Abdominal Aortic Aneurysm Size Research Articles

ScRNA-seq and bulk RNA-seq identified NUPR1 as novel biomarkers related to CD4 + T cells infiltration for abdominal aortic aneurysm.

Developing a molecular signature associated with CD4 + T cell infiltration is essential for identifying biomarkers in abdominal aortic aneurysms (AAA). Establishing such a signature is vital for improving diagnostic accuracy and therapeutic strategies for AAA. This study focuses on CD4 + T cells, which are pivotal in the immune microenvironment of AAA, to pinpoint key targets. We identified CD4 + T cell-related biomarkers in AAA using bulk and single-cell RNA sequencing data from the GEO database. We employed CIBERSORT to assess immune cell infiltration and applied weighted gene co-expression network analysis and differential expression analyses to pinpoint key genes. A nomogram and related score were developed based on these genes. Single-cell RNA sequencing further analyzed their expression across cell types, and KEGG/GO analyses were conducted for candidate genes. Four genes (NUPR1, CCL4L2, CCL3L3, MMP9) were identified finally. Validation via qPCR and immunohistochemistry showed NUPR1 downregulation in aneurysms and an inverse relationship with CD4 + T cells infiltration. Immunofluorescence results indicated NUPR1 was mainly expressed in the cytoplasm of vascular smooth muscle cells (VSMCs). After VSMCs-specific overexpression of NUPR1 via adeno-associated virus, the AAA diameter decreased, while treatment with the NUPR1 nuclear translocation inhibitor ZZW-115 hydrochloride had no effect on AAA size. Overexpression of NUPR1 in VSMCs suppresses the migration of CD4 + T cells. The four-gene signature accurately predicts CD4 + T cell infiltration in AAA patients and may serve as a clinical index. NUPR1 could be a therapeutic target for the interaction between CD4 + T cells and AAA.

Early results from the pivotal trial substudy of the GORE EXCLUDER conformable endoprosthesis in angulated necks

ObjectiveTo report the investigational device exemption study 1-year clinical outcomes of the high neck angulation (HNA) substudy of the GORE EXCLUDER Conformable AAA Endoprosthesis (EXCC) for treatment of infrarenal abdominal aortic aneurysms (AAAs). MethodsThis study is a prospective, multicenter clinical trial conducted in the United States and included core laboratory assessment of imaging and independent event adjudication. Anatomical criteria for enrollment in the HNA substudy included infrarenal aortic neck angulation >60° and ≤90° with aortic neck length ≥10 mm. Primary safety end points included estimated blood loss of >1000 mL, death, stroke, myocardial infarction, bowel ischemia, paraplegia, respiratory failure, renal failure, and thromboembolic events. Primary effectiveness end points included technical success, absence from type I and III endoleaks, migration (≥10 mm), sac enlargement (≥5 mm), sac rupture, and conversion to open repair. ResultsBetween January 2018 and February 2022, 95 patients were enrolled in the HNA substudy across 35 sites. Of the 95 patients, 71 (74.7%) were male and the cohort average age was 74.4 years. The mean infrarenal proximal aortic neck angle was 71.6° and the mean AAA size was 62.9 mm. Overall technical success was achieved in 93 patients (97.9%). Freedom from a primary safety end point through 30 days was 96.7%; 3 (3.3%) patients had an estimated blood loss of >1000 mL. Freedom from the primary effectiveness at 12 months was achieved in 94.8%. Four patients (4.3%) had a type IA endoleak; intervention after the procedure was not required and no subsequent interventions or sac enlargement were noted in these patients. At 12 months, 29 patients (39.7%) experienced a type II endoleak and 1 (1.3%) patient experienced AAA sac expansion of ≥5 mm. Through 12 months, 1 patient (1.3%) had a conversion to open surgical repair. There were no aneurysm-related deaths, ruptures, or migration through 12 months. ConclusionsThe investigational device exemption study demonstrates safety and effectiveness of the GORE EXCLUDER Conformable AAA Endoprosthesis device in AAA with highly angulated necks (>60° and ≤90°) are preserved at the 12-month follow-up.

Abstract 3005: Transgenerational Impact Of E-cigarette Nicotine Vaping On Abdominal Aortic Aneurysm

Background: Smoking and family history are major risk factors for abdominal aortic aneurysm (AAA). Smoking is a powerful modulator of DNA methylation, and nicotine can cause heritable epigenetic alterations in animals and humans. We found that nicotine infusion and e-cigarette (e-cig) vaping augment murine AAA, and that parental nicotine infusion augments model AAA in offspring, altering tissue DNA methylation patterns. Hypothesis: We investigated the effects of maternal e-cig vaping in mice on their offspring’s experimental AAA risk, and transgenerational DNA methylation. Methods: Two treatment arms were employed: 1) pre-fertilization or 2) peri-natal. Female ApoE-/- or C57BL6 mice (F0) were exposed to e-cig nicotine (24 mg/ml) puffs, 9 sec/min, 1 hour/day (or room air). Arm 1: treated 28 days, then mated to untreated controls. Arm 2: mated after 1 week of e-cig, then maintained on treatment until gestation was complete. Aortic tissue of 10-week-old F1 offspring was evaluated using RRBS-Seq DNA methylation analysis. Parallel offspring underwent angiotensin-II infusion (1μg/kg/min; ApoE-/-) or elastase infusion (2U/ml for 5 min at 120 mmHg; C57) to induce AAA. Aneurysm growth was ultrasound tracked over 28 days. Results: Maternal vape exposure altered aortic DNA methylation in offspring, with numerous differentially methylated regions (DMRs; q<0.1). Hundreds of these DMRs were located in the same genes previously identified in offspring of nicotine-infused mice (see Background). Vaping altered offspring aortic methylation patterns in AAA-related genes, including miRNAs. DMR pathway analysis was enriched in transcription factors. Further, many DMRs were located in genes harboring risk loci for human AAA from our recent collaborative publication. Maternal e-cig exposure augmented AAA size in both models, arms, and genders (p<0.05). AAA incidence and mortality were increased in ApoE-/- in both genders and arms. Effects were most significant in males. Conclusions: E-cig nicotine exposure augments experimental AAA growth in multiple models across generations. These effects are accompanied by broad aortic epigenetic changes, including in key AAA modulator genes, with enrichment in transcription factors that target known AAA-related genes.

Abstract 2128: Hepcidin Loss Demonstrates Sex Dependent Differences In Aortic Aneurysm Size

Background: Studies suggest circulating iron levels play a role in the pathophysiology of abdominal aortic aneurysms (AAAs). Low iron levels lead to medial degeneration and VSMC dysfunction while elevated iron levels promote oxidative stress. Hepcidin is a major iron regulatory hormone that binds ferroportin to reduce serum iron levels, and its removal in VSMCs has been shown to exacerbate AAAs; however, the role of sex in this mechanism remains understudied. The goal of the current study is to investigate the potential role of sex in iron metabolism in AAAs. Methods: Male and female C57BL/6 wild-type (WT/WT), heterozygous hepcidin knock-out (WT/KO) and hepcidin KO (KO/KO) underwent peri-adventitial application of porcine pancreatic elastase on the infrarenal aorta (n=10-19/group). At day 14, the aortas were measured using video micrometry and harvested for immunohistochemistry. In separate studies, male and female hepcidin WT/WT and KO/KO underwent elastase application and systemic b-aminopropionitrile (BAPN, 0.02%) administration and were harvested at 28 days. Finally, male and female LysM Cre Ferroportin flx/flx mice and their controls underwent elastase application and harvested at 14 days (n=5-10/group). Results: Hepcidin WT/KO and KO/KO male mice had dose dependent protection of aneurysm formation compared with controls (WT/WT: 145.5±33.8% vs WT/KO: 110.7±34.8% vs KO/KO: 53.7±13.7%, p=0.0001 by ANOVA). Female Hepcidin WT/KO and KO/KO mice exhibited increased AAA size compared with their controls (KO/KO: 119.0±23.5% vs WT/KO: 101.6 ±28.6% vs WT/WT: 71.2±22.0%, p =.0011 by ANOVA). In the elastase + BAPN model, Hepcidin KO/KO male mice had less aortic dilation compared to controls (KO/KO: 196.0 ±31.9% vs WT/WT: 476.8±82.2%, p =.0002 by Mann-Whitney) while female KO/KO mice exhibited greater aortic dilation (WT/WT: 186.7±26.0% vs. KO/KO: 406.9±62.2%, p=0.006). Male LysM Cre Ferroportin flx/flx mice had decreased aortic dilation (WT/WT: 132.5±19.3% vs flx/flx: 53.5±7.8%, p=0.001). Conclusion: Elimination of hepcidin in AAA formation exhibited protective effects in male and deleterious effects in female mice. This data suggests targeting of hepcidin using drug-based therapies could have gender-specific clinical implications.

Size thresholds for repair of abdominal aortic aneurysms warrant reconsideration

BackgroundThe historical size threshold for abdominal aortic aneurysm (AAA) repair is widely accepted to be 5.5 cm for men and 5.0 cm for women. However, contemporary AAA rupture risks may be lower than historical benchmarks, which has implications for when AAAs should be repaired. Our objective was to use contemporary AAA rupture rates to inform optimal size thresholds for AAA repair. MethodsWe used a Markov chain analysis to estimate life expectancy for patients with AAA. The primary outcome was AAA-related mortality. We estimated survival using Social Security Administration life tables and published contemporary AAA rupture estimates. For those undergoing repair, we modified survival estimates using data from the Vascular Quality Initiative and Medicare on complications, late rupture, and open conversion. We used this model to estimate the AAA repair size threshold that minimizes AAA-related mortality for 60-year-old average-health men and women. We performed a sensitivity analysis of poor-health patients and 70- and 80-year-old base cases. ResultsThe annual risk of all-cause mortality under surveillance for a 60-year-old woman presenting with a 5.0 cm AAA using repair thresholds of 5.5 cm, 6.0 cm, 6.5 cm, and 7.0 cm was 1.7%, 2.3%, 2.7%, and 2.8%, respectively. The corresponding risk for a man was 2.3%, 2.9%, 3.3%, and 3.4% for the same repair thresholds, respectively. For a 60-year-old average-health woman, an AAA repair size of 6.1 cm was the optimal threshold to minimize AAA-related mortality. Life expectancy varied by <2 months for repair at sizes from 5.7 cm to 7.1 cm. For a 60-year-old average-health man, an AAA repair size of 6.9 cm was the optimal threshold to minimize AAA-related mortality. Life expectancy varied by <2 months for repair at sizes from 6.0 cm to 7.4 cm. Women in poor health, at various age strata, had optimal AAA repair size thresholds that were >6.5 cm, whereas men in poor health, at all ages, had optimal repair size thresholds that were >8.0 cm. ConclusionsThe optimal threshold for AAA repair is more nuanced than a discrete size. Specifically, there appears to be a range of AAA sizes for which repair is reasonable to minmized AAA-related mortality. Notably, they all are greater than current guideline recommendations. These findings would suggest that contemporary AAA size thresholds for repair should be reconsidered.

Implicit screening of abdominal aortic aneurysms among veterans using lumbar spine MRI

BackgroundEarly detection of abdominal aortic aneurysms (AAAs) is critical given the high morbidity and mortality of a ruptured aneurysm. Screening ultrasound is recommended for men 65 and 75 years of age with a smoking history. However, studies have shown that the rate of ultrasound screening is low and that implicit AAA screening by abdominal imaging studies that were not originally intended for AAA screening can play a major role in AAA detection. ObjectiveThe main objective was to evaluate the role of lumbar spine MRIs as an implicit AAA screening study by assessing the detection rate of AAAs in a broader cohort of veterans that included screening and non-screening populations. Methods4085 consecutive lumbar spine MRIs from our institution between 2/2020 and 9/2023 were retrospectively reviewed. Each study was labeled AAA present, AAA not present, or indeterminate by radiologists. The correlation between the presence of AAAs and cardiovascular risk factors was assessed using multinomial logistic regression. ResultsAAAs were present in 89 studies (2.2 %) from 80 patients (mean age 75.8 (56–93), M:F 10:0) and absent in 3935 cases (96.3 %) from 3310 patients (mean age 61.7 (19–100), M:F 9:1). Indeterminate cases (n = 61, 1.5 %) were mainly due to incomplete visualization (70.5 %). Mean AAA size was 3.6 cm with most AAAs (n = 43) smaller than 3.5 cm. Sixteen AAAs were 3.5–3.9 cm, 16 between 4 and 4.9cm, and 6 between 5 and 5.9 cm. Artifact precluded measurements in 8 cases. Among the AAA-positive cases, 20 had no prior documentation of AAA. Twenty-one patients with AAAs would not have met the criteria for the routine AAA screening ultrasound. Higher rates of hypertension, hyperlipidemia, and smoking were observed for the AAA cohort at 78.8 % (OR 2.037, CI 1.160–3.576, P = .013), 82.5 % (2.808, 1.543-5.110, P < .001), and 75 % (3.340, 1.979–5.638, P < .001), respectively, compared to the matched no-AAA cohort (58.2 %, 57.6 %, and 50.8 %; n = 2055). Conclusion: Lumbar spine MRI is a valid modality for implicit screening of AAAs. Clinical impactThose interpreting lumbar spine MRIs should be vigilant about assessing for AAAs, especially in men with a history of hypertension, hyperlipidemia, or tobacco smoking.

Association of women-specific size threshold and mortality in elective abdominal aortic aneurysm repair.

It is unclear whether women derive mortality benefit from early repair of abdominal aortic aneurysms (AAA). The aim of this study was to compare short- and mid-term mortality for women treated at small versus large diameters. Women receiving elective repair of AAA at small (49-54 mm) and large (≥55 mm) diameters from 2008 to 2022 were extracted from the Swedish National Registry for Vascular Surgery (n = 1642 women). The effect of diameter on 90-day, 1- and 3-year mortality was studied in logistic regression and propensity score models. Age, co-morbidities, smoking and repair modality were considered as confounders. Men (n = 9047) were analysed in parallel. Some 1642 women were analysed, of whom 34% underwent repair at small diameters (versus 52% of men). Women with small (versus large) AAAs were younger (73 versus 75 years, P < 0.001), and 63% of women in both size groups had endovascular repairs (P = 0.120). Mortality was 3.5% (90 days), 7.1% (1 year) and 15.8% (3 years), with no differences between the size strata. There was no consistent association between AAA size and mortality in multivariable models. Sex differences in mortality were almost entirely due to mortality in younger-than-average women versus men (3-year mortality: small AAAs 11.1% versus 7.3%, P < 0.030, or large 14.4% versus 10.7%, P < 0.038). Mortality in women is high and unaffected by AAA size at repair. The optimal threshold for women remains undefined. The higher rupture risk in women should not automatically translate into a lower, women-specific threshold.

Влияние диаметра инфраренальной аневризмы брюшной аорты на исход лечения

INTRODUCTION: Abdominal aortic aneurysm (AAA) is usually asymptomatic, and its first manifestation in most cases is a dissection or rupture, with a mortality rate exceeding 90%. Until now, the aspect of the possible effect of the diameter of the AAA on mortality after surgical treatment has not been practically studied. AIM: To study the influence of the size of AAA as a risk factor for fatality in its surgical treatment. MATERIALS AND METHODS: This study is retrospective. The study included 226 patients who underwent open and endovascular procedures for an infrarenal abdominal aortic aneurysm (iAAA) in the period 2011–2015 on the basis of the Department of Cardiovascular Surgery of the Ryazan State Medical University (Ryazan, Russia) and in 2011–2017 at the Republican Scientific Center of Cardiovascular Surgery (RSCSC) (Dushanbe, Tajikistan). There were 60 patients from Dushanbe and 166 from Ryazan. The work is part of a study on the treatment of patients with AAA and registered on the platform ClinicalTrials.gov (NCT04935268). RESULTS: Of the total number of patients with iAAA (n = 226), the number of males and females was 174 (77%) and 52 (23%), respectively, and the average age was 69.4 ± 2.6 years. The diameters of aneurysms in the RT and in the RF did not differ statistically significantly, the comorbidity rate per patient reached 1.84. In the RF and RT the number of operated patients for AAA was 31.3% and 26.7% (p &gt; 0.05), respectively. The average diameter of the AAA in patients who survived surgery for the treatment of iAAA was 57.0 mm [53.5; 60.5] and 59.0 mm [48.0; 73.0] (p &gt; 0.05, U = 2953.5; Z = 0.91), respectively. The diameter of the AAA in deceased patients after surgery (planned and rupture) in the RT and the RF is 60.0 mm [55.0; 65.5] and 72.0 mm [53.5; 80.5] (p &gt; 0.05, U = 129.0; Z = 1.14), respectively. In the RT, the size of the AAA is not associated with a fatal outcome (57.0 mm [53.5; 60.5] and 60.0 mm [55.0; 65.5]; p &gt; 0.05 (U = 207.0; Z = 1.49)). In the RF the size of the AAA in deceased patients was statistically significantly larger than in survivors — 72.0 mm [53.5; 80.5] and 59.0 mm [48.0; 73.0], respectively; p = 0.029 (U = 1394.5; Z = 2.18). The 30-day mortality rate after planned and emergency operations was comparable between the patients of the two clinics. CONCLUSION: The diameter of the AAA is a risk factor for the development of a fatal outcome after treatment.

WTP1.13 The A-HeAD Study: Effects of socio-economic deprivation on modifiable preoperative health behaviours and outcomes after aortic aneurysms repair. A retrospective review

Abstract Aims Social Deprivation is associated with health inequalities and poor clinical outcomes. As yet outcomes for aneurysm surgery are not well understood. This study aims to explore the association of Abdominal Aortic Aneurysm (AAA) surgery and socio-economic status on postoperative complications and outcome. Methods All elective AAA repair (open and endovascular) performed between January 2015 and January 2020 at a tertiary vascular centre were analysed. Deprivation (index of multiple deprivation (IMD)) data was sourced from the English indices of deprivation 2019, by postcode. Primary outcome was overall survival by Kaplan-Meier. Secondary outcomes included comparison of pre-operative fitness assessments, and comorbidity. Clinical outcomes included length of hospital stay (LOS) and complications. Cox-proportional hazard analyses were conducted. Results Patients (n=472) were divided into two groups (IMD 1-3 (n=171) and IMD 4-10 (n=301)). Gender ratios were comparable, with similar AAA size, other co-morbidities and CPET assessment results. IMD 1-3 participants were younger (72.4(8.1) vs 74.6 (7.8), p=0.011), had higher smoking rates (61.4% vs 19.6%, P=0.03) and more frequent history of stroke (18.1% vs 11.3%, P=0.036). There was no difference in survival based upon IMD but patients from IMD 1-3 spent longer in level 2/3 care (2(2-3) vs 1(1-2), P=0.022) and experienced more re-admissions (14% vs. 6%. P=0.003). In addition, cox-regression indicated that patients without COPD were twice as likely to survive (HR 0.54 (0.31-0.94 P=0.03). Conclusion IMD was not associated with poor outcome. Smoking was more prevalent in lower IMD groups. As COPD was associated with increased likelihood of death, pre-operative optimisation can be targeted towards higher risk groups.

Elective Endovascular Aneurysm Repair (EVAR) for the Treatment of Infrarenal Abdominal Aortic Aneurysms of 5.0–5.5 cm: Differences between Men and Women

Background: There is significant debate regarding the existence of sex-related differences in the presentation, treatment, and outcomes of men versus women affected by abdominal aortic aneurysm (AAA). The purpose of this study is to compare endovascular aneurysm repair (EVAR) of infrarenal AAAs with the current sex-neutral 5.0–5.5 cm-diameter threshold for intervention between the two sexes. Methods: Retrospective review of consecutive cases from a single teaching institution over a period of five years of patients who had undergone elective EVAR for AAAs between 5.0 and 5.5 cm in diameter. Outcomes of interest were compared according to sex. Results: Ninety-four patients were included in the analysis, with a higher prevalence of men (53%). Females were older at the time of repair, 78 ± 5.1 years, versus 71.7 ± 7 years (p &lt; 0.01), and had higher incidence of underlying comorbidities, namely, arrhythmia, chronic kidney disease, and previous carotid revascularization. Women had higher incidence of immediate systemic complications (p = 0.021), post-operative AMI (p = 0.001), arrhythmia (p = 0.006), pulmonary oedema (p &lt; 0.001), and persistent renal dysfunction (p = 0.029). Multivariate analysis for post-operative factors associated to mortality and adjusted for sex confirmed that AMI (p = 0.015), arrhythmia (p = 0.049), pulmonary oedema (p = 0.015), persistent renal dysfunction (p &lt; 0.001), cerebral ischemia (p &lt; 0.001), arterial embolism of lower limbs (p &lt; 0.001), and deep-vein thrombosis of lower limbs (p &lt; 0.001) were associated to higher EVAR-related mortality; a higher incidence of post-operative AMI (p = 0.014), pulmonary edema (p = 0.034), and arterial embolism of lower limbs (p = 0.046) were associated to higher 30-days mortality. In females there was also a higher rate of suprarenal fixation (p = 0.026), insertion outside the instruction for use (p = 0.035), and a more hostile neck anatomy with different proximal aortic diameter (p &lt; 0.001) and angle (p = 0.003). Conclusions: A similar threshold of size of AAA for elective surgery for both males and females might not be appropriate for surgical intervention, as females tend to have worse outcomes. Further population-based studies are needed to guide on sex-related differences and intervention on AAA.

Factors associated with all-cause mortality following endovascular abdominal aortic aneurysm repair.

Background: Knowledge of factors that influence all-cause mortality after endovascular abdominal aortic aneurysm repair (EVAR) could improve therapeutic strategies post-EVAR and thus patient prognosis. Our study aimed to evaluate the association between sociodemographic information, comorbidities, laboratory parameters, treatment, selected anatomical and genetic factors and all-cause mortality post-EVAR. Patients and methods: We reviewed all patients who had undergone elective EVAR for non-ruptured abdominal aortic aneurysm (AAA) between January 2010 and December 2019. AAA size (maximum diameter and volume) was measured using CT-angiography. Sac expansion was defined as at least 5 mm increase, sac regression as at least 5 mm decrease in the sac diameter determined at 36±3 months post-EVAR in relation to pre-EVAR AAA diameter. Adjustments were performed for age, hypertension, diabetes mellitus, dyslipidaemia, sex, smoking, number of lumbar arteries, patency of inferior mesenteric artery and number of reinterventions post-EVAR. Results: One hundred and sixty-two patients (150 men, 12 women) with a mean age of 72.6±7.3 years were included in the analysis. Pre-EVAR AAA diameter (HR 1.07; 95% CI 1.03 - 1.12; p=0.001), pre-EVAR AAA volume (HR 1.01; 95% CI 1.002 - 1.011; p=0.008), post-EVAR sac diameter (HR 1.06; 95% CI 1.03 - 1.10; p=0.000), post-EVAR sac volume (HR 1.01; 95% CI 1.002 - 1.011; p=0.006) and anticoagulation therapy (HR 2.46; 95% CI 1.18 - 5.14; p=0.019) were associated with higher mortality in multivariate analysis. Sac regression (HR 0.42; 95% CI 0.22 - 0.82; p=0.011), and treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) (HR 0.71; 95% CI 0.36 - 0.97; p=0.047) were associated with lower mortality. Conclusions: Greater pre- and post-EVAR diameter and volume, failure of sac regression and anticoagulation were associated with higher mortality post-EVAR. Reduced mortality was observed in patients treated with ACE inhibitors or ARBs, and in patients with AAA sac regression.

Plasma Lipidomics Analysis Reveals the Potential Role of Lysophosphatidylcholines in Abdominal Aortic Aneurysm Progression and Formation.

Abdominal aortic aneurysm (AAA) is hallmarked by irreversible dilation of the infrarenal aorta. Lipid deposition in the aortic wall and the potential importance of a lipid disorder in AAA etiology highlight the need to explore lipid variation during AAA development. This study aimed to systematically characterize the lipidomics associated with AAA size and progression. Plasma lipids from 106 subjects (36 non-AAA controls and 70 AAA patients) were comprehensively analyzed using untargeted lipidomics. An AAA animal model was established by embedding angiotensin-II pump in ApoE-/- mice for four weeks and blood was collected at 0, 2 and 4 weeks for lipidomic analysis. Using a false-discovery rate (FDR) < 0.05, a group of lysophosphatidylcholines (lysoPCs) were specifically decreased in AAA patients and mice. LysoPCs were principally lower in the AAA patients with larger diameter (diameter > 50 mm) than those with a smaller size (30 mm < diameter < 50 mm), and levels of lysoPCs were also found to be decreased with modelling time and aneurysm formation in AAA mice. Correlation matrices between lipids and clinical characteristics identified that the positive correlation between lysoPCs and HDL-c was reduced and negative correlations between lysoPCs and CAD rate, lysoPCs and hsCRP were converted to positive correlations in AAA compared to control. Weakened positive correlations between plasma lysoPCs and circulating HDL-c in AAA suggested that HDL-lysoPCs may elicit instinctive physiological effects in AAA. This study provides evidence that reduced lysoPCs essentially underlie the pathogenesis of AAA and that lysoPCs are promising biomarkers for AAA development.

Women Have a Lower Rate of Abdominal Aortic Aneurysm Repair and Higher Long-term Aortic-related Mortality Compared With Men in a Population-based Study

Increased mortality has been reported after open or endovascular repair of abdominal aortic aneurysms (AAAs) in women. Our aim was to evaluate the natural history and outcomes of AAAs in women at a population level. A population-based cohort study was conducted (1980-2017) of all patients with AAA based on identification using International Classification of Diseases, 9th or 10th Revision and Current Procedural Terminology codes. The gender-specific incidences of AAAs were initially calculated. Medical records were reviewed to confirm diagnosis and identify late events and clinical reasons for opting against repair. Survival analysis for overall and aortic mortality was performed and stratified based on gender and repair status. There were 1537 patients with AAAs; 381 (25%) were female. The incidence of AAA in women was 4.5 times lower than men (23 vs 105 per 100,000 person-years). Compared with men, women were diagnosed at an older age (80 vs 73 years, P < .001), with smaller initial aneurysm size (4 vs 4.3 cm, P < .001). In 99 of 1537 patients, the initial presentation was with rupture (male:female; 79:20); 14 ruptured AAAs were <5.5 cm, 10 of 14 in women. Median follow-up was 18 years. AAA repair was less frequent in women (26% vs 41%, P < .001); with no change after availability of endovascular repair (16% vs 20%, P = .2), women had similar 30-day mortality from AAA repair (4% vs 5%, P = .5). However, on Kaplan-Meier analysis, aortic and all-cause mortality at 10 and 20 years were highest in women who did not undergo repair of their AAA (NRF, hazard ratio: 3, 95% confidence interval: 1.8-4.5, P < .001) as compared with all men and women who underwent repair (Table). This cumulative incidence of aortic-related death remained significantly higher in NRF when analyzed with non-aortic-related deaths as a competing risk, 15% vs 5%-8% in the other groups. All patients with aortic-related death (both women and men) had refused repair because of older age and risk from comorbidities, except in 2 females with rupture of 4.8 and 5.5 cm AAAs while awaiting repair. AAAs are diagnosed in women almost a decade later than men. In this study, mortality after AAA repair was not inferior in women compared with men; however, the incidence of repair was significantly lower in women. Based on the findings of threefold greater long-term aortic-related mortality in women not undergoing AAA repair, it may be advisable to consider repair in women earlier at a smaller AAA size.

Tributyrin Intake Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm in LDLR-/- Mice.

Abdominal aortic aneurysm (AAA) is a multifactorial cardiovascular disease with a high risk of death, and it occurs in the infrarenal aorta with vascular dilatation. High blood pressure acts on the aortic wall, resulting in rupture and causing life-threatening intra-abdominal hemorrhage. Vascular smooth muscle cell (VSMC) dysregulation and extracellular matrix (ECM) degradation, especially elastin breaks, contribute to structural changes in the aortic wall. The pathogenesis of AAA includes the occurrence of oxidative stress, inflammatory cell infiltration, elastic fiber fragmentation, VSMC apoptosis, and phenotypic transformation. Tributyrin (TB) is decomposed by intestinal lipase and has a function similar to that of butyrate. Whether TB has a protective effect against AAA remains uncertain. In the present study, we established an AAA murine model by angiotensin II (AngII) induction in low-density lipoprotein receptor knockout (LDLR-/-) mice and investigated the effects of orally administered TB on the AAA size, ratio of macrophage infiltration, levels of matrix metalloproteinase (MMP) expression, and epigenetic regulation. TB attenuates AngII-induced AAA size and decreases elastin fragmentation, macrophage infiltration, and MMP expression in the medial layer of the aorta and reduces the levels of SBP (systolic blood pressure, p < 0.001) and MMP-2 (p < 0.02) in the serum. TB reduces the AngII-stimulated expression levels of MMP2 (p < 0.05), MMP9 (p < 0.05), MMP12, and MMP14 in human aortic smooth muscle cells (HASMCs). Moreover, TB and valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, suppress AngII receptor type 1 (AT1R, p < 0.05) activation and increase the expression of acetyl histone H3 by HDAC activity inhibition (p < 0.05). Our findings suggest that TB exerts its protective effect by suppressing the activation of HDAC to attenuate the AngII-induced AT1R signaling cascade.

Abdominal aortic aneurysm monitoring via arterial waveform analysis: towards a convenient point-of-care device

Abdominal aortic aneurysms (AAAs) are lethal but treatable yet substantially under-diagnosed and under-monitored. Hence, new AAA monitoring devices that are convenient in use and cost are needed. Our hypothesis is that analysis of arterial waveforms, which could be obtained with such a device, can provide information about AAA size. We aim to initially test this hypothesis via tonometric waveforms. We study noninvasive carotid and femoral blood pressure (BP) waveforms and reference image-based maximal aortic diameter measurements from 50 AAA patients as well as the two noninvasive BP waveforms from these patients after endovascular repair (EVAR) and from 50 comparable control patients. We develop linear regression models for predicting the maximal aortic diameter from waveform or non-waveform features. We evaluate the models in out-of-training data in terms of predicting the maximal aortic diameter value and changes induced by EVAR. The best model includes the carotid area ratio (diastolic area divided by systolic area) and normalized carotid-femoral pulse transit time ((age·diastolic BP)/(height/PTT)) as input features with positive model coefficients. This model is explainable based on the early, negative wave reflection in AAA and the Moens-Korteweg equation for relating PTT to vessel diameter. The predicted maximal aortic diameters yield receiver operating characteristic area under the curves of 0.83 ± 0.04 in classifying AAA versus control patients and 0.72 ± 0.04 in classifying AAA patients before versus after EVAR. These results are significantly better than a baseline model excluding waveform features as input. Our findings could potentially translate to convenient devices that serve as an adjunct to imaging.

Effects of abdominal aortic aneurysm appropriateness dashboard on clinical practice

ObjectiveThe Society for Vascular Surgery published abdominal aortic aneurysm (AAA) practice guidelines in 2003, 2009, and 2018 to improve the management and treatment of AAAs. In 2014, our vascular surgery department implemented a quarterly AAA dashboard (AAAdb) to record the perioperative outcomes and guideline compliance with a focus on intervention appropriateness and procedural follow-up, which supplemented our Vascular Quality Initiative data. From the available reported evidence and expert consensus opinions, nine additional criteria for the appropriate treatment of AAAs <5 cm in women and <5.5 cm in men were noted, when applicable. The purpose of our study was to assess the effects of AAAdb implementation on adherence to society and institutional guidelines, documentation of treatment rationale, and the quality of follow-up. MethodsWe performed a retrospective review of elective open and endovascular AAA repair at a single institution from 2010 to 2018. The AAAdb was implemented in the middle of this period in 2014. The patient demographics, aortic size, repair indication, repair type, 30-day mortality, and postoperative and 1-year follow-up imaging findings were analyzed. The primary outcome was adherence to intervention appropriateness and the follow-up guidelines. The categorical factors were summarized using frequencies and percentages and compared using the Pearson χ2 test or Fisher exact test. Continuous measures were summarized using the mean ± standard deviation and compared between study periods using two-sample t tests. ResultsFrom 2010 to 2018, 1549 patients had undergone elective AAA repair: 657 before and 892 after AAAdb implementation. No differences were found in AAA size after AAAdb (5.6 ± 1.2 cm vs 5.6 ± 1.1 cm; P = .88). However, the proportion of size-appropriate repairs increased (64.1% vs 71.3%; P = .003). The proportion of small AAA repairs with a documented rationale had increased (64.4% vs 80.5%; P < .001), with rapid disease progression cited most often. No difference was found in 30-day mortality (1.2% vs 1.5%; P = .69). Follow-up imaging after endovascular abdominal aortic aneurysm repair increased at <60 days postoperatively (76% vs 84%; P = .004) and at 1 year of follow-up (78% vs 86%; P = .0005). The proportion of patients with endoleak at <60 days postoperatively had increased in the post-AAAdb cohort (21% vs 29%; P = .012). ConclusionsThe AAAdb served as a centerpiece for improving the appropriateness of care and compliance with national and institutional guidelines, including treatment of small AAAs in special circumstances. Its implementation was associated with higher quality follow-up and surveillance in a high-volume, regional aortic center. Consideration should be given to adding additional criteria to the Society for Vascular Surgery guidelines and Vascular Quality Initiative reporting.

S3427 Implicit Bias Contributing to Delayed Diagnosis in a Rare Case of Endoscopic Biopsy Proven Gastrointestinal Amyloidosis

Introduction: Gastrointestinal amyloidosis often requires extensive workup to diagnose, but early diagnosis and initiation of treatment improves mortality.1 Implicit bias leads to narrow workups which can misdiagnose rare diseases. We present a case of gastrointestinal amyloidosis ultimately diagnosed by endoscopic biopsy. The rarity of this disease as well as bias that led to anchoring on more common diagnoses resulted in months of misdiagnosis. Case Description/Methods: A 67 year old woman with a history of abdominal aortic aneurysm (AAA), substance use disorder in remission, and chronic malnutrition presented with worsening of chronic abdominal pain. Workup over the course of eight prior ED visits for abdominal pain was unremarkable. Her pain was attributed to functional pain or opioid use and withdrawal despite a lack of documented opioid relapse. On this presentation, expanding AAA size prompted surgical consult. The surgical team expressed concern that she would not tolerate an open repair with a BMI of 13.9; TPN was started. GI recommended endoscopy to assess for a malabsorptive process. Unfortunately the procedure was delayed 22 days as the patient felt her uncontrolled pain was not validated by the care team. After many care conferences, she agreed to upper endoscopy which showed flattening of the villi of the duodenum. Microscopic testing from biopsies showed extensive amyloidosis (Figure). Amyloidosis resulting in intestinal ischemia was thought to be the cause of her pain and malnutrition. Discussion: Implicit bias associated with the patient’s history of addiction led to anchoring bias and initial narrow workup and misdiagnosis. Implicit bias amongst physicians regarding substance use disorders has been associated with suboptimal care.2 The severity of the patient’s abdominal pain and malnutrition should have prompted earlier referral to GI and may have led to expedited diagnosis of intestinal amyloidosis. Additionally, the frequent misdiagnosis and dismissal of symptoms resulted in mistrust leading the patient to decline further workup. Recognizing implicit bias can allow clinicians to provide more equitable workup and care.Figure 1.: DUODENUM, BIOPSY Amyloidosis, extensive, involving mucosa and submucosa, perivascular and diffuse.

Relationship between the Levels of Calprotectin and Soluble Receptor for Advanced Glycation End Products with Abdominal Aortic Aneurysm Diameter: A Preliminary Clinical Trial.

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta greater than 50% of the diameter of a healthy aorta. Previous experimental studies confirm the effect of calprotectin (CAL) on the onset of arterial pathology. It has been suggested that low levels of soluble receptors for advanced glycation end products (RAGEs) increase levels of cytokines that lead to the inhibition of matrix metalloproteinases (MMPs), affecting AAA formation. This study aimed to analyze the correlation of levels of RAGE and CAL with AAA diameter. A group of 32 patients aged 50–75 with diagnosed AAA was enrolled in the study. This group of patients was further divided into three subgroups based on AAA diameter: (1) <4.5 cm, (2) 4.5–5.5 cm, (3) >5.5 cm. Peripheral blood was drawn from all participants on admission to measure the serum CAL and RAGE levels. An enumeration survey was performed three months after AAA surgical treatment. CAL and RAGE plasma levels were measured with the enzyme-linked immunosorbent assay (ELISA). The median CAL levels were 2273.0 ng/mL before and 1217.0 ng/mL after treatment. There was a statistically significant decrease in CAL levels following the surgical treatment (p = 0.003). The correlation analysis between CAL levels and RAGE levels before and after surgical treatment showed no statistically significant correlations. In addition, there were no statistically significant correlations between CAL and RAGE levels with AAA size. In conclusion, CAL levels appear to be a significant marker in patients with AAA. There is an almost twofold decrease in CAL levels after AAA excision.

Genetic and Pharmacological Disruption of Interleukin-1α Leads to Augmented Murine Aortic Aneurysm

Interleukin-1 (IL-1) signaling has an established role as a cytokine signaling pathway important for progression of abdominal aortic aneurysms (AAAs). While the IL-1β ligand and IL-1R1 have been previously investigated, the role of the IL-1α ligand in AAAs remains unknown. In this study, we sought to examine the role of IL-1α in AAAs using genetic and pharmacologic approaches. Eight-week-old wild-type (WT) or IL-1α knock-out (KO) male and female mice (n=10-16/group) underwent experimental AAA and were harvested 14days following surgery to assess AAA size and characteristics. In separate studies, 8-week-old WT mice were treated with an inhibitor to IL-1α during AAA formation and harvested 14days following surgery. Finally, WT and IL-1α KO mice were administered Anakinra, an IL-R1 inhibitor, during AAA formation to determine the effect of inhibiting IL-1R1 when IL-1α is knocked out. Male and female IL-1α KO mice had larger AAAs compared to WT AAAs (male: 153% vs. 89.2%, P=0.0001; female: 86.6% vs. 63.5%, P=0.02). IL-1α KO mice had greater elastin breakage (P=0.01), increased levels of macrophage staining (P=0.0045), and greater pro-metallo proteinase 2 (P=0.02). Pharmacologic inhibition of WT male mice with an IL-1α neutralizing antibody resulted in larger AAAs (133.1% vs. 77.0%, P<0.001). Finally, treatment of IL-1α KO male mice with Anakinra decreased AAA formation compared with vehicle control AAAs (Anakinra+IL-1α KO: 47.7% vs. WT: 147.1%; P=0.0001). IL-1α disruption using either genetic or pharmacologic approaches worsens AAAs.

“Large Diameter” Aortic Endografts are Associated With Aneurysm Sac Expansion

The purpose of this study was to evaluate the association between aortic endograft diameter and long-term outcomes following endovascular aneurysm repair (EVAR) performed in accordance with manufacturer instructions for use (IFU). A retrospective review of consecutive patients undergoing on-IFU EVAR (2000-2018) was performed to facilitate a comparative analysis of long-term patient outcomes based on device diameter. "Large diameter" devices were defined as >34mm. The primary outcome of interest was freedom from sac expansion throughout long-term follow-up. Analyses included standard bivariate analyses, Kaplan-Meier with log-rank comparison, and Cox proportional hazards multivariate analysis. A total of 1,099 underwent on-IFU EVAR from 2000-2018. Follow-up data were available for 980 patients. Of these, 75 patients (7.6%) were treated with >34-mm devices. There were no significant differences in demographics or comorbidities between the 2 groups, although preoperative abdominal aortic aneurysm size was greater in patients undergoing implantation of >34-mm devices (58±8.5mm vs. 56±17.4mm; P=0.05). Median follow-up was 10.3years. Patients with grafts >34mm had reduced freedom from sac expansion throughout follow-up (P=0.038). There were no significant differences in reintervention rates, open conversion, or rupture when stratified by graft diameter. A multivariate Cox regression identified patient age, preoperative abdominal aortic aneurysm size, need for reintervention, and use of >34-mm endografts as independent factors associated with expansion. The use of large diameter aortic endografts is associated with higher rates of sac expansion during long-term follow-up. Although there is undoubtedly a role for large diameter graft use in selected patients, it is important to recognize that these devices were typically approved post hoc without the same regulatory scrutiny of smaller endografts. These findings underscore the importance of ongoing surveillance for patients treated with >34-mm grafts, irrespective of compliance with manufacturer IFU.