Academic literature on the topic 'Vascular event'

Aims: To identify factors associated with vascular events in patients with giant cell arteritis (GCA). Methods: We performed a retrospective study of GCA patients diagnosed over a 20-year-period, who all underwent vascular imaging evaluation at diagnosis. Symptomatic vascular events were defined as the occurrence of any aortic event (aortic dissection or symptomatic aortic aneurysm), stroke, myocardial infarction, limb or mesenteric ischemia and de novo lower limbs arteritis stage 3 or 4. Patients with symptomatic vascular event (VE+) and without were compared, and risk factors were identified in a multivariable analysis. Results: Thirty-nine (15.4%) of the 254 included patients experienced at least one symptomatic vascular event during follow-up, with a median time of 21.5 months. Arterial hypertension, diabetes, lower limbs arteritis or vascular complication at diagnosis were more frequent in VE+ patients ( p < 0.05), as an abnormal computed tomography (CT)-scan at diagnosis ( p = 0.04), aortitis ( p = 0.01), particularly of the descending thoracic aorta ( p = 0.03) and atheroma ( p = 0.03). Deaths were more frequent in the VE+ group (37.1 versus 10.3%, p = 0.0003). In multivariable analysis, aortic surgery [hazard ratio (HR): 10.46 (1.41–77.80), p = 0.02], stroke [HR: 22.32 (3.69–135.05), p < 0.001], upper limb ischemia [HR: 20.27 (2.05–200.12), p = 0.01], lower limb ischemia [HR: 76.57 (2.89–2027.69), p = 0.009], aortic atheroma [HR: 3.06 (1.06–8.82), p = 0.04] and aortitis of the descending thoracic aorta on CT-scan at diagnosis [HR: 4.64 (1.56–13.75), p = 0.006] were independent predictive factors of a vascular event. Conclusion: In this study on GCA cases with large vessels imaging at diagnosis, aortic surgery, stroke, upper or lower limb ischemia, aortic atheroma and aortitis of the descending thoracic aorta on CT-scan, at GCA diagnosis, were independent predictive factors of a vascular event. Plain language summary Risk factors for symptomatic vascular events in giant cell arteritis This study was performed to identify the risk factors for developing symptomatic vascular event during giant cell arteritis (GCA) because these are poorly known. We performed a retrospective study of GCA patients diagnosed over a 20-year-period, who all underwent vascular imaging evaluation at diagnosis. Patients with symptomatic vascular event (VE+) and without (VE-) were compared, and risk factors were identified in a multivariable analysis. Thirty-nine patients experienced at least one symptomatic vascular event during follow-up, with a median time of 21.5 months. Arterial hypertension, diabetes, lower limbs arteritis or vascular complication at diagnosis were significantly more frequent in VE+ patients, as an abnormal CT-scan at diagnosis, aortitis, particularly of the descending thoracic aorta and atheroma. Deaths were more frequent in the VE+ group. Among 254 GCA patients, 39 experienced at least one vascular event during follow-up. Aortic surgery, stroke, upper and lower limb ischemia were vascular event risk factors. Aortic atheroma and descending thoracic aorta aortitis on CT-scan were vascular event risk factors. This study on GCA cases with large vessels imaging at diagnosis, showed that aortic surgery, stroke, upper or lower limb ischemia, aortic atheroma and aortitis of the descending thoracic aorta on CT-scan, at GCA diagnosis, were independent predictive factors of a vascular event.

Aim The aim of this article is to investigate the vascular safety profile of triptans through an analysis of the United States Food and Drug Administration Adverse Event Reporting System (FDA_AERS) database with a special focus on serious and unexpected adverse events. Methods A case/non-case analysis was performed on the reports entered in the FDA_AERS from 2004 to 2010: Cases were reports with at least one event included in the MedDRA system organ classes ‘Cardiac disorder’ or ‘Vascular disorders’, whereas non-cases were all the remaining reports. Co-reported cardiovascular drugs were used as a proxy of cardiovascular risk and the adjusted reporting odds ratio (adj.ROR) with 95% confidence intervals (95% CI) was calculated. Disproportionality signals were defined as adj.ROR value >1. Adverse events were considered unexpected if not mentioned on the relevant label. Results Among 2,131,688 reports, 7808 concerned triptans. Cases were 2593 among triptans and 665,940 for all other drugs. Unexpected disproportionality signals were found in the following high-level terms of the MedDRA hierarchy: ‘Cerebrovascular and spinal necrosis and vascular insufficiency’ (103 triptan cases), ‘Aneurysms and dissections non-site specific’ (15), ‘Pregnancy-associated hypertension’ (10), ‘Reproductive system necrosis and vascular insufficiency’ (3). Discussion Our analysis revealed three main groups of unexpected associations between triptans and serious vascular events: ischaemic cerebrovascular events, aneurysms and artery dissections, and pregnancy-related vascular events. A case-by-case assessment is needed to confirm or disprove their plausibility and large-scale analytical studies should be planned for risk rate estimation. In the meantime, clinicians should pay special attention to migraine diagnosis and vascular risk assessment before prescribing a triptan, also promptly reporting any unexpected event to pharmacovigilance systems.

SummaryPatients with peripheral arterial disease (PAD) are at high risk of major ischaemic events. Long-term data of all major ischaemic events in PAD patients are scarce and outdated, especially for patients with severe PAD requiring bypass surgery. Our objective was to define their longterm prognosis and develop a prediction model which quantifies this risk up to a decade after surgery. We conducted a retrospective cohort study in patients from the Dutch Bypass Oral anticoagulants or Aspirin (BOA) Study; a multicentre randomised trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery. The primary outcome was the composite event of nonfatal myocardial infarction, non-fatal ischaemic stroke, major amputation, and vascular death. Cumulative risks were assessed by Kaplan-Meier analysis and independent determinants by multivariable Cox regression models. From 1995 until 2009, 482 patients were followed for a median period of 7.8 years. Follow-up was complete in 94%. Overall 60% of patients experienced a primary outcome event, of which the majority was a vascular death (30%), followed by major amputations (12%). The primary cause of vascular death was a cardiovascular event (29%), whereas the minority was due to complications directly related to PAD (6%). Within five years after bypass surgery vascular death occurred in about a quarter of patients and within 10 years in nearly half of patients. This was double the rate as for non-vascular death. The primary outcome event occurred in over a third and over half of patients in 5 and 10 years after bypass surgery, respectively. From four independent determinants for the primary outcome event: age, diabetes, critical limb ischaemia, and prior vascular interventions, we developed a risk chart, which systematically classifies the 10-year risks of the primary outcome event, ranging from 25% to 85%. This study provided a detailed insight in the course of PAD long after peripheral bypass surgery and enables individual risk assessment of major fatal and non-fatal ischaemic events by means of cumulative incidences and a risk chart.

This thesis proposes a multidirectional methodological framework for a comprehensive ergonomic analysis and modelling of workflow for multi-modal vascular image-guided procedures (IGPs). Two approaches are employed to analyse the workflow: Discrete Event Simulation (DES) and purpose-oriented physical models. In contrast to previous studies, the proposed methodology looks in detail the actions carried out within the intervention rooms and the clinical experience during the procedures with three main objectives: to provide a deeper understanding of vascular procedures, to predict the impact of protocol modifications and to offer a framework to develop new image-guided protocols for the alternative use of Magnetic Resonance (MR) imaging in comparison with X-Ray Digital Subtraction Angiography (DSA). The methodological framework includes an assessment of commercial simulation software packages to evaluate their fitness to the specific requirements of this research. The novel methodology is applied to several cases studies of common vascular IGPs. In addition, a case of MR – guided focused ultrasound intervention demonstrates how it is possible to extend the framework to study non-vascular IGPs. The multi-disciplinary methodological framework described opens a new way to understand IGPs that could be used in prospective applications such as medical education and medical devices regulations.

La malaltia cardiovascular suposa un problema de salut mundial amb gran morbimortalitat associada. L’arteriosclerosi, que la ocasiona, és una malaltia inflamatòria sistèmica en la que hi influencien diversos factors de risc cardiovasculars: edat, gènere, hipertensió arterial (HTA), dislipèmia, tabac, diabetis mellitus (DM), obesitat i malaltia renal crònica (MRC). Altres factors com la fibril·lació auricular (FA) i la malaltia vascular prèvia (MVP) hi influencien. En ocasions es produeixen canvis en la placa d’ateroma que condueixen a l’infart, sigui en territori coronari, cerebrovascular o arterial perifèric. El per què es desenvolupen en unes artèries o unes altres no és del tot conegut però els pacients tendeixen a repetir esdeveniments en el mateix territori. La hipòtesi: Els factors de risc cardiovascular influencien d’una manera diferent que un accident vascular agut es presenti en un territori arterial o en un altre (Síndrome coronària aguda (SCA), accident cerebrovascular (AVC) o malaltia arterial perifèrica crítica (MAP)). S’han descrit les característiques d’una població de 2993 pacients consecutius que han ingressat a urgències d’un hospital general per SCA, AVC o MAP durant tres anys comparant els tres motius d’ingrés. La població estudiada presenta una elevada prevalença de factors de risc clàssic, té menys dones i més edat que d’altres poblacions descrites a la literatura. Els pacients estudiats presenten: 74.2 anys (62.9;81.4), 70.7% són homes, 75.6% HTA, 59% DLP, 20.2% DLP-aterogènica, 18.4% FA, 23% MRC, >35.7% MVP, DM en un 40%, i disglicèmia en 30.3%, diagnòstic de nou d’HTA en 7%. Determinar la HbA1C és una eina fàcil d’implementar i millora la detecció de nous casos de DM en pacients que ingressen per accident vascular agut. S’han diagnosticat 7.2% de DM de nou. Hi ha marge de millora en la prevenció secundària i el grau de control tant en SCA, AVC com en MAP. Destaca el menor ús de fàrmacs antihipertensius en el grup que ingressa per AVC. Un 6.6% dels pacients són èxitus durant l’ingrés, moren més els que ingressen per MAP i menys els SCA. Els factors que predisposen a reingressar per un nou accident vascular són: presència de MVP, MRC, DM i tabac. En canvi en els >75 anys aquests factors són: MVP i DM. En la població estudiada la dislipèmia, l’obesitat l’exposició al tabac (fumadors i exfumadors) i la MRC són els factors que més pesen a l’hora de presentar un primer SCA en comptes d’AVC o MAP. L’edat avançada, la HTA i la FA són els factors que més influencien a l’hora de presentar un AVC en comptes de SCA o MAP. L’edat avançada i la DM són els factors que influencien més a l’hora de presentar una MAP en comptes d’un accident vascular agut en forma de SCA o AVC. En els pacients amb DM el pes dels altres factors de risc per a presentar un accident en un determinat territori en comptes d’un altre s’atenua, mantenint-se la HTA i FA com a factors de major pes per patir un primer AVC respecte SCA i MAP.
Cardiovascular disease (CVD) represents a global health problem with high morbidity and mortality. Atherosclerosis, the cause of CVD, is a systemic inflammatory disease that is influenced by traditional cardiovascular risk factors: age, gender, high blood pressure (HBP), dyslipidaemia (DLP), smoking, diabetes mellitus (DM), obesity and chronic kidney disease ( CKD), as Atrial fibrillation (AF) and prior vascular disease (PVD) are also contributing factors to CVD. Changes in the atherosclerotic plaque can lead to an acute vascular event in different territories: acute coronary syndrome (ACS), cerebrovascular (stroke) or peripheral arterial critical limb disease (PAD). The development of a clinical atherosclerotic event in one arterial vascular territory is not fully understood, but patients tend to repeat events in the same territory. This thesis shows that an association between cardiovascular risk factors and the probability of developing an atherosclerotic event in a particular territory can be made. The study group consists on 2993 patients that were admitted consecutively in the emergency room due to an acute vascular event, ACS, CVA or PAD during a 3 years period. Demographic data, CVR factors, previous events (PVD), previous treatments, in hospital readmission and mortality during the study period were collected from the medical record in a data base. The study also included the evaluation lipid and glycaemic control (HvA1c) and renal function by blood samples analysis. The study compared the collected data for the three events. The analysis of data shows that the population included in this study had a high prevalence of classical CV risk factors, there were less proportion of women and first events appeared in older ages than other populations described in the literature. The characteristics of the studied group were: 74.2 years old [62.9; 81.4], 70.7% men, 75.6% HBP, 59% DLP 20.2% DLP-atherogenic, 18.4% FA, 23% MRC,> 35.7% PVD DM 40%, preDM in 30.3% and 7% of patients have been diagnosed of of new onset hypertension. HbA1C helped detecting 7.2% of new onset DM, showing that HbA1c study should be included for all patients diagnosed for an accute vascular event . The study shows that the secondary prevention for the vascular events included needs to be improved. In particular, we detected a lesser use of antihypertensive drugs in the patients admitted due to a first stroke even if they represented higher proportion of HBP. In our series there was 6.6% inhospital mortality. Mortality rate tended to be higher in patients admitted by PAD than by SCA. Predisposing readmission risk factors were: presence of PVD, CKD, DM and tobacco. However in the> 75 years these factors were: PVD and DM. Factors that have a positive influence on presenting ACS instead of the other two vascular accidents were: DLP, obesity, tobacco exposure (smokers and ex-smokers) and CKD. In the cerebrovascular territory predisposing factors are: the elderly, HBP and AF. Older age and DM are factors that influence in presenting PAD instead of an ACV or ACS. In DM patients the influence of other risk factors is attenuated when having the first acute vascular event. HBP and AF mantain their influence in suffering a first stroke in population with DM.

Contesto e scopo: La proproteina convertasi subtilisina/kexina di tipo 9 (PCSK9), uno dei principali regolatori del metabolismo del recettore delle LDL, è stata associata allo sviluppo di aterosclerosi. Diversi studi hanno confermato tale associazione attraverso vie lipidiche e non lipidiche. Tuttavia, le relazioni dirette tra PCSK9 circolante e marcatori di aterosclerosi subclinica e clinica sono ancora da chiarire. Pertanto, abbiamo valutato le relazioni tra i livelli plasmatici di PCSK9 ed alcuni indici di aterosclerosi subclinica (marcatori di imaging) e clinica (eventi vascolari; EV). Un altro obiettivo è stato l'identificazione dei determinanti indipendenti di PCSK9, con particolare attenzione ai lipidi e ai biomarcatori infiammatori. Infine, abbiamo anche valutato la relazione tra alcuni marcatori di imaging e quattro SNPs del gene PCSK9, noti per essere associati alla presenza di bassi livelli di colesterolo LDL. Per validare i risultati ottenuti in quest’ultima parte, le analisi genetiche sono state replicate in una coorte indipendente reclutata nel Regno Unito (UK). Metodi: Lo studio è stato realizzato sfruttando le banche dati, biobanche e la banca di immagini dello studio IMPROVE. 3,703 soggetti europei (54-79 anni; 48% uomini), privi di EV al basale e definiti ad alto rischio per la presenza di almeno tre fattori di rischio vascolare, sono stati reclutati e seguiti per 36 mesi. PCSK9 è stata misurata tramite ELISA e trasformata in logaritmo prima delle analisi. I marcatori di imaging convenzionali [spessore medio-intimale carotideo (cIMT, dall’inglese intima-media thickness) e dimensione della placca carotidea] ed emergenti [cambiamento di cIMT nel tempo, ecolucenza dello spessore del complesso medio intimale della carotide comune misurato in zone libere da placca (PF CC-IMTmean), ecolucenza della placca più grande rilevata in tutto l'albero carotideo e punteggio di calcio carotideo (cCS, dall’inglese carotid calcium score)] sono stati misurati su scansioni ultrasonografiche conservate nella banca di immagini. In particolare, l'ecolucenza è stata misurata in termini di mediana della scala dei grigi (GSM, dall’inglese grey scale median) della distribuzione dei pixel di una specifica regione d’interesse, mentre il cCS è stato calcolato come somma delle lunghezze dei coni d’ombra acustici generati dal calcio all'interno delle placche carotidee. I lipidi sono stati misurati con metodi enzimatici (ad eccezione del colesterolo LDL che è stato calcolato con la formula di Friedewald). Tra i marcatori infiammatori, la proteina C reattiva ad alta sensibilità (hs-PCR) è stata misurata con la turbidimetria, mentre il conteggio dei globuli bianchi (WBC, dall’inglese white blood cells) e la formula leucocitaria sono stati misurati localmente. Tutti i soggetti dello studio IMPROVE e della coorte UK (n=22,179; 48 % uomini) sono stati genotipizzati. Risultati: Nell'analisi univariata, PCSK9 correlava positivamente con colesterolo totale, LDL e HDL e con trigliceridi e basofili (tutte le p <0.0001), mentre correlava negativamente con neutrofili ed eosinofili (entrambe le p=0.04). Le correlazioni positive osservate con hs-PCR e con il conteggio dei WBC erano solo vicine alla significatività statistica (p=0.060 e 0.064, rispettivamente). Le terapie con fibrati o statine (positivamente; entrambe le p <0.0001), così come sesso maschile e storia familiare di diabete (negativamente; entrambe le p <0.05) erano i predittori indipendenti più forti dei livelli plasmatici di PCSK9. Nell'analisi non aggiustata, si osservava una correlazione negativa tra PCSK9 e variabili basali di cIMT (IMTmean, IMTmax, IMTmean-max, e PF CC-IMTmean), una correlazione negativa tra PCSK9 e la variazione di cIMT nel tempo (Fastest-IMTmax-progr) e cCS (tutte le p ≤0.01), mentre si osservava un trend positivo tra PCSK9 e GSM sia del PF CC-IMTmean che della placca carotidea (entrambe le p ≤0.0001). Il cCS (positivamente) e il GSM del PF CC-IMTmean (positivamente) erano associati significativamente (o vicini alla significatività) a PCSK9 in diversi modelli multivariati (tutte le p ≤0.064). Tutte le correlazioni osservate all’analisi univariata tra PCSK9 e le variabili basali di cIMT, Fastest-IMTmax-progr e GSM della placca carotidea perdevano la significatività statistica dopo aggiustamento delle stesse per età, sesso, latitudine ed altri potenziali confondenti. Durante il follow-up [mediana (intervallo interquartile): 3.01 (2.98; 3.12) anni], sono stati registrati 215 EV: 125 coronarici, 73 cerebrali e 17 EV periferici. Tra questi, 37 erano eventi hard (infarto miocardico, morte improvvisa ed ictus). Nell'analisi non aggiustata, PCSK9 era associata positivamente ad eventi combinati e coronarici (entrambe le p <0.01), ma non ad eventi cerebrovascolari. Anche in questo caso, tuttavia, tutte le associazioni osservate perdevano la significatività statistica dopo aggiustamento delle analisi per età, sesso e stratificazione per latitudine. La mancanza di associazione con EV era confermata anche nel modello aggiustato per tutti i fattori confondenti considerati e nelle analisi focalizzate sugli eventi hard. Per quanto riguarda il ruolo delle varianti genetiche, nessuno dei quattro SNPs considerati correlava con cIMT (IMTmean, IMTmax, IMTmean-max) quando l'analisi era effettuata nei soggetti reclutati nello studio IMPROVE. La variante rs11591147, invece, correlava negativamente con l’IMTmax misurato nella popolazione UK (p=0.002). Combinando le quattro varianti genetiche in uno score, la relazione con cIMT era non significativa nello studio IMPROVE, mentre era negativa e significativa nella popolazione UK (tutte le p <0.01). Conclusioni: I livelli plasmatici di PCSK9 non sono associati a EV. Per quanto riguarda i marcatori dell'aterosclerosi subclinica, i livelli plasmatici di PCSK9 non sono associati né alla dimensione della lesione, né all'ecolucenza della placca carotidea, ma sono associati all'ecolucenza dello spessore della parete carotidea e al carotid calcium score. Ulteriori studi sono pertanto necessari per comprendere meglio il ruolo di tale proproteina nell'ecolucenza dello spessore della parete carotidea e nel carotid calcium score. La terapia con fibrati o statine, così come il sesso maschile e la storia familiare di diabete sono i predittori indipendenti più forti di PCSK9 circolante. È stata inoltre confermata l'associazione, precedentemente osservata, tra PCSK9 circolante e alcuni marcatori lipidici ed infiammatori. La relazione tra i livelli plasmatici di PCSK9 ed altri marcatori infiammatori (neutrofili, basofili ed eosinofili) merita ulteriori indagini, così come merita ulteriori indagini l’associazione tra le quattro varianti genetiche di PCSK9 selezionate e il cIMT nella coorte britannica, in quanto lascia intravvedere un possibile ruolo di SNPs o polimorfismi genici di PCSK9 nell’aterosclerosi e nelle strategie della sua prevenzione.
Background and purpose: Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the main regulators of LDL receptor metabolism, has been associated with atherosclerosis development. Several studies have confirmed such association through both lipid and non-lipid pathways. However, the direct relationships between circulating PCSK9 and markers of subclinical and clinical atherosclerosis are still matter of debate. Therefore, we investigated the relationships between plasma PCSK9 levels and some indexes of subclinical (imaging markers) and clinical (vascular events; VEs) atherosclerosis. Another objective was the identification of the independent determinants of PCSK9, with particular attention to lipids and inflammatory biomarkers. Finally, we also assessed the relationship between some imaging markers and four SNPs of the PCSK9 gene, known to be associated with the presence of low levels of LDL-cholesterol. In order to validate the results obtained in this last part, the genetic analyses were replicated in an independent cohort recruited in the United Kingdom (UK). Methods: The study was carried out taking advantage of databases, biobanks and imaging-bank of the IMPROVE study. 3,703 European subjects (54-79 years; 48% men), free of VEs at baseline and defined at high risk for the presence of at least three vascular risk factors, were recruited and followed-up for 36 months. PCSK9 was measured by ELISA and log-transformed prior to analyses. Conventional imaging markers [carotid intima-media thickness (cIMT) and carotid plaque-size], and emerging imaging markers [cIMT change over time, echolucency of the intima-media thickess of common carotid measured in plaque free areas (PF CC-IMTmean), echolucency of the biggest plaque detected in the whole carotid tree, and carotid calcium score (cCS)] were measured on ultrasonographic scans stored in the imaging-bank. In particular, echolucency was measured in terms of grey scale median (GSM) of pixels distribution of a specific region of interest, whereas cCS was calculated as sum of lengths of acoustic shadow cones generated by calcium within carotid plaques. Lipids were measured with enzymatic methods (except for LDL-cholesterol, which was calculated by Friedewald's formula). Among inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) was measured by turbidimetry, whereas white blood cells (WBC) count and the leukocyte formula had already been measured locally. All the IMPROVE study and UK (n=22,179; 48% men) subjects have been genotyped. Results: In the univariate analysis, PCSK9 was positively correlated with total, LDL-, and HDL-cholesterol, and with triglycerides and basophils (all p <0.0001), whereas was negatively correlated with neutrophils and eosinophils (both p=0.04). The positive correlations observed with hs-CRP and WBC count were just close to the statistical significance (p=0.060 and 0.064, respectively). Fibrates or statins therapies (positively; both p <0.0001), as well as male sex and family history of diabetes (negatively; both p <0.05) were the strongest independent predictors of plasma PCSK9 levels. In the unadjusted analysis, a negative correlation was observed between PCSK9 levels and basal cIMT variables (i.e. carotid IMTmean, IMTmax, IMTmean-max, and PF CC-IMTmean), a negative correlation between PCSK9 and cIMT change over time (Fastest-IMTmax-progr) and cCS (all p ≤0.01), whereas a positive trend was observed between PCSK9 and GSM of both PF CC-IMTmean and carotid plaque (both p ≤0.0001). The cCS (positively) and the GSM of PF CC-IMTmean (positively) were significantly (or almost significantly) associated with PCSK9 in several multivariate models (all p ≤0.064). All correlations observed in the univariate analysis between PCSK9 and basal cIMT variables, Fastest-IMTmax-progr and GSM of carotid plaque lost the statistical significance after adjustment for age, sex, latitude, and other potential confounders. During the follow-up [median (interquartile range): 3.01 (2.98; 3.12) years], 215 VEs were recorded: 125 coronary, 73 cerebral and 17 peripheral VEs. Among these, 37 were hard events (i.e. myocardial infarction, sudden death and stroke). In the unadjusted analysis, PCSK9 was positively associated with combined and coronary events (both p <0.01), but not with cerebrovascular events. Also in this case, however, all the associations observed lost the statistical significance after adjustment of the analyses for age, sex, and stratification for latitude. The lack of association with VEs was confirmed also in the model adjusted for all confounding factors considered, and in the analyses focused on hard events. With regard to the role of genetic variants, none of the four SNPs considered was correlated with cIMT (i.e. IMTmean, IMTmax, IMTmean-max) when the analysis was performed in the subjects recruited in the IMPROVE study. The rs11591147 variant, by contrast, was negatively correlated with IMTmax measured in the UK population (p=0.002). By combining the four genetic variants in a score, the relationship with cIMT was not significant in the IMPROVE study, whereas was negative and significant in the UK population (all p <0.01). Conclusions: Plasma PCSK9 levels are not associated with VEs. Regarding markers of subclinical atherosclerosis, PCSK9 levels are associated neither with lesion size, nor with carotid plaque echolucency, but are associated with echolucency of carotid wall thickness and with carotid calcium score. Therefore, further studies are needed to better understand the role of such circulating proprotein in carotid wall thickness echolucency and in carotid calcium score. Fibrates or statins therapies, as well as male sex and family history of diabetes are the strongest independent predictors of PCSK9 levels. The associations, previously observed, between circulating PCSK9 and some lipid and inflammatory markers have been confirmed. The relationship between plasma levels of PCSK9 and other inflammatory markers (neutrophils, basophils and eosinophils) deserves further investigation, as does the association between the four selected PCSK9 variants and cIMT in the UK cohort, as it suggests a possible role of PCSK9 SNPs or gene polymorphisms in atherosclerosis and in its preventive strategies.

Diabetes in all its forms imposes unacceptably high human, social and economic costs on all countries and at all income levels, with Type 2 diabetes (T2D) consistently growing due to increasing rates of obesity, sedentary lifestyle and hypercaloric diets. The major cause of morbidity and premature mortality in people with diabetes is not so much the presence of diabetes itself, but the development of chronic diabetic complications, causing loss of vision, renal failure, amputations, coronary artery disease and stroke. In addition to hyperglycaemia, hypertension, dyslipidaemia and obesity, the related processes of inflammation, oxidative stress; and disturbed-angiogenesis, are important factors implicated in the development and progression of diabetic micro and macrovascular complications. These factors are also key therapeutic targets. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study is a landmark study of 9795 adults with T2D aged (at baseline) 50‐75 years from Australia, New Zealand and Finland. The double blinded randomised placebo controlled FIELD study demonstrated that the oral lipid lowering drug fenofibrate reduces the occurrence of serious vascular and new complications of T2D over 5-years, including sight-threatening diabetic retinopathy by 37%, nephropathy by 15%, and lower limb amputations by 36%; and also significant reductions in some types of cardiovascular disease. Interestingly, except for some of the renoprotection, the clinical benefits were independent of fenofibrate changes to traditional lipid levels. We propose that the pleiotropic effects of fenofibrate, such as related to growth factors, inflammation and oxidative stress may contribute to fenofibrate’s effects. We conducted a clinical research project to explore this hypothesis, with an emphasis on two growth factors, Pigment Epithelium Derived Factor (PEDF) and Kallistatin. Recent literature has identified two SERPIN growth factors, PEDF and Kallistatin, to have anti-angiogenic, anti-oxidant, and anti-inflammatory effects, and small cross-sectional studies have shown promising results for their involvement in vascular function and chronic diabetes complications. The overall aims of this research project were to investigate the T2D FIELD study cohort, to determine whether plasma PEDF and Kallistatin levels were associated with T2D and its vascular and neurologic complications, their correlations with traditional and novel vascular risk factors, and if and how they are changed by fenofibrate. This thesis consists of six chapters. Chapter one is an introduction and literature review related to diabetes and risk factors; and the FIELD study and PEDF and kallistatin. Chapter two describes the FIELD study, the substudy design, and the materials and methods for both PEDF and kallistatin analyses (by ELISA). Chapter three details an issue with the identification of suboptimal quantity of the batch to batch variation of the commercially available PEDF kits and the problem resolution. Chapter four outlines the study and results of the PEDF analysis. Mean PEDF levels were significantly higher in women than men. Baseline plasma PEDF levels significantly correlated positively, however weakly, with traditional and novel vascular risk factors, including HbA1c, BMI, insulin resistance, renal dysfunction, inflammation and oxidative stress, and inversely with HDL-C levels, and with eGFR. In addition, higher PEDF levels significantly predicted the development of on-trial composite macrovascular and microvascular complications, including nephropathy and amputations. Higher baseline PEDF was also associated with a reduced risk for retinopathy development. This data suggests a role for PEDF as a potential marker to evaluate future vascular health risk and as a potential therapeutic target and agent. Plasma PEDF levels are also significantly increased by fenofibrate. We suggest that some of fenofibrate’s clinical benefits may be via its effects on PEDF; and PEDF may be a therapeutic target. Chapter five outlines the study and results of kallistatin analysis in the FIELD study T2D subjects. Baseline plasma kallistatin levels significantly correlated positively, however weakly, with traditional and novel vascular risk factors, including HbA1c, TG, total cholesterol, HDL-C, abnormal apolipoprotein profiles, and renal dysfunction. Kallistatin was also found to inversely correlate with circulating levels of markers of inflammation, MPO, and cystatin C. Significant independent determinants of baseline plasma kallistatin levels were HDL-C, TG, systolic BP, HbA1c and BMI. Unlike PEDF levels, kallistatin levels were not found to significantly correlate with vascular complications at baseline, and on-trial. Kallistatin correlated with PEDF at baseline (r=0.15), and in response to fenofibrate, circulating kallistatin levels significantly decreased, opposite to that seen in PEDF. Chapter six is a thesis summary, summarising the key findings of each chapter, and suggests research directions to extend and enhance the study findings.

Fabry (FD) and Gaucher (GD) disease are lysosomal storage disorders, caused by single enzyme deficiencies on the glycosphingolipid degradation pathway as a result of genetic mutations in the GLA and GBA genes respectively. These result in a functional enzyme deficiency within the lysosome and accumulation of un-degraded substrate. GD is characterised by a bleeding tendency and bone infarction. Patients with FD suffer from a vasculopathy with strokes, proteinuric renal failure and cardiac conduction defects, but both disorders are highly heterogeneous. Abnormal cytokine profiles and a pro-inflammatory state have been found in both FD and GD, leading to the hypothesis that abnormalities at the blood-endothelial interface affecting coagulation and leucocyte adhesion contribute to the pathology of these disorders. This thesis demonstrates the importance of vascular manifestations in the presentation of both GD and FD with failure to identify the underlying cause of these manifestations resulting in delays between the onset of clinical manifestations and arrival at the correct diagnosis. Abnormalities at the blood-endothelial interface identified in GD include up-regulation of adhesion molecules on lymphocytes that may be of importance in the pathogenesis of bone disease, and increased thrombin generation in an endothelial cell model of GD. In FD, whilst cardiac and renal manifestations occur at earlier onset and with greater severity in men, cerebrovascular disease seems to affect both sexes to a similar degree. Monocytes from females with FD exhibit an age-dependent increase in adhesion mimicking the age-dependent increase in cardiac and renal disease seen in these patients but the mechanisms underlying cerebrovascular disease remain uncertain. Initial investigations of platelet prothrombinase activity suggest this may be enhanced in FD. Further investigation of these abnormalities at the cellular level may shed new insights on, and open up new therapeutic options, for the management of the vascular complications of these disorders.

What is known and objective: Although non-steroidal anti-inflammatory drugs (NSAIDs) have been studied in randomized, controlled trials and meta-analyses in an effort to determine their cardiovascular (CV) risks, no consensus has been reached. These studies continue to raise questions, including whether cyclooxygenase-2 (COX-2) selectivity plays a role in conferring CV risk. We performed a meta-analysis of current literature to determine whether COX-2 selectivity leads to an increased CV risk. Methods: We utilized randomized, controlled trials and prospective cohort studies. We selected eight NSAIDs based on popularity and COX selectivity and conducted a search of the MEDLINE, EMBASE, and Cochrane databases. Primary endpoints included any myocardial infarction (MI), any stroke, CV death, and a combination of all three (composite CV outcomes). Twenty-six studies were found that met inclusion and exclusion criteria. Comparisons were made between all included drugs, against placebo, and against non-selective NSAIDs (nsNSAIDs). Drugs were also compared against COX-2 selective inhibitors (COXIBs) with and without inclusion of rofecoxib. Results and discussion: Incidence of MI was increased by rofecoxib in all comparison categories [all NSAIDs (OR: 1·811, 95% CI: 1·379-2·378), placebo (OR: 1·655: 95% CI: 1·029-2·661), nsNSAIDs (OR: 2·155, 95% CI: 1·146-4·053), and COXIBs (OR: 1·800, 95% CI: 1·217-2·662)], but was decreased by celecoxib and naproxen in the COXIB comparison [(OR: 0·583, 95% CI: 0·396-0·857) and (OR: 0·609, 95% CI: 0·375-0·989, respectively]. Incidence of stroke was increased by rofecoxib in comparisons with all NSAIDs and other COXIBs [(OR: 1·488, 95% CI: 1·027-2·155) and (OR: 1·933, 95% CI: 1·052-3·549), respectively]. Incidence of stroke was decreased by celecoxib when compared with all NSAIDs, nsNSAIDs, and COXIBs [(OR: 0·603, 95% CI: 0·410-0·887), (OR: 0·517, 95% CI: 0·287-0·929), and (OR: 0·509, 95% CI: 0·280-0·925), respectively]. No NSAID reached statistical significance in regard to CV death. Incidence of the composite endpoint was increased by rofecoxib when compared against all NSAIDs, placebo, and other COXIBs [(OR: 1·612, 95% CI: 1·313-1·981), (OR: 1·572, 95% CI: 1·123-2·201) and (OR: 1·838, 95% CI: 1·323-2·554), respectively]. Incidence of composite endpoint was decreased by celecoxib in the all NSAIDs and COXIBs comparisons [(OR: 0·805, 95% CI: 0·658-0·986) and (OR: 0·557, 95% CI: 0.404-0.767), respectively]. When rofecoxib was removed from the COXIBs group, no difference was found with any comparison, suggesting rofecoxib skewed the data. What is new and conclusion: This instead of the meta-analysis suggests that COX-2 selectivity may not play a role in the CV risk of NSAIDs. Rofecoxib was the only drug to demonstrate harm and skewed the data of the COX-2 selective group.

La población española es considerada una población de bajo riesgo cardiovascular (RCV), a pesar de los eventos vasculares (EV) son una de las principales causes de muerte. Los eventos coronarios (EC) han sido la principal causa de muerte seguida de los eventos cerebrales (ECe). Objetivo: Determinar la incidencia de EV en una población mediterránea de bajo RCV después de 9 años de seguimiento, así como la influencia de los diferentes factores de riesgo vascular (FRV), en especial la arteriopatía periférica (AP) y la aparición de recurrencia. Material y métodos: El grupo ARTPER es un estudio poblacional prospectivo observacional iniciado en el ano 2006 y con un seguimiento hasta la actualidad, con una muestra inicial de 3.786 sujetos mayores de 49 anos, reclutados bajo muestreo simple aleatorio de diferentes centros de Atención Primaria. Se recogieron los datos socio-demográficos y las variables de RCV [Hipertensión arterial (HTA), Diabetes Mellitus (DM), Dislipemia (DSLP), tabaquismo, obesidad y AP]. Los EV y la morbi-mortalidad fueron las variables principales del estudio. Resultados: Los sujetos con AP presentan mayor incidencia de EV. El riesgo de mortalidad vascular es hasta 7 veces superior en individuos con AP respecto a los sanos. El riesgo de EC y ECe es mayor de 4 veces y 3 veces, respectivamente, en sujetos con AP, en relación con individuos con índice tobillo brazo (ITB) normal. Los sujetos con calcificación arterial (CA) no presentan diferencias en la incidencia de EV respecto a los sanos, excepto en ECe. La recurrencia de EV, independientemente de la etiología, es mayor en el grupo de AP (42%) respecto a los sanos (31%). La odds ratio (OR) de recurrencia de ECe de AP respecto a los sanos, tras ajustar por los FRV, es de 1,77. Conclusiones: La presencia de AP aumenta la incidencia de EV independientemente de FRV, así como el riesgo de recurrencia, especialmente en lo que se refiere a los ECe.
Spanish population is considered a low cardiovascular risk population although vascular events are the principal cause of death. Coronary events were ranked as the first in number of deaths in the general population, followed by cerebrovascular events. Objective: the aim of our study is to determine the incidence of vascular events in lowcardiovascular-risk general population after 9 years follow-up, as well as the influence of vascular risk factors, with a special interest in peripheral arterial disease patients and future events. Methods: ARTPER is an ongoing prospective observational population cohort study with 3786 subjects over 49 years old recruited (simple random sampling) from Primary Health Care Centers. We obtained demographic variables, different vascular risk scores, the presence of principal cardiovascular risk factors (hypertension, diabetes mellitus, hypercholesterolemia, smoking habit, obesity, abdominal obesity and peripheral arterial disease). Vascular events or morbi-mortality (vascular and non-vascular cause) were classified as end points. Results: Patient with peripheral arterial disease present higher incidence of vascular events. The risk of vascular mortality is up to 7 times higher in individuals with peripheral arterial disease than healthy population. The risk of coronary events and cerebrovascular events is greater than 4 times and 3 times respectively in subjects with peripheral arterial disease in contrast with healthy population. Subjects with arterial calcification do not present differences in the incidence of vascular events compared to healthy subjects, except in cerebrovascular events. The recurrence of vascular events independently of etiology is greater in in peripheral arterial disease (42%) compared to healthy group (31%). The Odds Ratio of recurrence of cerebrovascular events for patients with peripheral arterial disease vs healthy patients after adjusting for cardiovascular risk factor is 1.77. Conclusions: The presence of peripheral arterial disease increases the incidence of vascular evens independently of other vascular risk factors, as well as the risk of recurrence, especially in cerebrovascular events.

Methods: OXVASC is a population-based study of all acute vascular events (TIA, stroke, ACS and PVE) and those interventions for vascular disease in Oxfordshire. The pilot study covered a population of 90542 in 9 general practices. Summary of main findings: 1. The methods used in OXVASC achieved near-complete ascertainment. However, my analyses suggested that differences in case definition and ascertainment strategies between studies could each lead to differences in measured stroke incidence of up to 20%. 2. The early risk of recurrence can very twofold depending on which definition is used. The 90 day risks (95%CI) of recurrent stroke with a 24 hour definition of recurrence were 18.3%(10.8-25.8) in OXVASC and 14.5%(11.5-17.5) in OCSP. The equivalent risks using a 28 day definition of recurrence were 5.9%(1.0-10.9) in OXVASC and 4.8%(2.8-6.7) in OCSP. Recurrences occurring after 24 hours should be used as the standard to avoid underestimation and to allow valid comparison between studies. 3. In OXVASC the risks of stroke at 7 days after a TIA and minor stroke were 8.0% (95%CI=2.3-13.7) and 11.5%(95%CI=4.8-11.2) respectively. This is much higher than commonly quoted. 4. Recurrent stroke risk varies significantly between aetiological (TOAST) subtypes (p<0.001). Large artery atherosclerosis strokes have the highest odds of recurrence at 7 days (OR=3.3, 95%CI=1.5-7.0). They account for 37% of recurrences within 7 days highlighting the importance of urgent carotid imaging and avoiding delays before endarterectomy. 5. Incident stroke cases and their brain imaging were reviewed with the original OCSP principal investigator and neuroradiologist. 6. In OXVASC, acute cerebrovascular events accounted for 41.2% of all incident acute vascular events.

Arterial diseases are heavily intertwined with atherosclerosis and coronary artery disease and the presence of both symptomatic and asymptomatic peripheral artery diseases is known to affect the rate of cardiovascular events and deaths. Screening for abdominal aortic aneurysm (AAA) in selected populations is also a major issue for the cardiologist. Additionally, intima-media thickness and ankle-brachial index (ABI) measurements, screening for carotid or femoral plaques, and new techniques looking at the rigidity and elasticity of arteries may further help with risk stratification, especially in intermediary risk populations. Cardiologists may also encounter other conditions such as subclavian artery disease, arterial dissection, arterial entrapment, and arteritis (e.g. giant cell or Takayasu’s arteritis). Even if they don’t undertake imaging themselves, they should know about these diseases and when to refer patients. Although cardiac and vascular ultrasounds are complementary, they require a completely different skill set and formal training. The ultimate goal of this chapter is to define the basic principles that any cardiologist should know, and also provide guidance to cardiologists more interested in vascular diseases. For the benefit of the patient there is a need for collaboration between the different disciplines involved in vascular diseases according to local medical availability and skill.

Approximately 20 million strokes occur in the world each year and over one-quarter of these are fatal. This makes stroke the second most common cause of death, after ischaemic heart disease, and strokes are responsible for 6 million deaths (almost 10% of all deaths) annually. Stroke has major consequences in terms of residual physical disability, depression, dementia, epilepsy, and carer burden. Moreover, around 20% of survivors experience a further stroke or serious vascular event within a few years of the index event. The economic and societal costs of stroke are enormous. With ongoing demographic changes, including the ageing and urbanization of populations, and persistence of highly prevalent risk factors related to adverse lifestyles, the global burden of disease related to stroke is predicted to rise substantially by 2030.

That part of the clinical interface between neurology and general medicine occupied by inflammatory and immunological diseases is neither small nor medically trivial. Neurologists readily accept the challenges of ‘primary’ immune diseases of the nervous system: these tend to be focussed on one particular target such as oligodendrocytes or the neuro-muscular junction present in predictable ways, and are amenable as a rule to rational, methodological diagnosis, and occasionally even treatment. This is proper neurology.‘Secondary’ neurological involvement in diseases mainly considered systemic inflammatory conditions—for example, SLE, sarcoidosis, vasculitis, and Behçet’s—is a rather different matter. It may be difficult enough to secure such a diagnosis even when systemic disease has previously been diagnosed and new neurological features need to be differentiated from iatrogenic disease, particularly drug side effects or the consequences of immune suppression. But all the diseases mentioned may present with and confine themselves wholly to the nervous system; they may mimic one another, and pursue erratic and unpredictable clinical courses. In central nervous system disease, diagnosis by tissue biopsy is potentially hazardous and unattractive. Few neurologists enjoy excesses of confidence or expertise when faced with such clinical problems: the cautious diagnostician is perplexed, and the evidence-based neuroprescriber confounded. Unsurprisingly, great variations in approaches to diagnosis and management are seen (Scolding et al. 2002b).But rheumatologically inclined general, renal or respiratory physicians, comfortable when managing inflammation affecting their system or indeed other parts of the body designed to support the nervous system, are generally also ill at ease when faced with neurological features whose differential diagnosis may be large, particularly given the near universal diagnostic non-specificity of either imaging or CSF analysis.Here then is the subject material for this chapter: the diagnosis and management of central nervous system involvement in inflammatory and immunological systemic diseases (Scolding 1999a). In not one of these neurological conditions has a single controlled therapeutic trial been reported, and much that is published on these conditions is misleading or inaccurate. And yet the frequency with which the diagnosis is only confirmed or even first emerges at autopsy bears stark witness to both the severity and evasiveness of these disorders.

♦ 81–89% overall patient satisfaction following total knee replacement♦ 1 in 8 patients experience unexplained postoperative pain♦ Obesity, increasing age, and medical comorbidities increase the risk of postoperative complications♦ Prosthetic infection rate at 1 year is 1–2%♦ Preoperative range of movement often determines postoperative range♦ Low risk of acute vascular event and neurological and ligamentous injury♦ Duration and method of venous thromboprophylaxis remains controversial♦ Periprosthetic femoral and tibial fractures require stabilisation. Fixation of periprosthetic patella fractures is not recommended♦ New surgical techniques and innovations require long term evaluation.

Erectile dysfunction (ED) is defined as the inability to obtain or maintain a penile erection to support satisfactory sexual performance. It is considered an early manifestation of generalized vascular disease and recognized as a marker of increased cardiovascular risk both acutely and chronically by predicting all-cause mortality, cardiovascular mortality, coronary events, stroke, and peripheral artery disease in men with and without known coronary artery disease. The link between ED and cardiovascular disease might reside in the interaction between androgen level, chronic inflammation, and cardiovascular risk factors that determine endothelial dysfunction and atherosclerosis both in the penile and coronary circulation. Because penile artery size is smaller compared with coronary arteries, the same degree of endothelial dysfunction and atherosclerotic burden causes a more significant reduction of blood flow in erectile tissues compared with that in coronary circulation. From a clinical standpoint, because ED may precede cardiovascular disease, it can be used as an early marker to identify men at higher risk of cardiovascular events. The average 3-year time period between the onset of ED symptoms and a cardiovascular event offers the opportunity for detailed cardiological assessment and intensive treatment of risk factors.

Approximately 20 million strokes occur in the world each year and over one-quarter of these are fatal. This makes stroke the second most common cause of death, after ischaemic heart disease, and strokes are responsible for 6 million deaths (almost 10% of all deaths) annually. Stroke has major consequences in terms of residual physical disability, depression, dementia, epilepsy, and carer burden. Moreover, around 20% of survivors experience a further stroke or serious vascular event within a few years of the index event. Ischaemic stroke contributes the greatest share of the impact of stroke, with a rate of approximately 1 in 1000 person-years and accounting for between 60% (in Asia) and 90% (in Western ‘white’ populations) of all strokes around the world. Diagnosis and assessment are essentially clinical and confirmed by CT or MRI scanning. Prognostication is difficult in the early phase of haemorrhagic stroke and in ischaemic stroke is affected by the availability and timely use of treatments to recanalize the occluded vessel.

Despite being almost ubiquitous within the critically- ill population, vascular access remains a frequent cause of iatrogenic injury, manifested as both procedural complications and later events, such as infection and thrombosis. Untoward events are minimized by expert tuition and meticulous practical technique. Consensus guidelines on training in vascular access are discussed. Vascular access, particularly central catheterization, should not be undertaken lightly. Can a patient be managed without vascular access or can the number of vascular access devices be rationalized? Other routes for drug and fluid administration exist, particularly enterally during the recovery phase. This chapter covers vascular access during critical illness and discusses the development of more advanced techniques.

Stroke is a major public health issue. Many are treatable in the acute stage, provided patients are admitted soon enough. The overall incidence of stroke in Western countries is approximately 2400 per year per million inhabitants, and 80% are due to cerebral ischaemia. The prevalence is approximately 12 000 per million inhabitants. Stroke is associated with increased long-term mortality, handicap, cognitive and behavioural impairments, recurrence, and an increased risk of other types of vascular events. It is of major interest to take the heterogeneity of stroke into account, because of differences in the acute management, secondary prevention, and outcomes, according to the subtype and cause of stroke. In all types of stroke, early epileptic seizures, delirium, increased intracranial pressure, and non-specific complications are frequent. In ischaemic strokes, specific complications, such as malignant infarcts, spontaneous haemorrhagic transformation, early recurrence, and a new ischaemic event in another vascular territory, are frequent. In haemorrhagic strokes, the major complication is the subsequent increased volume of bleeding. There is strong evidence that stroke patients should be treated in dedicated stroke units; each time 24 patients are treated in a stroke unit, instead of a conventional ward, one death and one dependence are prevented. This effect does not depend on age, severity, and the stroke subtype. For this reason, stroke unit care is the cornerstone of the treatment of stroke, aiming at the detection and management of life-threatening emergencies, stabilization of most physiological parameters, and prevention of early complications. In ischaemic strokes, besides this general management, specific therapies include intravenous recombinant tissue plasminogen activator, given as soon as possible and before 4.5 hours, otherwise aspirin 300 mg, immediately or after 24 hours in case of thrombolysis, and, in a few patients, decompressive surgery. In intracerebral haemorrhages, blood pressure lowering and haemostatic therapy, when needed, are the two targets, but surgery does not seem effective to reduce death and disability.

AbstractErection is the final event of a complex phenomenon which involves psychological, neuronal, hormonal, vascular, and muscular systems. Nitric oxide (NO) is the most important molecule involved in many aspects of your health in vasodilation pathway. Erectile dysfunction (ED) is defined as the persistent inability to attain and/or maintain penile erection sufficient to permit satisfactory sexual performance with an high incidence worldwide and important impact on the quality of life.

Background: Cognitive vascular impairment (CCV) is a frequent, but overlooked, possible consequence of stroke. The most relevant markers in Magnetic Resonance Imaging (MRI) seem to be, among others, strategic location, severity of white matter changes, as well as the degree of atrophy of the medial temporal lobe. Objective: To assess the relationship between stroke and CCV using markers from MRI. Methods: Systematic review of observational studies published between 2005 and 2020. The search was carried out in the PubMed and SciELO databases with the keywords “stroke”, “MRI”, “Vascular cognitive impairment”. The PRISMA check-list was used to guide this review. Results: 8 studies were selected. “Event location” was the marker in MRI of the skull most frequently considered (7 studies). It proved to be a statistically significant marker (p <0.05) for the prediction of CCV in 6 out 7 studies. 75% of the studies included in this review evaluated the relationship between the presence of “hyperintensity in the white matter” at MRI and CCV. However, this marker was shown to be statistically significant in 50% of these studies. Conclusion: A review that brought together the assessment of a wide range of possible neuroradiological predictors of CVD after stroke had not been carried out so far. Yet it would be particularly useful to evaluate the markers in a more homogeneous way in a study with a larger sample size.

Background: Cognitive vascular impairment (CCV) is a frequent, but overlooked, possible consequence of stroke. Neuroimaging is essential for the evaluation of these patients with cognitive deficits supposedly secondary to vascular lesions, with Nuclear Magnetic Resonance (NMR) of the skull being the most sensitive method for identifying markers associated with CCV. The most relevant markers seem to be, among others, strategic location, severity of white matter changes, as well as the degree of atrophy of the medial temporal lobe. Objective: To assess the relationship between stroke and CCV using markers from skull MRI. Methodology: This is a systematic review of observational studies published between 2005 and 2020. The search was carried out in the PubMed and SciELO databases with the keywords consulted by the following MeSH and DeCS sites: “stroke”, “MRI”, “Vascular cognitive impairment”, using the boolean operator “and”. The PRISMA check-list was used to guide this review. Results: According to the eligibility criteria, eight studies were selected. “Event location” was the marker in MRI of the skull most frequently considered, being the object of evaluation in seven of the eight studies analyzed and proving to be a statistically significant marker (p <0.05) for the prediction of CCV in six of them. 75% of the studies included in this review evaluated the relationship between the presence of “hyperintensity in the white matter” at MRI and CCV. However, this marker was shown to be statistically significant in 50% of these studies. Conclusion: A review that brought together the assessment of a wide range of possible neuroradiological predictors of CVD after stroke had not been carried out so far. It would be particularly useful to evaluate the markers in a more homogeneous way in a study with a larger sample size, which would allow quantitative analysis to measure the influence of each predictor.

Abstract Over 350,000 percutaneous translumenal coronary angioplasty (balloon angioplasty) procedures are performed each year. This procedure offers a less invasive alternative to coronary by-pass surgery for patients whose coronary vessels have become occluded due to the process of atherosclerosis. Its potential has not been fully realized due to the high rate of restenosis — the rapid reocclusion of the vessel due to the pathological growth of the vascular smooth muscle (VSM) in response to the trauma of the balloon inflation. Despite the recognition of smooth muscle injury as an initiating event in the process of restenosis, there has been no systematic study to determine the mechanical loading conditions required to produce VSM injury and elicit the restenosis response. In this study, a cell culture model was developed to define the loading conditions required to produce VSM injury. The model system allows precise control of the applied strain and strain rate and quantification of the injury severity in terms of membrane damage. The determination of the threshold criteria for cell injury will allow the angioplasty procedure to be modified, and possibly automated, to minimize VSM injury and avoid the restenosis response.

Traumatic brain injury (TBI) is a leading cause of death and disability, affecting 1.7 million Americans annually, 50,000 of whom die [1]. Victims who survive the initial injury often suffer debilitating neurologic deficits. The total annual cost of TBI in the United States has been estimated at $60 billion [2]. While damage to brain tissue is of primary concern in TBI, nearly all head trauma includes some element of vascular injury or dysfunction [3], putting neural tissue uninjured in the primary event at subsequent risk. Contusion, which includes injury to both brain and vessel tissue in the cortex, is considered the hallmark of head injury, but little is known about the specific mechanisms of vascular injury in contusion. Previous efforts to elucidate mechanisms and thresholds for contusion, including inanimate gel, animal, and computational models [e.g. 4–7], have defined bulk tissue deformations that are associated with contusion, but the relationship to vascular injury is not clear. In order to address this question, our laboratory is studying acute disruption of the blood-brain barrier using a controlled cortical impact (CCI) mouse model. The objective of this study was to compare acute vascular injury in CCI with cortical mechanics predicted by a computational model of the experiment. This comparison is then discussed in the context of results from isolated vessels testing in our laboratory.

Context:The importance of a thorough neurological examination of the patient should always include research into differential diagnoses such as vascular syndromes, increasingly common in our population. Case report: A 46-year-old man evaluated and screened by the Neurosurgery’s department team, after an initial complaint of sudden onset low back pain and acute weakness in both lower limbs. The patient was healthy before the event. Patient didn’t have pathological history or use of chronic medications, referring only to use sporadic medication for sexual impotence, approximately 6 months ago. Observation revealed pale cold lower limbs, with livedo reticularis. Pulses of the femoral artery were absent bilaterally. Neurological examination revealed complete flaccid paraplegia with neurological level of L1. Below this level loss of pain, light touch and temperature sensation (0/2 in all dermatomes on both extremities), muscle weakness (0/5 in all neurotomes bilaterally), absent tendon and plantar reflexes. Axial tomography of the lumbar spine didn’t reveal vertebral lesions or pressure within the spinal canal. Consultation of the vascular surgeon confirmed absence of blood flow through femoral arteries and emergency angiotomography of the abdominal aorta showed complete occlusion of the descending aorta, upper renal arteries. Patient underwent percutaneous embolectomy treatment, with successful revascularization of lower extremities; unfortunately died about 10 hours after surgery due the development of revascularization syndrome. Conclusions: Acute aortic occlusion is a catastrophic event and can present itself as flaccid paraplegia, leading to misdiagnosis and loss of valuable time for positive outcome. Vascular examination should always be performed on each patient with neurological deficit in lower limbs, especially patients with clinical history of peripheral vascular disease. Immediate start of treatment is imperative to improve survival rates.

Metastasis is a complex process mediated by both adhesion molecules and chemokine secretion [1]. One important event during cancer metastasis is tumor cell extravasation through the endothelium [1]. In melanoma cancer, tumor cell extravasation is mediated by very late antigen (VLA)-4 molecule adhesion to vascular cell adhesion molecules (VCAM)-1 on endothelial cells [2]. High expression levels of VLA-4 integrin are associated with a marked increase in melanoma extravasation through endothelial layers [2]. The binding of VLA-4 to VCAM -1 induces the activation of downstream mitogen activated protein kinase (MAPK) signaling cascades, which regulate the vascular endothelial (VE)-cadherin junctions that hold together endothelial cells [2].

End-stage renal disease (ESRD) occurs as a result of any renal injury that chronically decreases renal excretory and regulatory function. ESRD patients are most commonly treated with hemodialysis (HD) to manage their renal failure while awaiting kidney transplant. Current practices for maintenance of HD vascular access consist of arteriovenous fistulas (AVFs) or grafts (AVGs), which are both fraught with problems that compromise the patency and use of these surgically created shunts. The major cause of shunt failure is thrombosis caused by occlusion of the outflow venous anastomosis and draining vein. Intimal hyperplasia (IH), which consists of the thickening of the innermost layer of the vessel wall, is the initial pathological event leading to shunt stenosis/thrombosis and has been associated with the presence of flow disturbances and abnormal wall shear stress (WSS) at the graft-vein anastomosis. Therefore, the improvement of HD via the enhancement of vascular access patency requires the development of a novel vascular access technology preserving the normal hemodynamics of the native vein.

Abdominal Aortic Aneurysm (AAA) is a vascular disease that occurs predominantly in people over 60 years of age. The rupture of an AAA is a catastrophic event associated with up to a 90% mortality rate. Hence, it is important for vascular surgeons to justify the risk of repair vis-à-vis the risk of aneurysm rupture. In clinical practice, rupture risk assessment is based on measuring the maximum aneurysm diameter where 5.5 cm is accepted as the critical size for recommending (surgical or endovascular) intervention. However, this criterion is based on an extensive history of evidence-based medicine rather than an individualized assessment of the aneurysm’s potential to rupture. Primary among the biomechanical factors associated with the rupture assessment of an AAA is mechanical wall stress, which is dependent on the accuracy of the geometry reconstruction, intraluminal pressure loading and the constitutive material model used for the aortic wall. We hypothesize that in unruptured, asymptomatic AAA, the wall mechanics is the outcome of primarily the patient specific aneurysm shape and to a lesser extent, the constitutive material property model used to characterize the vascular wall. Evaluating the relative contributions of wall material properties and AAA geometry to wall mechanics estimation will increase our understanding of the factors that influence peak wall stress as an indicator for rupture risk assessment. In the present work, we evaluate the aforementioned hypothesis using a size-matched approach.

Cell adhesion to postcapillary vascular endothelium in the fluid dynamic environment is an important event in many physiological and pathological processes, e.g. leukocyte emigration is critical for the successful host defense against tissue injury and infection. Since cell-blood interaction is strongly coupled with cell adhesion in the microchannel, we have developed an integrated mathematical model of cell adhesion, deformation, and rolling. Cells are modeled as elastic solids interacting with the flat wall of a micro-channel. The ligand-receptor bonds between the cell and micro-channel wall are simulated as many simple springs. The formation and dissociation rates of bonds are characterized by a reversible kinetic model (Dembo et al., 1988).

Pulse wave (PW) is a physiological event, observable and measurable in the arterial system during blood circulation. One of characteristics that can be determined from a PW record is heart rate variability (HRV), an indication of beat-to-beat alterations in the heart rate. HRV is an accurate and reliable reflection of several physiological factors modulating the normal rhythm of the heart. HRV has escalated in use as an important diagnostic tool which indicates the balance between sympathetic and parasympathetic branches of the autonomous nervous system (ANS) and the synchronization between them. HRV patterns are also sensitive to changes in emotional state and can be used to distinguish positive and negative emotions. However, HRV is just one of characteristics that can be extracted from a good quality pulse wave record. Other characteristics of the PW in the time and frequency domains can serve as an indication of the status of a cardio-vascular system. Modern personal health monitoring tools, which use data processing capability of smartphones and personal computers, make daily or even continuous HRV analysis available for users who are affected by sedentary life style, high stress, and fatigue. The practical application of the PW monitoring requires, besides software and electronic, selection of clinically meaningful characteristics of the pulse wave and communicating them to a non-medical user. For this purpose, it is proposed to use, in addition to HRV, to use the characteristics based on duration of the four phases of the pulse wave, and compare them with the baseline level obtained for the same user under non-stressed conditions. Deviations from the baseline are presented to the user. Correlation of these readings with objective parameters of the cardio-vascular system is supported by clinical data.

The Southeast Coast Network (SECN) conducts long-term terrestrial vegetation monitoring as part of the nationwide Inventory and Monitoring Program of the National Park Service (NPS). The vegetation community vital sign is one of the primary-tier resources identified by SECN park managers, and it is currently conducted on 15 network parks (DeVivo et al. 2008). Monitoring plants and their associated communities over time allows for targeted understanding of ecosystems within the SECN geography, which provides managers information about the degree of change within their parks’ natural vegetation. 2019 marks the first year of conducting this monitoring effort on four SECN parks, including Timucuan Ecological and Historic Preserve (TIMU). A total of 23 vegetation plots were established in the park in May and June. Data collected in each plot include species richness across multiple spatial scales, species-specific cover and constancy, species-specific woody stem seedling/sapling counts and adult tree (greater than 10 centimeters [3.9 inches (in)]) diameter at breast height (DBH), overall tree health, landform, soil, observed disturbance, and woody biomass (i.e., fuel load) estimates. This report summarizes the baseline (year 1) terrestrial vegetation data collected at Timucuan Ecological and Historic Preserve in 2019. Data were stratified across three dominant broadly defined habitats within the park (Coastal Plain Nonalluvial Wetlands, Coastal Plain Open Uplands and Woodlands, and Maritime Upland Forests and Shrublands) and three land parcels (Cedar Point, Theodore Roosevelt, and Thomas Creek). Noteworthy findings include: A total of 157 vascular plant taxa (species or lower) were observed across 23 vegetation plots, including nine species not previously known from the park. Three plots were located in the footprint of the Yellow Bluff Fire, and were sampled only two weeks following the fire event. Muscadine (Muscadinia rotundifolia), cat greenbrier (Smilax glauca), water oak (Quercus nigra), and swamp tupelo (Nyssa biflora) were the most frequently encountered species in Coastal Plain Nonalluvial Wetland habitat; saw palmetto (Serenoa repens), slash pine (Pinus elliottii), and gallberry (Ilex glabra) were the most frequently encountered species in Coastal Plain Open Upland and Woodland habitat; and Darlington oak (Quercus hemisphaerica), Spanish moss (Tillandsia usenoides), and red bay (Persea borbonia) were the most frequently encountered species in Maritime Upland Forests and Shrublands. There were no exotic species of the Florida Exotic Pest Plant Council list of invasive plants (FLEPPC 2020) observed on any of these plots. Both red bay and swamp bay (Persea palustris) were largely absent from the tree stratum in these plots; however, they were present (occasionally in high abundance) in the seedling and sapling strata across all habitat types. Buckthorn bully (Sideroxylon lycioides)—listed as Endangered in the state of Florida by the Florida Department of Agriculture and Consumer Services (FDACS 2020)—was observed in three Maritime Upland Forest and Shrubland plots. The tree strata in each broadly defined habitat were dominated by the following species: Coastal Plain Nonalluvial Wetlands-loblolly bay (Gordonia lasianthus) Coastal Plain Open Uplands and Woodlands-longleaf pine (Pinus palustris) Maritime Upland Forests and Shrublands-oaks (Quercus sp.) Most stems within the tree strata exhibited healthy vigor and only moderate dieback across all habitat types. However, there was a large amount of standing dead trees in plots within Maritime Upland Forests and Shrublands. Downed woody biomass (fuel loads) were highest in the Cedar Point and Thomas Creek land parcels.