Oxidative Stress and Inflammatory Markers in Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is increasing due to aging of the population and is a major cause of death among the elderly. Ultrasound screening programs are useful in early diagnosis, but aneurysm size is not always a good predictor of rupture. Our aim was to analyze the value of circulating molecules related to oxidative stress and inflammation as new biomarkers to assist the management of AAA. The markers were quantified by ELISA, and their expression in the aneurysmal wall was studied by real-time PCR and by immunostaining. Correlation analysis of the studied markers with aneurysm diameter and peak wall stress (PWS), obtained by finite element analysis, and multivariate regression analysis to assess potential confounding factors were performed. Our study shows an extensive inflammatory infiltration in the aneurysmal wall, mainly composed by T-cells, macrophages and B-cells and altered levels of reactive oxygen species (ROS), IgM, IgG, CD38, GDF15, S100A4 and CD36 in plasma and in the aneurysmal tissue of AAA patients compared with controls. Circulating levels of IgG, CD38 and GDF15 positively correlated with abdominal aortic diameter, and CD38 was correlated with PWS. Our data show that altered levels of IgG, CD38 and GDF15 have potential diagnostic value in the assessment of AAA.

Systematic review on abdominal aortic aneurysm screening cost-efficiency and methodological quality assessment.

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a silent, progressive disease that can lead to death. It is easily diagnosed with noninvasive methods and its routine treatment has excellent results. This creates an optimal situation for population screening programs. The aim of this paper was to assess results and methodological quality of cost-utility studies on screening versus no screening scenarios for AAA to assess future establishment of new AAA screening programs. EVIDENCE ACQUISITON: A systematic review of efficiency (cost-effectiveness and cost-utility) studies was performed, finally selecting cost-utility studies on AAA screening versus no screening. Papers were selected that dealt with efficiency of screening for AAA according to PICOTS framework and the methodological quality assessed according to the economic evaluation analyses described by Drummond and Caro. Two independent reviewers were involved in the procedure. EVIDENCE SYNTHESIS: Research retrieved 88 studies. From those, 26 showed cost-effectiveness and cost-utility results. Finally, 10 studies had cost-utility results and suited criteria (published in the last 10 years; time-horizon: 10 years or more) for exhaustive analysis. All publications, except one, showed adequate incremental cost-utility ratios according to different national perspectives. Methodological assessment showed some quality limitations, but the majority of items analyzed were favorably answered after applying the questionnaires. CONCLUSIONS: Confirmation of the cost-utility results in this revision at a national/regional level should be the basis for the implantation of new national screening programs worldwide. The methodological evaluation applied in this revision is crucial for the corresponding future piggy-back trials to assess routine application of national AAA screening programs.

Finite element analysis in symptomatic and asymptomatic abdominal aortic aneurysms for aortic disease risk stratification.

BACKGROUND: Advanced biomechanical models can provide additional information concerning rupture risk in abdominal aortic aneurysms (AAA). Here we evaluated the predictive value of finite element analysis (FEA) to assess AAA rupture risk. METHODS: In a case-control study, we compared FEA parameters in a group of symptomatic AAA (sAAA) patients, considered as a high risk of rupture group, with FEA parameters in asymptomatic AAA patients (aAAA). RESULTS: We included 15 sAAA and 28 aAAA patients matched for age- and maximum diameter diagnosed with infrarenal non-ruptured AAA at our center between 2009 and 2013. Mean age was 75±69 years and mean maximum diameter was 77±17 mm. Peak wall stress (PWS) was significantly higher in sAAA patients than in aAAA patients (354.3±139.6 kPa vs. 248.6±81.9 kPa; P=0.001). The C statistic for the ROC curve based on PWS was 0.748 (95% CI: 0.592-0.903; P=0.008). CART analysis classified patients into high and low PWS groups. The high-PWS group (>305.15 kPa; N.=15) had a higher incidence of sAAA (33.3% aAAA, 66.7% sAAA) than the low-PWS-group (≤305.15 kPa; N.=28. 82.1% aAAA, 17.9% sAAA). CONCLUSIONS: In conclusion, PWS was significantly higher in sAAA patients. Measuring PWS may help estimate the individual rupture risk in patients with AAA, but larger studies are needed to confirm our results.

Increased Peak Wall Stress, but Not Maximum Diameter, Is Associated with Symptomatic Abdominal Aortic Aneurysm.

OBJECTIVE: Maximum diameter (MD) is the established rupture predictor for abdominal aortic aneurysm (AAA). However, biomechanical markers from finite element analysis (FEA) could be more accurate predictors for these patients. In this study, the association between peak wall stress (PWS) and MD with symptoms of AAA was evaluated. METHODS: Patients diagnosed with infrarenal non-ruptured AAA at the centre between 2009 and 2015 were included. Clinical data, morphological variables (including MD), and the biomechanical variables PWS and diameter normalised PWS (dnPWS) in symptomatic (sAAA) and asymptomatic AAA patients (aAAA) were included. RESULTS: A total of 170 patients were analysed, 153 aAAA and 17 sAAA. MD was significantly greater in sAAA patients than in aAAA patients (70.4 mm, 95% CI 66.4-86.0 vs. 59.1 mm, 95% CI 53.7-67.8, respectively; p = .002). PWS was also significantly higher in the sAAA group (324.6 kPa, 95% CI 217.4-399.5 vs. 199.2 kPa, 95% CI 165.6-239.5; p < .01). No differences in MD were found in patients with an AAA ≥ 65 mm (43 aAAA and 14 sAAA); however, both PWS (327.4 kPa, 95% CI 239.0-473.3 vs. 229.4 kPa, 95% CI 210.0 to 289.4; p = .020) and dnPWS (4.3, 95% CI 3.17-4.67 vs. 3.03, 95% CI 2.8-3.49; p = .004) were higher in sAAA than in aAAA. CONCLUSIONS: This study suggests that MD and the biomechanical parameters obtained by finite element analysis are greater in sAAA than in aAAA. However, considering patients with MD ≥ 65 mm alone, only PWS, and particularly dnPWS, were able to differentiate sAAA from aAAA.

Expression and Cellular Localization of 15-Hydroxy-Prostaglandin-Dehydrogenase in Abdominal Aortic Aneurysm.

PGE2 has been implicated in abdominal aortic aneurysm (AAA) associated hypervascularization. PGE2-metabolism involves 15-hydroxyprostaglandin-dehydrogenase (15-PGDH) the expression of which in AAA is unknown. The aim of this study was to examine the expression and cell distribution of 15-PGDH in AAA. Here, we show that 15-PGDH mRNA levels were significantly higher in aorta samples from patients undergoing AAA repair than in those from healthy multiorgan donors. Consequently, the ratio of metabolized PGE2 secreted by aortic samples was significantly higher in AAA. AAA production of total PGE2 and PGE2 metabolites correlated positively with PGI2 production, while the percentage of metabolized PGE2 correlated negatively with the total amount of PGE2 and with PGI2. Transcript levels of 15-PGDH were statistically associated with leukocyte markers but did not correlate with microvascular endothelial cell markers. Immunohistochemistry revealed 15-PGDH in the areas of leukocyte infiltration in AAA samples, mainly associated with CD45-positive cells, but not in normal aorta samples. We provide new data concerning 15-PGDH expression in human AAA, showing that 15-PGDH is upregulated in AAA and mainly expressed in infiltrating leukocytes. Our data suggest that microvasculature was not involved in PGE2 catabolism, reinforcing the potential role of microvasculature derived PGE2 in AAA-associated hypervascularization.