the risk of stroke increased in parallel with the degree of stenosis in conservatively treated patients, but remained unchanged in patients undergoing CAS. CONCLUSIONS: Patients with asymptomatic severe carotid narrowing (> or =80%) might benefit from CAS with respect to stroke-free survival. Randomized controlled trials are needed to confirm these findings.

Abstract: PURPOSE: To report a retrospective cohort study of nitinol stent implantation in patients at high risk for restenosis owing to long-segment (> or =10 cm) femoropopliteal disease. METHODS: Sixty-five consecutive patients with peripheral artery disease underwent long-segment (> or =10 cm) femoropopliteal stent implantation using self-expanding nitinol stents after initial failure of plain balloon angioplasty (i.e., residual stenosis >30% or a flow-limiting dissection). Patients were followed for first occurrence of in-stent restenosis, defined as a >50% lumen diameter reduction by color-coded duplex sonography, with angiographic confirmation. RESULTS: Cumulative median length of the stented segments was 16 cm (interquartile range [IQR] 12-25, absolute range 10-40) using up to 5 overlapping stents. During the median 8-month follow-up (IQR 6-11), no early thrombotic reocclusions occurred within 30 days, but 26 (40%) patients developed an in-stent restenosis. Cumulative freedom from restenosis at 6 and 12 months was 79% and 54% overall, respectively; at the same time periods, the rates were 84% and 71% in nondiabetic patients (n=41) versus 68% and 22% in diabetics (n=24) (adjusted hazard ratio 3.8, p=0.01). Cumulative stent length and number of implanted stents were not associated with restenosis. CONCLUSION: Midterm restenosis after long-segment femoropopliteal stenting using self-expanding nitinol stents remains a major problem, particularly in patients with diabetes mellitus. The midterm results in nondiabetics are encouraging.

Abstract: PURPOSE: To report procedure-related complications and neurological adverse events of unprotected over-the-wire (OTW) and protected rapid exchange (RX) carotid artery stenting (CAS) in a single-center patient series during an 8-year period. METHODS: Between 1997 and 2004, 651 consecutive patients (445 men; median age 72 years, interquartile range 64-77) were enrolled in a registry database of carotid stent procedures; from 1997 to 2002, 471 patients underwent unprotected CAS using an OTW technique, while the other 180 patients were treated with protected CAS using RX monorail systems from 2003 to 2004. Technical success and complications (neurological, hemodynamic instability, and access site) up to 30 days post intervention were analyzed. RESULTS: Technical success improved from 95% with unprotected OTW CAS to 99% with protected RX CAS (p=0.025). Procedure-related complications occurred in 86 (18.3%) of 471 unprotected OTW CAS versus 18 (10.0%) of 180 protected RX CAS procedures (p=0.010). Transient ischemic attacks (3.2% versus 2.8%), minor stroke (1.7% versus 0.6%), and major stroke (2.1% versus 0.6%) showed a trend toward a difference between unprotected OTW and protected RX CAS (p=0.076); combined 30-day stroke/death rates were 3.8% for OTW versus 1.2% for RX CAS (p=0.073). During the 8-year period from 1997 to 2004, the annual rates of procedure-related complications (p=0.002), neurological events (p=0.040), and stroke and death (p=0.14) markedly decreased. CONCLUSIONS: Carotid stenting became substantially safer in the era of protected RX technology. In addition to a reduction in neurological complications, which may be due to cerebral protection devices, the improved technical success and reduced non-neurological procedure-related complications are likely due to recent technical advances unrelated to cerebral protection.

Abstract: BACKGROUND AND PURPOSE: There is considerable variability in the antiplatelet effects of the thienopyridine agent "clopidogrel." We tested for an association of gene sequence variations in P2Y12 and occurrence of neurological adverse events in patients with symptomatic peripheral artery disease (PAD) during clopidogrel treatment. METHODS: We studied 137 patients undergoing antiplatelet therapy with clopidogrel and 336 patients with aspirin for the occurrence of neurological events (ischemic stroke and/or carotid revascularization). Prevalence of 2 previously described exonic polymorphisms of the P2Y12 gene, 34C>T and 52G>T, was determined by polymerase chain reaction. RESULTS: Genotype frequencies for mutated, heterozygous, and wild-type alleles for the 34C>T and the 52G>T polymorphisms were 9% (n=40), 44% (n=210), and 47% (n=223), and 4% (n=17), 27% (n=127), and 70% (n=329), respectively. During the median follow-up of 21 months, neurological events occurred in 8% of patients. In patients with aspirin therapy, neither polymorphism was associated with neurological events. However, in clopidogrel patients, carriers of at least one 34T allele had a 4.02-fold increased adjusted risk for neurological events compared with carriers of only 34C alleles (95% confidence interval, 1.08 to 14.9). Neither polymorphism was associated with all-cause mortality. CONCLUSIONS: In PAD patients, clopidogrel response variability exists, which may result in increased risk for cerebrovascular events. Sequence alterations of the target receptor gene represent one possible mechanism for clopidogrel failure. Whether identification of the 34C>T polymorphism as a contributor to this process could serve as risk stratification tool, an indicator for higher clopidogrel doses, or the use of alternate agents warrants further investigation.

Abstract: PURPOSE: Endogenous and exogenous insulin is suggested to stimulate hypertrophic wound-healing responses and therefore may promote neointimal hyperplasia and restenosis after balloon angioplasty. The ratio of C-peptide to insulin reflects endogenous insulin secretion. In diabetic patients with insulin substitution, lower ratios display a higher proportion of exogenous insulin. The association and interaction of insulin and C-peptide with restenosis after percutaneous transluminal angioplasty (PTA) was investigated in type II diabetic and nondiabetic patients. MATERIALS AND METHODS: The study group included 76 patients (median age, 68 years; interquartile range [IQR], 58-74 years; 55 men [72%]; 31 patients [41%] with type II diabetes) with intermittent claudication (n = 49; 64%) or critical limb ischemia (n = 27; 36%) who underwent primary successful femoral PTA. C-peptide and insulin levels were measured at baseline, and patients were followed to determine restenosis (> or =50%) at 12 months by color-coded duplex sonography. RESULTS: Restenosis was found in 34 patients (45%) at 12 months. Patients with restenosis had higher insulin levels (median, 21.3 microU/mL IQR, 11.3-35.5 microU/mL) and a lower C-peptide/insulin ratio (median, 16; IQR, 10-21) compared with patients without restenosis (median insulin level, 11.6 microU/mL; IQR, 9.1-22.0 microU/mL [P = .008]; median ratio, 19 [IQR, 17-25], P = .039). In nondiabetic patients, insulin levels were significantly associated with restenosis (P = .046), whereas the ratio of C-peptide to insulin showed no association with restenosis. In patients with type II diabetes (n = 31; 41%), in contrast, the C-peptide/insulin ratio was associated with restenosis (P = .047), whereas insulin levels showed no significant association with restenosis (P = .14). CONCLUSIONS: Insulin levels and the C-peptide/insulin ratio were associated with restenosis after femoral PTA. Exogenous and endogenous insulin may play a role in the pathogenesis of recurrent lumen loss after balloon angioplasty.

Abstract: PURPOSE: To determine and compare the rates of in-stent restenosis, late clinical deterioration, and stent fractures in nitinol stents versus Wallstents implanted for suboptimal angioplasty in the superficial femoral artery (SFA). METHODS: Interrogation of an angioplasty database identified 286 consecutive patients (178 men; mean age 67+/-10 years, range 44-87) with severe claudication (n=254) or critical limb ischemia (n=32) who had stents implanted after suboptimal angioplasty over a 5-year period. Wallstents with a mean stented lesion length of 107+/-71 mm were implanted in 116 patients, while nitinol stents were used in 170 patients: 45 SMART stents (mean stented lesion length 139+/-88 mm) and 125 Dynalink/Absolute stents (mean stented lesion length 125+/-84 mm). Patients were followed for in-stent restenosis (>50%) by duplex ultrasound, clinical deterioration by at least 1 Fontaine stage compared to baseline, and stent fractures by biplanar radiography. RESULTS: In-stent restenosis rates at 1, 2, and 3 years were 46%, 66%, and 72% for Wallstents compared to 20%, 36%, and 53% for nitinol stents (p<0.001), respectively, without significant difference between the 2 nitinol stent groups (p=0.59). Clinical deterioration at 1, 2, and 3 years was found in 10%, 15%, and 18% with Wallstents versus 4%, 5%, and 5% with nitinol stents (p=0.014), respectively, without difference between the 2 nitinol stent groups (p=0.47). Fracture rates were 19% for Wallstents after a mean 43+/-24 months, 28% for SMART stents after mean 32+/-16 months, and 2% for Dynalink/Absolute stents after a mean 15+/-9 months. CONCLUSIONS: Intermediate-term in-stent restenosis remains a major problem even with current nitinol stent technology; however, clinical deterioration seems no matter of serious concern with SMART and Dynalink/Absolute stents. Stent fractures may be lower with Dynalink/Absolute stents, but randomized head-to-head comparisons are needed to validate these data.

Abstract: PURPOSE: To compare neurologic outcome after elective internal carotid artery (ICA) stents have been placed in patients with and in patients without contralateral ICA obstructions. MATERIALS AND METHODS: This study included 471 consecutive patients from a registry database who underwent elective ICA stent placement without cerebral protection for high-grade (greater than 70% stenosis of the ICA, according to the North American Symptomatic Carotid Endarterectomy Trial) symptomatic (n = 147) or asymptomatic (n = 324) ICA stenosis. Contralateral carotid arteries were investigated with angiography. Patients with and patients without contralateral high-grade stenosis (70%-99% stenosis, according to the North American Symptomatic Carotid Endarterectomy Trial) or occlusion were compared with respect to 30-day neurologic outcome by using the chi2 test and multivariate logistic regression analysis. RESULTS: Neurologic events were observed in 33 patients (7%) with 15 transient ischemic attacks, eight minor strokes, and 10 major strokes that led to death in two patients (combined stroke and death rate, 4%). Eighty-eight patients (19%) with contralateral high-grade ICA stenosis and 43 patients (9%) with contralateral ICA occlusion exhibited a similar rate of postintervention combined neurologic events (n = 9, 7%) compared with patients without contralateral high-grade ICA stenosis or occlusion (n = 24, 7%) (P =.94). No differences were observed between symptomatic and asymptomatic patients. Combined stroke and death rates were also comparable between symptomatic (four of 131, 3%) and asymptomatic (14 of 340, 4%) patients (P =.59). Of all variables tested, multivariate analysis did not detect any predictor for peri- or postinterventional neurologic events. CONCLUSION: Contralateral high-grade ICA stenosis or occlusion was not associated with an increased risk for neurologic events after elective ICA stent placement.

Abstract: Low serum albumin is a powerful predictor of cardiovascular adverse events in healthy subjects and patients with subclinical, atherosclerosis. We investigated the association between serum albumin, traditional cardiovascular risk factors, markers of inflammation and cardiovascular outcome in 515 patients with advanced atherosclerosis and severe peripheral artery disease. Cardiovascular risk profile, serum albumin, serum amyloid A (SAA) and fibrinogen were obtained at baseline, and patients were followed for median 21 months (interquartile range 12 to 25) for the occurrence of major adverse cardiac events (MACE: myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, and death). We observed 135 MACE in 109 patients (21%). Cumulative event-free survival rates at 6, 12, and 24 months were 95%, 91%, and 80%, respectively. Low albumin predicted MACE independently of SAA and fibrinogen. Adjusted hazard ratios for the occurrence of MACE, any death, and the composite of death and MI according to increasing quartiles of albumin were 2.40, 1.14 and 1.09 (p<0.001), 2.94, 1.34 and 1.11 (p=0.003) and 3.63, 1.86 and 1.29 (p<0.001), respectively, as compared to the highest quartile. Considering albumin in conjunction with traditional cardiovascular risk factors (smoking, hyperlipidemia, hypertension and diabetes), we found that low albumin predicted MACE only in patients with a low risk profile (less than 3 risk factors) (p<0.001), whereas low albumin was not associated with MACE in patients with three or more risk factors (p=0.66). We conclude that low serum albumin is associated with cardiovascular outcome of patients with advanced atherosclerosis adding to the prognostic information of other inflammatory markers, and may be particularly useful for risk prediction in patients with few traditional risk factors.

Abstract: OBJECTIVES: We investigated the association of the heme oxygenase-1 (HO-1) promoter genotype with the inflammatory response and restenosis after balloon angioplasty. BACKGROUND: Heme oxygenase-1, which is induced by balloon angioplasty, can inhibit neointima formation and vascular remodeling. A dinucleotide repeat in the HO-1 gene promoter shows a length polymorphism that modulates HO-1 gene transcription. Short (<25 guanosine thymidine [GT]) repeats are associated with a 10-fold greater up-regulation of HO-1 than are longer repeats. METHODS: We studied 381 consecutive patients who underwent femoropopliteal balloon angioplasty (n = 210) and comparison groups with femoropopliteal stenting (n = 68) and lower limb angiography (n = 103). C-reactive protein (CRP) was measured at baseline, 24, and 48 h. We evaluated patency at six months by duplex sonography and assessed the association of the length of GT repeats in the HO-1 gene promoter with postintervention CRP and restenosis. RESULTS: Restenosis within six months was found in 74 patients (35%) after balloon angioplasty and in 21 patients (31%) after stenting. After balloon angioplasty, carriers of the short length (<25 GT) dinucleotide repeats had a lower postintervention CRP at 24 h (p = 0.009) and 48 h (p < 0.001) and a reduced risk for restenosis (adjusted relative risk 0.43, 95% confidence interval: 0.24 to 0.71, p < 0.001) compared with patients with longer alleles. After stenting or angiography, we found no association between the HO-1 genotype with CRP or restenosis. CONCLUSIONS: The HO-1 promoter genotype that controls the degree of HO-1 up-regulation in response to stress stimuli is associated with the postintervention inflammatory response and the restenosis risk after balloon angioplasty.

Abstract: PURPOSE: To investigate whether endovascular brachytherapy diminishes vascular inflammation in response to femoropopliteal percutaneous transluminal angioplasty (PTA) or stent implantation in two double-blind randomized-controlled trials. MATERIALS AND METHODS: Forty-seven consecutive patients from two double-blind randomized-controlled trials were studied. Patients either underwent femoropopliteal PTA with endovascular gamma irradiation (n = 8) or placebo irradiation (n = 7) or underwent PTA and stent implantation with brachytherapy (n = 15) or placebo irradiation (n = 17). High-sensitivity C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen levels were measured at baseline and 8, 24, and 48 hours after the intervention. The change of acute phase parameters from baseline to 48 hours after intervention indicated the extent of the inflammatory response and was compared between patients undergoing brachytherapy and those undergoing placebo irradiation. Fisher exact test was used for comparison of categorical data, and nonparametric statistical methods were applied for analysis of continuous data (Mann-Whitney U tests for unpaired data and Friedman analysis for repetitive measurements). RESULTS: Median patient age was 70 years (interquartile range, 56-74 years); 33 (70%) patients were men and 14 (30%) were women. Clinical characteristics and baseline values of acute phase parameters were similar between groups. A statistically significant increase in CRP, SAA, and fibrinogen values was observed after PTA and stent implantation, both in the patients who underwent brachytherapy and in those who underwent placebo irradiation. Compared with placebo irradiation, however, brachytherapy did not significantly reduce any acute phase parameter from baseline to 8, 24, or 48 hours after the intervention (P >.05 for all comparisons). CONCLUSION: Endovascular brachytherapy did not diminish early vascular inflammation in response to PTA or stent implantation and even induced a trend toward an increased inflammatory response.

Abstract: BACKGROUND AND PURPOSE: Magnesium (Mg) deficiency is thought to be a risk factor for cerebrovascular atherosclerosis and complications. We investigated the prognostic impact of Mg serum levels with respect to the occurrence of neurological events in patients with advanced atherosclerosis. METHODS: We prospectively studied 323 patients with symptomatic peripheral artery disease and intermittent claudication (197 men; median age, 68 years). Serum Mg was determined, and patients were followed for a median of 20 months (interquartile range, 12 to 25 months) for the occurrence of neurological events, defined as ischemic stroke and/or carotid revascularization (carotid endarterectomy or carotid stenting). Multivariate Cox proportional hazards analysis was applied to assess the association of serum Mg (in tertiles) and neurological events. RESULTS: Neurological events occurred in 35 patients (11%) (15 patients with stroke, 13 with carotid revascularization, and 7 with stroke and subsequent revascularization). Compared with patients in the highest tertile of Mg serum levels (>0.84 mmol/L), patients with Mg serum values <0.76 mmol/L (lowest tertile) exhibited a 3.29-fold increased adjusted risk (95% CI, 1.34 to 7.90; P=0.009) for neurological events, but patients with Mg serum values of 0.76 mmol/L to 0.84 mmol/L (middle tertile) had no increased risk (adjusted hazard ratio, 1.10; 95% CI, 0.35 to 3.33; P=0.88). Mg serum levels were not associated with all-cause mortality (P=0.87) or coronary events (P=0.67) during follow-up. CONCLUSIONS: Low Mg serum levels indicate an increased risk for neurological events in patients with symptomatic peripheral artery disease, favoring Mg substitution therapy in those patients with advanced atherosclerosis.

Abstract: Perivascular inflammation plays a key role in the development of restenosis after percutaneous transluminal angioplasty (PTA). The adherence of leucocytes to the activated endothelium, an essential feature in the restenotic process, is mediated by the cellular adhesion molecule E-Selectin. A DNA polymorphism in the regulator region of E-Selectin at codon 561 (Ser128Arg) is suggested to modulate the molecule's physiological effects. Therefore, we investigated the association between the E-Selectin Ser128Arg genotype, E-Selectin plasma levels and restenosis after femoropopliteal PTA.We prospectively studied 175 consecutive patients with peripheral artery disease and intermittent claudication (n=126) or critical limb ischemia (n=49) who underwent primary successful femoropopliteal balloon angioplasty. E-Selectin Ser128Arg genotype and base-line E-Selectin plasma levels were determined and patients were followed up for median 12 months (IQR 11 to 14, total range 6 to 24) for the occurrence of postangioplasty restenosis(>/=50%). E-Selectin plasma levels in homozygous Arg128Arg and heterozygous Ser128Arg patients were significantly higher compared to wildtype Ser128Ser patients (p=0.041). Patency rates for wildtype Ser128Ser, heterozygous Ser128Arg and homozygous Ser128Ser patients were 57%, 44% and 50% at 6 months, and 46%, 40% and 17%, at 12 months, respectively (Log Rank p=0.31). Patency rates for increasing tertiles of E-Selectin were 61%, 58% and 37% at 6 months, and 54%, 45% and 30% at 12 months, respectively (Log Rank p=0.020). Patients with an E-Selectin plasma level above 44.9 mg/dL (third tertile) had an 1.9-fold increased adjusted risk for restenosis (95% CI 1.09 to 3.30). E-Selectin plasma levels are modulated by the E-Selectin Ser128Arg genotype, and predict the risk for restenosis after PTA in patients with PAD. A direct association of the Ser128Arg polymorphism with late postangioplasty failure could not be demonstrated.

Abstract: Aortoiliac disease can be either treated with surgery-endarterectomy for localized aortic disease or with bypass graft placement for more extensive aortoiliac disease--or with percutaneous transluminal angioplasty (PTA), which has become an established method. Long term results of surgery are well documented in literature, but long term results of distal aortic PTA are scarce, furthermore angiographic follow-up is very uncommon. We report about a patient with isolated aorta abdominalis stenosis due to atherosclerotic disease who underwent PTA in 1982 and had an angiographic follow-up four and twenty years later, thus we demonstrate that patency can be obtained even after twenty years.

Abstract: PURPOSE: To investigate whether there is an association between a functional polymorphism in the interleukin (IL)-6 gene promoter (-174)G/C and restenosis after percutaneous transluminal angioplasty (PTA) of the femoropopliteal artery. MATERIALS AND METHODS: A total of 281 patients underwent PTA of the femoropopliteal artery during the study period; 23 (8%) patients had to be excluded due to missing genetic data. We studied 258 patients with intermittent claudication (n = 174) or critical limb ischemia (n = 84). The IL-6 promoter genotype was determined from venous blood samples before intervention by using a mutagenically separated polymerase chain reaction, and patients were followed up for 6 months with duplex ultrasonography for the occurrence of restenosis (> or =50%) after angioplasty. Multivariate Cox proportional hazards analysis was performed to assess the association between the IL-6 promoter genotype and restenosis, with adjustment for possible confounders such as atherosclerotic risk factors and angiographic covariates. RESULTS: The 6-month restenosis rate was 26% (23 of 90) in patients with the (-174)GG genotype, 28% (33 of 117) with the (-174)GC genotype, and 43% (22 of 51) with the (-174)CC genotype (P =.044). Homozygous carriers of the (-174)C allele ([-174]CC) exhibited a 2.42-fold increased adjusted risk for restenosis (95% CI: 1.28, 4.58; P =.007) compared with homozygous (-174)G allele carriers ([-174]GG). Heterozygous carriers ([-174]GC) had no significantly increased restenosis risk (hazard ratio, 1.37; 95% CI: 0.84, 2.22; P =.21). CONCLUSION: The IL-6 promoter polymorphism (-174)G/C seems to influence the occurrence of restenosis after PTA. Homozygous carriers of the (-174)C allele have an increased rate of intermediate-term restenosis.

Abstract: PURPOSE: To evaluate, in a propensity score-adjusted analysis, the intermediate-term primary patency rates associated with nitinol versus stainless steel self-expanding stent placement for treatment of atherosclerotic lesions in femoropopliteal arteries. MATERIALS AND METHODS: The authors analyzed the clinical and imaging data of 175 consecutive patients with peripheral artery disease and either intermittent claudication (n = 150) or critical limb ischemia (n = 25) who underwent femoropopliteal artery implantation of nitinol (n = 104) or stainless steel (n = 123) stents in a nonrandomized setting. The stents were placed owing to either significant residual stenosis (ie, >30% lumen diameter reduction) or flow-limiting dissection after initial balloon angioplasty of the femoropopliteal artery. Patients were followed up for a median period of 9 months (mean, 13 months; range, 6-66 months) for the detection of a first in-stent restenosis, defined as a greater than 50% lumen diameter reduction that was seen at color-coded duplex ultrasonography and confirmed at angiography. RESULTS: Cumulative patency rates at 6, 12, and 24 months were 85%, 75%, and 69%, respectively, after nitinol stent placement versus 78%, 54%, and 34%, respectively, after stainless steel stent placement (P =.008, log-rank test). There were no statistically significant differences in associated patency among the three different nitinol stents used (P =.72, log-rank test). Multivariate Cox proportional hazard analysis, in which the effect of propensity to receive a nitinol stent was considered, revealed a significantly reduced risk of restenosis with the nitinol stents compared with the risk of restenosis with the stainless steel stents (adjusted hazard ratio, 0.44; 95% confidence interval: 0.22, 0.85; P =.014). CONCLUSION: Nitinol stents are associated with significantly improved primary patency rates in femoropopliteal arteries compared with stainless steel stents. Randomized controlled trials are needed to confirm these results.

Abstract: High heparin cofactor II (HCII) activity has recently been described to protect from coronary instent restenosis, presumably by inactivating thrombin in injured arteries. In this study, we investigated the association of HCII activity and restenosis after femoropopliteal stenting. We studied 63 consecutive patients with peripheral artery disease who underwent femoropopliteal stent implantation after initial failure of plain balloon angioplasty due to a significant residual stenosis (>30% lumen diameter reduction) or a flow limiting dissection. HCII activity was measured before stenting and patients were followed for median 10 months (interquartile range 6 to 17) for the occurrence of a first instent restenosis, defined as a >50% lumen diameter reduction by color coded duplex sonography and confirmed by angiography. Cumulative freedom from restenosis at 6 and 12 months in patients with lower HCII activity (100%, lower tertile, n=20) was 84% and 35% as compared to 93% and 72% in patients with high HCII activity (>100%, middle and upper tertile, n=43; p=0.024 by Log Rank test). Adjusting for the material of the implanted stents (nitinol vs. Wallstents), patients with a high HCII activity had a 0.39-fold reduced risk for instent restenosis (95% CI 0.17 to 0.90, p=0.028), additional adjustment for diabetes mellitus, poor run-off, critical limb ischemia and cumulative length of the stented segment did not alter the observed effect. Higher activity of heparin cofactor II may exert a protective effect against instent restenosis also in the femoropopliteal vessel area, confirming a prior observation after coronary stenting.

Abstract: PURPOSE: To compare 13 previously published sets of duplex ultrasonographic (US) criteria with the US criteria used at the authors' institution in terms of agreement with carotid artery angiographic results. MATERIALS AND METHODS: The authors studied 1,006 carotid arteries in 503 patients at duplex US and angiography. The degree of stenosis was determined by using duplex flow US velocities and applying 13 previously published sets of criteria and the criteria used at the authors' institution. Two independent observers evaluated the angiograms according to North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. kappa statistics, sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and generalized linear mixed regression models were used to assess agreement between duplex US and angiographic findings. RESULTS: Stenoses of 0%-29%, 30%-49%, 50%-69%, 70%-99%, and 100% could be differentiated with 73% overall agreement between duplex US and angiographic findings according to flow velocity criteria (kappa = 0.57; 95% confidence interval [CI]: 0.54, 0.60); however, with duplex US, the angiographic degree of stenosis tended to be overestimated. In the differentiation of stenoses of less than 70%, only 45% agreement (kappa = 0.26; 95% CI: 0.23, 0.29) was observed, whereas in the differentiation of high-grade (> or =70%) stenoses, 96% agreement was observed (kappa = 0.85; 95% CI: 0.83, 0.87). The PPV and NPV for the identification of 70%-99% angiographic stenosis were 69% and 98%, respectively, with use of the most sensitive duplex US criteria. CONCLUSION: Duplex US is an excellent examination to screen for high-grade carotid artery stenosis; however, it tends to lead to an overestimation of the degree of stenosis. Exclusion of 70%-99% angiographic stenosis can be achieved with a sensitivity of up to 98%.

Abstract: PURPOSE: To investigate whether smoking has an effect on recurrent lumen narrowing after percutaneous transluminal angioplasty (PTA) or stent placement in lower-limb arteries. MATERIALS AND METHODS: A total of 650 patients (median age, 70 years; 389 men) with peripheral artery disease who underwent iliac artery PTA (n = 95), iliac artery stent placement (n = 83), femoropopliteal PTA (n = 406), or femoropopliteal stent placement (n = 66) were selected from a prospective database. Patients were categorized according to their preintervention smoking habits as nonsmokers (n = 352), light smokers (one to nine cigarettes daily) (n = 54), habitual smokers (10-20 cigarettes daily) (n = 82), or heavy smokers (>20 cigarettes daily) (n = 162). Multivariate Cox proportional hazards analysis was used to determine whether there was an association between smoking habits and restenosis (> or =50%) in the treated vessel segment within 1 year after treatment. RESULTS: Cumulative restenosis rates at 6 and 12 months according to patients' smoking habits were 99 and 190 nonsmokers, 18 and 22 light smokers, 16 and 29 habitual smokers, and 26 and 47 heavy smokers, respectively (P <.001). Adjusted hazard ratios for restenosis in smokers compared with nonsmokers were 1.51 (95% CI: 0.92, 2.50) for light smokers, 0.49 (95% CI: 0.28, 0.87) for habitual smokers, and 0.46 (95% CI: 0.30, 0.71) for heavy smokers, indicating a reduced restenosis risk in patients who smoked 10 or more cigarettes daily. These patients had reduced restenosis rates after either iliac (P =.011) or femoropopliteal intervention (P =.009). However, endovascular treatment at a younger age, coronary artery disease, and history of myocardial or cerebrovascular infarction were more frequently found in smokers. CONCLUSION: Smoking 10 or more cigarettes daily is associated with a reduced rate of intermediate-term restenosis after lower-limb endovascular interventions.

Abstract: AIMS: We sought to examine the interrelationship between statin use, inflammation, and outcome of high-risk patients with advanced atherosclerosis. METHODS AND RESULTS: We prospectively studied 515 patients with severe peripheral artery disease (median age 70 years, 296 males). The cardiovascular risk profile and laboratory parameters of inflammation (high-sensitivity C-reactive protein [hs-CRP], serum amyloid A [SAA], fibrinogen, serum albumin, neutrophil counts) were obtained, and patients were followed for a median of 21 months (interquartile range 12-25) for the occurrence of myocardial infarction (MI) and death. We observed 19 MIs (5 fatal and 14 nonfatal) and 65 deaths. Cumulative survival and event-free survival rates (freedom from death and MI) at 6, 12, and 24 months were 97%, 95%, and 89%, and 96%, 93% and 87%, respectively. Patients receiving statin therapy (n=269, 52%) had a lower level of inflammation (hs-CRP p<0.001, SAA p=0.001, fibrinogen p=0.007, albumin p<0.001, neutrophils p=0.049) and better survival (adjusted hazard ratio [HR] 0.52, p=0.022) and event-free survival rates (adjusted HR 0.48, p=0.004) than patients not treated with statins. However, patients with low inflammatory activity (hs-CRP < or =0.42 mg/dl) had no significant benefit from statin therapy (p=0.74 for survival; p=0.83 for event-free survival), whereas in patients with high hs-CRP (>0.42 mg/dl) statin therapy was associated with a significantly reduced risk for mortality (adjusted HR 0.58, p=0.046) and the composite of myocardial infarction and death (adjusted HR 0.46, p=0.016). CONCLUSION: Statin therapy is associated with a substantially improved intermediate-term survival of patients with severe peripheral artery disease and a high inflammatory activity, whereas in patients with low hs-CRP no survival benefit was observed.

Abstract: BACKGROUND: Prostanoids are in widespread use for the treatment of critical limb ischemia and are suggested to improve arterial compliance. However, dose- and time-dependency of these drug effects are indeterminate. We investigated the influence of intravenous application of prostanoids on arterial compliance parameters in patients with critical limb ischemia due to peripheral artery disease (PAD). PATIENTS AND METHODS: We included 82 consecutive patients with PAD Fontaine stage III and IV in a patient-blinded, randomized controlled trial. Patients were randomly assigned to either single dose intravenous treatment with 40 microg (n = 29) or 60 microg (n = 27) of Alprostadil (PGE1) in 250 ml 0.9% saline over 2 hours, or 250 ml 0.9% saline solution as a placebo group (n = 26). Large and small artery compliance was measured by peripheral pulse contour analysis at baseline, at one hour during intravenous infusion of Alprostadil, immediately after and 24 hours after the end of the infusion. For study purposes the patients received Alprostadil only once during the observation period of 2 days. RESULTS: Large artery compliance, blood pressure, heart rate and cardiac output were unaffected by PGE1 administration irrespectively of drug-dosage or time interval. Small artery compliance increased at 1 hour during intravenous application of Alprostadil (40 microg Alprostadil p = 0.001; 60 microg Alprostadil p < 0.0001) compared to placebo and increased median +47% (IQR +5% to +100%) after administration of 40 microg Alprostadil and median +32% (IQR -11% to +88%) after 60 microg Alprostadil (p = 0.5). Immediately after the end of Alprostadil infusion small artery compliance decreased to baseline levels. CONCLUSIONS: Prostaglandin E1 causes a significant improvement of small artery compliance during the time of intravenous application. However, this effect rapidly diminishes after the end of administration and no dose-dependency between 40 microg and 60 microg Alprostadil is observed.

Abstract: BACKGROUND: Patients with renal insufficiency tend to suffer from advanced atherosclerosis and exhibit a reduced life expectancy. We investigated the association of renal impairment, traditional cardiovascular risk factors and all-cause mortality in patients with symptomatic peripheral artery disease (PAD). METHODS: We studied 515 patients with advanced PAD (intermittent claudication, n = 410; critical ischemia, n = 105). Cardiovascular risk profile and calculated glomerular filtration rate (GFR) were obtained at baseline and patients were followed for median 21 months (interquartile range 12 to 25) for mortality. RESULTS: Sixty-five patients (13%) died. Cumulative survival rates at 6, 12, and 24 months were 97%, 95%, and 89%, respectively. Adjusted hazard ratios for mortality according to decreasing quartiles of GFR were 1.2, 2.5, and 5.9 compared to the highest quartile (P < 0.001). The association between renal impairment and mortality was independent of diabetes and hypertension, suggesting that decreased GFR adds to the prognostic value of traditional cardiovascular risk factors. CONCLUSION: Renal impairment is associated with an increased risk for mortality in patients with advanced peripheral artery disease, irrespective of the coincidence of arterial hypertension and diabetes mellitus. This suggests that impaired renal function exerts an unfavorable effect on patient's outcome, independently of these cardiovascular and renal risk factors.

Abstract: The interleukin-1 system is fundamentally involved in the pathogenesis of restenosis after percutaneous transluminal angioplasty (PTA). In order to further define the clinical impact of genetic variation in this potent proinflammatory pathway we investigated the joint effects of two single nucleotide polymorphisms in the interleukin-1 beta gene [IL-1B(-511) and IL-1B(+3954)] and a variable number tandem repeat polymorphism in intron 2 of the interleukin 1 receptor antagonist gene (IL-1RN VNTR) on postintervention inflammation and occurrence of restenosis in 183 consecutive patients who underwent successful femoropopliteal PTA. C-reactive protein (CRP) and serum amyloid A (SAA) were determined pre- and 48 hours postintervention. Patients were followed up to 12 months for the occurrence of postangioplasty restenosis (> or = 50%). When analyzed separately, none of the polymorphisms was associated either with inflammation or restenosis. However, when the IL-1B (-511) and the IL-1RN VNTR genotypes were combined, a highly significant relationship was observed: Non-carriers of the two repeat allele of the IL-1RN VNTR (IL-1RN*2) who were heterozygous and homozygous for the IL-1B (-511)T allele exhibited a gradually increased inflammatory response and a higher restenosis risk. In contrast, carriers of the IL-1RN*2 and the IL-1B (-511)T allele showed a significantly better outcome. This remarkable gene dose-dependent association emphasizes the advantage of considering combinations of genetic markers rather that isolated polymorphisms in the analysis of multifactorial vascular disease.

Abstract: BACKGROUND: C-reactive protein (CRP) and glycohemoglobin (HbA1c) are established risk factors for the development of cardiovascular disease. We investigated the joint effects of these parameters on cardiovascular outcome of patients with advanced atherosclerosis. METHODS AND RESULTS: We studied 454 patients with advanced atherosclerosis (median age, 69 years; 264 male). Cardiovascular risk profile, high-sensitivity CRP (hs-CRP), and HbA1c were obtained at baseline, and patients were followed for a median of 21 months (interquartile range, 13 to 26) for the occurrence of major adverse cardiovascular events (MACE) (myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, carotid revascularization, stroke, and death). We observed 166 MACE in 128 patients (28%). Cumulative event-free survival rates at 6, 12, and 24 months were 91%, 85%, and 73%, respectively. Adjusted hazard ratios for the occurrence of MACE according to increasing quartiles of hs-CRP and HbA1c were 1.35 (P=0.31), 1.90 (P=0.026) and 2.13 (P=0.007), and 1.40 (P=0.26), 1.81 (P=0.059), and 2.36 (P=0.023), respectively, compared with the lowest quartiles. Considering both parameters jointly, we found that patients with hs-CRP >0.44 mg/dL and HbA1c >6.2% (upper quartiles) were at highest risk for MACE, with each parameter adding to the prognostic information of the other. CONCLUSIONS: Inflammation, indicated by hs-CRP, and hyperglycemia, indicated by HbA1c, jointly contribute to the cardiovascular risk of patients with advanced atherosclerosis. Patients with both hs-CRP and HbA1c in the upper quartiles (>0.44 mg/dL and >6.2%, respectively) are at particularly high risk for poor cardiovascular outcome.

Abstract: PURPOSE: To determine the prognostic importance of periintervention serum levels of acute-phase reactants in 6-month restenosis after stent implantation in the carotid artery. MATERIALS AND METHODS: One hundred eight consecutive patients with 70% or greater stenosis of the internal carotid artery (ICA) according to the North American Symptomatic Carotid Endarterectomy Trial criteria underwent successful stent implantation in the ICA in a prospective cohort study. Six-month patency was evaluated at color-coded duplex ultrasonography. The association between in-stent restenosis (> or =50%, North American Symptomatic Carotid Endarterectomy Trial criterion) and C-reactive protein (CRP) and serum amyloid A levels at baseline and at 24 and 48 hours after intervention was assessed. RESULTS: Restenosis was found in 15 (14%) patients within 6 months. CRP level at 48 hours, exemplary for the postintervention acute-phase response, was significantly (P =.01) associated with 6-month restenosis by using multiple logistic regression analysis. Recurrent stenosis after prior stent implantation in the carotid artery (odds ratio, 9.2; 95% CI: 1.6, 53.2; P =.01) and residual stenosis of 10%-30% after stent implantation (odds ratio, 9.7; 95% CI: 1.6, 59.3; P =.01) were independent clinical predictors of restenosis. CONCLUSION: Extent of vascular inflammatory response after stent implantation in the carotid artery measured with acute-phase reactants is associated with 6-month patency. Recurrent stenosis after prior stent implantation and initial suboptimal technical result seem to be clinically relevant predictors of postangioplasty outcome.

Abstract: PURPOSE: To determine the association between pre- and postintervention serum C-reactive protein (CRP) levels and 6-month restenosis after endovascular treatment of atherosclerotic lesions in arteries below the knee. MATERIALS AND METHODS: Eighty-nine patients with peripheral arterial disease underwent primary successful percutaneous transluminal angioplasty (PTA) of the distal popliteal, anterior tibial, posterior tibial, and fibular arteries. Six-month patency was evaluated with the ankle brachial index (ABI) and color-coded duplex ultrasonography (US). The association between restenosis and preintervention and 48-hour postintervention CRP levels was assessed with multiple logistic regression analysis. RESULTS: ABI improved from a preintervention median of 0.54 to a postintervention median of 0.75 (P <.001). The primary technical success rate was 94% (100 of 106). In 50 patients, a suboptimal technical result was achieved with 30%-40% residual stenosis at the dilated segment. The median ABI at 6 months was 0.65, and it was inversely correlated with preintervention (r = -0.27, P =.009) and 48-hour postintervention (r = -0.40, P <.001) CRP levels. With duplex US at 6 months, restenosis (> or =50%) occurred in 36 patients. Patients with a preintervention CRP level of 0.23-0.92 mg/dL (2.3-9.2 mg/L) had a 3.7-fold increased adjusted risk for restenosis (P =.05); patients with a preintervention CRP level greater than 0.92 mg/dL (9.2 mg/L) had a 4.7-fold increased adjusted risk (P =.03). Postintervention CRP values greater than 2.42 mg/dL (24.2 mg/L) were associated with a 10.7-fold adjusted risk for restenosis (P =.002). Suboptimal PTA result was the only other parameter associated with an increased risk for restenosis (odds ratio, 3.7; P =.03). CONCLUSION: Pre- and postintervention CRP levels were associated with restenosis after PTA of the distal popliteal and tibioperoneal arteries, which indicates that inflammation plays a crucial role in the pathophysiology of this process.

Abstract: PURPOSE: To investigate patency rates after percutaneous transluminal angioplasty (PTA) and PTA plus elective stenting in de novo versus recurrent femoropopliteal lesions. METHODS: The data were collected from a prospective registry including 533 consecutive patients (284 men; median age 71 years, interquartile range [IQR] 72-78) with severe claudication (n=387) or critical limb ischemia (n=146) who underwent femoropopliteal percutaneous interventions during a 36-month period. PTA was used to treat 357 de novo and 99 recurrent lesions; PTA plus elective stent implantation was performed in 58 de novo and 19 recurrent lesions. Patients were followed for a median 12 months (IQR 7-14) using color duplex sonography. Rates of restenosis (>/=50%) were compared by multivariate analysis. RESULTS: Overall primary technical success was achieved in 517 (97%) patients; 31 (6%) periprocedural complications were encountered. Restenosis occurred in 213 (40%) patients after a median 6 months (IQR 4-7). Twelve-month patency after PTA was 61% in de novo and 33% in recurrent lesions (p<0.0001). Patients with recurrent lesions had a 2.3-fold increased adjusted risk for restenosis after PTA (95% confidence interval 1.7 to 3.2). Twelve-month patency after stenting was 58% in de novo and 52% in recurrent lesions (p=0.9). In patients with de novo lesions, patency rates after PTA and stent were similar (p=0.8); however, in patients with recurrent lesions, elective stenting performed better (p=0.05). CONCLUSIONS: Recurrent stenosis after prior femoropopliteal balloon angioplasty is an independent risk factor for restenosis; these lesions exhibit disappointing patency after repeated PTA. Stent implantation may improve intermediate-term results in these patients.

Abstract: PURPOSE: To investigate the association of baseline peripheral blood monocyte counts and restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA) and PTA plus elective stent implantation. METHODS: Three hundred thirty consecutive patients (170 men; median age 71 years, interquartile range 61-78) with peripheral artery disease underwent femoropopliteal PTA (n=258) or PTA plus elective stent implantation (n=72). Multivariate Cox regression analysis was used to determine the predictive value of baseline peripheral blood monocyte counts on the rate of restenosis (> or =50% luminal reduction) in follow-up. RESULTS: Cumulative patency at 6 and 12 months was 55% and 39% after PTA and 70% and 41% after elective stenting, respectively (p=0.19). Pretreatment monocyte counts (in tertiles) were associated with restenosis after PTA (p=0.002) and stent implantation (p=0.02). Compared to patients with monocyte counts <0.3x10(9)/L (lower tertile, n=128), patients with monocytes from 0.3 to 0.4x10(9)/L (middle tertile, n=91) had a 1.8-fold increased adjusted risk for restenosis (95% CI 1.1 to 2.8, p=0.01). Patients with monocytes >0.4x10(9)/L (upper tertile, n=87) had a 2.3-fold increased adjusted risk (95% CI 1.4 to 3.5, p<0.0001). CONCLUSIONS: Baseline monocyte counts were associated with restenosis after femoropopliteal PTA and elective stent implantation, suggesting that circulating monocytes play a pivotal role in the development of recurrent lumen narrowing.

Abstract: PURPOSE: To investigate the frequency of and risk factors for hypotension and bradycardia in response to elective carotid stenting and their association with neurological complications. METHODS: A retrospective analysis was conducted of 471 patients (321 men; median age 72 years, interquartile range 64-77) who underwent elective carotid artery stenting without cerebral protection for high-grade (>70%) symptomatic (n=147) or asymptomatic (n=324) internal carotid artery stenosis at a single center. Frequency and potential risk factors for severe hypotension (systolic blood pressure <80 mmHg) or bradycardia (heart rate <50 bpm) were studied. RESULTS: Thirty-four (7%) patients had severe hypotension (n=23), bradycardia (n=2), or both (n=9) despite routine premedication with atropine and adequate fluid balance. Intravenous catecholamines (dopamine) were necessary in 8 patients with prolonged hypotension; none of the patients with bradycardia needed pacemaker support. Neurological complications (transient ischemic attack, minor stroke, major stroke, death) occurring in 33 (7%) patients were not significantly associated with hemodynamic instability (4/34 [12%] versus 29/437 [7%], p=0.26). Age >77 years (fourth quartile; OR 6.40, 95% CI 1.80 to 22.78, p=0.004) and coronary artery disease (OR 2.81, 95% CI 1.29 to 6.14, p=0.010) were associated with an increased adjusted risk for hypotension or bradycardia. CONCLUSIONS: Hemodynamic instability due to hypotension and bradycardia in response to carotid artery stenting occurs in a relatively low proportion of patients. Elderly patients and those with coronary artery disease are at highest risk. Although the rate of neurological complications was not significantly increased in patients with hemodynamic instability, the higher frequencies of neurological complications in these patients admonish us to be careful.

Abstract: Plasminogen activator inhibitor-1 (PAI-1) is suggested to be involved in the pathophysiology of early thrombosis and late restenosis after percutaneous transluminal angioplasty (PTA). The role of the PAI-1 promoter genotype in this context is indeterminate. We investigated the association of the (4G/5G) polymorphism at nucleotide position (-675) in the PAI-1 gene promoter, PAI-1 plasma levels, and postangioplasty outcome after femoropopliteal PTA. We studied 251 consecutive patients who underwent femoro-popliteal PTA. In a subgroup of 86 patients PAI-1 plasma levels at baseline, 8, 24 and 48 hours postintervention were measured and correlated to the genotype. Patients were followed for early thrombosis and the late restenosis (> or =50%) within 12 months. Multivariate Cox proportional hazards analysis was performed to assess the association between the PAI-1 genotype and PTA failure. Results show that the PAI-1 genotype was neither associated with PAI-1 plasma levels (p=0.40) nor the change of PAI-1 from baseline to 8 (p=0.39), 24 (p=0.86) and 48 hours (p=0.89). Three out of 35 homozygous (4G/4G) patients (9%) had early thrombotic reocclusions, compared to two out of 153 heterozygous (4G/5G) patients (1%) and none of the 63 homozygous (5G/5G) patients (p=0.007). Restenosis after median 5 months (interquartile range 3 to 9) was found in 117 patients (42%), without significant association between the PAI-1 genotype and late postangioplasty failure (Log Rank p=0.95). We can conclude that carriers of the 4G allele exhibited a higher frequency of early thrombotic reocclusions after percutaneous angioplasty. However, the PAI-1 gene promoter polymorphism (4G/5G) was not associated with PAI-1 plasma levels or late postangioplasty restenosis.

Abstract: BACKGROUND: Lipoprotein (a) is suggested to cause endothelial dysfunction, alteration of elastic arterial properties, and decreased arterial compliance. We investigated the relation of arterial compliance and lipoprotein (a) serum [Lp(a)] levels in patients with atherosclerosis. METHODS: Prospective study included 118 consecutive patients with atherosclerosis. Noninvasive computerized pulse wave analysis was used to measure large and small artery elasticity indices in a nondiseased vessel area. Compliance parameters were correlated to Lp(a) levels. Stratified and multivariate analyses were performed to adjust for confounding factors. RESULTS: Small artery elasticity index was inversely correlated with Lp(a) serum levels (r = -0.64, P <.001). The association between Lp(a) and small artery elasticity index remained significant adjusting for age, sex, diabetes mellitus, smoking, hyperlipidemia, and lipid-lowering medication (r = -0.37, P <.0001). Lp(a) accounted for approximately 60% of the variation of small artery compliance in nondiabetic patients (n = 80) (r = -0.76, P <.0001), in diabetic patients (n = 38) no significant correlation between Lp(a) and small artery compliance was observed (r = -0.27, P =.09). No correlation was found between large artery elasticity index and Lp(a). CONCLUSIONS: Small artery compliance was negatively correlated to Lp(a) in nondiabetic patients with atherosclerosis. Increased Lp(a) serum levels might cause endothelial dysfunction measurable by decreased small artery elasticity index in these patients. Elastic properties of diabetic vessels were not directly related to Lp(a) serum levels.

Abstract: BACKGROUND: Chlamydia species are suspected of being involved in the pathogenesis and progression of aortic aneurysms. We investigated serum levels of Chlamydia antibodies in patients with thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA) compared to levels in healthy individuals. METHODS: We included 35 consecutive patients with TAA, 42 patients with AAA and 42 age- and sex-matched healthy controls in a case control study. Serum antibodies (IgM and IgG) against Chlamydia lipopolysaccharide (LPS), Chlamydia pneumoniae and Chlamydia trachomatis were measured by recombinant ELISA and quantified by measurement of optical density. RESULTS: Patients with TAA exhibited median immunoglobulin levels against Chlamydia LPS (IgM 0.090, IgG 0.266), C. pneumoniae (IgM 0.023, IgG 0.264) and C. trachomatis (IgG 0.247) comparable to those of healthy subjects [Chlamydia LPS IgM 0.209 (p = 0.1), IgG 0.301 (p = 0.2); C. pneumoniae IgM 0.051 (p = 0.07), IgG 0.516 (p = 0.1); C. trachomatis IgG 0.153 (p = 0.2)]. Patients with AAA had higher serum levels of IgG against Chlamydia LPS (0.560) compared to healthy individuals [0.301 (p = 0.04)], but no significant elevation of antibodies against C. pneumoniae [IgM 0.029 (p = 0.1), IgG 0.545 (p = 0.9)] and C. trachomatis [IgG 0.219 (p = 0.3)]. CONCLUSION: Thoracic aortic aneurysms were not associated with signs of Chlamydia infection or immunopathogenicity. In contrast, patients with abdominal aortic aneurysms exhibited elevated levels of immunoglobulin against Chlamydia LPS, reflecting an unspecific Chlamydia immunopathogenicity. However, elevated levels of antibodies against distinct Chlamydia species were also not found in AAA patients.

Abstract: OBJECTIVE: To investigate long-term clinical and morphological outcome of patients with subclavian-axillary vein thrombosis treated with systemic thrombolysis compared to anticoagulation in a retrospective, nonrandomised study. METHODS: We studied 95 consecutive inpatients with subclavian-axillary vein thrombosis treated either with systemic urokinase thrombolysis and subsequent oral anticoagulation (n=33) or with anticoagulation only (n=62). Anticoagulation was performed with heparin and phenprocoumon. Patients were followed for median 40 months (IQR 14 to 94) for symptomatic upper extremity post-thrombotic syndrome and for venous recanalisation by duplex ultrasound. RESULTS: Primary technical success rate of the systemic thrombolysis was 88% (n=29) with seven peri-intervention bleeding complications (21%). No complication was observed in patients with anticoagulation only (p<0.0001). At the time of follow-up, duplex sonography showed a thrombotic subclavian vein in 40 of 83 patients (48%), but only 9 of 95 patients (10%) had a symptomatic upper extremity post-thrombotic syndrome. Patients with systemic thrombolysis exhibited a 60% adjusted reduced risk for a thrombotic subclavian vein at the time of follow-up compared to patients with anticoagulation only (95% CI: 0.2 to 0.9, p=0.03). However, the frequency of symptomatic post-thrombotic syndrome after thrombolysis and anticoagulation was similar (adjusted p=0.6). CONCLUSION: Systemic thrombolysis of subclavian-axillary vein thrombosis has an acceptable primary technical success rate and improves venous recanalisation rates compared to anticoagulation. However, the high rate of complications during thrombolysis and the lack of clinical benefit suggest that conservative treatment may be favoured.

Abstract: PURPOSE: To assess the impact of age on technical success and complications of carotid stenting in a prospective single-center cohort study. METHODS: One hundred eleven consecutive patients (74 men; median age 70 years) with >or=70% symptomatic (n=33) or >or=90% asymptomatic (n=78) internal carotid artery (ICA) stenosis underwent carotid artery stent implantation. Primary technical success and periprocedural complications were compared in patients aged >75 years (n=28) to patients <75 years (n=83). RESULTS: Patient groups below and above 75 years compared well with respect to baseline demographic and clinical data. Successful stenting was achieved in 108 (97%) patients. The combined neurological complication rate was 7% (n=8), with 1 (1%) major stroke, 1 (1%) minor stroke, and no 30-day mortality. Technical angiographic complications occurred in 8 (7%) patients. No significant differences between patients >75 years and those <75 years were observed for primary success rates (100% [28/28] versus 96% [80/83]; p=0.8), overall complications (14% [4/28] versus 16% [13/83]; p=1.0), neurological complications (7% [2/28] versus 7% [6/83]; p=1.0), or technical complications (7% [2/28] versus 4% [3/83]; p=0.6). CONCLUSIONS: Elective carotid stenting can be performed safely in older patients with several comorbidities. Patient age does not seem to be an independent risk factor for poor outcome after endovascular treatment of internal carotid artery stenosis.

Abstract: OBJECTIVE: Since non-invasive diagnostic methods have become available and screening programs have become popular, abdominal aortic aneurysms are more frequently being detected at an early stage of the disease. We analyzed the course of conservatively treated patients with infrarenal abdominal aortic aneurysms (AAA), and determined independent risk factors for aneurysm expansion. METHODS: The study was designed as a retrospective-cohort study including 110 consecutive patients with AAA. Cardiovascular risk factors, comorbidities, current medication, and the findings of color coded duplex sonography and computed tomography were recorded. Ninety-two conservatively treated patients were re-investigated every 6 or 12 months (depending on an initial aneurysm size of > 45 mm or < 45 mm respectively) after initial detection by color coded duplex sonography. We performed a multivariate Cox regression analysis to determine independent predictors of diameter progression (diameter increase > or = 5 mm). RESULTS: We found AAA expansion in 46 conservatively treated patients (50%) during the median follow up period of 23 months (IQR 13 to 33), but no rupture occurred. Baseline diameter > 45 mm (HR 2.3, 95% CI 1.0 to 5.3, P = .04) and signs of aortic dissection in duplex ultrasound (HR 2.2, 1.0 to 4.6, P = .04) were independently associated with aneurysm expansion. The presence of an intraluminal thrombus showed a trend towards higher rates of disease progression (HR 2.6, 95% CI 0.9 to 7.6, P = .08). CONCLUSION: Patients with an aneurysm diameter > 45 mm or ultrasound signs of aortic dissection have an increased risk for AAA progression and need careful evaluation, optimization of risk factors and close (six-month) follow-up intervals. For patients with an aneurysm diameter below 45 mm and without additional risk factors, follow-up intervals of 12 months seem to be safe.

Abstract: OBJECTIVE: To investigate the incidence and risk factors for renal function deterioration after renal angiography and angioplasty or stenting. METHODS: A retrospective study of 85 consecutive patients undergoing selective renal artery arteriography (n = 53) or renal artery angioplasty % (PTRA) stenting (n = 32) for renal artery stenosis. Multivariate logistic regression analysis was used to determine independent predictors of deterioration of renal function, defined as an increase of serum creatinine by at least one third within 24 h. RESULTS: Deterioration of renal function occurred in 13 patients (15%), [8/53 (15%) after angiography and 5/32 (16%) after PTRA/stenting]. Only pre-existing renal impairment (se-creatinine > or = 177 mumol/l) (Odds ratio: 40; 95% confidence interval 1.2-72, p = 0.02) and administered dosage of contrast agent (more than 225 ml) (OR 67; 95% CI 11.8-100, p = 0.02) were independently associated with renal function deterioration. CONCLUSION: Transient renal dysfunction after renal artery angiography or PTRA/stenting occurs in about 15% of patients, but persistent renal failure is uncommon. Pre-existing renal impairment and amount of contrast agent are independent risk factors. Endovascular treatment of renal artery stenosis is not associated with a higher risk of renal deterioration compared to selective renal angiography.

Abstract: PURPOSE: To investigate the postintervention course of serum acute-phase reactants after stent implantation in the femoropopliteal, iliac, and carotid arteries. MATERIALS AND METHODS: This prospective cohort study included 274 consecutive patients who underwent stent implantation in the femoropopliteal (n = 95), iliac (n = 70), and carotid (n = 109) arteries. C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen levels were measured at baseline and at 48 hours after intervention. Polynomial logistic regression analysis was applied to assess the independent association of the course of acute-phase reactants and the site of stent implantation. RESULTS: Stent implantation in the femoropopliteal artery was associated with a higher postintervention increase in CRP (P =.01), SAA (P =.04), and fibrinogen (P =.01) values compared with values with iliac artery stent implantation, with adjustment for age, sex, fluoroscopy duration, contrast agent dose, complication occurrence, stenosis grade, total vessel occlusion, and stent cumulative length. No significant difference in the postintervention course of CRP (P =.9) and SAA (P =.1) levels was determined for stents implanted in the carotid artery compared with those implanted in the iliac artery; however, a higher increase in fibrinogen levels (P =.04) was noted. CONCLUSION: Stent implantation in the muscular femoropopliteal artery was associated with a more extensive vascular inflammatory response than was stent implantation in the elastic iliac and carotid arteries, independent of lesion morphology and interventional factors.

Abstract: PURPOSE: To investigate whether peripheral balloon angioplasty with and without stent implantation independently causes an inflammatory vascular response measured by serum acute-phase reactants. METHODS: This was a prospective cohort study enrolled 388 consecutive patients (218 men; median age 70 years, interquartile range 59-76) with peripheral artery disease undergoing balloon angioplasty (n = 187), stent implantation (n = 140), and diagnostic angiography (control group, n = 61). C-reactive protein (CRP) measured by standard and high-sensitivity assays, serum amyloid A (SAA), fibrinogen, and white blood cell (WBC) count were obtained at baseline and at 8, 24, and 48 hours postintervention. Polynomial logistic regression analysis was used to assess the independent association of acute-phase reactants and the interventional group. RESULTS: CRP levels measured by both standard and the high-sensitivity assays significantly increased after balloon angioplasty (standard CRP, p = 0.02; high-sensitivity CRP, p = 0.02) and stent implantation (standard CRP, p = 0.004; high-sensitivity CRP, p = 0.008) compared to the control group adjusting for age, sex, duration of fluoroscopy, volume of contrast, and periprocedural complications. SAA values differed only between the stent group and controls (p = 0.05). Fibrinogen and WBCs were not different among the 3 interventional groups. CONCLUSIONS: Balloon injury and stent implantation induce a vascular inflammatory response at the dilated vessel segment measurable by serum acute-phase parameters. The standard CRP assay is adequate to quantify acute-phase response in these patients.

Abstract: PURPOSE: To compare the outcome of conservative treatment versus percutaneous transluminal angioplasty (PTA) of subclavian artery stenosis in terms of long-term hemodynamic and symptomatic outcome in a retrospective, nonrandomized study. METHODS: Within a 14-year period, 295 consecutive inpatients were treated for subclavian artery stenosis. Excluding 21 (7%) surgical cases, the remaining 274 patients were treated either conservatively (n = 165) or with PTA (n = 109). Medical history, physical findings, and sonographic and angiographic data were recorded from the medical records of the 223 (81%) patients who were followed until the year 2000; 166 patients were then reinvestigated with oscillography, Doppler measurements, and duplex sonography. Outcomes of conservative versus interventional therapy were analyzed based on the intention to treat principle. RESULTS: After a median 42-month follow-up (interquartile range 18-85), patients treated with PTA had a 60% risk reduction for hemodynamic subclavian stenosis compared to conservative treatment (adjusted hazard ratio 0.4, 95% confidence interval 0.2-0.6, p<0.0001). However, the risk of having a symptomatic stenosis at the time of follow-up did not differ between the treatment groups (p=0.3). CONCLUSIONS: Endovascular revascularization improves the long-term hemodynamic outcome in patients with subclavian stenosis, but many conservatively treated patients become asymptomatic during follow-up. Interventional treatment may be considered primarily for patients with severe symptoms of vertebrobasilar insufficiency, critical ischemia, or peripheral emboli.

Abstract: OBJECTIVE: Vascular inflammation is a hallmark in the development of abdominal aortic aneurysms (AAA). Heme oxygenase-1 (HO-1) is a novel vascular anti-inflammatory factor. A (GT)(n) dinucleotide repeat in the HO-1 gene promoter shows a length polymorphism that modulates the level of gene transcription. Short (< 25 GT) repeats are associated with an increased HO-1 upregulation in response to inflammatory stimuli than are longer repeats. We hypothesised that patients with AAA had less frequently short repeats in the HO-1 gene promoter compared to patients with coronary (CAD) or peripheral artery disease (PAD), or healthy controls. METHODS: 70 consecutive patients with atherosclerotic AAA, each 70 age- and sex-matched patients with CAD and PAD as well as 61 unmatched healthy atherosclerosis-free controls for a total of 271 individuals were studied. The frequency of carriers of short repeats in the HO-1 gene promoter was determined and compared between the groups. RESULTS: In the AAA group, 29 patients (41%) were carriers of short (GT)(n) repeats compared to 47 patients (67%) in the CAD group, 44 patients (63%) in the PAD group and 35 healthy controls (59%). Patients with AAA were less frequently carriers of short repeats compared to age- and sex-matched patients with CAD (OR = 0.38, p = 0.006) and PAD (OR = 0.35, p = 0.01). Healthy controls exhibited short alleles more frequently than patients with AAA (p = 0.04), but comparable to CAD (p = 0.3) and PAD patients (p = 0.7). CONCLUSION: Patients with AAA were less frequently carriers of short (< 25 GT) repeats in the HO-1 gene promoter than patients with atherosclerosis or healthy subjects. This suggests that short alleles, and thus, facilitated upregulation of HO-1, may be a protective anti-inflammatory factor against the development of AAA.

Abstract: PURPOSE: To investigate the association of the heme oxygenase-1 (HO-1) genotype, which has potent anti-inflammatory capability, and the inflammatory response induced by balloon angioplasty. METHODS: Three hundred seventeen patients (188 men; median age 70 years, range 57-77) undergoing femoropopliteal balloon angioplasty (n=150) or stenting (n=61) were evaluated for upregulation of the HO-1 genotype; 106 patients undergoing lower limb angiography served as controls. The acute phase reactants C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen were measured 24 and 48 hours postintervention and compared to baseline values. An association of the relative increase (Delta, %) of these inflammatory markers with short (<25) (GT)(n) dinucleotide repeats in the HO-1 gene promoter was assessed. RESULTS: The HO-1 genotype was significantly associated with Delta CRP(24) (p<0.0001), Delta CRP(48) (p<0.0001), Delta SAA(24) (p=0.02), and Delta SAA(48) (p=0.006) after balloon angioplasty; Delta fibrinogen showed no association. Patients with a higher Delta CRP(48) after balloon angioplasty exhibited significantly reduced odds for the presence of short (<25) (GT)(n) repeats. The adjusted odds reduction in the multivariate model was 80% (p=0.002) in the third quartile of Delta CRP(48) values and 90% (p=0.001) in the fourth quartile. No association of HO-1 genotype and inflammatory response was found 24 and 48 hours after stenting (p=0.3, p=0.5) or angiography (p=0.2, p=0.6). CONCLUSIONS: The HO-1 promoter genotype is independently associated with the inflammatory response seen after balloon angioplasty. Short alleles (<25 GT repeats) seem to be an intrinsic vascular anti-inflammatory factor.

Abstract: 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.

Abstract: OBJECTIVE: Fibrinogen is an acute phase protein as well as a component of the coagulation cascade. Vascular inflammation and disturbed coagulation are suggested to cause restenosis after percutaneous transluminal angioplasty (PTA). We investigated the prognostic impact of fibrinogen on restenosis after endovascular treatment of iliac artery occlusive disease. METHODS: In a prospective cohort study 137 consecutive patients after iliac artery PTA (n = 74) and PTA plus selective stent implantation (n = 63) were included, 109 patients after lower limb angiography served as a control group. Patients were followed for 6 months with oscillography, ankle brachial index and duplex sonography for occurrence of restenosis. Fibrinogen and serum amyloid A (SAA), as a control parameter of inflammation, were obtained at baseline, 8, 24 and 48 h postintervention. RESULTS: PTA (adjusted OR 3.1, p = 0.05) and stenting (adjusted OR 13.3, p = 0.001) were independently associated with a higher postintervention increase of fibrinogen compared to angiography. Restenosis was found in 29 patients (21%). Patients with pre-intervention fibrinogen values in the third quartile (411-463 mg/dl) had a 6.2-fold increased adjusted risk for restenosis (p = 0.03), patients in the fourth quartile (> 463 mg/dl) had a 8.9-fold increased adjusted risk (p = 0.007). Pre-intervention SAA values were also significantly associated with restenosis (p < 0.0001). Postintervention fibrinogen and SAA levels showed no association with outcome. CONCLUSION: Balloon angioplasty and stenting of the iliac arteries cause an elevation of postintervention fibrinogen levels independently of angiographic factors. A higher pre-procedure fibrinogen level, presumably a marker of inflammatory activity, indicates a higher risk for restenosis.

Abstract: PURPOSE: To determine the association of pre- and postprocedural serum levels of C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen at 6-month evaluation of restenosis after percutaneous transluminal angioplasty (PTA) of the femoropopliteal artery. MATERIALS AND METHODS: In a prospective cohort study, 172 consecutive patients with peripheral artery disease of Fontaine stage IIa, IIb, or III who underwent successful PTA of the superficial femoral and popliteal arteries were included. Patency at 6 months was evaluated by using oscillography, ankle-brachial index, and color-coded duplex ultrasonography. The association of restenosis and CRP, SAA, and fibrinogen levels at baseline, 24 hours, and 48 hours after intervention was assessed by means of multivariate analysis with adjustment for known risk factors for restenosis. RESULTS: Restenosis was found in 56 patients (33%) within 6 months. CRP values at baseline (adjusted odds ratio, 2.2; 95% CI: 1.1, 4.2) and 48 hours after intervention (adjusted odds ratio, 2.3; 95% CI: 1.6, 3.1) were independently associated with 6-month restenosis. SAA and fibrinogen values at any time interval were not significantly associated with patency in the multivariate models. CONCLUSION: The extent of vascular inflammation as measured by means of acute-phase reactants before and after PTA of the femoropopliteal artery is associated with 6-month restenosis. Baseline and 48-hour CRP levels were independent predictors of postangioplasty outcome.

Abstract: BACKGROUND: Renal artery stenosis (RAS) is a potentially curable cause of secondary hypertension, but the indications for interventional treatment of renovascular hypertension are still a matter of debate. The aim of the study was to investigate immediate and long-term results of percutaneous renal artery revascularization (PTRA). Primary technical success, peri-intervention complications, patency, the course of arterial hypertension and renal function were analyzed. METHODS: 32 renal interventions in 24 consecutive patients (15 PTA, 17 stents) were investigated in a retrospective cohort study. Comorbidities, interventional data and serum creatinine were recorded. Patients were followed for a median period of 45 months (IQR, 32 to 68). Clinical evaluation of the course of blood pressure, serum creatinine, Doppler ultrasound evaluation and multi-slice spiral-CT angiography were performed at follow-up. RESULTS: Primary technical success was achieved in 30 interventions (94%), and in 2 patients during a secondary intervention. The rate of complications was 16% (n = 5). Three major complications were encountered (9%): 1 renal artery thrombosis and 2 acute renal failures. Three patients developed late renal failure after 1, 4 and 37 months, but the overall serum creatinine levels remained stable during the observation period. Hypertension was improved after intervention in 17 patients (71%). However, recurrent hypertension was found in 9 patients (38%) after a median period of 49 months (IQR, 47 to 96). Patency rates at 12, 24 and 72 months were 94%, 94% and 64%, respectively. CONCLUSION: Renal artery PTA can be performed with an acceptable rate of major complications and good long term morphological results. However, clinical outcome in terms of sustained improvement of hypertension is moderate.

Abstract: PURPOSE: To determine if an association exists between postdilation restenosis and heme oxygenase-1 (HO-1), which is induced by balloon injury and inhibits neointimal formation through the action of endogenous carbon monoxide. A dinucleotide repeat in the promoter region of the HO-1 gene shows a length polymorphism that modulates the level of gene transcription. METHODS: This cohort study included 96 consecutive patients (64 men; median age 69 years, interquartile range 60-75) who underwent successful balloon dilation in the femoropopliteal segment. Six-month patency was evaluated using oscillography, ankle-brachial index, and duplex sonography. The association of patency and the length of (GT) repeats in the HO-1 gene promoter was assessed in univariate and multivariate analyses. RESULTS: Restenosis was found in 23 (24%) patients within the first 6 months. Patients with short (<25 GT) dinucleotide repeats in the HO-1 gene promoter on either allele had restenosis significantly less often than patients with longer (> or = 25 GT) dinucleotide repeats (p = 0.01). Multivariate analysis revealed a significantly reduced risk for restenosis in these patients compared to patients without the short allele (odds ratio 0.2, 95% Cl 0.06 to 0.70, p = 0.007). CONCLUSIONS: Genetic risk factors for restenosis after percutaneous transluminal angioplasty have not been investigated. In this patient population, short repeat alleles of the heme oxygenase-1 gene promoter polymorphism were associated with reduced postdilation restenosis at 6 months. Upregulation of HO-1 may be an important protective factor after balloon angioplasty by inhibition of vascular smooth muscle cell proliferation.

Abstract: PURPOSE: To assess the incidence and predictors of acute renal failure after percutaneous transluminal angioplasty (PTA) in a cohort of patients with generalized atherosclerosis. METHODS: A retrospective review of 213 consecutive patients (127 men; median age 71 years, interquartile range 63-77) undergoing femoropopliteal PTA was undertaken. Renal function was measured by creatinine clearance at baseline and 24 hours after the intervention; acute renal dysfunction was defined as > or = 20% decrease of creatinine clearance. The predictive value of potential risk factors was determined in a multivariate model adjusting for comorbidities, pre-existing renal impairment, and angiographic data. RESULTS: Overall serum creatinine values and creatinine clearance remained stable within 24 hours after PTA. Acute renal dysfunction occurred in 25 (12%) patients. Two (1%) patients developed oliguria; one required transient hemodialysis and developed persistent renal failure. Pre-existing impaired renal function (OR 12.2, p < 0.0001) and contrast dosage (OR 1.1, p = 0.03) were independent predictors of acute renal failure; hypertension (OR 7.9, p = 0.06) and congestive heart failure (OR 4.5, p = 0.06) were associated factors. CONCLUSIONS: While transient acute renal dysfunction occurs in approximately 10% of patients with peripheral artery disease within 24 hours after angioplasty, persistent renal failure or end-stage renal disease is rare.

Abstract: PURPOSE: To determine the value of baseline C-reactive protein (CPR), fibrinogen, and white blood cell (WBC) counts in predicting 1-year patency after percutaneous transluminal angioplasty (PTA) in the femoropopliteal segment. METHODS: In a retrospective cohort study, 168 consecutive patients (103 men; median age 70 years, interquartile range 61-77) who underwent successful PTA of the femoral and/or popliteal arteries were analyzed. Twelve-month patency was evaluated using oscillography, ankle brachial index, duplex sonography, and angiography. The predictive value of inflammatory markers was assessed in a multivariate model controlling for cardiovascular risk factors, technical success, and hemodynamic factors. RESULTS: Transient WBC elevation was found 6 hours after PTA, but this returned to baseline after 24 hours. Fibrinogen was elevated at 24 hours. Duplex scanning disclosed restenosis in 66 (39%) patients within the first 12 months after PTA. Only residual postdilation stenosis (> or = 30%) in the target segment (odds ratio 3.6, p=0.001) and baseline CRP levels (odds ratio 4.2, p=0.02) were independent predictors of outcome; neither WBC counts nor fibrinogen levels at any time point was associated with restenosis. CONCLUSIONS: Primary technical success and postinterventional hemodynamic flow at the dilated segment seem to be more important for intermediate-term patency than atherogenic risk factors. The predictive value of preprocedural serum CRP levels on restenosis should be further investigated.