AAA disease remains a common and life threatening condition, predominantly affecting men of retirement age. Whilst clinical studies have done much to predict the course of this disease, understanding the pathogenesis has been complicated by both a multi-factorial aetiology as well as several poorly defined stages to the disease (formation, growth and rupture). Evidence points to a considerable inheritable component to this condition, but as yet, associations with identified genetic variants are few and weak. This thesis describes the current understanding of the molecular mechanisms behind AAA pathogenesis, concentrating on aneurysm formation and growth. A meta-analysis of published candidate gene studies identified three genes with small but significant effects on risk of developing AAA (ACE, MTHFR and MMP9) and none with a significant effect on AAA growth. Further examination of five genes connected the Renin-Angiotensin System, using three distinct case control series, demonstrated the strongest reported association to date with AAA disease risk, with AGTR1+1166A>C. (OR 1.55 [1.30-1.83, p=5x10-7]). An interest in the role of the TGF-β pathway in AAA formation and growth has developed from the recent illumination of the mechanism behind aneurysm aetiology in Marfan syndrome. Haplotype analysis was used to investigate five genes coding for TGF-β and its binding protein (LTBP). Variants in TGFB3 and LTBP4 were significantly associated with altered AAA growth. The importance of inflammatory process was also supported by observations made in a very large longitudinal data set of AAA growth. Anti-inflammatory drugs, together with anti-platelet drugs and drugs used in diabetes, were significantly associated with decreased AAA growth independent of confounding factors. In conclusion, this thesis demonstrates; a role for the RAS in AAA formation; TGF-β in AAA growth; and anti-inflammatory drugs as potentially disease modifying. In addition, observations have also been made concerning a two tier effect illuding to the nature AAA progression.

No description available.

In 1963 – 1965, a large-scale health screening survey was undertaken in Sweden and this data set was linked to data from the national cause of death register. The data set involved more than 60,000 participants whose age at death less than 80 years. During the follow-up period until 2007, a total of 437 (338 males and 99 females) participants died from aortic aneurysm. The survival analysis, continuation ratio model, and logistic regression were applied in order to identify significant risk factors. The Cox regression after stratification for AGE revealed that SEX, Blood Diastolic Pressure (BDP), and Beta-lipoprotein (BLP) were the most significant risk factors, followed by Cholesterol (KOL), Sialic Acid (SIA), height, Glutamic Oxalactic Transaminase, Urinary glucose (URIN_SOC), and Blood Systolic Pressure (BSP). Moreover, SEX and BDP were found as risk factors in almost every age group. Furthermore, BDP was strongly significant in both male and female subgroup.   The data set was divided into two sets: 70 percent for the training set and 30 percent for the test set in order to find the best technique for predicting aortic aneurysm. Five techniques were implemented: the Cox regression, the continuation ratio model, the logistic regression, the back-propagated artificial neural network, and the decision tree. The performance of each technique was evaluated by using area under the receiver operating characteristic curve. In our study, the continuation ratio and the logistic regression outperformed among the other techniques.

Thèse--Faculté de médecine de Paris.

Kollberg, S. Torbjörnsson, E. (2012). The lived experience in patients with screening-diagnosed abdominal aortic aneurysm (AAA).     ABSTRACT The aim of this study was to describe the patients’ experiences of living with the knowledge of having an abdominal aortic aneurysm (AAA) that was found during screening. Eleven patients from two different screening centers, with initially measured aneurysms of 40-46 mm, were invited to participate in the interview study. Three of the men declined to participate, so in total eight men were interviewed. The interviews were analyzed by qualitative content analysis.  Four categories were identified: the informant’s reasons for taking part in the screening program for abdominal aortic aneurysm, the experience of the screening, the experience of living with their abdominal aortic aneurysm and the thoughts on the present screening program. The result showed that the men joined the screening program (SCP) with very little knowledge of both aneurysms and the purpose of the screening. In connection with the ultrasound the men became upset over the information about them having an AAA. After they had received information about the diagnose from the vascular surgeon , all of the men felt soothed and understood that despite of their aneurysm, they could continue to live their life as they used to do. The men didn’t believe that the AAA affected their lives, though most of them had made changes in their way of living.   The result of this interview study shows that the men experience a lack of information between the ultrasound and the appointment with the physician. It could be of interest to investigate if an aortic nurse with the same function as the breast nurse in the mammography screening could be the solution of this problem.   Keywords: Abdominal Aortic Aneurysm, screening, information / Kollberg, S. Torbjörnsson, E. (2012). The lived experience in patients with screening-diagnosed abdominal aortic aneurysm (AAA).   SAMMANFATTNING Syftet med den här studien var att beskriva patienternas upplevelse av att leva med kunskapen av att ha en förstorad kroppspulsåder som är hittat via screening. Elva patienter från två olika screeningcenter, med en ursprunglig diameter på sin aorta uppmätt till 40 – 46 mm, bjöds in för deltagande i studien. Tre avböjde att delta, så totalt utfördes åtta intervjuer. Intervjuerna analyserades med kvalitativ innehållsanalys. Fyra kategorier identifierades: Informanternas anledning till att delta i screeningprogrammet, upplevelsen av screeningen, upplevelsen av att leva med AAA och patienternas tankar om det nuvarande screeningprogrammet. Resultatet visade att männen deltog i screeningsprogrammet (SCP) med en begränsad kunskap både om vad aneurysm är och vad syftet med screeningen är. I samband med ultraljudsundersökningen blev männen upprörda över beskedet att de har ett förstorat aneurysm, men efter besöket hos en kärlkirurg som gav information om diagnosen blev de lugnade och förstod att det går bra att fortsätta leva som vanligt trots deras diagnos. Männen i studien tyckte inte att diagnosen påverkade de i deras dagliga liv, trots att många av dem hade genomfört förändringar. Resultatet av den här studien visar att männen upplever en brist i informationen mellan ultraljudsundersökningen och besöket hos läkaren. Det skulle vara intressant att se om en aortasjuksköterska, med samma funktion som en bröstsjuksköterska inom mammografiscreeningen har, skulle kunna vara en lösning på problemet.   Nyckelord: Abdominellt aorta aneurysm, screening, information   Abstraktet är justerat efter instruktioner i Journal of Vascular Nursing

Thesis (Ph. D.)--University of Wisconsin--Madison, 1963. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Made available in DSpace on 2014-06-11T19:22:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2003Bitstream added on 2014-06-13T19:08:21Z : No. of bitstreams: 1 mello_fmc_me_botfm.pdf: 590394 bytes, checksum: 6bd49179dbdb5496cc2a8f6a9ebad2ed (MD5) / Com o objetivo de avaliar a ocorrência de aneurisma da aorta abdominal infra-renal (AAAIR), estudou-se uma amostra da população masculina do Município de Marília, com idade igual ou acima de 50 anos, no período de 2000 a 2002. Foram avaliados 240 homens por meio da ultrasonografia abdominal (USAb), com média de idade de 65,1 anos (±9,8 anos). A aorta abdominal foi medida no sentido ânteroposterior (AP) e látero-lateral (LL) aproximadamente a 2cm abaixo da artéria mesentérica superior (AMS) e 2cm acima de sua bifurcação. O critério utilizado para considerar aneurisma foi o maior diâmetro encontrado igual ou maior que 3,1cm. Também por questionário, foram avaliados os fatores de risco (tabagismo, sedentarismo, alimentação) e as doenças associadas (HAS, DPOC, IM, DM, AOP ou hiperlipidemia). Nos 240 homens, foram encontrados 11 aneurismas, sendo, portanto, a freqüência de 4,6%. Desses 11 aneurismas, 8 mediam entre 3,1 e 4cm (72,7%) e 3, entre 4,1 e 5cm (27,3%). O maior diâmetro da aorta aneurismática foi de 5 cm (sentido AP a 2cm abaixo da AMS). Foi encontrada uma associação significativa entre aneurisma e AOP e DM, não ocorrendo o mesmo com os demais fatores de risco ou outras doenças associadas. A freqüência de aneurisma encontrada em nossa amostra não foi diferente da referida nos estudos populacionais publicados na literatura, o que mostra a importância da doença em nosso meio, e os indivíduos com AOP e DM têm risco maior de desenvolver a doença. / In order to evaluate the occurrence of Infra-Renal Abdominal Aortic Aneurysm (AAAIR), a sample of the male population in the city of Marília aged 50 years or older was studied from 2000 to 2002. A group of 240 men with mean age of 65,1 years (±9,8 years) was evaluated through abdominal ultra-sonography examination. The abdominal aorta was measured in the anteroposterior (AP) and in the latero-lateral directions (LL) approximately 2cm below the superior mesenteric artery and 2cm above its bifurcation. The largest diameter equal or larger than 3.1cm found was the criterion used for aneurysm. Risk factors such as smoking, eating, and exercise habits and associated diseases (systemic arterial hypertension, chronic obstructive pulmonary disease, myocardial infarction, diabetes mellitus, occlusive peripheral arterial disease, or hyperlipidemia) were also evaluated through questionnaires. Eleven aneurysms were found in the 240 men, which meant a frequency of 4,6%. Out of these 11 aneurysms, 8 measured from 3.1 to 4cm (72,7%) and 3 measured from 4.1 to 5cm (27,3%). The largest diameter of the aneurysmatic aorta was 5cm (AP direction approximately 2cm of the superior mesenteric artery). A significant association between aneurysm and peripheral vascular disease and diabetes mellitus was found. The same did not occur with the other risk factors or other associated diseases. The frequency of aneurysm found in our sample was not different from the frequency mentioned in population studies published in the literature, which shows the importance of the disease in our environment and that patients with peripheral vascular disease and diabetes mellitus have a higher risk to develop the disease.

Abstract Fibrillar type I and III collagens are the major constituents of the extracellular matrix, providing the tissue with tensile strength and influencing cell attachment and migration. The amount of type III collagen and the extent of its processing and cross-link maturation were studied in human atherosclerotic plaques, abdominal aortic aneurysms, colon and ovarian cancer, and finally, colon diverticulosis, using a novel radioimmunoassay for the cross-linked aminoterminal telopeptide of type III collagen. In addition, immunoassays for different structural domains of type I and type III collagens, together with immunohistochemical methods, were applied. In atherosclerotic plaques, the fully cross-linked type III collagen was the major collagen type. Type III collagen was completely processed, since the amount of type III pN-collagen was negligible. The amounts of free type I and III procollagen propeptides in the soluble fraction were small, indicating a low rate of collagen turnover. The proportion of type III collagen was lower in abdominal aortic aneurysms than in atherosclerotic aortic control samples. Furthermore, the amount of type III pN-collagen was significantly increased in aneurysms. Type I and III collagens were also maturely cross-linked in colon diverticulosis, the only difference from normal colon tissue being the increased amount of the aminoterminal propeptide of type III procollagen in the soluble tissue extract, indicating a slightly increased metabolic activity of type III collagen. In malignant ovarian tumors, the cross-linking of type I and III collagens was defective. A similar trend was also seen for type I collagen in colon cancer. Even though procollagen synthesis was increased in these malignancies, the total collagen content and the amounts of cross-linked collagens were decreased. The amount of type III pN-collagen was increased in malignant ovarian tumors, whereas no such tendency was seen in colon cancer. These findings suggest a wide variety of changes in the metabolism of type I and III collagens in diseases. Defective processing and cross-link maturation of these collagen types might result in impaired fibril formation or increased susceptibility of collagens to proteolytic attack - both of them processes with a potential role in the pathogenesis of diseases.

Le principal objectif de cette thèse est de caractériser l'écoulement dans un anévrisme abdominal aortique (AAA) sous différentes conditions physiologiques et à différents stades de son développement. Cette étude est consacrée aux AAA axisymétriques, modélisés comme une dilatation de profil gaussien et de section circulaire. Ainsi, les résultats s'appliquent surtout aux étapes précoces du développement d'un AAA. Le modèle d'AAA est caractérisé par une hauteur maximale H et une largeur W, l'unité de mesure étant le diamètre d'entrée de l'artère. Pour commencer, la dynamique est étudiée pour les écoulements stationnaires. La stabilité globale de ces écoulements de base est analysée en calculant les valeurs propres et les fonctions propres pour des perturbations de faible amplitude. Pour comprendre les mécanismes d'instabilité, le transfer d'énergie entre l'écoulement de base et les perturbations est calculé. L'écoulement pour des AAA peu profonds (ou de grande longueur) se déstabilise par un mécanisme de ‘lift-up' et les perturbations amplifiées sont stationnaires. Des anévrismes plus localisés (ou plus profonds) deviennent instables pour des nombres de Reynolds plus élevés, sans doute par instabilité elliptique ; dans cette situation, les perturbations sont des modes oscillants. Dans le cas des écoulements pulsés, deux types de profil de débit physiologique ont été considérés dans cette étude, correspondant à une situation de repos ou d'exercice physique. Ces écoulements restent collés aux parois pendant la phase de systole et un écoulement décollé est généralement observé pendant la décélération après le maximum de systole. Dans cette phase, un vortex se forme à l'extrémité aval. Ce vortex s'agrandit au cours du temps et impacte l'extrémité aval de l'AAA, ce qui conduit à de forts gradients de contrainte pariétale, qui ne sont pas observés dans les cas sains. Il a été observé que les conditions d'écoulement varient significativement avec les nombre de Womersley (Wo) et de Reynolds (Re); l'écoulement reste attaché aux parois plus longtemps pour des nombres de Womersley croissants. Le principal effet d'une augmentation de Re est un renforcement du vortex primaire qui se forme après le maximum de systole. Les décollements de l'écoulement, l'impact de vortex au bord aval de l'AAA ou encore de faibles contraintes pariétales oscillantes (des caractéristiques importantes dans les cas d'anévrismes pathologiques) sont observés même pour des anévrismes de faible profondeur. Pour des anévrismes plus développés, des vortex multiples sont observés tout au long du cycle dans la cavité de l'AAA. Une analyse de stabilité de ces écoulements de base pulsés a montré que le maximum des perturbations se développe vers l'extérmité aval des AAA. Cependant, les perturbations ne sont pas complètement confinées dans la cavité de l'AAA et se développent aussi au-delà en aval. On en déduit qu'une fois qu'un AAA s'est développé, les perturbations affectent aussi les artères saines en aval de l'AAA. Enfin, en considérant deux profils équivalents d'AAA, de formes sinusoïdale et gaussienne, la sensibilité des résultats aux détails de la géométrie a pu être établie / The main objective of this thesis is to characterise the flow fields observed in an abdominal aortic aneurysm (AAA) under different physiological conditions during its progressive enlargement. An axisymmetric AAA, modeled as an inflation of Gaussian shape on a vessel of circular cross-section, is considered in the present study. This means that the results are more significant for the early stages of growth of an AAA. The model AAA is characterized by a maximum height H and width W, made dimensionless by the upstream vessel diameter. To begin with, the flow characteristics in AAAs are investigated using steady flows. The global linear stability of the base flows is analysed by determining the eigenfrequencies and eigenfunctions of small-amplitude perturbations. In order to understand the instability mechanisms, the energy transfer between the base flow and the perturbations is computed. The flow in relatively shallow aneurysms (of relatively large width) become unstable by the lift-up mechanism and have a perturbation flow which is characterized by stationary, growing modes. More localized aneurysms (with relatively small width) become unstable at larger Reynolds numbers, presumably by an elliptic instability mechanism; in this case the perturbation flow is characterized by oscillatory modes. For the case of pulsatile flows, two types of physiological flowrate waveforms are considered in our study, corresponding to rest and exercise conditions. The flows are observed to remain attached to the walls during the systolic phase, with flow separation generally observed during the deceleration after the peak systole. During this phase, the vorticity is found to roll-up into a vortex at the proximal end. This vortex enlarges with time and impinges at the downstream end of the AAA, resulting in large spatial gradients of wall shear stress (WSS) along the wall, which are not found in the healthy case. The flow conditions are observed to vary significantly with Womersley (Wo) and Reynolds (Re) numbers, with the flow remaining attached to the walls for longer times, as the Womersley number Wo increases. The principal effect of increasing Re is that the primary vortex formed after peak systole is stronger. Clinically relevant flow characteristics of aneurysmal flow, i.e. detachement of flow and impingement on the distal end, the presence of low oscillatory WSS within the AAA, are observed even for very shallow aneurysms. For deep aneurysms, multiple vortices are observed throughout the cycle within the AAA cavity. Stability analysis of pulsatile base flows reveals that the maximum values of the perturbations are observed near the distal end of the AAA. However, they are not entirely confined to the AAA cavity and extend downstream, implying that once an AAA is formed, the disturbed flow conditions spread even to the undeformed arterial walls downstream of the AAA. Finally, by considering two equivalent AAA shapes modeled by a sinusoidal and a gaussian function, the sensitivity

Abdominal aortic aneurysms (AAA) are a pathological dilation of the aorta greater than 2.5cm and affect more than 4% of the male population and 1% of women aged 60 years or older. Screening is recommended among men and women older than age 65, and is covered by Medicare for patients with a family history and men with a history of smoking. Due to its asymptomatic nature, AAA is usually found incidentally during another radiological investigation. Many factors are associated with AAA development, but it is most commonly found in conjunction with atherosclerosis. There is currently no pharmacological intervention specifically for AAA, though statin therapy has shown some promise. The aneurysm will invariably grow, with an average rate of expansion of less than 0.5cm per year. As the aneurysm grows larger the chance of the rupture increases significantly with this outcome carrying an extremely high rate of mortality. Surgical intervention is recommended once the diameter reaches 5.5cm in men or about 5cm in women. There are two approaches to the repair of the aorta: the open surgical approach and the endovascular approach. The open surgical procedure replaces the affected portion of the aorta with a graft. The endovascular procedure places an endograft within the intact aneurysm, effectively excluding the affected section of vessel. The endovascular method carries a lower perioperative mortality rate than the open procedure, but over time can require additional surgeries to prevent continued aneurysm expansion due to blood flow in the aneurysm sac. Additionally, lifetime surveillance of the endograft is required to monitor its integrity and effectiveness. Lifestyle changes and possible pharmacological interventions in patients with AAA should focus on cardiovascular health changes to improve overall health and minimize risk factors for continued development of the aneurysm. In patients who will require repair particular attention should be paid to individual risks and preferences. The open repair procedure may be preferable in patients with better overall health and a longer life expectancy, while endovascular repair may be beneficial for more elderly or frail patients. Research and technology in this area are developing quickly, particularly for endovascular procedures, and the near future may see important changes in the risk-benefit analysis of AAA surgical interventions.