Abdominal aortic aneurysm (AAA) remains an important cause of morbidity and mortality in elderly men, and prevalence is predicted to increase in parallel with a global ageing population. AAA is commonly asymptomatic, and in the absence of routine screening, diagnosis is usually incidental when imaging to assess unrelated medical complaints. In the absence of approved diagnostic and prognostic markers, AAAs are monitored conservatively via medical imaging until aortic diameter approaches 50-55mm and surgical repair is performed. There is currently significant interest in identifying molecular markers of diagnostic and prognostic value for AAA. Here we outline the current guidelines for AAA management, and discuss modern scientific techniques currently employed to identify improved diagnostic and prognostic markers. KeywordsAbdominal aortic aneurysm; diagnosis; prognosis; biomarker INTRODUCTIONAn abdominal aortic aneurysm (AAA) is a dilation of the infra-renal aorta, which appears to result from chronic weakening of the arterial wall, increasing the risk of fatal rupture.1 -3 AAA is also associated with an increased risk of other major cardiovascular events in aneurysmal patients. For example the UK small aneurysm trial (UKSAT), demonstrated that only 16% of deaths in patients with 40-55mm AAAs was related to AAA repair or rupture while ~50% were due to other cardiovascular causes (mainly myocardial infarction and stroke).4 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access AAA pathologyMacroscopically, an AAA can be considered a dilatation of the infrarenal aorta, giving rise to a permanent vessel diameter >30mm (typical abdominal aortic diameter ranges from 15 to 25mm). 23-27 AAA vessel dilation is commonly progressive, and is often accompanied by the formation of a laminated, non-occlusive, intraluminal thrombus.28 -29 Thrombus size and location varies between patients, and the arterial wall may be partially or completely covered by the thrombus ( Figure 1A and B). 30 The thrombus remains in permanent contact with circulating blood and is continually remodeled, 31,32 and thrombus size increases in parallel with aortic dilation. Due to constant remodeling the thrombus is a laminated structure comprising a red blood cell-rich luminal layer in contact with the flowing blood, progressing to a brown fibrinolysed layer at the aortic wall. 29 Localised hypoxia has been demonstrated in regions of the aorta covered by the thrombus and this has been suggested to contribute to physiological stresses within the arterial wall. 33 Similar to other vascular dise...

Background Patients with abdominal aortic aneurysms (AAA) are predisposed to cardiovascular events and often experience continual expansion of their aneurysm. Cardiovascular events and expansion rates are positively correlated with aneurysm size. AAA is usually associated with intraluminal thrombus, which has previously been implicated in AAA pathogenesis. Objectives The aims of this study were to prospectively assess the association of infra-renal abdominal aortic thrombus volume with cardiovascular events and AAA growth. Methods 98 patients with AAAs underwent computed tomography angiography (CTA). The volume of infra-renal aorta thrombus was measured by a previously validated technique. Patients were followed prospectively for a median of 3 (inter-quartile range 2.0–3.6) years and cardiovascular events (non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, amputation and cardiovascular death) recorded. 39 of the original patients underwent repeat CTA a median of 1.5 (inter-quartile range, 1.1–3.3) years after entry to the study. Kaplan-Meier and Cox-proportional analysis were used to examine the association of aortic thrombus with cardiovascular events and average weighted AAA growth. Results A total of 28 cardiovascular event occurred during follow-up. The incidence of cardiovascular events was 23.4 and 49.2% for patients with small (

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Intra-luminal thrombus has been suggested to play a role in the progression of abdominal aortic aneurysm (AAA). The aims of this study were twofold. Firstly, to assess the reproducibility of a computer tomography (CT)-based technique for measurement of aortic thrombus volume. Secondly, to examine the determinants of infrarenal aortic thrombus volume in a cohort of patients with aortic dilatation. A consecutive series of 75 patients assessed by CT angiography with maximum aortic diameter > or = 25 mm were recruited. Intra-luminal thrombus volume was measured by a semi-automated workstation protocol based on a previously defined technique to quantitate aortic calcification. Intra- and inter-observer reproducibility were assessed using correlation coefficients, coefficient of variation and Bland-Altman plots. Infrarenal aortic thrombus volume percentage was related to clinical, anatomical and blood characteristics of the patients using univariate and multivariate tests. Infrarenal aortic thrombus volume was related to the severity of aortic dilatation assessed by total aortic volume (r = 0.87, P < 0.0001) or maximum aortic diameter (r = 0.74, P < 0.0001). We therefore examined the clinical determinates of aortic thrombus expressed as a percentage of total aortic volume. Aortic thrombus percentage was negatively correlated with serum high density lipoprotein (HDL, r = -0.31). By ordinal multiple logistic regression analysis serum HDL below median (< or = 1.2 mM: ) was associated with aortic thrombus percentage in the upper quartile adjusting for other risk factors (odds ratio 5.3, 95% CI 1.1-25.0). Infrarenal aortic thrombus volume can be measured reproducibly on CT. Serum HDL, which can be therapeutically raised, may play a role in discouraging aortic thrombus accumulation with implications in terms of delaying progression of AAA.

Objective-To assess the association of circulating bone marrow-derived osteo-progenitors with vascular calcification in mouse models and patients with peripheral artery disease.Methods-We estimated the percentage of circulating mononuclear cells expressing osteocalcin in 2 mouse models of aortic calcification developed in osteoprotegerin-deficient mice (OPG −/− ) using flow cytometry. Aortic calcification was assessed in mice principally by a bioassay of harvested aortas. In patients with peripheral artery disease osteocalcin-positive cells (estimated by flow cytometry) were related to aortic calcification volume assessed from computed tomography.Results-The amount of extractable aortic calcium was increased in both mouse models used in comparison to controls. The percentage of circulating mononuclear cells expressing osteocalcin was correlated to the amount of extractable aortic calcium in male (r=0.525, p=0.02) and female OPG −/− (r=0.564, p=0.02) mice and also in animals in which calcification was accelerated using calcitriol (r=0.64, p=0.01). Patients with more severe aortic calcification had a greater percentage of circulating OCN + MNCs (median 4.07 %, IQR 3.76-4.39, n=12) than those with less severe aortic calcification (median 3.10 %, IQR 2.32-3.60, n=11, p=0.05).Conclusions-This study demonstrates that aortic calcification can be robustly quantified in 2 mouse models. In these models and patients with peripheral artery disease circulating osteocalcin positive mononuclear cells are associated with the severity of aortic calcification.