Abdominal Aortic Aneurysm Expansion Rate Research Articles

Evaluation of Roxithromycin as a Treatment Option for Small Abdominal Aortic Aneurysms: An Integrated Study of Meta-analysis and Network Pharmacology.

Abdominal aortic aneurysm (AAA) is a segmental, progressive, and fatal vascular disorder, and the current strategy for small AAAs is close observation alone.The purpose of this study is to summarize the available evidence to assess the effects of antibiotics on small abdominal aortic aneurysms (AAA). We searched PubMed, EMBASE, Web of Science, and Scopus from inception to September 29, 2023, and included randomized controlled trials (RCTs) that evaluated the effects of antibiotics on small AAAs in humans. We first performed a meta-analysis to assess the effects of antibiotics on small AAAs. Afterward, network pharmacology analysis was applied to investigate the optimal drug generated from the meta-analysis results. We searched Pharmmapper and GeneCards to obtain the common potential targets of the selected drug and AAA-related targets. The protein-protein interaction network and functional enrichment analysis were performed by the STRING database, Cytoscape 3.7.2 software, and R, respectively. Docking studies were carried out for validation. We incorporated data from six RCTs involving a total of 997 patients. The results of this meta-analysis revealed that roxithromycin exhibited a modest yet statistically significant protective effect in terms of slowing down the AAA expansion rate. Furthermore, our subsequent bioinformatics analysis pinpointed MMP-2, MMP-9, ALB, MMP-3, and CCL-5 as potential therapeutic targets that could be explored for the treatment of AAA using roxithromycin. In conclusion, the study indicates roxithromycin is a promising drug for treating small AAAs and supports its underlying clinical use in small AAAs.

PS-BPB01-5: LOX-1 DEFICIENCY INCREASES RUPTURED ABDOMINAL AORTIC ANEURYSM VIA THINNING OF ADVENTITIAL COLLAGEN

Objective: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a key mediator of inflammation and plays an important role in the pathogenesis of atherosclerosis. Both inflammation and atherosclerosis have been proposed as contributors to abdominal aortic aneurysm (AAA) pathogenesis. However, the role of LOX-1 in AAA pathogenesis remains unknown. We aimed to investigate effects of Olr1, which encodes LOX-1, deletion on angiotensin II (Ang II)-induced AAA in apolipoprotein E knockout (ApoE KO) mice to determine whether LOX-1 deficiency mitigates AAA development. Design and method: Either Ang II (1.44 mg/kg/day) or saline (control) was administered continuously through a subcutaneously implanted osmotic pump for 4 weeks in the following 8-week-old male mice: Apoe-/-Olr1+/+ mice (Ang II, n = 40; saline, n = 10), Apoe-/-Olr1+/- mice (Ang II, n = 30; saline, n = 9), and Apoe-/-Olr1-/- mice (Ang II, n = 39; saline, n = 9). Results: Ang II infusion raised systolic blood pressure by tail-cuff methods in all three groups. Serial non-invasive assessment with ultrasound demonstrated that Ang II gradually increased the maximum area of the suprarenal abdominal aortas leading to AAAs. Although the incidence and expansion rate of AAA were comparable among genotypes, Olr1 deletion significantly increased the severity and rupture rate of AAAs (p = 0.01; incidence of type IV and ruptured AAA was 25% in Apoe-/-Olr1-/- mice vs 5% in Apoe-/-Olr1+/+ mice). Since atherosclerosis is considered a major contributor to the development of AAAs, the extent of the atheroma burden localized in aneurysmal lesions was evaluated by Oil Red O staining. Olr1 deletion did not decrease atherosclerosis formation in the aneurysmal wall. Interestingly, further histopathological analysis revealed that aneurysmal lesions in LOX-1-deficient mice had fewer fibroblasts and myofibroblasts, as well as thinner adventitial collagen, although the degree of elastin fragmentation or disruption was similar between LOX-1-deficient and control mice. These in vivo data suggested that adventitial fibroblasts play a pivotal role in the increased severity of AAA in LOX-1-deficient mice. To further determine the effects of Olr1 deletion on fibroblast differentiation, fibroblasts were isolated from the adventitia of abdominal aortas harvested from 8-week-old Apoe-/-Olr1+/+ and Apoe-/-Olr1-/- mice, and then cultured with Ang II stimulation. An in vitro study confirmed that Olr1 deletion completely abolished the Ang II-induced proliferative activity in the aortic adventitial fibroblasts (p = 0.02). Conclusions: Olr1 deletion may not mitigate aneurysm development but rather increase the vulnerability to rupture by suppressing adventitial fibroblast proliferation and collagen.

Double-edged sword of diabetes mellitus for abdominal aortic aneurysm.

Diabetes mellitus (DM) has been proved to contribute to multiple comorbidities that are risk factors for abdominal aortic aneurysm (AAA). Remarkably, evidences from epidemiologic studies have demonstrated a negative association between the two disease states. On the other hand, hyperglycemic state was linked to post-operative morbidities following AAA repair. This review aims to provide a thorough picture on the double-edged nature of DM and major hypoglycemic medications on prevalence, growth rate and rupture of AAA, as well as DM-associated prognosis post AAA repair. We performed a comprehensive search in electronic databases to look for literatures demonstrating the association between DM and AAA. The primary focus of the literature search was on the impact of DM on the morbidity, enlargement and rupture rate, as well as post-operative complications of AAA. The role of antidiabetic medications was also explored. Retrospective epidemiological studies and large database researches associated the presence of DM with decreased prevalence, slower expansion and limited rupture rate of AAA. Major hypoglycemic drugs exert similar protective effect as DM against AAA by targeting pathological hallmarks involved in AAA formation and progression, which were demonstrated predominantly by animal studies. Nevertheless, presence of DM or postoperative hyperglycemia was linked to poorer short-term and long-term prognosis, primarily due to greater risk of infection, longer duration of hospital stays and death. While DM is a positive factor in the formation and progression of AAA, it is also associated with higher risk of negative outcomes following AAA repair. Concomitant use of antidiabetic medications may contribute to the protective mechanism of DM in AAA, but further studies are still warranted to explore their role following AAA repair.

LOX-1 deficiency increases ruptured abdominal aortic aneurysm via thinning of adventitial collagen.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a key mediator of inflammation and plays an important role in the pathogenesis of atherosclerosis. Conversely, LOX-1 deficiency has been shown to decrease inflammation and atherosclerosis, both of which have been proposed to contribute to abdominal aortic aneurysm (AAA) pathogenesis. However, the role of LOX-1 in AAA pathogenesis remains unknown. Here, we investigated the effects of Olr1 (which encodes LOX-1) deletion on angiotensin II (Ang II)-induced AAA in apolipoprotein E knockout (ApoE KO) mice to determine whether LOX-1 deficiency mitigates AAA development. To accomplish this, we used serial, non-invasive ultrasound assessment, which revealed that the incidence and expansion rate of AAA were similar regardless of Olr1 deletion. However, Olr1 deletion significantly increased severe AAAs, including ruptured AAAs resulting in death. Oil Red O staining of the harvested aortas showed that the extent of atheroma burden localized in aneurysmal lesions did not differ between LOX-1-deficient and control mice, suggesting that Olr1 deletion did not decrease atheroma burden in the aneurysmal wall. Further histopathological analysis revealed that aneurysmal lesions in LOX-1-deficient mice had fewer fibroblasts and myofibroblasts, as well as thinner adventitial collagen, although the degree of elastin fragmentation or disruption was similar between LOX-1-deficient and control mice. An in vitro study confirmed that the proliferation of adventitial fibroblasts collected from LOX-1-deficient mice was significantly attenuated despite Ang II stimulation. In conclusion, Olr1 deletion may not mitigate aneurysm development but rather increases the vulnerability of rupture by suppressing adventitial fibroblast proliferation and collagen synthesis.

Epicardial adipose tissue volume is associated with abdominal aortic aneurysm expansion.

The epicardial adipose tissue volume (EATV) is associated with cardiovascular diseases such as coronary artery disease. However, no information is available regarding the relationship between the EATV and abdominal aortic aneurysm (AAA) expansion. In the present study, we evaluated the association between the EATV and AAA growth and sought to identify the predictors of AAA expansion. Between June 2009 and December 2019, 906 patients had undergone endovascular or open repair of AAAs at our institution. Patients with previous cardiac surgery, previous ascending thoracic aortic surgery, a ruptured AAA, an infected AAA, an inflammatory AAA, a saccular aneurysm, a solitary iliac aneurysm, or reintervention after treatment of the AAA were excluded. A total of 237 patients with at least two preoperative computed tomography (CT) scans performed >180days apart were included in the present study. The EATV within the pericardium was retrospectively quantified from the preoperative non-contrast-enhanced CT images using a three-dimensional workstation. The EATV index was defined as the EATV divided by the body surface area. The AAA expansion rate was defined as an increase in the AAA diameter annually, and the patients were divided into the slow-expansion group (expansion rate,<5mm/y) and the fast-expansion group (expansion rate, ≥5mm/y). The correlation between the expansion rate and the EATV index was analyzed, and the cutoff value for the EATV index was determined using a receiver operating characteristics curve. Multivariate analysis was used to assess the predictors of the AAA expansion rate. The expansion rate of AAA correlated positively with the EATV index (R= 0.237; P< .001). The initial aneurysm diameter (P< .001) and EATV index (P= .009) differed significantly between the two groups. The cutoff for the EATV index was 60.3cm3/m2 (area under the curve, 0.658; 95% confidence interval [CI], 0.568-0.749; sensitivity, 1.000; specificity, 0.309). Multivariate analysis revealed that the initial aneurysm diameter and an EATV index of >60.3cm3/m2 were significantly associated with the AAA expansion rate. The results of the present study have demonstrated that the EATV index is associated with AAA expansion.

Low Shear Stress at Baseline Predicts Expansion and Aneurysm-Related Events in Patients With Abdominal Aortic Aneurysm.

Low shear stress has been implicated in abdominal aortic aneurysm (AAA) expansion and clinical events. We tested the hypothesis that low shear stress in AAA at baseline is a marker of expansion rate and future aneurysm-related events. Patients were imaged with computed tomography angiography at baseline and followed up every 6 months >24 months with ultrasound measurements of maximum diameter. From baseline computed tomography angiography, we reconstructed 3-dimensional models for automated computational fluid dynamics simulations and computed luminal shear stress. The primary composite end point was aneurysm repair and/or rupture, and the secondary end point was aneurysm expansion rate. We included 295 patients with median AAA diameter of 49 mm (interquartile range, 43-54 mm) and median follow-up of 914 (interquartile range, 670-1112) days. There were 114 (39%) aneurysm-related events, with 13 AAA ruptures and 98 repairs (one rupture was repaired). Patients with low shear stress (<0.4 Pa) experienced a higher number of aneurysm-related events (44%) compared with medium (0.4-0.6 Pa; 27%) and high (>0.6 Pa; 29%) shear stress groups (P=0.010). This association was independent of known risk factors (adjusted hazard ratio, 1.72 [95% CI, 1.08-2.73]; P=0.023). Low shear stress was also independently associated with AAA expansion rate (β=+0.28 mm/y [95% CI, 0.02-0.53]; P=0.037). We show for the first time that low shear stress (<0.4 Pa) at baseline is associated with both AAA expansion and future aneurysm-related events. Aneurysms within the lowest tertile of shear stress, versus those with higher shear stress, were more likely to rupture or reach thresholds for elective repair. Larger prospective validation trials are needed to confirm these findings and translate them into clinical management.

The effect of doxycycline on abdominal aortic aneurysm growth: a meta-analysis

Abstract Introduction There have been many studies on the benefits of chronic doxycycline therapy on slowing down the rate of abdominal aortic aneurysm (AAA) expansion by decreasing matrix metalloproteinase (MMPs) levels in AAA, known contributors to AAA growth. However, there have been few studies performed on the clinical effect of doxycycline on reducing the rate of AAA expansion. Purpose The objective of this meta-analysis was to evaluate the effect of doxycycline on the expansion of AAA. Methods We performed a comprehensive literature search using PubMed, Embase, and Cochrane Libraries from inception to October 2020 for all studies evaluating the effect of chronic doxycycline therapy on AAA growth. The primary outcome was the effect doxycycline therapy on AAA growth rate compared to the placebo. The mean difference and 95% confidence intervals (CI) were obtained by the Inverse Variance method within a random effect model. Results A total of three randomized control trials (485 total patients) were included in the final analysis. The analysis showed that there was no significant benefit of chronic doxycycline therapy in reducing AAA dilation rate compared to placebo [Mean difference of 0.03; 95% CI −0.05 to 0.11, P=0.43, I2=90%]. Conclusion This is the first meta-analysis evaluating the effects of chronic doxycycline therapy on the growth rate of AAAs. The current data suggests that there is no significant decrease in rate of expansion of AAA diameter in patients treated with chronic doxycycline vs. placebo. Funding Acknowledgement Type of funding sources: None.

Neutrophils as Regulators and Biomarkers of Cardiovascular Inflammation in the Context of Abdominal Aortic Aneurysms.

Neutrophils represent up to 70% of circulating leukocytes in healthy humans and combat infection mostly by phagocytosis, degranulation and NETosis. It has been reported that neutrophils are centrally involved in abdominal aortic aneurysm (AAA) pathogenesis. The natural course of AAA is growth and rupture, if left undiagnosed or untreated. The rupture of AAA has a very high mortality and is currently among the leading causes of death worldwide. The use of noninvasive cardiovascular imaging techniques for patient screening, surveillance and postoperative follow-up is well established and recommended by the current guidelines. Neutrophil-derived biomarkers may offer clinical value to the monitoring and prognosis of AAA patients, allowing for potential early therapeutic intervention. Numerous promising biomarkers have been studied. In this review, we discuss neutrophils and neutrophil-derived molecules as regulators and biomarkers of AAA, and our aim was to specifically highlight diagnostic and prognostic markers. Neutrophil-derived biomarkers may potentially, in the future, assist in determining AAA presence, predict size, expansion rate, rupture risk, and postoperative outcome once validated in highly warranted future prospective clinical studies.

Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells

Autophagy is associated with the cytoprotection of physiological processes against inflammation and oxidative stress. Salvia miltiorrhiza possesses cardiovascular protective actions and has powerful anti-oxidative and anti-inflammatory effects; however, whether and how Salvia miltiorrhiza-derived microRNAs (miRNAs) protect vascular smooth muscle cells (VSMCs) by inducing autophagy across species are unknown. We first screened and identified Sal-miR-58 from Salvia miltiorrhiza as a natural autophagy inducer. Synthetic Sal-miR-58 suppresses chronic angiotensin II (Ang II) infusion-induced abdominal aortic aneurysm (AAA) formation in mice, as well as induces autophagy in VSMCs and attenuates the inflammatory response elicited by Ang II in vivo and in vitro. Mechanistically, Sal-miR-58 downregulates Krüppel-like factor 3 (KLF3) expression through direct binding to the 3′ UTR of KLF3, which in turn relieves KLF3 repression of E3 ubiquitin ligase neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) expression, whereas NEDD4L upregulation increases the ubiquitination and degradation of the platelet isoform of phosphofructokinase (PFKP), subsequently leading to a decrease in the activation of Akt/mammalian target of rapamycin (mTOR) signaling and facilitating VSMC autophagy induced by Sal-miR-58 in the context of chronic Ang II stimulation and aneurysm formation. Our results provide the first evidence that plant-derived Sal-miR-58 induces autophagy and attenuates inflammation in VSMCs through cross-species modulation of the KLF3/NEDD4L/PFKP regulatory pathway.

Diabetes and Its Effect on Abdominal Aortic Aneurysm Growth Rate in Hispanic Patients

The growth rate of abdominal aortic aneurysms (AAA) can vary depending on age, baseline diameter, blood pressure, race, and history of smoking. Paradoxically, previous studies show evidence of a protective effect of diabetes on the rate of AAA expansion despite its well-established role in the morbidity and mortality of cardiovascular disease. This study aims to investigate the impact diabetes plays on AAA growth within a Hispanic population. Data were collected from patients who were predominantly Mexican-American at a single hospital site. Baseline and follow-up measures for AAA diameter were obtained from serial imaging studies. Demographics, medical history, the presence of type 2 diabetes, and medication use were extracted from hospital records. Linear mixed-effects growth models were used to calculate the overall AAA growth rate and to assess the difference in AAA growth rate between demographics, comorbidities, and medication use. The study comprised 201 patients (70.4% male) with a mean baseline age of 79.1years, of whom 43.2% were diabetic. The average monthly AAA growth rate across all study participants was 0.15mm (SE=0.02mm). Independently, the average AAA expansion rate for the diabetic and nondiabetic groups was 0.07mm (SE=0.04mm) and 0.21mm (SE=0.03mm) per month, respectively. This demonstrates a 65% lower linear AAA expansion rate per month in patients with diabetes. This study confirms a difference of AAA physiology between diabetics and nondiabetics in the Hispanic community. The observed significant difference in AAA growth rate may be a combination of factors associated with race/ethnicity, prevalence of diabetes mellitus, and low compliance with diabetic control exhibited in the Mexican-American population.

The Potential Role of Neutrophil Gelatinase-Associated Lipocalin in the Development of Abdominal Aortic Aneurysms

In abdominal aortic aneurysm (AAA), pathophysiology deterioration of the medial aortic layer plays a critical role. Key players in vessel wall degeneration are reactive oxygen species (ROS), smooth muscle cell apoptosis, and extracellular matrix degeneration by matrix metalloproteinase-9 (MMP-9). Lipocalin-2, also neutrophil gelatinase-associated lipocalin (NGAL), is suggested to be involved in these degenerative processes in other cardiovascular diseases. We aimed to further investigate the role of NGAL in AAA development and rupture. In this observational study, aneurysm tissue and blood of ruptured (n=13) AAA patients were investigated versus nonruptured (n=26) patients. Nondilated aortas (n=5) from deceased patients and venous blood from healthy volunteers (n=10) served as controls. NGAL concentrations in tissue and blood were measured by enzyme-linked immunosorbent assay and immunofluorescence microscopy. Nitrotyrosine (marker of ROS), MMP-9, and caspase-3 (marker of apoptosis) in aneurysm tissue were measured by immunofluorescence microscopy. AAA expansion rates were calculated retrospectively. NGAL (in μg/mL) blood concentration in ruptured AAA was 46 (range 22-122) vs. 26 (range 6-55) in nonruptured AAA (P<0.01) and 14 (range 12-22) in controls (P<0.01). In the aneurysm wall of ruptured AAA, NGAL concentration was 4.7 (range 1.4-25) vs. 4.4 (range 0.2-14) in nonruptured AAA (not significant) and 1.8 (range 1.2-2.7) in nondilated aortas (P=0.04). In the medial layer, NGAL correlated positively with nitrotyrosine (Rs=0.80, P<0.01), MMP-9 (Rs=0.56, P=0.02), and caspase-3 (Rs=0.75, P=0.01). NGAL did not correlate to AAA expansion rate in blood or tissue (P=0.34 and P=0.95, respectively). This study demonstrates that NGAL blood concentration is higher in ruptured AAA patients than in nonruptured AAA. NGAL expression in the AAA wall is also higher than in nondilated aorta. Furthermore, its expression is associated with factors of vessel wall deterioration. Based on our study results, we could not determine NGAL as a biomarker for AAA growth or rupture. However, our findings do support a potential role of NGAL in the development of AAA.

Abstract 489: A Data Driven Approach to Identify Subtypes of Abdominal Aortic Aneurysm With Distinct Clinical and Genetic Characteristics

Background: Abdominal aortic aneurysm (AAA) is a complex and heterogeneous disorder. We hypothesized that dense phenomapping using electronic health records (EHR) can identify subtypes of AAA with distinct clinical and genetic characteristics. Methods &amp; Results: AAA cases (n=1108) and controls (n=4694) were identified from the Mayo vascular disease biorepository and had available high-density genotyping data. 132 Candidate genetic variants (p &lt; 10E-5) associated with atherosclerotic cardiovascular disease (ASCVD) or AAA were selected from GWAS catalog. Using model-based Gaussian-mixture cluster analysis of 46 clinical features from 6 data domains, 24 data elements, 204 variables (including age, sex, vital signs, laboratory data, medication use, family history), spanning over 20 years of observational time in the EHR, we identified two subtypes of AAA: subtype 1(S1, n=421) with faster AAA growth rate (baseline size adjusted mean difference, 95% CI: 0.013, 0.001 to 0.020 cm / year faster, p = 0.03), higher all-cause mortality (age &amp; sex adjusted hazard ratio, 95% CI: 1.36, 1.09 - 1.70, p &lt; 0.01) than subtype 2 (S2, n=687). As compared with the controls, thyroid disorder / rheumatoid or osteoarthritis / infectious conditions were uniquely associated with increased odds ratio for S1; ASCVD / hyperlipidemia / hypertension were uniquely associated with increased odds ratio for S2. After adjustment for all group-specific diseases, genetic variants in CDKN2B-AS1, NOA1-REST, ERG, ZNF335-MMP9 and SMAD3 were associated with S1 and variants in MMP12, DAB2IP, LHFPL2, LPA, FSTL5 and SORT1 were associated with S2 (all FDR p &lt; 0.05). After adjustment for disease comorbidities and genetic variants differently associated with S1 and S2, the increased risk for all-cause death of S1 than S2 and the difference in AAA expansion rate in subgroups attenuated (Both p-values &gt; 0.09) Conclusions: We identified two subtypes of AAA with different rates of aneurysm expansion and all-cause mortality, which were associated with subtype-specific disease comorbidities and genetic markers, suggesting the potential of leveraging EHR to facilitate individualized medicine in patients with AAA.

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion - Positive Association.

The maximum axial diameter (MAD) of a fusiform abdominal aortic aneurysm (AAA) is an indicator of the risk of expansion or rupture. Apart from smoking and MAD itself, few expansion risk factors have been reported. In this study, we investigated expansion risk factors for AAA.Methods and Results:This retrospective cohort study included 176 patients who attended Tohoku University Hospital with infrarenal fusiform AAA. AAA expansion rate was determined on multidetector computed tomography, and the correlations between expansion rate and the clinical data were analyzed. The median expansion rate was 2.405 mm/year. On univariate analysis, a significant positive correlation with expansion rate was observed for the initial MAD (P<0.001) and significant negative correlations for oral angiotensin receptor blocker usage (P=0.025), height (P=0.005), body weight (P=0.017), total cholesterol (P=0.007), low-density lipoprotein cholesterol (P=0.004), and HbA1c (P=0.037). On logistic regression analysis, significant positive associations with expansion rate were observed for initial MAD (P<0.001) and oral steroid usage (P=0.029) and a negative association for height (P=0.041). Oral steroid usage is an important risk factor for AAA expansion, independent of other risk factors of atherosclerosis and MAD.

Association of Hypertension with Abdominal Aortic Aneurysm Expansion

Hypertension is positively associated with abdominal aortic aneurysm (AAA) presence, which supports a hypothesis that hypertension may also be positively associated with AAA expansion. To determine whether hypertension is associated with AAA expansion, we reviewed currently available studies with a systematic literature search and meta-analytic estimate. Databases including MEDLINE and EMBASE were searched through July 2015 using Web-based search engines (PubMed and OVID). Studies considered for inclusion met the following criteria: the study population was AAA patients with and without hypertension, and outcomes included data regarding AAA expansion. For each study, expansion rates in both the hypertensive and nonhypertensive groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Of 614 potentially relevant publications screened initially, we identified 20 eligible studies including data on 6,619 AAA patients. No individual study indicated a statistically significant (positive or negative) association of hypertension with AAA expansion rates. A pooled analysis of all the 20 studies demonstrated that hypertension was not associated with AAA expansion rates in the fixed-effect model (SMD 0.03, 95% CI -0.01 to 0.17, P=0.19). There was no evidence of significant publication bias. Hypertension is not associated with AAA expansion. Further investigations would be required to elucidate why hypertension is not associated with AAA expansion despite its positive association with AAA presence.

Factors Associated With Small Abdominal Aortic Aneurysm Expansion Rate

Factors Associated With Small Abdominal Aortic Aneurysm Expansion Rate

The role of intraluminal thrombus formation for expansion of abdominal aortic aneurysms.

Though the pathophysiology of initiation, formation, and expansion of abdominal aortic aneurysm (AAA) has been intensely researched, the distinct mechanisms driving these processes still remain unclear. In particular, human studies on predictors of AAA progression as a major determinant of rupture risk are scarce. All consecutive abdominal aortic ultrasound sonographic examinations performed at the duplex laboratory of the Division of Angiology of the Medical University of Vienna between 1999 and 2012 were reviewed. Patients with repeated measurements of the infrarenal aortic diameter, who had no prior AAA repair were included. Detailed informations on AAA, including length, anterior-posterior and transversal measurements of diameter, and intraluminal thrombus formation/size were obtained from ultrasound examination; patients' comorbidities, cardiovascular risk factors, and medications were obtained from outpatient charts. The expansion rate of AAA in relation to intraluminal thrombus size, gender, age, comorbidities, cardiovascular risk factors, and pharmacotherapy was evaluated. Independent predictors of AAA growth were identified through mixed effects models. In total, 166 patients (123 men and 43 women, mean age 68 ± 9 years) were included. Patients were followed over a mean period of 1.4 ± 1.2 years with a mean number of follow-up investigations of 4.4 ± 2.7. Overall, mean maximum AAA diameter at baseline was 37.4 ± 8.2 mm. The average expansion rate of AAA diameter throughout the follow-up period was 2.0 mm per year (95 % confidence interval: 1.6-2.4). At initial investigation, intraluminal thrombus formation was present in 56.6 % of all patients. AAA diameter at baseline, time of follow-up as well as presence and size of intraluminal thrombus formation were identified as independent predictors of AAA expansion rate. Importantly, gender and presence of cardiovascular risk factors were not associated with AAA progression rate. Intraluminal thrombus formation seems to be a key determinant for progression of AAA diameter. Further prospective longitudinal studies are warranted to confirm the potential impact of thrombus formation on AAA development and its implication on monitoring and treatment decisions in patients with AAA.

Diameter-Related Variations of Geometrical, Mechanical, and Mass Fraction Data in the Anterior Portion of Abdominal Aortic Aneurysms

Maximum aortic diameter is an important measure in rupture prediction of abdominal aortic aneurysms (AAAs). Analyzing the variations of geometrical, material, and biochemical properties with increased AAA diameters advances understanding of the effect of lesion enlargement on patient specific vascular properties. 96 AAA samples were harvested during open surgical aneurysm repair. Geometrical factors such as the maximum intraluminal thrombus (ILT) thickness, wall thickness, and AAA expansion rate were measured. Biaxial extension and peeling tests were performed to characterize the biaxial mechanical responses and to quantify the dissection properties of aneurysmal tissue. Mass fraction analysis quantified the dry weight percentages of elastin and collagen within the AAA wall. Linear regression models were used to correlate geometrical, mechanical, and mass fraction data with maximum AAA diameter. Both ILT thickness and AAA expansion rate increased and were positively correlated with maximum AAA diameter, while there was a slight increase in wall thickness for AAAs with a larger maximum diameter. For the biaxial mechanical responses, mean peak stretches and maximum tangential moduli in the circumferential and longitudinal axes did not correlate with maximum AAA diameters. However, the quantified energy to propagate tissue dissections within intima-media composites showed a significant inverse correlation with maximum AAA diameter. Elastin content decreased significantly with increasing AAA diameter. Larger AAA diameters are associated with thicker ILTs, higher AAA expansion rates, and pronounced elastin loss, and may also lead to a higher propensity for tissue dissection and aneurysm rupture.

Abstract 223: Is Oxidative Stress Important in AAA pathogenesis?

OBJECTIVE Active investigations continue to identify markers other than size that would predict a risk of abdominal aortic aneurysms (AAA) rupture. Circulating biomarkers could also indicate optimal intervals between the surveillance intervals. Finally, the identification of biomarkers also may identify potential pathogenic pathways, and thus may open possibilities for pharmacological inhibition of growth. In the search of novel biomarkers of AAA progression, serum and wall material proteins were analyzed by a differential proteomic approach. METHODS AND RESULTS The same layers of AAA wall from ruptured (rAAA) and non-ruptured AAA were incubated, and the proteins released were analyzed by 2-dimensional difference in-gel electrophoresis. Proteins from serum were analyzed and correlated with AAA annual expansion rate. Several differentially expressed proteins involved in main AAA pathological mechanisms were identified by mass spectrometry. Among the 8 proteins identified in AAA wall, peroxiredoxin-2 (PRX-2) was more permanent, which was further validated by Western blot and immunohistochemistry. We demonstrated increased PRX-2 levels in rAAA patient wall material compared with AAA subjects and also positive correlation in serum among PRX-2 and AAA diameter and annual AAA expansion rate. CONCLUSIONS Eight proteins associated with AAA pathogenesis have been identified in AAA wall by a proteomic approach. Protein profiles identified in the wall from the rAAA and the serum would appear to be a convenient monitoring tool that has the ability to be both sensitive and specific for AAAs. Among them, PRX-2 serum levels are increased in AAA patients and correlate with AAA size and growth rate, suggesting the potential use of PRX-2 as a biomarker for AAA evolution. Characterizing such diagnostic protein profiles, combined with known risk factors as well as emerging genetic data, would contribute to the long-term objective of applying effective non-surgical therapies to the treatment of small AAA disease. Larger studies are required to confirm the potential and clinical role of the identified proteins.

Gender Differences in Biomechanical Properties, Thrombus Age, Mass Fraction and Clinical Factors of Abdominal Aortic Aneurysms

The main purpose of the present study is the investigation of gender differences in the biomechanical properties, thrombus age, mass fraction and key clinical factors of abdominal aortic aneurysms (AAAs). A total of 90 AAA samples (78 males and 12 females) were harvested from open surgical aneurysm repairs. Biaxial extension and peeling tests were performed to characterise the biaxial mechanical responses and to determine dissection properties of both the intraluminal thrombi (ILTs) and the thrombus-covered walls. Relative thrombus age was determined by characterising the ILT histological microstructure. Mass fraction analyses quantified dry weight percentages of elastin and collagen within the AAA walls. Moreover, we statistically compared clinical factors between male and female. The luminal layers of the female thrombi and the female AAA walls showed a significantly lower tissue stiffness (modulus) in the longitudinal direction when compared to males. Gender differences were also shown in the dissection properties of the intima-media composite within the AAA walls, in which a statistically significantly lower energy to propagate a dissection was quantified for females than for males. Moreover, 82% of female thrombi were relatively older (ILT age phases III and IV), twice that of male thrombi (43%). A pronounced lower elastin content was identified for the intima-media composites of male AAA walls, whereas female AAA walls had significantly lower dry weight percentages of collagen. Regarding clinical factors, nicotine pack years, serum creatinine and AAA expansion rate were found to be much higher for male patients. These findings may help to explain higher risks for AAA growth in males and the ruptures of smaller-sized AAAs in females.

Medical treatment for small abdominal aortic aneurysms

Screening for abdominal aortic aneurysm (AAA) in selected groups is now performed in England, the USA and Sweden. Patients with aneurysms over 55 mm in diameter are generally considered for elective surgical repair. Patients with aneurysm diameters below or equal to 55 mm (termed 'small AAAs') are managed with aneurysm surveillance as there is currently insufficient evidence to recommend surgery in these cases. As more patients are screened, there will be an increasing number of small AAAs identified. There is interest in pharmaceutical interventions (for example angiotensin converting enzyme (ACE) inhibitors, antibiotics, beta-blockers, statins) which could be given to such patients to delay or reverse aneurysm expansion and reduce the need for elective surgical repair. To assess the effects of medical treatment on the expansion rate of small abdominal aortic aneurysms. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (May 2012) and CENTRAL (2012, Issue 5). Clinical trials databases were searched for details of ongoing or unpublished studies. The reference lists of articles retrieved by electronic searches were searched for additional citations. We selected randomised trials in which patients with small AAAs allocated to medical treatment with the intention of retarding aneurysm expansion were compared to patients allocated to a placebo treatment, alternative medical treatment, a different regimen of the same drug or imaging surveillance alone. Two authors independently extracted the data and assessed the risk of bias in the trials. Meta-analyses were used when heterogeneity was considered low. The two primary outcomes were the mean difference (MD) in aneurysm diameter and the odds ratio (OR) calculated to compare the number of individuals referred to AAA surgery in each group over the trial period. Seven trials involving 1558 participants were included in this review; 457 were involved in four trials of antibiotic medication, and 1101 were involved in three trials of beta-blocker medication. Five of the studies were rated at a high risk of bias.Individually, all of the included trials reported non-significant differences in AAA expansion rates between their intervention and control groups.The two major drug groups were then analysed separately. For AAA expansion it was only possible to combine two of the antibiotic trials in a meta-analysis. This demonstrated that roxithromycin had a small but significant protective effect (MD -0.86 mm; 95% confidence interval (CI) -1.57 to -0.14). When referral to AAA surgery was compared (including all four antibiotic trials in the meta-analysis), non-significantly fewer patients were referred in the intervention groups (OR 0.96; 95% CI 0.59 to 1.57) than the control groups. When only the trials reporting actual elective surgery were included in a subgroup analysis, the result remained statistically non-significant (OR 1.17; 95% CI 0.57 to 2.42).For the beta-blocker trials, when all were combined in a meta-analysis, there was a very small, non-significant protective effect for propranolol on AAA expansion (MD -0.08 mm; 95% CI -0.25 to 0.10), and non-significantly fewer patients were referred to AAA surgery in the propranolol group (OR 0.74; 95% CI 0.52 to 1.05). Bronchospasm and shortness of breath were the main adverse effects from the beta-blockers. In one trial the adverse effects were reportedly so severe that the trial was stopped early after two years. There is some limited evidence that antibiotic medication may have a slight protective effect in retarding the expansion rates of small AAAs. The quality of the evidence makes it unclear whether this translates into fewer referrals to AAA surgery, owing mainly to the small sample sizes of the studies.Antibiotics were generally well tolerated with minimal adverse effects. Propranolol was poorly tolerated by patients in all of the beta-blocker trials and demonstrated only minimal and non-significant protective effects. Further research on beta-blockers for AAA needs to consider the use of drugs other than propranolol.In general, there is surprisingly little high quality evidence on medical treatment for small AAAs, especially in relation to the use of newer beta-blockers, ACE inhibitors and statins.