Femke A. M. V. I. Hellenthal

Biomarkers of AAA progression. Part 1: extracellular matrix degeneration

Abdominal aortic aneurysm (AAA) is an important health problem. Elective surgical treatment is recommended on the basis of an individuals risk of rupture, which is predicted by AAA diameter. However, the natural history of AAA differs between patients and a reliable and individual predictor of AAA progression (growth and expansion rates) has not been established. Several circulating biomarkers are candidates for an AAA diagnostic tool. However, they have yet to meet the triad of biomarker criteria: biological plausibility, correlation with AAA progression, and prediction of treatment effect on disease outcome. Circulating levels of markers of extracellular matrix degeneration, such as elastin peptides, aminoterminal propeptide of type III procollagen, elastase–α1-antitrypsin complexes, matrix metalloproteinase 9, cystatin C, plasmin–antiplasmin complexes and tissue plasminogen activator, have been correlated with AAA progression and have biological plausibility. Although studies of these markers have shown promising results, they have not yet led to a clinically applicable biomarker. In future studies, adjustment for initial AAA size, smoking history and the measurement error for determination of AAA size, among other variables, should be taken into account. A large, prospective, standardized, follow-up study will be needed to investigate multiple circulating biomarkers for their potential role in the prediction of AAA progression, followed by a study to investigate the effect of treatment on the circulating levels of biomarkers.

Biomarkers of abdominal aortic aneurysm progression. Part 2: inflammation

Defining progression of abdominal aortic aneurysm (AAA) is complicated by several factors, including measurement error, duration of follow-up, and the imaging modality used to assess AAA expansion. Investigations of biomarkers of AAA progression should be standardized so that valid comparisons can be made. Previous research has shown some promising advances towards identifying a reliable and individual predictor of AAA progression. In this second part of our Review on biomarkers of AAA progression, we examine direct and indirect markers of inflammation including various cytokines, C-reactive protein, activators of tissue plasminogen activator and urokinase plasminogen activator, and osteopontin.

Histological features of human abdominal aortic aneurysm are not related to clinical characteristics

BACKGROUND Clinical presentation, maximal aortic diameter (Dmax), and growth rate are considered important clinical characteristics of the abdominal aortic aneurysm (AAA). Histologically, AAA is characterized by pathological changes of the media. In the present study, we investigated whether and how the histological features of AAA were related to clinical characteristics. METHODS Clinical characteristics and anterior aneurysm wall biopsies were collected prospectively. Histological characteristics were determined by immunohistochemistry and morphometric analysis. RESULTS Thirty-nine consecutive patients with elective or emergency aneurysm repair were included. AAA was located infra- or juxtarenal in 77% and 23%, respectively. Mean maximal aortic diameter was 67 mm with a mean growth rate of 6 mm/year. The histological features included a low elastin content, distorted elastin configuration, high collagen content, diminutive number of smooth muscle cells, and a high number of medial microvessels and inflammatory cells dominated by T cells. However, no intra- or interrelationship between histological and clinical characteristics was present. In particular, Dmax and clinical presentation were not related to media thickness or inflammatory cell count. CONCLUSIONS We conclude that histologically AAA could not be classified in analogy to clinical characteristics. We suggest that progression of large AAA is mainly determined by parameters other than histological features of the diseased vessel wall.

Suitability of pharmacokinetic models for dynamic contrast-enhanced MRI of abdominal aortic aneurysm vessel wall: a comparison.

Purpose Increased microvascularization of the abdominal aortic aneurysm (AAA) vessel wall has been related to AAA progression and rupture. The aim of this study was to compare the suitability of three pharmacokinetic models to describe AAA vessel wall enhancement using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Materials and Methods Patients with AAA underwent DCE-MRI at 1.5 Tesla. The volume transfer constant (Ktrans), which reflects microvascular flow, permeability and surface area, was calculated by fitting the blood and aneurysm vessel wall gadolinium concentration curves. The relative fit errors, parameter uncertainties and parameter reproducibilities for the Patlak, Tofts and Extended Tofts model were compared to find the most suitable model. Scan-rescan reproducibility was assessed using the interclass correlation coefficient and coefficient of variation (CV). Further, the relationship between Ktrans and AAA size was investigated. Results DCE-MRI examinations from thirty-nine patients (mean age±SD: 72±6 years; M/F: 35/4) with an mean AAA maximal diameter of 49±6 mm could be included for pharmacokinetic analysis. Relative fit uncertainties for Ktrans based on the Patlak model (17%) were significantly lower compared to the Tofts (37%) and Extended Tofts model (42%) (p<0.001). Ktrans scan-rescan reproducibility for the Patlak model (ICC = 0.61 and CV = 22%) was comparable with the Tofts (ICC = 0.61, CV = 23%) and Extended Tofts model (ICC = 0.76, CV = 22%). Ktrans was positively correlated with maximal AAA diameter (Spearman’s ρ = 0.38, p = 0.02) using the Patlak model. Conclusion Using the presented imaging protocol, the Patlak model is most suited to describe DCE-MRI data of the AAA vessel wall with good Ktrans scan-rescan reproducibility.

Quantification of abdominal aortic aneurysm wall enhancement with dynamic contrast‐enhanced MRI: Feasibility, reproducibility, and initial experience

To investigate the feasibility and reproducibility of dynamic contrast‐enhanced MRI (DCE‐MRI) to quantify abdominal aortic aneurysm (AAA) vessel wall enhancement dynamics which may reflect the amount of wall microvasculature. AAA vessel wall microvasculature has been linked with aneurysm progression and rupture.

The Influence of Wall Stress on AAA Growth and Biomarkers

In the decision for surgical repair of abdominal aortic aneurysms (AAAs), the risk of rupture is weighed carefully against the risk of the surgical procedure. The risk of rupture is estimated based on the maximum diameter and the growth rate of the AAA. Previous studies indicate that AAA growth rate increases with the diameter of the AAA [1, 2]. However, this growth rate is not the same for each AAA, as some AAA’s remain stable over a long period of time, while others show a fast growth or grow discontinuously.Copyright

99 Percentile Wall Stress and Not Peak Stress Correlates With AAA Diameter

Abdominal Aortic Aneurysm (AAA) is a dilation of the aorta of at least 50% increase in diameter, or an aortic diameter over 3 cm. If left untreated, an AAA will increase in size until rupture of the aortic wall causes a life threatening hemorrhage [1]. The current criterion for a repair procedure is a maximum diameter of the AAA of at least 5.5 cm. However, the diameter is not adequate for some small AAAs that rupture early [2]. Therefore, multiple studies have focused on and published data on patient-specific wall stress analyses. Fillinger et al. (2002) found higher peak wall stresses in ruptured AAAs than in electively repaired AAAs [3].Copyright