Abdominal Aortic Aneurysm Expansion Research Articles

Identification and Evaluation of Blood-Based Biomarkers for Abdominal Aortic Aneurysm.

Blood-based biomarkers for abdominal aortic aneurysm (AAA) have been studied individually; however, we considered a panel of proteins to investigate AAA prognosis and its potential to improve predictive accuracy. Using a prospectively recruited cohort of patients with/without AAA (n = 452), we conducted a prognostic study to develop a model that accurately predicts AAA outcomes using clinical features and circulating biomarker levels. Serum concentrations of 9 biomarkers were measured at baseline, and the cohort was followed for 2 years. The primary outcome was major adverse aortic event (MAAE; composite of rapid AAA expansion [>0.5 cm/6 months or >1 cm/12 months], AAA intervention, or AAA rupture). Using 10-fold cross-validation, we trained a random forest model to predict 2 year MAAE using (1) clinical characteristics, (2) biomarkers, and (3) clinical characteristics and biomarkers. Two-year MAAE occurred in 114 (25%) patients. Two proteins were significantly elevated in patients with AAA compared with those without AAA (angiopoietin-2 and aggrecan), composing the protein panel. For predicting 2 year MAAE, our random forest model achieved area under the receiver operating characteristic curve (AUROC) 0.74 using clinical features alone, and the addition of the 2-protein panel improved performance to AUROC 0.86. Using a combination of clinical/biomarker data, we developed a model that accurately predicts 2 year MAAE.

The role of diabetes on the development of abdominal aortic aneurysms (AAA)

An abdominal aortic aneurysm (AAA) is a pathological local dilatation of the abdominal aorta that may develop from a variety of causes. With a 80% mortality rate, it is mainly linked to male gender, age above 65 years, smoking, and a family history of AAA. Ultrasonography is an effective method for screening males who are 65 or older for AAA. Endovascular aneurysm repair (EVAR) procedure reduces 30-day operative mortality and hospital stay, becoming a global standard. Both open and endovascular surgery aim to cut off the aneurysm's circulation, preventing it from rupturing. Diabetes mellitus (DM) may provide protection against regrowth and the need for additional intervention after endovascular AAA repair, thereby limiting the enlargement and rupture of AAAs. Hyperglycemia thickens the aortic walls and reduces wall stress in diabetic patients' abdominal aortas. It stabilizes collagen structure and promotes the synthesis of collagen type IV. Anti-diabetic drugs like metformin, thiazolidinedione, and dipeptidyl peptidase 4 inhibitors (DPP-4i) have been shown in both animal and human studies to protect against aortic aneurysms. In a dose-response pattern, these antidiabetic drugs may lower the prevalence, incidence, and enlargement rate of AAA.

Ketosis prevents abdominal aortic aneurysm rupture through C–C chemokine receptor type 2 downregulation and enhanced extracellular matrix balance

Abdominal aortic aneurysms (AAAs) are prevalent with aging, and AAA rupture is associated with increased mortality. There is currently no effective medical therapy to prevent AAA rupture. The monocyte chemoattractant protein (MCP-1)/C–C chemokine receptor type 2 (CCR2) axis critically regulates AAA inflammation, matrix-metalloproteinase (MMP) production, and extracellular matrix (ECM) stability. We therefore hypothesized that a diet intervention that can modulate CCR2 axis may therapeutically impact AAA risk of rupture. Since ketone bodies (KBs) can trigger repair mechanisms in response to inflammation, we evaluated whether systemic ketosis in vivo could reduce CCR2 and AAA progression. Male Sprague–Dawley rats underwent surgical AAA formation using porcine pancreatic elastase and received daily β-aminopropionitrile to promote AAA rupture. Rats with AAAs received either a standard diet, ketogenic diet (KD), or exogenous KBs (EKB). Rats receiving KD and EKB reached a state of ketosis and had significant reduction in AAA expansion and incidence of rupture. Ketosis also led to significantly reduced aortic CCR2 content, improved MMP balance, and reduced ECM degradation. Consistent with these findings, we also observed that Ccr2−/− mice have significantly reduced AAA expansion and rupture. In summary, this study demonstrates that CCR2 is essential for AAA expansion, and that its modulation with ketosis can reduce AAA pathology. This provides an impetus for future clinical studies that will evaluate the impact of ketosis on human AAA disease.

Abdominal Aortic Aneurysm Response to Interleukin-10 Hydrogel-Based “Bio-Ink” Therapy in Rodent Models

Abdominal Aortic Aneurysms (AAA) are the pathological expansion of the aorta, which can rupture and cause significant mortality. Approximately 200,000 AAA cases occur annually in the US, with more than 15,000 cases resulting in death. Risk factors for AAA are similar to those of cardiovascular disease states, particularly cigarette smoking, and AAA patients are generally elderly, Caucasian males. Currently, no medical therapy exists for AAA outside of surgical intervention. We previously hypothesized that the early initiation and propagation of stages in AAA development are inflammatory driven. This process results in a weaker aortic wall, whichwe have evidenced through increased elastin breakdown products and inflammatory markers in AAA patients in comparison to matched controls. This project investigated the use of a novel anti-inflammatory hydrogel to ameliorate AAA progression.
 Our study uses a gelatin-based biodegradable bio-ink containing the anti-inflammatory cytokine interleukin-10 (IL-10), which was applied to the aorta with a novel hydrogel extruding “BIOPENCIL” device. We used a previously described rodent model consisting of intra-luminal injection of elastase in the infrarenal aorta combined with topical application of calcium chloride; alternatively, topical calcium chloride was used alone for AAA development. The BIOPENCIL was used to deliver the hydrogel containing IL-10 or control at the time of AAA creation. The animals were euthanized 14 or 21 days post-procedure and evaluated for AAA volume, surface area, and diameter alongside molecular analyses to evaluate for immunological changes between control and treatment groups. We predict that the rodent groups treated with IL-10 will not have AAA expansion, while the control group will see AAA expansion. This is based onlongitudinal data from weekly ultrasounds and will be confirmed with microCT.

Suppression of Inflammation-induced Abdominal Aortic Aneurysm Formation by Induction of Elastin Tolerance

Abdominal aortic aneurysm (AAA) is a vascular disease process whereby the aorta expands to apoint where rupture may occur. This serious condition is diagnosed in approximately 200,000 people in the United States per year and accounts for over 15,000 deaths annually. The only medical intervention proven to reduce the risk of AAA rupture is surgical repair; however, such repair is associated with high risk of death, reduced quality of life, and high expense. AAA is caused by the weakening of the artery wall due to inflammation-induced destruction of its structural components. Our clinical data shows increased levels of circulating elastin degradation products in patients with AAA, especially smokers, compared to risk factor matched controls. This observation led us to hypothesize that an immune reaction to elastin fragments initiates the inflammatory cascade in the aorta that leads to AAA formation. To test this hypothesis, C57BL/6 mice were injected with poly(lactide-co-glycolide) nanoparticle-encapsulated IL-10 to induce immune tolerance or nanoparticle-encapsulated control ovalbumin. Injection of elastin fragments was performed 7 days later to induce an immune response. AAA of the infrarenal aorta was induced by topical application of elastase during laparotomy procedure 14 days after nanoparticle injection. Aorta diameter was measured 16 days post-operatively with Microfil. Immunologic changes were evaluated by cytokine analysis, Tr1/Th17 cell ratio inperipheral blood, and splenic Th17 and Tr1 response to elastin. Based on prior work, we expect that induction of elastin tolerance using poly(lactide-co-glycolide) nanoparticle-encapsulated IL-10 will suppress abdominal aortic aneurysm expansion and promote an anti-inflammatoryenvironment characterized by increased Tr1/Th17 cell ratio, increased levels of anti-inflammatory cytokines, and decreased pro-inflammatory cytokine expression.

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.

Antiplatelet or Anticoagulant Therapy for Abdominal Aortic Aneurysms: Growth and Clinical Outcomes.

Intraluminal thrombi in the abdominal aortic aneurysms (AAA) were demonstrated to increase aneurysm growth. The effect of treatments on thrombus reduction upon AAA enlargement and clinical endpoints is uncertain Therefore, this study aimed to investigate the effect of antiplatelet and anticoagulant therapy on AAA growth and clinical outcomes. A total of 357 patients with AAAs were enrolled in this study. They were divided into 2 groups based on their medical therapies. Patients on antiplatelet and anticoagulant therapy were assigned to group 1 (n = 234) and group 2 (n = 92), respectively. The greatest reduction in thrombus diameter change was observed in patients with anticoagulant therapy (group 1, -2.26 mm; group 2, -8.16 mm; P =.001). The greatest aneurysmal enlargement was found in patients with antiplatelet therapy. There was less AAA progression with anticoagulant therapy than with the other therapy (group 1, 2.08 mm; group 2, 1.31 mm P =.027. The more operational need was observed in patients with antiplatelet therapy than in patients with anticoagulant therapy ( group 1 67, group 2 16, P =.036) Conclusion: In our study, it was revealed that anticoagulant therapy has been associated with decreased thrombus diameter and less aneurysmal enlargement compared with antiplatelet therapy. Furthermore, this beneficial effect on the thrombus size and aneurysmal diameter decreased the operational need in patients with anticoagulant therapy.

Abstract 13582: Interferon Regulatory Factor 8 Promotes Abdominal Aortic Aneurysm via Inducing Type I Conventional Dendritic Cell Differentiation

Introduction: Abdominal aortic aneurysm (AAA) remains to be the most common true aneurysm worldwide. Previous studies identified the participation of dendritic cells (DC) in the pathogenesis of AAA. However, the detailed subtypes involved and mechanisms remain unknown. Our previous RNA-Seq data determined dramatically increased Irf8 in AAA samples, which drives DC differentiating to Type I conventional dendritic cells (cDC1). Aim: The aim of the work is to determine the role of interferon regulatory factor 8 (IRF8) in the development of AAA. Methods and Results: Murine AAA were induced via elastase infusion. The single-cell transcriptomic sequencing of CD45+ cells in murine AAA samples identified the dramatically increased cDC1. By flow cytometry, we found that the ratio of CD103 + cDC1s reached maximum at day 7. Compared with the control group, Irf8 CAG-LSL Itgax Cre mice ( Irf8 overexpression in DC) suffered significantly more severe aneurysm expansion, elastin degradation and apoptosis of smooth muscle cells, while the AAA development in Irf8 flox/flox Itgax Cre mice ( Irf8 deletion in DC) was less sharp. Batf3 -/- mice which were cDC1 depleted, showed similar characteristic in AAA expansion with Irf8 flox/flox Itgax Cre mice. The effective CD8 + T cells increased significantly in Irf8 CAG-LSL Itgax Cre mice than the control group, while decreased in Irf8 flox/flox Itgax Cre ones. Deletion of Clec9a which blocks cross-present dead-cell-associated antigens to the CD8 + T cells, also attenuated AAA development, in accordance with Irf8 flox/flox Itgax Cre mice in gross anatomy and pathology changes. Conclusion: Our findings suggest that the activation of IRF8 promotes cDC1 differentiation, which subsequently activate CD8 + T cells and contribute to destruction of the aortic-wall and AAA formation.

Preemptive Embolization of the Lumbar Arteries and Inferior Mesenteric Artery to Prevent Abdominal Aortic Aneurysm Enlargement Associated with Type 2 Endoleak Following Endovascular Aneurysm Repair.

This study aims to evaluate the efficacy of preemptive embolization (PE) of the lumbar arteries (LAs) and inferior mesenteric artery (IMA) (PELI) for preventing abdominal aortic aneurysm (AAA) enlargement associated with type 2 endoleak (T2EL). Patients who underwent endovascular aneurysm repair (EVAR) between January 2015 and December 2020 were classified into the control (without PE), IMA (PE of a patent IMA with a diameter ≥2.5 mm), and PELI (PE of patent LAs with a diameter ≥2 mm and IMA) groups. The rate of freedom from AAA enlargement following EVAR (enlargement ≥5 mm from pre-EVAR) was compared using the log-rank test. The prevalence of T2EL at 6 months and 1 year after EVAR was compared using Fisher's exact test. The cumulative rates of freedom from AAA enlargement at 54 months after EVAR (maximum observational period in the PELI group) were as follows: control group, 77.5%; IMA group, 62.5%; and PELI group, 100%. The mean CT follow-up periods of the control, IMA, and PELI groups were 46.4 ± 22.3, 31.1 ± 20.6, and 22.9 ± 15.5 months, respectively. None of the 31 patients in the PELI group experienced AAA enlargement after EVAR, whereas 2 out of the 16 patients in the IMA group and 20 out of the 98 patients in the control group had AAA enlargement. No significant differences were observed in the rate of freedom from AAA enlargement (PELI group vs. IMA group, P = 0.11; PELI group vs. control group, P = 0.11). The prevalence of T2EL was significantly lower in the PELI group than in the control group at 6 months (13.6% in PELI group vs. 42.1% in control group, P = 0.02) and 1 year (14.3% in PELI group vs. 40.0% in control group, P = 0.04). PELI was significantly associated with a low prevalence of T2EL and may prevent T2EL-associated AAA enlargement.

Intermediate pressure-normalized principal wall strain values are associated with increased abdominal aortic aneurysmal growth rates.

Current abdominal aortic aneurysm (AAA) assessment relies on analysis of AAA diameter and growth rate. However, evidence demonstrates that AAA pathology varies among patients and morphometric analysis alone is insufficient to precisely predict individual rupture risk. Biomechanical parameters, such as pressure-normalized AAA principal wall strain (/PP, %/mmHg), can provide useful information for AAA assessment. Therefore, this study utilized a previously validated ultrasound elastography (USE) technique to correlate /PP with the current AAA assessment methods of maximal diameter and growth rate. Our USE algorithm utilizes a finite element mesh, overlaid a 2D cross-sectional view of the user-defined AAA wall, at the location of maximum diameter, to track two-dimensional, frame-to-frame displacements over a full cardiac cycle, using a custom image registration algorithm to produce /PP. This metric was compared between patients with healthy aortas and AAAs (≥3 cm) and compared between small and large AAAs (≥5 cm). AAAs were then separated into terciles based on /PP values to further assess differences in our metric across maximal diameter and prospective growth rate. Non-parametric tests of hypotheses were used to assess statistical significance as appropriate. USE analysis was conducted on 129 patients, 16 healthy aortas and 113 AAAs, of which 86 were classified as small AAAs and 27 as large. Non-aneurysmal aortas showed higher /PP compared to AAAs (0.044 ± 0.015 vs. 0.034 ± 0.017%/mmHg, p = 0.01) indicating AAA walls to be stiffer. Small and large AAAs showed no difference in /PP. When divided into terciles based on /PP cutoffs of 0.0251 and 0.038%/mmHg, there was no difference in AAA diameter. There was a statistically significant difference in prospective growth rate between the intermediate tercile and the outer two terciles (1.46 ± 2.48 vs. 3.59 ± 3.83 vs. 1.78 ± 1.64 mm/yr, p = 0.014). There was no correlation between AAA diameter and /PP, indicating biomechanical markers of AAA pathology are likely independent of diameter. AAAs in the intermediate tercile of /PP values were found to have nearly double the growth rates than the highest or lowest tercile, indicating an intermediate range of /PP values for which patients are at risk for increased AAA expansion, likely necessitating more frequent imaging follow-up.

Pharmacological Inhibition of Gasdermin D Suppresses Angiotensin II-Induced Experimental Abdominal Aortic Aneurysms.

Gasdermin D, a molecule downstream of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing inflammasome, forms the membrane pore for the secretion of interleukin (IL)-1β and IL-18, and also mediates pyroptosis. This study was to explore the influence of treatment with disulfiram, a small molecule inhibitor to gasdermin D, on the formation and progression of experimental abdominal aortic aneurysms (AAA). AAAs were induced in 10-week-old male apolipoprotein E deficient mice by subcutaneous infusion of angiotensin II (1000 ng/min/kg body weight) for 28 days via osmotic minipumps. Three days prior to angiotensin II infusion, disulfiram (50 mg/kg) or an equal volume of saline as the vehicle control was administered daily via oral gavage. The influence on experimental AAAs was analyzed by serial measurements of aortic diameters via ultrasonography, grading AAA severity and histopathology at sacrifice. Serum IL-1β and IL-18 levels, systolic blood pressure, total cholesterol, and triglyceride were also measured. Additional experiments assayed the influences on the cell viability and IL-1β secretion of in vitro activated macrophages. Disulfiram significantly reduced the enlargement, incidence, and severity of angiotensin II-induced experimental AAAs with attenuation of medial elastin breaks, mural macrophage accumulation, and systolic blood pressure. The AAA suppression was also associated with reduced systemic levels of IL-1β but not IL-18. However, disulfiram treatment had no impact on body weight gain and lipid levels in aneurysmal mice. Additionally, disulfiram treatment also markedly reduced the secretion of IL-1β from activated macrophages with a limited effect on cell viability in vitro. Gasdermin D inhibition by disulfiram attenuated angiotensin II-induced experimental AAAs with reduced systemic IL-1β levels and in vitro activated macrophage IL-1β secretion. Our study suggests that pharmacological gasdermin D inhibition may have translational potential for limiting clinical AAA progression.

Nicotine Administration Augments Abdominal Aortic Aneurysm Progression in Rats.

Inflammation and elastin degradation are key hallmarks in the pathogenesis of abdominal aortic aneurysms (AAAs). It has been acknowledged that activation of alpha7 nicotinic acetylcholine receptors (α7nAChRs) attenuates inflammation, termed the cholinergic anti-inflammatory pathway (CAP). Thus, we hypothesize that low-dose nicotine impairs the progression of elastase-induced AAAs in rats by exerting anti-inflammatory and anti-oxidative stress properties. Male Sprague-Dawley rats underwent surgical AAA induction with intraluminal elastase infusion. We compared vehicle rats with rats treated with nicotine (1.25 mg/kg/day), and aneurysm progression was monitored by weekly ultrasound images for 28 days. Nicotine treatment significantly promoted AAA progression (p = 0.031). Additionally, gelatin zymography demonstrated that nicotine significantly reduced pro-matrix metalloproteinase (pro-MMP) 2 (p = 0.029) and MMP9 (p = 0.030) activity in aneurysmal tissue. No significant difference was found in the elastin content or the score of elastin degradation between the groups. Neither infiltrating neutrophils nor macrophages, nor aneurysmal messenger RNA (mRNA) levels of pro- or anti-inflammatory cytokines, differed between the vehicle and nicotine groups. Finally, no difference in mRNA levels of markers for anti-oxidative stress or the vascular smooth muscle cells' contractile phenotype was observed. However, proteomics analyses of non-aneurysmal abdominal aortas revealed that nicotine decreased myristoylated alanine-rich C-kinase substrate and proteins, in ontology terms, inflammatory response and reactive oxygen species, and in contradiction to augmented AAAs. In conclusion, nicotine at a dose of 1.25 mg/kg/day augments AAA expansion in this elastase AAA model. These results do not support the use of low-dose nicotine administration for the prevention of AAA progression.

Abstract 270: Multi-transcriptomic Profiling Reveals Novel Molecular Mediators During Abdominal Aortic Aneurysm Expansion.

Abdominal aortic aneurysm (AAA), a life-threatening condition associated with high morbidity and mortality rates, is despite decades of intense research still mostly treated by surgical repair as currently no medical therapy is available. Long non-coding RNAs (lncRNAs) are highly cell type specific and potential molecular disease modulators, posing potential drug targets. We performed single cell (sc) RNA and combined total (bulk) RNA sequencing to study the transcriptome of AAAs from patients undergoing open aortic repair. Further, we implemented hybridization-based RNA in situ sequencing (HybRISS) to localize highly intriguing genes within the tissue.In this current study, we examined three different sequencing datasets (total RNA from dilated vs. non- dilated AAA specimen from an individual patient each, AAA vs. control from individual patients and one scRNA-seq dataset). Six lncRNAs could be cross-referenced between all three datasets. All of these lncRNAs presented a cell-type specific expression pattern, with three lncRNAs being highly enriched within the SMC cluster. We found all newly identified lncRNAs conserved in our bulk and scRNA-seq datasets of experimentally-induced AAA in mice and LDLR-deficient Yucatan mini-pigs. Further, potential novel regulator genes could be visualized in human AAA tissue sections using HybRISS to resolve their distinct location and co-expression pattern within the diseased tissue. In summary, our approach utilizing dilated and non-dilated human tissue specimens, different preclinical models and resulting datasets demonstrate that combining bulk Seq, scRNA-Seq data and spatially resolved sequencing methods are powerful tools to detect and describe novel lncRNAs as disease modulators.

Outcomes of embolization procedures for type II endoleaks following endovascular abdominal aortic repair.

The objective of this study was to investigate the mid-term outcomes of embolization procedures for type II endoleak after endovascular abdominal aortic repair, and clarify the risk factors for aneurysm enlargement after embolization procedures. This was a retrospective multicenter registry study enrolling patients who underwent embolization procedures for type II endoleaks after EVAR from January 2012 to December 2018 at 19 Japanese centers. The primary end point was the rate of freedom from aneurysm enlargement, more than 5mm in the aortic maximum diameter, after an embolization procedure. Demographic, procedural, follow-up, and laboratory data were collected. Continuous variables were summarized descriptively, and Kaplan-Meier analyses and a Cox regression model were used for statistical analyses. A total of 315 patients (248 men and 67 women) were enrolled. The average duration from the initial embolization procedure to the last follow-up was 31.6± 24.6months. The rates of freedom from aneurysm enlargement at 3 and 5years were 55.4± 3.8% and 37.0± 5.2%, respectively. A multivariate analysis revealed that a larger aortic diameter at the initial embolization procedure and the presence of a Moyamoya endoleak, defined as heterogeneous contrast opacity with an indistinct faint border, were associated with aneurysm enlargement after embolization management. The embolization procedures were generally ineffective in preventing further expansion of abdominal aortic aneurysms in patients with type II endoleaks after EVAR, especially in patients with a large abdominal aortic aneurysm and/or a presence of a Moyamoya endoleak.

Assessing Abdominal Aortic Aneurysm Progression by Using Perivascular Adipose Tissue Attenuation on Computed Tomography Angiography.

Recent studies have highlighted the active and potential role of perivascular adipose tissue (PVAT) in atherosclerosis and aneurysm progression, respectively. This study explored the link between PVAT attenuation and abdominal aortic aneurysm (AAA) progression using computed tomography angiography (CTA). This multicenter retrospective study analyzed patients with AAA who underwent CTA at baseline and follow-up between March 2015 and July 2022. The following parameters were obtained: maximum diameter and total volume of the AAA, presence or absence of intraluminal thrombus (ILT), maximum diameter and volume of the ILT, and PVAT attenuation of the aortic aneurysm at baseline CTA. PVAT attenuation was divided into high (> -73.4 Hounsfield units [HU]) and low (≤ -73.4 HU). Patients who had or did not have AAA progression during the follow-up, defined as an increase in the aneurysm volume > 10 mL from baseline, were identified. Kaplan-Meier and multivariable Cox regression analyses were used to investigate the association between PVAT attenuation and AAA progression. Our study included 167 participants (148 males; median age: 70.0 years; interquartile range: 63.0-76.0 years), of which 145 (86.8%) were diagnosed with AAA accompanied by ILT. Over a median period of 11.3 months (range: 6.0-85.0 months), AAA progression was observed in 67 patients (40.1%). Multivariable Cox regression analysis indicated that high baseline PVAT attenuation (adjusted hazard ratio [aHR] = 2.23; 95% confidence interval [CI], 1.16-4.32; P = 0.017) was independently associated with AAA progression. This association was demonstrated within the patients of AAA with ILT subcohort, where a high baseline PVAT attenuation (aHR = 2.23; 95% CI, 1.08-4.60; P = 0.030) was consistently independently associated with AAA progression. Elevated PVAT attenuation is independently associated with AAA progression, including patients of AAA with ILT, suggesting the potential of PVAT attenuation as a predictive imaging marker for AAA expansion.

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.

Abstract 15566: The Impact of Aspirin Use on Progression and Mortality of Abdominal Aortic Aneurysm

Introduction: Preclinical studies demonstrated a potential role for aspirin (ASA) to slow the progression of abdominal aortic aneurysms (AAA) to rupture. We aim to investigate the association of long-term ASA use with progression and mortality in AAA. Methods: We queried the vascular ultrasound database at Cleveland Clinic for patients who underwent consecutive abdominal vascular ultrasound 2010-2020 if at least two available ultrasounds were conducted, without prior history of aneurysm repair, dissection, or rupture. ASA use was defined as at least one prescription of ASA during the during the follow-up period. The primary outcome was all-cause mortality, assessed by survival analysis with multivariable-adjust Cox regression. The secondary outcome was the mean annualized change of aneurysm diameter, assessed by multivariable-adjusted linear regression. Results: A total of 3,803 patients were included, with an average age of 73, and of which 826 (22%) were female and 2,380 (62.5%) were prescribed ASA (median duration of use ~ 9 years). ASA use was not significantly associated with all-cause mortality irrespective of age, sex and smoking status, except among those with a baseline diameter > 3.5 cm (Figure 1). ASA use was negatively associated with the mean annualized AAA diameter change only in males (0.25 vs 0.38 cm/year, p = 0.002) and in nonsmokers (0.26 vs 0.37 cm/year, p = 0.003). Conclusions: ASA use reduces the expansion of abdominal aortic aneurysms with altering all-cause mortality except in certain high-risk individuals in men and non-smokers. Mechanistic and randomized studies are needed to ascertain the role of ASA in patients with abdominal aortic aneurysms.

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.

A Multi-Bioactive Nanomicelle-Based "One Stone for Multiple Birds" Strategy for Precision Therapy of Abdominal Aortic Aneurysms.

Abdominal aortic aneurysm (AAA) remains a lethal aortic disease in the elderly. Currently, no effective drugs can be clinically applied to prevent the development of AAA. Herein, a "one stone for multiple birds" strategy for AAA therapy is reported. As a proof of concept, three bioactive conjugates are designed and synthesized, which can assemble into nanomicelles. Cellularly, these nanomicelles significantly inhibit migration and activation of inflammatory cells as well as protect vascular smooth muscle cells (VSMCs) from induced oxidative stress, calcification and apoptosis, with the best effect for nanomicelles (TPTN) derived from a conjugate defined as TPT. After intravenous delivery, TPTN efficiently accumulates in the aneurysmal tissue of AAA rats, showing notable distribution in neutrophils, macrophages and VSMCs, all relevant to AAA pathogenesis. Whereas three examined nanomicelles effectively delay expansion of AAA in rats, TPTN most potently prevents AAA growth by simultaneously normalizing the pro-inflammatory microenvironment and regulating multiple pathological cells. TPTN is effective even at 0.2mgkg-1 . Besides, TPTN can function as a bioactive nanoplatform for site-specifically delivering and triggerably releasing anti-aneurysmal drugs, affording synergistic therapeutic effects. Consequently, TPTN is a promising multi-bioactive nanotherapy and bioresponsive targeting delivery nanocarrier for effective therapy of AAA and other inflammatory vascular diseases.

Preventing Aortic Aneurysm Initiation And Expansion By Inducing Immune Tolerance To Aortic Specific Antigens Embedded In Biodegradable Poly(lactide-co-glycolide) Nanoparticles

Abdominal aortic aneurysm (AAA) is a life-threatening disease diagnosed in over 200,000 Americans each year. There are currently no effective strategies to prevent AAA expansion and avoid the need for surgery. Our prior work has shown that patients with AAA have elevated plasma levels of elastin fragments, anti-elastin antibodies, and elevated levels of Th17 cells sensitized to elastin degradation products (EDPs), the sum of which suggests that AAA is the result of an autoimmune response targeting elastin, the main extra-cellular matrix protein in the aorta.