Background:There is controversial evidence with regard to the significance of peripheral arterial disease (PAD) as an indicator for future stroke risk. We aimed to quantify the risk increase for mortality and morbidity associated with PAD. Methods:In an open, prospective, noninterventional cohort study in the primary care setting, a total of 6,880 unselected patients ≧65 years were categorized according to the presence or absence of PAD and followed up for vascular events or deaths over 5 years. PAD was defined as ankle-brachial index (ABI) <0.9 or history of previous peripheral revascularization and/or limb amputation and/or intermittent claudication. Associations between known cardiovascular risk factors including PAD and cerebrovascular mortality/events were analyzed in a multivariate Cox regression model. Results:During the 5-year follow-up [29,915 patient-years (PY)], 183 patients had a stroke (incidence per 1,000 PY: 6.1 cases). In patients with PAD (n = 1,429) compared to those without PAD (n = 5,392), the incidence of all stroke types standardized per 1,000 PY, with the exception of hemorrhagic stroke, was about doubled (for fatal stroke tripled). The corresponding adjusted hazard ratios were 1.6 (95% confidence interval, CI, 1.1–2.2) for total stroke, 1.7 (95% CI 1.2–2.5) for ischemic stroke, 0.7 (95% CI 0.2–2.2) for hemorrhagic stroke, 2.5 (95% CI 1.2–5.2) for fatal stroke and 1.4 (95% CI 0.9–2.1) for nonfatal stroke. Lower ABI categories were associated with higher stroke rates. Besides high age, previous stroke and diabetes mellitus, PAD was a significant independent predictor for ischemic stroke. Conclusions:The risk of stroke is substantially increased in PAD patients, and PAD is a strong independent predictor for stroke. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

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Introdução: Inúmeros estudos estabeleceram correlações entre o índice tornozelo-braço (ITB), um marcador de aterosclerose subclínica, e o prognóstico cardiovascular em diferentes populações. No entanto, poucos estudos avaliaram a correlação entre os valores do ITB e lesões cardiovasculares e renais, exclusivamente, em pacientes com hipertensão arterial e diabetes. Objetivo: Estudar a prevalência de alterações morfofuncionais cardíacas, carotídeas, retinianas e renais de acordo com a presença ou não de valores de ITB alterados (ITB <= 0,9 ou ITB > 1,4) em pacientes hipertensos com diabetes tipo 2. Métodos: Foram incluídos no estudo 99 pacientes hipertensos diabéticos com idade entre 50 e 80 anos. A aferição do ITB foi realizada em todos os pacientes por método validado e estes foram classificados em Grupo 1 (ITB normal, n = 49) ou Grupo 2 (ITB alterado, n =50). Todos os pacientes foram submetidos, em até 06 meses, à realização de ecodopplercardiograma, ultrassonografia de carótidas, retinografia colorida, aferição da taxa de filtração glomerular (TFG) e da albuminúria de 24h. Os pacientes foram analisados para a ocorrência ou não de um desfecho-composto ecocardiográfico que incluiu alterações morfológicas e funcionais cardíacas relevantes para a prática clínica. Os pacientes dos grupos 1 e 2 foram também comparados quanto à prevalência de placas carotídeas com ou sem repercussão hemodinâmica, TFG < 60 ml/mim/m2, albuminúria de 24h > 30mg e presença ou não de retinopatia. Por fim, foram comparadas as frequências médias das seguintes lesões de órgãos-alvo de ambos os grupos, considerando-se valor unitário para a presença de cada uma delas: hipertrofia do ventrículo esquerdo, retinopatia hipertensiva, TFG < 60 ml/min/m2 e estenose da artéria carótida interna > 50% do seu diâmetro. Resultados: A média de idade dos pacientes foi 65,4 ± 7 anos, sendo 61,6% deles do sexo feminino. A presença de níveis elevados de pressão arterial sistólica (153,4 ± 18 versus 170 ± 26 mmHg), de albuminúria de 24h > 30mg (55,3% versus 82,6%) e de TFG < 60 ml/min/m2 (12,8% versus 33,3%) foi significativamente maior (p < 0.05) entre os pacientes do Grupo 2. O desfecho-composto ecocardiográfico foi mais prevalente no grupo 2 (84,0% versus 59,2%; p = 0,006) e a frequência média de lesões de órgãos-alvo também foi maior nos pacientes do grupo 2 (0,36 ± 0,31 versus 0,19 ± 0,19; p = 0,001). Análise por regressão logística binária revelou que o ITB foi uma das variáveis preditoras independentes para o desfecho-composto ecocardiográfico (OR = 3,43; IC 95% = 1,07 - 11,0; p = 0,04). A partir da análise por regressão linear obteve-se um modelo final no qual o ITB foi uma das três variáveis preditoras independentes para a estimativa da frequência média de lesões de órgãos-alvo com coeficiente beta = 13,22 (1,81 - 24,63), ao lado da idade e do infarto prévio. Conclusão: Nossos dados mostram que valores de ITB alterados estão associados à maior prevalência de lesões em órgãos-alvo, principalmente alterações ecocardiográficas, em pacientes com hipertensão arterial e diabetes / Introduction: A lot of studies have established strong correlations between the ankle-brachial index (ABI), a marker of subclinical atherosclerosis and cardiovascular prognosis in different populations. However, few studies have assessed the correlation between the values of the ABI and cardiovascular and renal lesions in patients with hypertension and diabetes. Objective: To study the prevalence of cardiac, carotid, renal and retinal morphological and functional changes according to the presence or not of altered ABI values (ABI <= 0.9 or ABI > 1.4) in hypertensive patients with type 2 diabetes. Methods: It was included 99 diabetic hypertensive patients aged between 50 and 80 years. The measurement of the ABI was performed in all patients by validated method and they were classified in Group 1 (normal ABI, n = 49) or group 2 (altered ABI, n = 50). All patients were submitted, up to 6 months, to Doppler echocardiography, carotid ultrasound, color retinography, assessment of glomerular filtration rate (GFR) and 24h albuminuria. Patients were analyzed for the occurrence or not of a composite echocardiographic outcome which included morphological and functional cardiac alterations relevant to clinical practice. Patients in groups 1 and 2 were compared regarding the prevalence of carotid plaques with or without hemodynamic repercussion, TFG < 60 ml/min/m2, 24h albuminuria > 30 mg and the presence or not of retinopathy. Finally, we compared the prevalence of mean frequency of the following end-organ lesions of both groups, considering unit value for each one: left ventricular hypertrophy, hypertensive retinopathy, TFG < 60 ml/min/m2 and internal carotid artery stenosis > 50%. Results: The mean age of the patients was 65.4 ± 7 years, with 61.6% of them female. The presences of elevated levels of systolic blood pressure (153.4 ± 18 versus 170.0 ± 26 mmHg), of 24h albuminuria > 30 mg (55.3% versus 82.6%) and TFG < 60 ml/min/m2 (12.8% vs. 33.3%) were significantly greater (p < 0.05) among the patients of Group 2. The composite echocardiographic outcome was more prevalent in Group 2 (84.0% versus 59.2%, p = 0.006) and the average frequency of subclinical injury of target organs was also greater in patients of Group 2 (0.36 ± 0.31 versus 0.19 ± 0.19; p = 0.001). Binary logistic regression analysis revealed that the ABI was one of the independent predictors of composite echocardiographic outcome (OR = 3.43; IC 95% = 1.07 - 11.0; p = 0.04). From the linear regression analysis it was obtained a final model in which the ABI was one of three independent predictors for the estimation of the average frequency of end-organ damage with ? coefficient = 13.22 (1.81-24.63), besides age and previous myocardial infarction. Conclusion: Our data demonstrates that changed ABI values are associated with higher prevalence of subclinical end-organ lesions, principally changes in echocardiographic parameters, in patients with hypertension and diabetes

Dans la dysfonction endothéliale, le compartiment endothélial circulant joue simultanément le rôle d’acteur impliqué dans la régénération du tissu lésé et celui d’indicateur de l’état d’altération ou de régénération de l’endothélium. Dans l’artérite oblitérante des membres inférieurs (AOMI), l’un des axes de recherche porte sur le développement d’un produit de thérapie cellulaire capable d’induire la formation de néo-Vaisseaux. Face à la difficulté d’obtenir et d`amplifier des cellules progénitrices endothéliales (CPE) chez l’adulte sain, et a fortiori chez le patient, l’une des hypothèses laisse envisager le recours à d’autres types cellulaires ayant des propriétés vasculogéniques. Chez patients atteints de maladies cardiovasculaires, et d’AOMI en particulier, les cellules mononuclées de moelle osseuse et les CPE montrent des propriétés angiogéniques diminuées. Nous avons mis en évidence la capacité des cellules souches mésenchymateuses (CSM) isolées de patients atteints d’AOMI à induire une reperfusion, par recrutement de cellules endothéliales in situ, avec la même efficacité que celles de donneurs sains. Les CSM ne se différencient pas en cellules endothéliales mais agissent par paracrinie. La seconde hypothèse d’obtention d’un produit de thérapie cellulaire autologue angiogène est de trier des cellules plus immatures que les CPE afin de les différencier secondairement vers la lignée endothéliale à l’image du modèle pathologique de la cellule souche d’hémangiome CD133+ qui laisse envisager les Very Small Embryonic Like stem cells (VSEL), cellules souches multipotentes CD133+, comme un candidat de cellules post-Natales à potentiel vasculaire. Nous avons dérivés, en culture en conditions angiogéniques, des VSEL qui acquièrent un phénotype mésenchymateux mais présentent un profil sécrétoire proche de celui des CPE. Les VSEL favorisent la revascularisation post-Ischémique et acquièrent un phénotype endothélial in vitro et in vivo suggérant que les VSEL peuvent être à l’origine de la lignée endothéliale. Les VSEL se présentent également comme un biomarqueur de la dysfonction endothéliale mobilisé de la moelle osseuse (MO) vers le sang périphérique (PB) chez les patients souffrant d’AOMI. Les biomarqueurs cellulaires circulants représentent non seulement des marqueurs non invasifs de l’endothélium mais peuvent également apporter des informations utiles pour le diagnostic, le pronostic et le suivi thérapeutique des patients souffrant de pathologies associées à une dysfonction endothéliale. Une modification du nombre de CPE et de cellules endothéliales circulantes (CEC) dans la circulation a été rapportée dans différentes situations pathologiques respectivement associées à une régénération et une altération endothéliale telle l’augmentation du taux de CEC chez des patients présentant une hypertension artérielle pulmonaire (HTAP). La technique de référence pour le dénombrement des CEC dans le sang périphérique est l’immunoséparation magnétique (IMS). Cette méthode non automatisée et chronophage, repose sur l’énumération par microscopie à fluorescence des cellules CD146+ préalablement isolées. Bien que reproductible, cette numération est soumise à de nombreux biais de quantification, difficile à mettre en oeuvre et sujette à interprétation. La mise au point d’une méthode de détection automatisée des CEC par cytométrie à focalisation acoustique (AFC) s’est montrée fiable et robuste, dans une cohorte de patients atteints d’HTAP traitée ou non, constituant une alternative pertinente à l’analyse par microscopie. L’ensemble de ces travaux ouvre donc de nouvelles perspectives dans la détection des biomarqueurs cellulaires circulants impliqués dans la dysfonction endothéliale, proposant les VSEL comme nouvel acteur vasculogénique. / In endothelial dysfunction, circulating endothelial compartment simultaneously plays the role of actor involved in the regeneration of injured tissue and reflects endothelium state. In peripheral arterial disease (PAD), one of the research areas is the development of a cellular therapy product capable of inducing the formation of neo-Vessels. Faced with the difficulty to obtain and amplify endothelial progenitor cells (EPC) in adults, one of the assumptions lets consider the use of other cell types with vasculogenic properties. In patients with cardiovascular disease, and PAD in particular, bone marrow mononuclear cells and EPC show reduced angiogenic properties. We have demonstrated the ability of isolated mesenchymal stem cells (MSCs) from PAD patients to induce reperfusion by recruitment of endothelial cells in situ, with the same efficiency as that of healthy donors MSCs. MSCs do not differentiate into endothelial cells but act by paracrine. The second hypothesis of obtaining an autologous angiogenic cell therapy product is to sort cells more immature than the CPE and to differentiate them secondarily into endothelial lineage as the pathological cell model of hemangioma stem cells CD133 + which lets consider the Very Small Embryonic like stem cells (VSEL), CD133 + multipotent stem cells as a potential candidate of postnatal vascular cell. We have derived and cultured in angiogenic conditions VSEL that acquired a mesenchymal phenotype but exhibited a secretory profile similar to that of EPC. VSEL promote post-Ischemic revascularization and acquire an endothelial phenotype in vitro and in vivo suggesting that VSEL may be responsible for the endothelial lineage. VSEL also appear as a biomarker of endothelial dysfunction mobilized from bone marrow (BM) to peripheral blood (PB) in patients with PAD. Cellular circulating biomarkers are not only non-Invasive markers of endothelium but can also provide useful information for the diagnosis, prognosis and therapeutic monitoring of patients with endothelial dysfunction associated pathologies. Changing the number of EPC and circulating endothelial cells (CEC) in the circulation has been reported in different pathological situations respectively associated with endothelial regeneration and alteration such as the increase of CEC in patients with pulmonary arterial hypertension (PAH). The reference technique for the enumeration of CEC in peripheral blood is magnetic immunoseparation (IMS). This non-Automated and time-Consuming method, based on the enumeration by fluorescence microscopy of CD146 + cells isolated. Although reproducible, this count is subject to many through quantification, difficult to implement and subject to interpretation. The development of an acoustic focusing cytometry (AFC) method for automated detection of CEC has proved reliable and robust results, in a cohort of patients with PAH treated or not, constituting a relevant alternative analysis to microscopy. All of this work opens new perspectives in the detection of cellular circulating biomarkers involved in endothelial dysfunction, suggesting VSEL as new vasculogenic actor.

Introdução: Inúmeros estudos estabeleceram correlações entre o índice tornozelo-braço (ITB), um marcador de aterosclerose subclínica, e o prognóstico cardiovascular em diferentes populações. No entanto, poucos estudos avaliaram a correlação entre os valores do ITB e lesões cardiovasculares e renais, exclusivamente, em pacientes com hipertensão arterial e diabetes. Objetivo: Estudar a prevalência de alterações morfofuncionais cardíacas, carotídeas, retinianas e renais de acordo com a presença ou não de valores de ITB alterados (ITB <= 0,9 ou ITB > 1,4) em pacientes hipertensos com diabetes tipo 2. Métodos: Foram incluídos no estudo 99 pacientes hipertensos diabéticos com idade entre 50 e 80 anos. A aferição do ITB foi realizada em todos os pacientes por método validado e estes foram classificados em Grupo 1 (ITB normal, n = 49) ou Grupo 2 (ITB alterado, n =50). Todos os pacientes foram submetidos, em até 06 meses, à realização de ecodopplercardiograma, ultrassonografia de carótidas, retinografia colorida, aferição da taxa de filtração glomerular (TFG) e da albuminúria de 24h. Os pacientes foram analisados para a ocorrência ou não de um desfecho-composto ecocardiográfico que incluiu alterações morfológicas e funcionais cardíacas relevantes para a prática clínica. Os pacientes dos grupos 1 e 2 foram também comparados quanto à prevalência de placas carotídeas com ou sem repercussão hemodinâmica, TFG < 60 ml/mim/m2, albuminúria de 24h > 30mg e presença ou não de retinopatia. Por fim, foram comparadas as frequências médias das seguintes lesões de órgãos-alvo de ambos os grupos, considerando-se valor unitário para a presença de cada uma delas: hipertrofia do ventrículo esquerdo, retinopatia hipertensiva, TFG < 60 ml/min/m2 e estenose da artéria carótida interna > 50% do seu diâmetro. Resultados: A média de idade dos pacientes foi 65,4 ± 7 anos, sendo 61,6% deles do sexo feminino. A presença de níveis elevados de pressão arterial sistólica (153,4 ± 18 versus 170 ± 26 mmHg), de albuminúria de 24h > 30mg (55,3% versus 82,6%) e de TFG < 60 ml/min/m2 (12,8% versus 33,3%) foi significativamente maior (p < 0.05) entre os pacientes do Grupo 2. O desfecho-composto ecocardiográfico foi mais prevalente no grupo 2 (84,0% versus 59,2%; p = 0,006) e a frequência média de lesões de órgãos-alvo também foi maior nos pacientes do grupo 2 (0,36 ± 0,31 versus 0,19 ± 0,19; p = 0,001). Análise por regressão logística binária revelou que o ITB foi uma das variáveis preditoras independentes para o desfecho-composto ecocardiográfico (OR = 3,43; IC 95% = 1,07 - 11,0; p = 0,04). A partir da análise por regressão linear obteve-se um modelo final no qual o ITB foi uma das três variáveis preditoras independentes para a estimativa da frequência média de lesões de órgãos-alvo com coeficiente beta = 13,22 (1,81 - 24,63), ao lado da idade e do infarto prévio. Conclusão: Nossos dados mostram que valores de ITB alterados estão associados à maior prevalência de lesões em órgãos-alvo, principalmente alterações ecocardiográficas, em pacientes com hipertensão arterial e diabetes / Introduction: A lot of studies have established strong correlations between the ankle-brachial index (ABI), a marker of subclinical atherosclerosis and cardiovascular prognosis in different populations. However, few studies have assessed the correlation between the values of the ABI and cardiovascular and renal lesions in patients with hypertension and diabetes. Objective: To study the prevalence of cardiac, carotid, renal and retinal morphological and functional changes according to the presence or not of altered ABI values (ABI <= 0.9 or ABI > 1.4) in hypertensive patients with type 2 diabetes. Methods: It was included 99 diabetic hypertensive patients aged between 50 and 80 years. The measurement of the ABI was performed in all patients by validated method and they were classified in Group 1 (normal ABI, n = 49) or group 2 (altered ABI, n = 50). All patients were submitted, up to 6 months, to Doppler echocardiography, carotid ultrasound, color retinography, assessment of glomerular filtration rate (GFR) and 24h albuminuria. Patients were analyzed for the occurrence or not of a composite echocardiographic outcome which included morphological and functional cardiac alterations relevant to clinical practice. Patients in groups 1 and 2 were compared regarding the prevalence of carotid plaques with or without hemodynamic repercussion, TFG < 60 ml/min/m2, 24h albuminuria > 30 mg and the presence or not of retinopathy. Finally, we compared the prevalence of mean frequency of the following end-organ lesions of both groups, considering unit value for each one: left ventricular hypertrophy, hypertensive retinopathy, TFG < 60 ml/min/m2 and internal carotid artery stenosis > 50%. Results: The mean age of the patients was 65.4 ± 7 years, with 61.6% of them female. The presences of elevated levels of systolic blood pressure (153.4 ± 18 versus 170.0 ± 26 mmHg), of 24h albuminuria > 30 mg (55.3% versus 82.6%) and TFG < 60 ml/min/m2 (12.8% vs. 33.3%) were significantly greater (p < 0.05) among the patients of Group 2. The composite echocardiographic outcome was more prevalent in Group 2 (84.0% versus 59.2%, p = 0.006) and the average frequency of subclinical injury of target organs was also greater in patients of Group 2 (0.36 ± 0.31 versus 0.19 ± 0.19; p = 0.001). Binary logistic regression analysis revealed that the ABI was one of the independent predictors of composite echocardiographic outcome (OR = 3.43; IC 95% = 1.07 - 11.0; p = 0.04). From the linear regression analysis it was obtained a final model in which the ABI was one of three independent predictors for the estimation of the average frequency of end-organ damage with ? coefficient = 13.22 (1.81-24.63), besides age and previous myocardial infarction. Conclusion: Our data demonstrates that changed ABI values are associated with higher prevalence of subclinical end-organ lesions, principally changes in echocardiographic parameters, in patients with hypertension and diabetes

Peripheral vascular grafts are used for the treatment of peripheral arterial disease and arteriovenous grafts for vascular access in end stage renal disease. The development of neo-intimal hyperplasia and thrombosis in the distal anastomosis remains the main reason for occlusion in that region. The local haemodynamics produced by a graft in the host vessel is believed to significantly affect endothelial function. Single spiral flow is a normal feature in medium and large sized vessels and it is induced by the anatomical structure and physiological function of the cardiovascular system. Grafts designed to generate a single spiral flow in the distal anastomosis have been introduced in clinical practice and are known as spiral grafts. In this work, spiral peripheral vascular and arteriovenous grafts were compared with conventional grafts using ultrasound and computational methods to identify their haemodynamic differences. Vascular-graft flow phantoms were developed to house the grafts in different surgical configurations. Mimicking components, with appropriate acoustic properties, were chosen to minimise ultrasound beam refraction and distortion. A dual-beam two-dimensional vector Doppler technique was developed to visualise and quantify vortical structures downstream of each graft outflow in the cross-flow direction. Vorticity mapping and measurements of circulation were acquired based on the vector Doppler data. The flow within the vascular-graft models was simulated with computed tomography based image-guided modelling for further understanding of secondary flow motions and comparison with the experimental results. The computational assessments provided a three-dimensional velocity field in the lumen of the models allowing a range of fluid dynamic parameters to be predicted. Single- or double-spiral flow patterns consisting of a dominant and a smaller vortex were detected in the outflow of the spiral grafts. A double- triple- or tetra-spiral flow pattern was found in the outflow of the conventional graft, depending on model configuration and Reynolds number. These multiple-spiral patterns were associated with increased flow stagnation, separation and instability, which are known to be detrimental for endothelial behaviour. Increased in-plane mixing and wall shear stress, which are considered atheroprotective in normal vessels, were found in the outflow of the spiral devices. The results from the experimental approach were in agreement with those from the computational approach. This study applied ultrasound and computational methods to vascular-graft phantoms in order to characterise the flow field induced by spiral and conventional peripheral vascular and arteriovenous grafts. The results suggest that spiral grafts are associated with advanced local haemodynamics that may protect endothelial function and thereby may prevent their outflow anastomosis from neo-intimal hyperplasia and thrombosis. Consequently this work supports the hypothesis that spiral grafts may decrease outflow stenosis and hence improve patency rates in patients.

Η οπτική συνεκτική τομογραφία με τη χρήση συχνοτήτων ( FD-OCT) είναι μια ενδαγγειακή απεικονιστική μέθοδος που χρησιμοποιεί εγγύς στο υπέρυθρο φως, για να παράγει υψηλής ανάλυσης εικόνες του τοιχώματος του αυλού του αγγείου. Όπως και στην τεχνολογία υπερήχων, εκπέμπεται φωτεινή ενέργεια η οποία ανακλάται και εξασθενεί, σύμφωνα με την υφή του προσπιπτομένου ιστού. Το OCT μπορεί να απεικονίσει, με ανάλυση από 10 έως 20 μm, μικροδομές του αγγειακού τοιχώματος με εξαίσια λεπτομέρεια. Μέχρι σήμερα, η δυνατότητα εφαρμογής της μεθόδου είχε περιοριστεί σε μικρές αρτηρίες διαμέτρου έως 4mm και δεν είχε εφαρμοστεί in vivo στα αγγεία των κάτω άκρων, κάτωθεν του επιπέδου των βουβώνων. Σκοπός της παρούσας μελέτης είναι να αναφερθεί για παγκοσμίως πρώτη φορά η ασφάλεια και η σκοπιμότητα της απεικόνισης με Οπτική Συνεκτική Τομογραφία του αρτηριακού άξονα των κάτω άκρων , κάτωθεν του επιπέδου της βουβώνας ( μηροϊγνυακός άξονας και κνημιαία αγγεία), καθώς και οι σχετιζόμενες με το FD-OCT επιπλοκές. Επιπρόσθετα, να διερευνηθούν για πρώτη φορά, με τη χρήση FD-OCT, τα χαρακτηριστικά του αγγειακού τοιχώματος του ανωτέρω άξονα (τόσο πριν όσο και μετά από αγγειοπλαστική ή/και τοποθέτηση stent), η μορφολογία της αθηρωματικής πλάκας, η μορφολογία και η ποσοτικοποίηση της υπερπλασίας του νέου εσωτερικού χιτώνα (neointima) εντός του stent, η επαναστένωση εντός του stent (ISR) και η κακή εναπόθεση (malapposition) των stent struts σε μια σειρά από ασθενείς που πάσχουν από περιφερική αρτηριοπάθεια (PAD). Μελετήθηκαν, με ποσοτική ανάλυση του αυλού τους (Quantitative vascular analysis), αρτηρίες με διάμετρο έως 7 χιλιοστά. Μικτά χαρακτηριστικά από περιοχές πλούσιες σε λιπίδια, εναποθέσεις ασβεστίου και ασβεστοποιημένες πλάκες, νεκρωτικές περιοχές και ίνωση εντοπίστηκαν σε όλες τις απεικονιζόμενες αθηροσκληρωτικές βλάβες. Ωστόσο, με βάση το επικρατέστερο από τα παραπάνω απεικονιστικά χαρακτηριστικά, οι βλάβες στο πλαίσιο της έρευνας ταξινομήθηκαν ως αμιγώς ινωτικές, ως ινοασβεστοποιημένες, ως πλούσιες σε λιπίδια και τέλος ως νεκρωτικές/ασβεστοποιημένες. Συσσώρευση των μακροφάγων εντός της αθηρωματικής πλάκας σημειώθηκε σε μικρό ποσοστό των de novo αθηρωματικών αλλοιώσεων. Ποικίλοι βαθμοί υπερπλασίας του νέου έσω χιτώνα απεικονίσθηκαν σε όλες τις περιπτώσεις ISR αλλοιώσεων, με καθαρά ινωτικά χαρακτηριστικά και σημαντική νεοαγγείωση σε κάποιες από αυτές. Η νεοαγγείωση συνέπεσε με το επίπεδο της μέγιστης στένωσης του αγγειακού αυλού. Σημαντικού βαθμού διαχωρισμός με μεγάλο περιορισμό του αγγειακού αυλού, τέτοιος ώστε να απαιτηθεί να τοποθετηθεί ενδοαυλικό stent, ανιχνεύθηκε σε αρκετές περιπτώσεις της de novo αθηρωμάτωσης. Η ψηφιακή αφαιρετική αγγειογραφία παρέλειψε να προσδιορίσει μεγάλο ποσοστό των σοβαρών διαχωρισμών μετά από αγγειοπλαστική. Η νεοαθηροσκλήρυνση εντός του νέου έσω χιτώνα των κνημιαίων φαρμακευτικών stents (DES), είναι ένα συχνό εύρημα τόσο στους συμπτωματικούς όσο και στους ασυμπτωματικούς ασθενείς. Μπορούμε να υποθέσουμε ότι, κατά αναλογία με τα εμφυτευμένα DES στα στεφανιαία αγγεία, η ελαττωματική ενδοθηλιοποίηση που προκαλείται από την εκλυόμενη φαρμακευτική ουσία, μαζί με την νεοαγγείωση που αναπτύσσεται μεταξύ των stent struts, μπορούν να υποδαυλίσουν την νεοαθηροσκλήρυνση εντός του νέου έσω χιτώνα των κνημιαίων DES, η οποία μπορεί να οδηγήσει σε επαναστένωση εντός του stent (ISR) και απώλεια του εμβαδού του αυλού των περιφερικών αρτηριών. Οι παρατηρήσεις της μελέτης αυτής θέτουν σε αμφισβήτηση το παραδοσιακό τρόπο κατανόησης της περιφερειακής επαναστένωσης εντός του stent ως μιας απλής υπερπολλαπλασιαστικής απάντησης στο βαρότραυμα. Η απεικόνιση με FD-OCT είναι ένα βέλτιστο πειραματικό εργαλείο για την αξιολόγηση της εξέλιξης της αθηροσκληρωματικής νόσου και την επαναστένωση του αγγείου. Μπορεί να παρέχει υψηλής ευκρίνειας ενδοαγγειακή απεικόνιση κατά τη διάρκεια αγγειοπλαστικών επεμβάσεων στα κάτω άκρα και θα μπορούσε να αποδειχθεί κλινικά χρήσιμο για τον προσδιορισμό της εντός του stent πρόπτωσης ιστού και του strut malapposition. Παρ 'όλα αυτά, δεν πρέπει να χρησιμοποιηθεί ως εργαλείο για τη συνήθη κλινική πρακτική μέχρι να προκύψουν στοιχεία από περαιτέρω κλινικές δοκιμές για τον καθορισμό των ειδικών ενδείξεων της απεικόνισης με FD-OCT στις περιφερικές αρτηρίες. / Optical coherence tomography (OCT) is a catheter-based imaging method that employs near-infrared light to produce high-resolution intravascular images. OCT can readily visualize vessel microstructure at a 10- to 20-μm resolution with exquisite detail. To date, however, applicability of the method has been limited to small diameter arteries (≤4 mm). To the best of the author’s knowledge, this study is the first worldwide that demonstrates the safety and clinical feasibility of frequency domain Optical Coherence Tomography (FD-OCT) imaging of infrainguinal vessels in vivo during infrainguinal angioplasty procedures. It is also the first study that reports the use of intravascular FD-OCT to detect and characterize in-stent neointimal tissue following infrapopliteal drug eluting stent (DES) placement in patients suffering from critical limb ischemia. Quantitative lumen analysis of arteries with diameter up to 7 mm was performed. High-resolution OCT images provided exquisite two-dimensional axial and longitudinal views of the infrainguinal arteries and allowed thorough investigation of a variety of angioplasty sequela, including and not limited to intimal tears and dissection flaps, white and red thrombus, stent mesh malapposition, and intrastent plaque prolapse. Of interest, OCT identified cases of suboptimal postangioplasty outcome that single-plane subtraction angiography did not recognize and accounted. Mixed features of lipid pool areas, calcium deposits and calcified plaques, necrotic areas, and fibrosis were identified in all of the imaged atherosclerotic lesions. However, based on the predominant baseline imaging findings, lesions under investigation were classified as purely fibrotic, fibrocalcific, mostly lipid-laden and necrotic/calcified. Intraplaque accumulation of macrophages was noted in some of de novo atheromatic lesions. Varying degrees of neointimal hyperplasia were demonstrated in all cases of in stent restenosis (ISR) lesions with purely fibrotic features and considerable neovascularization in some of them. The latter finding coincided with the level of maximum vessel stenosis in all cases. Neoatherosclerosis following infrapopliteal DES placement is a frequent finding in both symptomatic and asymptomatic patients. Our preliminary observations allow us to speculate that analogous to coronary implanted DES, defective endothelialization induced by the eluted drug, along with neovascularization developing between the stent struts, may incite neointimal neoatherosclerosis, which may result in ISR and lumen loss of the peripheral arteries. It also seems that infrapopliteal neoatherosclerosis may be a significant contributing factor for ISR rather than a minor and sporadic process, highlighting the clinical significance of the phenomenon. Our observations put in dispute the traditional way of understanding peripheral in-stent restenosis as a simple hyperproliferative response to barotraumas and may explain the paramount importance of aggressive risk factor modification strategies. Neointimal neoatherosclerosis as identified by FD-OCT may have a role in the development of below-the-knee restenosis and thus warrants further investigation by larger controlled studies. Moreover, it may prove clinically useful for the determination of intrastent tissue prolapse and strut malapposition. FD-OCT should not be utilized as a tool for routine clinical practice until evidence from further clinical trials emerge to determine the specific indications for OCT imaging of the peripheral arteries.