The role of reactive oxygen species in the modulation of the contraction induced by angiotensin II in carotid artery from diabetic rat

The modulation played by reactive oxygen species on the angiotensin II-induced contraction in type I-diabetic rat carotid was investigated. Concentration-response curves for angiotensin II were obtained in endothelium-intact or endothelium-denuded carotid from control or streptozotocin-induced diabetic rats, pre-treated with tiron (superoxide scavenger), PEG-catalase (hydrogen peroxide scavenger), dimethylthiourea (hydroxyl scavenger), apocynin [NAD(P) H oxidase inhibitor], SC560 (cyclooxygenase-1 inhibitor), SC236 (cyclooxygenase-2 inhibitor) or Y-27632 (Rho-kinase inhibitor). Reactive oxygen species were measured by flow cytometry in dihydroethidium (DHE)-loaded endothelial cells. Cyclooxygenase and AT1-receptor expression was assessed by immunohistochemistry. Diabetes increased the angiotensin II-induced contraction but reduced the agonist potency in rat carotid. Endothelium removal, tiron or apocynin restored the angiotensin II-induced contraction in diabetic rat carotid to control levels. PEG-catalase, DMTU or SC560 reduced the angiotensin II-induced contraction in diabetic rat carotid at the same extent. SC236 restored the angiotensin II potency in diabetic rat carotid. Y-27632 reduced the angiotensin II-induced contraction in endothelium-intact or -denuded diabetic rat carotid. Diabetes increased the DHE-fluorescence of carotid endothelial cells. Apocynin reduced the DHE-fluorescence of endothelial cells from diabetic rat carotid to control levels. Diabetes increased the muscular cyclooxygenase-2 expression but reduced the muscular AT1-receptor expression in rat carotid. In summary, hydroxyl radical, hydrogen peroxide and superoxide anion-derived from endothelial NAD(P) H oxidase mediate the hyperreactivity to angiotensin II in type I-diabetic rat carotid, involving the participation of cyclooxygenase-1 and Rho-kinase. Moreover, increased muscular cyclooxygenase-2 expression in type I-diabetic rat carotid seems to be related to the local reduced AT1-receptor expression and the reduced angiotensin II potency. (C) 2011 Elsevier B. V. All rights reserved.

Correlation between carotid bifurcation calcium burden on non-enhanced CT and percentage stenosis, as confirmed by digital subtraction angiography

Objectives: Previous evidence supports a direct relationship between the calcium burden (volume) on post-contrast CT with the percent internal carotid artery (ICA) stenosis at the carotid bifurcation. We sought to further investigate this relationship by comparing non-enhanced CT (NECT) and digital subtraction angiography (DSA). Methods: 50 patients (aged 41-82 years) were retrospectively identified who had undergone cervical NECT and DSA. A 64-multidetector array CT (MDCT) scanner was utilised and the images reviewed using preset window widths/levels (30/300) optimised to calcium, with the volumes measured via three-dimensional reconstructive software. Stenosis measurements were performed on DSA and luminal diameter stenoses >40% were considered "significant". Volume thresholds of 0.01, 0.03, 0.06, 0.09 and 0.12 cm(3) were utilised and Pearson's correlation coefficient (r) was calculated to correlate the calcium volume with percent stenosis. Results: Of 100 carotid bifurcations, 88 were available and of these 7 were significantly stenotic. The NECT calcium volume moderately correlated with percent stenosis on DSA r=0.53 (p<0.01). A moderate-strong correlation was found between the square root of calcium volume on NECT with percent stenosis on DSA (r=0.60, p<0.01). Via a receiver operating characteristic curve, 0.06 cm(3) was determined to be the best threshold (sensitivity 100%, specificity 90.1%, negative predictive value 100% and positive predictive value 46.7%) for detecting significant stenoses. Conclusion: This preliminary investigation confirms a correlation between carotid bifurcation calcium volume and percent ICA stenosis and is promising for the optimal threshold for stenosis detection. Future studies could utilise calcium volumes to create a "score" that could predict high grade stenosis.

Ultrasonic tissue characterization of vulnerable carotid plaque: correlation between videodensitometric method and histological examination

Abstract Background To establish the correlation between quantitative analysis based on B-mode ultrasound images of vulnerable carotid plaque and histological examination of the surgically removed plaque, on the basis of a videodensitometric digital texture characterization. Methods Twenty-five patients (18 males, mean age 67 ± 6.9 years) admitted for carotid endarterectomy for extracranial high-grade internal carotid artery stenosis (≥ 70% luminal narrowing) underwent to quantitative ultrasonic tissue characterization of carotid plaque before surgery. A computer software (Carotid Plaque Analysis Software) was developed to perform the videodensitometric analysis. The patients were divided into 2 groups according to symptomatology (group I, 15 symptomatic patients; and group II, 10 patients asymptomatic). Tissue specimens were analysed for lipid, fibromuscular tissue and calcium. Results The first order statistic parameter mean gray level was able to distinguish the groups I and II (p = 0.04). The second order parameter energy also was able to distinguish the groups (p = 0,02). A histological correlation showed a tendency of mean gray level to have progressively greater values from specimens with < 50% to >75% of fibrosis. Conclusion Videodensitometric computer analysis of scan images may be used to identify vulnerable and potentially unstable lipid-rich carotid plaques, which are less echogenic in density than stable or asymptomatic, more densely fibrotic plaques.

Histological composition and progression of carotid plaque

Abstract Background To analyse histological composition and progression of carotid plaque. Methods Thirty-one patients (22 males, mean age 68.03 ± 7.3 years) admitted for carotid endarterectomy for extracranial high-grade internal carotid artery stenosis (≥ 70% luminal narrowing) were enrolled. The patients were divided into 2 groups according to symptomatology (group I, 17 symptomatic patients; and group II, 14 asymptomatic patients). A histological analysis and inflammatory cell quantification of each excised carotid plaque was made. Nine carotid arteries were removed from human cadavers that were not preselected for carotid artery disease. These specimens were used as a control tissue without any macroscopic signs of atherosclerotic plaques. Results Fifty eight percent of all carotid plaques were classified as complex plaque with possible surface defect, hemorrhage or thrombus. The inflammatory cells concentration did not differ between the two groups. All specimens from human cadavers were classified as preatheroma with extracellular lipid pools. Conclusion Asymptomatic and symptomatic patients could have the same histological components on their carotid plaques. Fibrotic and calcific plaques could become vulnerable as complex plaques with surface defect, hemorrhage and thrombus could remain silent. Asymptomatic carotid stenosis should be followed close with no invasive diagnostic methods and clinical evaluation.

Assessment of MMP-9, TIMP-1, and COX-2 in normal tissue and in advanced symptomatic and asymptomatic carotid plaques

Abstract Background Mature carotid plaques are complex structures, and their histological classification is challenging. The carotid plaques of asymptomatic and symptomatic patients could exhibit identical histological components. Objectives To investigate whether matrix metalloproteinase 9 (MMP-9), tissue inhibitor of MMP (TIMP), and cyclooxygenase-2 (COX-2) have different expression levels in advanced symptomatic carotid plaques, asymptomatic carotid plaques, and normal tissue. Methods Thirty patients admitted for carotid endarterectomy were selected. Each patient was assigned preoperatively to one of two groups: group I consisted of symptomatic patients (n = 16, 12 males, mean age 66.7 ± 6.8 years), and group II consisted of asymptomatic patients (n = 14, 8 males, mean age 67.6 ± 6.81 years). Nine normal carotid arteries were used as control. Tissue specimens were analyzed for fibromuscular, lipid and calcium contents. The expressions of MMP-9, TIMP-1 and COX-2 in each plaque were quantified. Results Fifty-eight percent of all carotid plaques were classified as Type VI according to the American Heart Association Committee on Vascular Lesions. The control carotid arteries all were classified as Type III. The median percentage of fibromuscular tissue was significantly greater in group II compared to group I (p < 0.05). The median percentage of lipid tissue had a tendency to be greater in group I than in group II (p = 0.057). The percentages of calcification were similar among the two groups. MMP-9 protein expression levels were significantly higher in group II and in the control group when compared with group I (p < 0.001). TIMP-1 expression levels were significantly higher in the control group and in group II when compared to group I, with statistical difference between control group and group I (p = 0.010). COX-2 expression levels did not differ among groups. There was no statistical correlation between MMP-9, COX-2, and TIMP-1 levels and fibrous tissue. Conclusions MMP-9 and TIMP-1 are present in all stages of atherosclerotic plaque progression, from normal tissue to advanced lesions. When sections of a plaque are analyzed without preselection, MMP-9 concentration is higher in normal tissues and asymptomatic surgical specimens than in symptomatic specimens, and TIMP-1 concentration is higher in normal tissue than in symptomatic specimens.

Phage display identification of CD100 in human atherosclerotic plaque macrophages and foam cells

Atherosclerosis is a complex disease in which vessels develop plaques comprising dysfunctional endothelium, monocyte derived lipid laden foam cells and activated lymphocytes. Considering that humans and animal models of the disease develop quite distinct plaques, we used human plaques to search for proteins that could be used as markers of human atheromas. Phage display peptide libraries were probed to fresh human carotid plaques, and a bound phage homologous to plexin B1, a high affinity receptor for CD100, was identified. CD100 is a member of the semaphorin family expressed by most hematopoietic cells and particularly by activated T cells. CD100 expression was analyzed in human plaques and normal samples. CD100 mRNA and protein were analyzed in cultured monocytes, macrophages and foam cells. The effects of CD100 in oxLDL-induced foam cell formation and in CD36 mRNA abundance were evaluated. Human atherosclerotic plaques showed strong labeling of CD100/SEMA4D. CD100 expression was further demonstrated in peripheral blood monocytes and in in vitro differentiated macrophages and foam cells, with diminished CD100 transcript along the differentiation of these cells. Incubation of macrophages with CD100 led to a reduction in oxLDL-induced foam cell formation probably through a decrease of CD36 expression, suggesting for the first time an atheroprotective role for CD100 in the human disease. Given its differential expression in the numerous foam cells and macrophages of the plaques and its capacity to decrease oxLDL engulfment by macrophages we propose that CD100 may have a role in atherosclerotic plaque development, and may possibly be employed in targeted treatments of these atheromas.

Longterm peripheral baroreflex and chemoreflex function after bilateral eversion carotid endarterectomy

Introduction The “eversion” technique for carotid endarterectomy (e-CEA), that involves the transection of the internal carotid artery at the carotid bulb and its eversion over the atherosclerotic plaque, has been associated with an increased risk of postoperative hypertension possibly due to a direct iatrogenic damage to the carotid sinus fibers. The aim of this study is to assess the long-term effect of the e-CEA on arterial baroreflex and peripheral chemoreflex function in humans. Methods A retrospective review was conducted on a prospectively compiled computerized database of 3128 CEAs performed on 2617 patients at our Center between January 2001 and March 2006. During this period, a total of 292 patients who had bilateral carotid stenosis ≥70% at the time of the first admission underwent staged bilateral CEAs. Of these, 93 patients had staged bilateral e-CEAs, 126 staged bilateral s- CEAs and 73 had different procedures on each carotid. CEAs were performed with either the eversion or the standard technique with routine Dacron patching in all cases. The study inclusion criteria were bilateral CEA with the same technique on both sides and an uneventful postoperative course after both procedures. We decided to enroll patients submitted to bilateral e-CEA to eliminate the background noise from contralateral carotid sinus fibers. Exclusion criteria were: age >70 years, diabetes mellitus, chronic pulmonary disease, symptomatic ischemic cardiac disease or medical therapy with b-blockers, cardiac arrhythmia, permanent neurologic deficits or an abnormal preoperative cerebral CT scan, carotid restenosis and previous neck or chest surgery or irradiation. Young and aged-matched healthy subjects were also recruited as controls. Patients were assessed by the 4 standard cardiovascular reflex tests, including Lying-to-standing, Orthostatic hypotension, Deep breathing, and Valsalva Maneuver. Indirect autonomic parameters were assessed with a non-invasive approach based on spectral analysis of EKG RR interval, systolic arterial pressure, and respiration variability, performed with an ad hoc software. From the analysis of these parameters the software provides the estimates of spontaneous baroreflex sensitivity (BRS). The ventilatory response to hypoxia was assessed in patients and controls by means of classic rebreathing tests. Results A total of 29 patients (16 males, age 62.4±8.0 years) were enrolled. Overall, 13 patients had undergone bilateral e-CEA (44.8%) and 16 bilateral s-CEA (55.2%) with a mean interval between the procedures of 62±56 days. No patient showed signs or symptoms of autonomic dysfunction, including labile hypertension, tachycardia, palpitations, headache, inappropriate diaphoresis, pallor or flushing. The results of standard cardiovascular autonomic tests showed no evidence of autonomic dysfunction in any of the enrolled patients. At spectral analysis, a residual baroreflex performance was shown in both patient groups, though reduced, as expected, compared to young controls. Notably, baroreflex function was better maintained in e-CEA, compared to standard CEA. (BRS at rest: young controls 19.93 ± 2.45 msec/mmHg; age-matched controls 7.75 ± 1.24; e-CEA 13.85 ± 5.14; s-CEA 4.93 ± 1.15; ANOVA P=0.001; BRS at stand: young controls 7.83 ± 0.66; age-matched controls 3.71 ± 0.35; e-CEA 7.04 ± 1.99; s-CEA 3.57 ± 1.20; ANOVA P=0.001). In all subjects ventilation (VÝ E) and oximetry data fitted a linear regression model with r values > 0.8. Oneway analysis of variance showed a significantly higher slope both for ΔVE/ΔSaO2 in controls compared with both patient groups which were not different from each other (-1.37 ± 0.33 compared with -0.33±0.08 and -0.29 ±0.13 l/min/%SaO2, p<0.05, Fig.). Similar results were observed for and ΔVE/ΔPetO2 (-0.20 ± 0.1 versus -0.01 ± 0.0 and -0.07 ± 0.02 l/min/mmHg, p<0.05). A regression model using treatment, age, baseline FiCO2 and minimum SaO2 achieved showed only treatment as a significant factor in explaining the variance in minute ventilation (R2= 25%). Conclusions Overall, we demonstrated that bilateral e-CEA does not imply a carotid sinus denervation. As a result of some expected degree of iatrogenic damage, such performance was lower than that of controls. Interestingly though, baroreflex performance appeared better maintained in e-CEA than in s-CEA. This may be related to the changes in the elastic properties of the carotid sinus vascular wall, as the patch is more rigid than the endarterectomized carotid wall that remains in the e-CEA. These data confirmed the safety of CEA irrespective of the surgical technique and have relevant clinical implication in the assessment of the frequent hemodynamic disturbances associated with carotid angioplasty stenting.

Valutazione dello spessore intima-media carotideo come fattore di rischio cardiovascolare nei pazienti affetti da psoriasi moderato-severa

Evaluation of carotid artery intima-media thickness in patients affected by psoriasis Psoriasis is associated with an increased risk of atherosclerosis. This study compared subclinical atherosclerosis, evaluating intima-media thickness the of the carotid in psoriasis vulgaris patients and healthy controls using high-resolution ultrasonography and the correlation of this parameter with other cardiovascular risk factors, like insulin resistance and dyslipidemia, METHODS: We will study 40 psoriasis patients, asymptomatic for cardiovascular diseases, and 40 healthy controls matched for age and sex. Intima-media thickness of the common carotid arteries will be measured ultrasonographically. Diabetes mellitus, hypertension, renal failure, a history of cardiovascular or cerebrovascular disease will be exclusion criteria. Subjects who are receiving lipid-lowering therapy, antihypertensive or anti-aggregant drugs, nitrates or long-term systemic steroids will be also excluded. Objective of this study is the evaluation of carotid artery intima-media thickness and its correlation with other blood cardiovascular risk factors in patients affected by psoriasis but asinptomatic for coronary comparing this data with the healthy control subjects. Considering that the presence of psoriasis is an independent risk factor for subclinical atherosclerosis, we want to consider this method of evaluation of cardiovascular risk and to control this risk to prevent IMA.

Charakterisierung atherosklerotischer Plaques am Beispiel der A. carotis mittels Histologie, CT und semiautomatischer Farbcodierung

Auf der Suche nach dem „vulnerablen Plaque“, der ein besonders hohes Risiko für Schlaganfall und Herzinfarkt besitzt, findet momentan ein Paradigmenwechsel statt. Anstelle des klassischen Stenosegrades gewinnt die Darstellung der Plaquemorphologie zunehmend an Bedeutung. Fragestellung: Ziel dieser Arbeit ist es, die Fähigkeiten eines modernen 16-Kanal-CT hinsichtlich der Auflösung des Plaqueinneren bei Atherosklerose der Karotiden zu untersuchen und den Halo-Effekt in vivo zu erforschen. Methoden: Für die Studie wurden von 28 Patienten mit bekannter, symptomatischer Karotisstenose vor der gefäßchirurgischen Intervention CT-Bilder angefertigt, die nachfolgend mit der Histologie der Gefäßpräparate korreliert wurden. Auf diese Weise konnten die mikroskopisch identifizierten Lipidkerne im CT-Bild eingezeichnet und hinsichtlich ihrer Fläche und Dichtewerte evaluiert werden. In einem weiteren Schritt führten 2 Radiologen in Unkenntnis der histologischen Ergebnisse unabhängig voneinander eine Befundung durch und markierten mutmaßliche Lipidkerne. Zudem wurden sowohl in der verblindeten als auch in der histologiekontrollierten Auswertung die Plaquetypen anhand der AHA-Klassifikation bestimmt. Ein dritter Befundungsdurchgang geschah unter Zuhilfenahme einer von uns entwickelten Software, die CT-Bilder farbkodiert um die Detektion der Lipidkerne zu verbessern. Anhand der Farbkodierung wurde zudem ein Indexwert errechnet, der eine objektive Zuordnung zur AHA-Klassifikation ermöglichen sollte. Von 6 Patienten wurde zusätzlich noch eine native CT-Aufnahme angefertigt, die durch MPR exakt an die Kontrastmittelserie angeglichen wurde. Auf diese Weise konnte der Halo-Effekt, der die Plaqueanteile im lumennahen Bereich überstrahlt, quantifiziert und charakterisiert werden. Ergebnisse: Während die Einstufung in die AHA-Klassifikation sowohl durch den Befunder als auch durch den Softwarealgorithmus eine hohe Korrelation mit der Histologie aufweist (Typ IV/Va: 89 %, Typ Vb: 70 %, Typ Vc: 89 %, Typ VI: 55 %), ist die Detektion der Lipidkerne in beiden Fällen nicht ausreichend gut und die Befunderabhängigkeit zu groß (Cohens Kappa: 18 %). Eine Objektivierung der AHA-Klassifikation der Plaques durch Indexberechnung nach Farbkodierung scheint möglich, wenn auch dem Befunder nicht überlegen. Die fibröse Kappe kann nicht abgegrenzt werden, da Überstrahlungseffekte des Kontrastmittels dessen HU-Werte verfälschen. Dieser Halo-Effekt zeigte sich im Median 1,1 mm breit mit einer Standardabweichung von 0,38 mm. Eine Abhängigkeit von der Kontrastmitteldichte im Gefäßlumen konnte dabei nicht nachgewiesen werden. Der Halo-Effekt fiel im Median um -106 HU/mm ab, bei einer Standardabweichung von 33 HU/mm. Schlussfolgerung: Die CT-Technologie zeigt sich, was die Darstellung von einzelnen Plaquekomponenten angeht, den bekannten Fähigkeiten der MRT noch unterlegen, insbesondere in Bezug auf die fibröse Kappe. Ihre Fähigkeiten liegen bisher eher in der Einstufung von Plaques in eine grobe Klassifikation, angelehnt an die der AHA. Die klinische Relevanz dessen jedoch gilt es in Zukunft in größeren Studien weiter zu untersuchen. Auch lässt die Weiterentwicklung der Computertomographie auf eine zukünftig höhere Auflösung der Plaquemorphologie hoffen.

The vulnerable carotid plaque. Identification of endothelial markers predictive of plaque weakness, rupture predisposition and neoangiogenesis

Background. Neoangiogenesis is crucial in plaque progression and instability. Previous data from our group demonstrated that intra-plaque neovessels show both a Nestin+/WT+ and a Nestin+/WT1- phenotype, the latter being correlated with complications and plaque instability. Aims. The aims of the present thesis are: (i) to confirm our previous results on Nestin/WT1 phenotype in a larger series of carotid atheromatous plaques, (ii) to evaluate the relationship between the Nestin+/WT1- neoangiogenesis phenotype and plaque morphology, (iii) to evaluate the relationship between the immunohistochemical and histopathological characteristics and the clinical instability of the plaques. Materials and Methods. Seventy-three patients (53 males, 20 females, mean age 71 years) were consecutively enrolled. Symptoms, brain CT scan, 14 histological variables, including intraplaque hemorrhage and diffuse calcifications, were collected. Immunohistochemistry for CD34, Nestin and WT1 was performed. RT-PCR was performed to evaluate Nestin and WT1 mRNA (including 5 healthy arteries as controls). Results. Diffusely calcified plaques (13 out of 73) were found predominantly in females (P=0.017), with a significantly lower incidence of symptoms (TIA/stroke) and brain focal lesions (P=0.019 and P=0.013 respectively) than not-calcified plaques, but with the same incidence of intraplaque complications (P=0.156). Accordingly, both calcified and not calcified plaques showed similar mean densities of positivity for CD34, Nestin and WT1. The density of Nestin and WT1 correlated with the occurrence of intra-plaque hemorrhage in all cases, while the density of CD34 correlated only in not-calcified plaques. Conclusions. We confirmed that the Nestin+/WT1- phenotype characterizes the neovessels of instable plaques, regardless the real amount of CD34-positive neoangiogenesis. The calcified plaques show the same incidence of histological complications, albeit they do not influence symptomatology and plaque vulnerability. Female patients show a much higher incidence of not-complicated or calcified plaques, receiving de facto a sort of protection compared to male patients.

The use of flat panel angioCT (DynaCT) for navigation through a deformed and fractured carotid stent

Navigation through a previously deployed and deformed stent is a difficult interventional task. Inadvertent navigation through the struts of a stent can potentially lead to incomplete secondary stent extension and vessel occlusion. Better visualisation of the pathway through the stent can reduce the risks of the procedural complications and reduce the reluctance of the interventionalist to navigate through a previously deployed stent. We describe a technique of visualisation of the pathway navigated by a guidewire through a previously deployed deformed and fractured carotid stent by the use of DynaCT. Three-dimensional reconstruction of the stent/microwire allows excellent visualisation of the correct pathway of the microwire within the stent.

An angiographic analysis of atherosclerosis progression in below-the-knee arteries after femoropopliteal angioplasty in claudicants

Purpose: To report an angiographic investigation of midterm atherosclerotic disease progression in below-the-knee (BTK) arteries of claudicants. Methods: Angiograms were performed in 58 consecutive claudicants (35 men; mean age 68.3±8.7 years) with endovascular treatment of femoropopliteal arteries in 58 limbs after a mean follow-up of 3.6±1.2 years. Angiograms were reviewed in consensus by 2 experienced readers blinded to clinical data. Progression of atherosclerosis in 4 BTK arterial segments (tibioperoneal trunk, anterior and posterior tibial arteries, and peroneal artery) was assessed according to the Bollinger score. The composite per calf Bollinger score represented the average of the 4 BTK arterial segment scores. The association of the Bollinger score with cardiovascular risk factors and gender was scrutinized. Results: A statistically significant increase in atherosclerotic burden was observed for the mean composite per calf Bollinger score (5.7±8.3 increase, 95% CI 3.5 to 7.9, p<0.0001), as well as for each single arterial segment analyzed. In multivariate linear regression analysis, diabetes mellitus was associated with a more pronounced progression of atherosclerotic burden in crural arteries (β: 5.6, p=0.035, 95% CI 0.398 to 10.806). Conclusion: Progression of infrapopliteal atherosclerotic lesions is common in claudicants during midterm follow-up. Presence of diabetes mellitus was confirmed as a major risk factor for more pronounced atherosclerotic BTK disease progression.

Impact of long-term corticosteroid therapy on the distribution pattern of lower limb atherosclerosis

OBJECTIVE: Ectopic calcification and mediacalcinosis can be promoted by corticosteroid use. Aim of the present investigation is to describe macrovascular disease features in patients with long-term corticosteroid therapy and symptomatic lower limb peripheral arterial occlusive disease (PAD). METHODS: A consecutive series of 2783 patients undergoing clinical and angiographic work-up of PAD were screened for long-term (>5 years) corticosteroid use (group A). Comparison was performed to a randomly selected age-, sex- and risk factor-matched PAD control cohort from the same series without corticosteroid use (group B). Patients with diabetes mellitus or severe renal failure were excluded. Arterial calcification was evaluated by qualitative assessment on radiographic images. Severity of atherosclerotic lesions was analysed from angiographic images using a semi-quantitative score (Bollinger score). RESULTS: In general, 12 patients (5 males, mean age 78.5 +/- 9.0 years) with 15 ischaemic limbs qualified to be enrolled in group A and were compared to 23 matching control patients (6 2 males, mean age 79.5 +/- 6 years) with 32 ischaemic limbs. Incompressibility of ankle arteries determined by measurement of the ankle-brachial index was seen in 12 limbs (80%) in group A compared to 3 limbs (9%) in group B (p = 0.0009). No significant difference was found comparing group A and B for segmental calcification, whereas comparison of the atherosclerotic burden using the angiographic severity score showed a significantly higher score at the infragenicular arterial level in group A (p = 0.001). CONCLUSION: Findings suggest that the long-term corticosteroid therapy is associated with a distally accentuated, calcifying peripheral atherosclerosis inducing arterial incompressibility. This occlusion pattern is comparable to patients with renal failure or diabetes. Further research is required to support our observations.

Renal insufficiency is independently associated with a distal distribution pattern of symptomatic lower-limb atherosclerosis

Objectives The purpose of this study was to assess the impact of renal insufficiency (RI) on the distribution pattern of peripheral arterial disease (PAD). We hypothesised that RI is associated with a distally accentuated involvement of the peripheral arterial tree. Design This is a retrospective analysis. Materials and Methods Analysis was based on a consecutive series of 2709 patients with chronic PAD of atherosclerotic origin undergoing primary endovascular treatment of lower-extremity arteries. Atherosclerotic pattern was grouped into femoropopliteal (n = 2085) and infragenicular (n = 892) disease according to target lesions treated while using iliac disease (n = 1133) as reference. Univariable and multivariable multinomial regression analyses were performed to assess relation with RI. Results are shown as relative risk ratio (RRRs) with 95% confidence intervals (95% CIs). A p < 0.05 was considered statistically significant. RI was defined as glomerular filtration rate (GFR) < 60 ml min−1 1.73 m−2. Results Presence of RI was an independent risk factor for a centrifugal lesion pattern (RRR 1.48, 95% CI: 1.17–1.86, p = 0.001). Moreover, a decrease in GFR by 10 ml min−1 1.73 m−2 was associated with an RRR of 1.08 for below-the-knee arterial disease (95% CI: 1.03–1.13, p = 0.003). Conclusion Presence and severity of RI are independent predictors of a distal obstructive pattern in patients with symptomatic PAD.

Standardized definitions and clinical endpoints in carotid artery and supra-aortic trunk revascularization trials

Endovascular therapy has emerged as a promising alternative to open surgery for stroke prevention in patients with obstructive disease of the supra-aortic arteries. Although most previous studies have used similar safety and efficacy endpoints, differences in definitions, timing of assessments, and standards of reporting have hampered direct comparisons across various trials.