Prevalence Of Abdominal Aortic Aneurysm Research Articles

Prevalence of abdominal aortic aneurysms in patients with lung cancer

ObjectiveConcomitance of abdominal aortic aneurysm (AAA) and primary lung cancer (LC) is not uncommon due to several shared risk factors. To evaluate the incidence of this association, analysis of the National Inpatient Sample database was utilized. MethodsA retrospective analysis of the National Inpatient Sample database between 2014 and 2018 for all patients diagnosed with primary LC was performed. The differences in the reported findings between the LC and control groups were assessed using the Pearson χ2, Fisher exact, Student t, and/or Mann-Whitney U tests where appropriate. Multivariable logistic regression analysis was conducted to determine independent predictors of the presence of documented AAA. ResultsA total of 158,904 patients were identified. Of these, 2430 patients (1.53%) were diagnosed with AAA and 156,474 (98.47%) without AAA. In the multivariable model, LC patients had higher odds of AAA compared with the general population (odds ratio, 1.43; 95% confidence interval, 1.35-1.51). In all age groups, female smokers had a higher rate of AAA compared with female nonsmokers (age <60 years, 0.13% vs 0.04%; 60-69 years, 0.77% vs 0.34%; 70-79 years, 1.65% vs 0.69%; and >80 years, 2.63% vs 1.31%; all P < .001). ConclusionsLC and AAA share similar risk factors, which may explain the higher AAA prevalence among patients with LC. Given the higher prevalence of AAA in smokers compared with nonsmokers across all age groups in both male and female patients with LC, further sex-based studies investigating the overall mortality and morbidity benefits of AAA screening among patients with LC are highly warranted. This consideration would potentially address the sex disparity in outcomes for AAA management.

No Effect of Hypercholesterolemia on Elastase-Induced Experimental Abdominal Aortic Aneurysm Progression.

Objective: Epidemiological studies link hyperlipidemia with increased risk for abdominal aortic aneurysms (AAAs). However, the influence of lipid-lowering drugs statins on prevalence and progression of clinical and experimental AAAs varies between reports, engendering controversy on the association of hyperlipidemia with AAA disease. This study investigated the impact of hypercholesterolemia on elastase-induced experimental AAAs in mice. Methods: Both spontaneous (targeted deletion of apolipoprotein E) and induced mouse hypercholesterolemia models were employed. In male wild type (WT) C57BL/6J mice, hypercholesterolemia was induced via intraperitoneal injection of an adeno-associated virus (AAV) encoding a gain-of-function proprotein convertase subtilisin/kexin type 9 mutation (PCSK9) followed by the administration of a high-fat diet (HFD) (PCSK9+HFD) for two weeks. As normocholesterolemic controls for PCSK9+HFD mice, WT mice were infected with PCSK9 AAV and fed normal chow, or injected with phosphate-buffered saline alone and fed HFD chow. AAAs were induced in all mice by intra-aortic infusion of porcine pancreatic elastase and assessed by ultrasonography and histopathology. Results: In spontaneous hyper- and normo-cholesterolemic male mice, the aortic diameter enlarged at a constant rate from day 3 through day 14 following elastase infusion. AAAs, defined as a more than 50% diameter increase over baseline measurements, formed in all mice. AAA progression was more pronounced in male mice, with or without spontaneous hyperlipidemia. The extent of elastin degradation and smooth muscle cell depletion were similar in spontaneous hyper- (score 3.5 for elastin and 4.0 for smooth muscle) and normo- (both scores 4.0) cholesterolemic male mice. Aortic mural macrophage accumulation was also equivalent between the two groups. No differences were observed in aortic accumulation of CD4+ or CD8+ T cells, B cells, or mural angiogenesis between male spontaneous hyper- and normocholesterolemic mice. Similarly, no influence of spontaneous hypercholesterolemia on characteristic aneurysmal histopathology was noted in female mice. In confirmatory experiments, induced hypercholesterolemia also exerted no appreciable effect on AAA progression and histopathologies. Conclusion: This study demonstrated no recognizable impact of hypercholesterolemia on elastase-induced experimental AAA progression in both spontaneous and induced hypercholesterolemia mouse models. These results add further uncertainty to the controversy surrounding the efficacy of statin therapy in clinical AAA disease.

Abstract P107: Celastrol Supplementation Profoundly Activates Aortic Mmp-9 And Abolishes Sexual Dimorphism Of Abdominal Aortic Aneurysm In Mice.

Background and Objective: Abdominal Aortic Aneurysms (AAAs) are permanent dilations of the abdominal aorta with greater than 80% mortality after rupture. AAA prevalence is 4-5 times greater in males than females. AAA formation involves a complex process of destruction of aortic media through degradation of extracellular matrix proteins, elastin and collagen. Angiotensin II (AngII) infusion model of AAA in mice recapitulates major features of human AAA mainly male gender specificity. Celastrol, a pentacyclic triterpene from the root extracts of Thunder God Vine ( Tripterygium wilfordii ), strongly suppressed AngII-induced cardiovascular complications in mice. The purpose of this study is to test the effect of Celastrol supplementation on AngII-induced AAAs in mice. Methods and Results: Male and female LDL receptor -/- mice (8 weeks old; n= 12 per group) were fed a fat-enriched diet (21% wt/wt fat; 0.15% wt/wt cholesterol) supplemented with or without Celastrol (10mg/kg/day) for 5 weeks. After 1 week of diet feeding, mice were infused with AngII (500 or 1000 ng/kg/min) for 28 days by osmotic minipumps. Dietary supplementation of celastrol significantly promoted AngII-induced abdominal aortic luminal dilation (Con = 1.25 ± 0.05 versus Celas = 1.55 ± 0.09 mm, P&lt;0.05) and external aortic width (Con= 1.01 ± 0.09 versus Celas = 1.62 ± 0.14 mm, P&lt;0.05) in male mice as measured by ultra-sonography and ex vivo measurement, with 90% incidence (10/11) compared to 36% (4/11) in control group. Interestingly, celastrol supplementation to AAA female mice, resulted in a significant increase in AngII-induced aortic luminal dilation (Con = 1.17 ± 0.30 versus Celas = 1.57 ± 0.21 mm, P&lt;0.001) and AAA formation (Con= 0.94 ± 0.03 versus Celas = 1.36 ± 0.25 mm, P&lt;0.05) mice with 80% incidence (12/15) compared to 6% (1/15) in control group. Celastrol supplementation dramatically increased AngII-induced aortic leukocyte accumulation, MMP-9 activity and medial elastin degradation in both male and female mice compared to saline and AngII controls. Conclusion: These findings demonstrate that celastrol supplementation to LDLr -/- mice ablates sexual dimorphism and promotes AngII-induced AAA formation, which is associated with increased leukocytic infiltration and MMP-9 activation.

Incidental abdominal aortic aneurysms are largely undocumented and unmonitored

In countries without organized population screening, incidental detection remains the major form of abdominal aortic aneurysm (AAA) diagnosis. Despite the presumed homogeneity in AAA prevalence, its rate of repair is highly variable, with Portugal treating 2 to 6 times fewer AAA per habitant than other western countries. To evaluate the detection rate and monitoring of incidental AAA in a multicentre cohort from Portuguese hospitals. All abdominal CT scans performed in men ≥ 65 years old in three major Portuguese hospitals between January and June 2018 were selected for review. CT scans prescribed by the Vascular Surgery or Emergency Departments were excluded. Patients with previously known AAA were also excluded. Subjects with newly detected aneurysms were assessed for the two primary outcomes: the description of the finding by the radiologist in the written report; the effective follow-up recommendations by the prescriber of the CT or by the general practitioner (GP). Patients with newly found AAA that met criteria for monitoring or treatment and failed to be given guidance were contacted and included in surveillance programs. Overall, 3292 abdominal CT scans were selected for review. A total of 133 newly found aneurysms were detected (4.2% prevalence in the cohort). Of those, 48 cases (36%) were not described by the radiologist in the written report. Further 42 patients (32%) were not successfully oriented by the ordering physician or GP, despite having had their AAA mentioned. Overall, only 32% (n=42) of the newly diagnosed AAA were correctly identified and referred to monitoring. Incidental AAA is a common occurrence in in-hospital abdominal CTs. A significant number is not documented by the radiologist and the vast majority is not referred to monitoring. This could be a major reason for the low elective treatment rate of AAA in Portugal.

Ultrasound screening for abdominal aortic aneurysm in high-risk women

BackgroundPopulation-wide ultrasound screening programmes for abdominal aortic aneurysm (AAA) for men have already been established in some countries. Women account for one third of aneurysm-related mortality and are four times more likely to experience an AAA rupture than men. Whole-population screening for AAA in women is unlikely to be clinically or economically effective. The aim of this study was to determine the outcomes of a targeted AAA screening programme for women at high risk of AAA.MethodWomen aged 65–74 years deemed at high risk of having an AAA (current smokers, ex-smokers, or with a history of coronary artery disease) were invited to attend ultrasound screening (July 2016 to March 2019) for AAA in the Female Aneurysm screening STudy (FAST). Primary outcomes were attendance for screening and prevalence of AAA. Biometric data, medical history, quality of life (QoL) and aortic diameter on ultrasound imaging were recorded prospectively.ResultsSome 6037 women were invited and 5200 attended screening (86.7 per cent). Fifteen AAAs larger than 29 mm were detected (prevalence 0.29 (95 per cent c.i. 0.18 to 0.48) per cent). Current smokers had the highest prevalence (0.83 (95 per cent c.i. 0.34 to 1.89) per cent) but lowest attendance (75.2 per cent). Three AAAs greater than 5.5 cm were identified and referred for consideration of surgical repair; one woman underwent repair. There was a significant reduction in patient-reported QoL scores following screening.ConclusionA low prevalence of AAA was detected in high-risk women, with lowest screening uptake in those at highest risk. Screening for AAA in high-risk women may not be beneficial.

Screening for Prevalence of Abdominal Aortic Aneurysm During Transthoracic Echocardiography in Patient With Significant Coronary Artery Disease.

BackgroundPrevalence of abdominal aortic aneurysm (AAA) has ethnic differences, and coronary artery disease (CAD) shares several risk factors with AAA. Sparse Indian data are available on this. We evaluated the prevalence of AAA during transthoracic echocardiography (TTE) and risk factors of AAA in patients with CAD. MethodsThis was a prospective observational study carried out in the cardiology department at a tertiary care center from January 1, 2017 to November 30, 2017. All patients with CAD/acute coronary syndrome (ACS) were included in the study, and patients with AAA due to other etiology were excluded. Screening for an AAA was performed directly using an echocardiographic 3.5-MHz cardiac probe.ResultsA total of 526 patients were screened; and AAA was present in 25 (4.8%) of CAD patients. Smoking, hypertension and hyperlipidemia were predominant risk factors for AAA in our study, but were not statistically significant because same risk factors were also prevalent in the comparison group. Diabetes, peripheral vascular disease and family history were statistically significant risk factors for AAA in our study. The mean size of AAA was 34 mm.ConclusionsPresence of AAA is significantly higher among CAD patients. CAD shares several risk factors with AAA. Therefore, opportunistic examination of the abdominal aorta during routine TTE could be an effective way of screening. Diabetes mellitus, peripheral artery disease and family history were the significant associated risk factors of AAA in CAD patients.

Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice

Abdominal aortic aneurysm (AAA) disease causes dilation of the aorta, leading to aortic rupture and death if not treated early. It is the 14th leading cause of death in the U.S. and 10th leading cause of death in men over age 55, affecting thousands of patients. Despite the prevalence of AAA, no safe and efficient pharmacotherapies exist for patients. The deterioration of the elastic lamina in the aneurysmal wall is a consistent feature of AAAs, making it an ideal target for delivering drugs to the AAA site. In this research, we conjugated nanoparticles with an elastin antibody that only targets degraded elastin while sparing healthy elastin. After induction of aneurysm by 4-week infusion of angiotensin II (Ang II), two biweekly intravenous injections of pentagalloyl glucose (PGG)-loaded nanoparticles conjugated with elastin antibody delivered the drug to the aneurysm site. We show that targeted delivery of PGG could reverse the aortic dilation, ameliorate the inflammation, restore the elastic lamina, and improve the mechanical properties of the aorta at the AAA site. Therefore, simple iv therapy of PGG loaded nanoparticles can be an effective treatment option for early to middle stage aneurysms to reverse disease progression and return the aorta to normal homeostasis.

EVAR – preliminary results from a single-center experience of a Mediterranean city: case report

Abdominal aortic aneurysm prevalence is estimated between 4 and 8% in screening programs, predominantly in males. The risk of rupture is directly proportionate to the size of the aneurysm; thus, prophylactic repair is justifiable. The three chief randomized trials comparing Endovascular Aneurysm Repair (EVAR) with conventional repair of abdominal aortic aneurysm have all shown a benefit of EVAR with respect to 30-day operative mortality and these results have been reinforced by data from large registries. Therefore, endovascular repair is now a common treatment option that offers a less-invasive alternative to standard surgical repair with the likely reduced hospitalization, morbidity, and mortality. In this work, we report the short-term results of six cases treated by Thoracic Endovascular Aneurysm Repair (TEVAR)/EVAR at Alexandria Vascular Center.

Society for Vascular Surgery implementation of clinical practice guidelines for patients with an abdominal aortic aneurysm: Screening for an abdominal aortic aneurysm

•High morbidity and mortality associated with abdominal aortic aneurysm (AAA) rupture.•Most effective mechanism to prevent death from rupture is the prevention of rupture itself.•Ultrasound based abdominal screening, in multiple randomized controlled clinical trials,1Cosford P.A. Leng G.C. Screening for abdominal aortic aneurysm.Cochrane Database Syst Rev. 2007; : CD002945PubMed Google Scholar associated with:○40% reduction aneurysm-related mortality○50% reduction in aneurysm rupture•AAA prevalence, growth and rupture are most strongly predicted by smoking history.•First-degree relatives of patients with AAA have approximately 20% likelihood for AAA development. Consider one-time ultrasound screening for AAA in:•Men and women aged 65 to 75 with a history of tobacco use (Grade 1A).•Men and women older than 75 in good health with history of tobacco use and not previously screened (Grade 2C).•First-degree relatives aged 65 to 75 or older than 75 in good health of patients presenting with AAA (Grade 2C).2Chaikof E.L. Dalman R.L. Eskandari M.K. Jackson B.M. Lee W.A. Mansour M.A. et al.The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm.J Vasc Surg. 2018; 67: 2-77.e2Abstract Full Text Full Text PDF PubMed Scopus (783) Google Scholar •Lower AAA prevalence in women balanced by estimated fourfold higher rupture rate and quicker progression to rupture than men (Fig).3Ulug P. Powell J.T. Sweeting M.J. Bown M.J. Thompson S.G. Group S.C. Meta-analysis of the current prevalence of screen-detected abdominal aortic aneurysm in women.Br J Surg. 2016; 103: 1097-1104Crossref PubMed Scopus (52) Google Scholar•A contemporary review estimates a 1.34% pooled prevalence of AAA in women over age 60 with a history of tobacco use, with evidence suggesting selective screening of women is cost effective beyond a threshold prevalence of 1%.2Chaikof E.L. Dalman R.L. Eskandari M.K. Jackson B.M. Lee W.A. Mansour M.A. et al.The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm.J Vasc Surg. 2018; 67: 2-77.e2Abstract Full Text Full Text PDF PubMed Scopus (783) Google Scholar,3Ulug P. Powell J.T. Sweeting M.J. Bown M.J. Thompson S.G. Group S.C. Meta-analysis of the current prevalence of screen-detected abdominal aortic aneurysm in women.Br J Surg. 2016; 103: 1097-1104Crossref PubMed Scopus (52) Google Scholar •Despite Medicare SAAAVE Act in 2007, less than 15% of eligible patients undergo AAA screening.•Consider implementing a primary care clinical alert in the electronic health record prompting an order set or mailed screening invitations for patients that meet screening criteria and include in the subsequent ultrasound report a standardized algorithm for further surveillance and management.5Hye R.J. Smith A.E. Wong G.H. Vansomphone S.S. Scott R.D. Kanter M.H. Leveraging the electronic medical record to implement an abdominal aortic aneurysm screening program.J Vasc Surg. 2014; 59: 1535-1542Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar

Aortic enlargement in chronic obstructive pulmonary disease (COPD) and emphysema: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD study

BackgroundThe prevalence of abdominal aortic aneurysm is high in chronic obstructive pulmonary disease (COPD) population. Emphysema involves proteolytic destruction of elastic fibers. Therefore, emphysema may also contribute to thoracic aorta dilatation. This study assessed aorta dilation in smokers stratified by presence of COPD, emphysema and airway thickening. MethodsAorta diameters were measured on 3D magnetic resonance angiography in smokers recruited from the Multi-Ethnic Study of Atherosclerosis (MESA), the Emphysema and Cancer Action Project (EMCAP), and the local community. COPD was defined by standard spirometric criteria; emphysema was measured quantitatively on computed tomography and bronchitis was determined from medical history. ResultsParticipants (n = 315, age 58–79) included 150 with COPD and 165 without COPD, of whom 56% and 19%, respectively, had emphysema. Subjects in the most severe quartile of emphysematous change showed the largest diameter at all four aorta locations compared to those in the least severe quartiles (all p < 0.001). Comparing subjects with and without COPD, aorta diameters were larger in participants with severe COPD in ascending and arch (both p < 0.001), and abdominal aorta (p = 0.001). Chronic bronchitis and bronchial wall thickness did not correlate with aorta diameter. In subjects with emphysema, subjects with coexistence of COPD showed larger aorta than those without COPD in ascending (p = 0.003), arch (p = 0.002), and abdominal aorta (p = 0.04). ConclusionsThis study showed larger aorta diameter in subjects with COPD and severe emphysema compared to COPD related to chronic bronchitis or bronchial wall thickening.

Feasibility and Efficiency Study of a Population-Based Abdominal Aortic Aneurysm Screening Program in Men and Women in Spain

Based on current evidence, one-time screening for abdominal aortic aneurysm (AAA) in men using ultrasound evaluation reduces mortality related to AAA rupture and is considered cost-effective, although all-cause mortality reduction still remains in question. In Spain, there is no population screening program for AAA, so the aim of our study was to perform a pilot population screening program in our area to assess feasibility and efficiency of an AAA screening program for men and women. A population AAA screening pilot program was performed in a Barcelona area, including 400,000 inhabitants. According to inclusion criteria, 4,730 individuals aged 65 years at the moment of the trial were invited for screening (2,089 men and 2,641 women). Primary care doctors, trained in duplex ultrasound abdominal evaluations, performed an abdominal aortic measurement. Individuals with a previous diagnosis of AAA, limited life expectancy, or wrong contact data were excluded. Participation data, aortic diameters, AAA prevalence, and related cardiovascular risk factors were analyzed. The results were used in a cost-utility model to assess the efficiency of the screening program. Participation was 50.3% in men and 44% in women. Eleven patients were excluded because of previously diagnosed AAA. Five new asymptomatic AAA were detected in 65-year-old men (0.5% prevalence), all being active smokers. When considering patients excluded for previous AAA diagnosis, the prevalence in 65-year-old men reached 1.4%. Global AAA prevalence in smoking men reached 2.67%. No AAA was detected in women. Subaneurysmal aorta prevalence in men was 2.9% (n=29), and in women, it was 0.08% (n=2). A cost-utility analysis model on screening versus no screening retrieved 13,664€ per quality-adjusted life years at a 10-year horizon and 39,455€ per quality-adjusted life years at a 30-year horizon. AAA population-based screening by ultrasound evaluation in primary care is logistically feasible in our area. Despite that, AAA prevalence is lower than expected in men, and null in women. Cost-utility model results indicate that a local AAA screening program is only efficient in a 30years' time horizon. Such inefficient results for a population screening make it necessary to consider other strategies such as opportunistic or subgroup screening in our area.

Racial Differences in Isolated Aortic, Concomitant Aortoiliac, and Isolated Iliac Aneurysms: This is a Retrospective Observational Study.

Our aim was to describe the racial and ethnic differences in presentation, baseline and operative characteristics, and outcomes after aortoiliac aneurysm repair. Previous studies have demonstrated racial and ethnic differences in prevalence of abdominal aortic aneurysms and showed more complex iliac anatomy in Asian patients. We identified all White, Black, Asian, and Hispanic patients undergoing aortoiliac aneurysm repair in the VQI from 2003 to 2019. We compared baseline comorbidities, operative characteristics, and perioperative outcomes by race and ethnicity. In our 60,435 patient cohort, Black patients, followed by Asian patients, were most likely to undergo repair for aortoiliac (W:23%, B:38%, A:31%, H:22%, P < 0.001) and isolated iliac aneurysms (W:1.0%, B:3.1%, A:1.5%, H:1.6%, P < 0.001), and White and Hispanic patients were most likely to undergo isolated aortic aneurysm repair (W:76%, B:59%, A:68%, H:76%, P < 0.001). Black patients were more likely to undergo symptomatic repair and underwent rupture repair at a smaller aortic diameter. The iliac aneurysm diameter was largest in Black and Asian patients. Asian patients were most likely to have aortic neck angulation above 60 degree, graft oversizing above 20%, and completion endoleaks. Also, Asian patients were more likely to have a hypogastric artery aneurysm and to undergo hypogastric coiling. Asian and Black patients were more likely to undergo repair for aortoiliac and isolated iliac aneurysms compared to White and Hispanic patients who were more likely to undergo repair for isolated aortic aneurysms. Moreover, there were significant racial differences in the demographics and anatomic characteristics that could be used to inform operative approach and device development.

Abstract 15501: Repeated Social Defeat Exaggerates Cacl2-induced Abdominal Aortic Aneurysm Expansion by Suppression of Periaortic Fibrosis in Tissue Repair Phase

Background and Objective: Depression is an independent risk factor of cardiovascular disease and significantly associated with the prevalence of abdominal aortic aneurysm (AAA). We investigated the impact of repeated social defeat (RSD) on AAA formation. Methods and Results: Eight-week-old male WT mice were exposed to RSD by housing with a larger CD-1 mouse in a shared cage. They were subjected to vigorous physical contact daily for 10 consecutive days. Control mice were housed in the same cage without physical contact. After social interaction test to confirm depressive-like behaviors, mice underwent application of 0.5M calcium chloride (CaCl 2 ) on the infrarenal aorta. At one-week, maximum diameter and circumference of external elastic membrane were comparable between the two groups. The number of F-4/80 and MMP-9-positive cells in immunofluorescent images were also comparable. Consistently, fluorescent image taken by IVIS revealed no difference in MMP activity, suggesting that acute inflammatory response was comparable between the two groups. In contrast, at two weeks, maximum diameter and circumference of external elastic membrane were significantly increased in defeated mice ( p &lt; 0.01). Intriguingly, periaortic fibrotic area in aneurysmal portion was markedly decreased in defeated mice (12.5х10 3 μm 2 vs. 3.7х10 3 μm 2 , Control vs. Defeat, p &lt; 0.01). Consistently, accumulation of α-SMA-positive cells in adventitia of aneurysmal portion was much lesser in defeated mice (876 cells/mm 2 vs. 319 cells/mm 2 , Control vs. Defeat, p &lt; 0.05), whereas those in tunica media of non-aneurysmal portion did not show any difference between the two groups. LPS-induced iNOS gene and protein expressions in bone marrow-derived macrophages (BMDMs) were significantly decreased in defeated mice, whereas the TGF-β-induced phosphorylation of Smad2 and ERK1/2 in primary cultured aortic VSMCs were comparable between the two groups. Conclusions: Our findings demonstrate that RSD enhances AAA expansion by suppressing the periaortic fibrosis following inflammatory response, and suggest that decreased NO production from accumulated macrophages contributes to the reduced VSMCs proliferation and collagen deposition.

Repeated social defeat exaggerates CaCl2-induced abdominal aortic aneurysm expansion by eliminating periaortic fibrosis in tissue repair phase: possible involvement of specific subtypes of macrophages

Abstract Background and objective Depression is an independent risk factor of cardiovascular disease (CVD) and significantly associated with the prevalence of abdominal aortic aneurysm (AAA). We have recently shown that repeated social defeat (RSD) precipitates depressive-like behaviors in apoE−/− mice and exaggerates atherosclerosis development by enhancing leukocyte activation. Here, we investigated the impact of RSD on AAA formation. Methods and results Eight-week-old male WT mice were exposed to RSD by housing with a larger CD-1 mouse in a shared home cage. They were subjected to vigorous physical contact daily for 10 consecutive days. Control mice were housed in the same gage without physical contact. After social interaction test to confirm depressive-like behaviors, defeated mice (28 of 48) and control mice (31 of 36) underwent application of 0.5 M calcium chloride (CaCl2) on the infrarenal aorta to induce AAA. At 1 week after application, maximum diameter and circumference of external elastic membrane were comparable between the two groups. The number of F-4/80, MMP-9, and TNF-α-positive cells in immunofluorescent images were also comparable. Further, in vitro bone marrow derived macrophages stimulation by LPS did not show any difference in mRNA expression levels of inflammatory cytokines, suggesting no discernable difference in acute inflammatory response between the two groups. In contrast, at 2 weeks after application, at the time point when MMP-9 and TNF-α-positive cells were scarcely observed, maximum diameter and circumference of external elastic membrane were significantly increased in defeated mice (0.72 mm vs. 0.90 mm, 1.59 mm vs. 2.00 mm, respectively, Control vs. Defeat, p&amp;lt;0.01). Intriguingly, periaortic fibrotic area in aneurysmal portion was markedly decreased in defeated mice (12.5×103 μm2 vs. 3.7×103 μm2, Control vs. Defeat, p&amp;lt;0.01). Consistently, accumulation of α-SMA-positive cells in adventitia of aneurysmal portion was much less in defeated mice than control mice (876 cells/mm2 vs. 319 cells/mm2, Control vs. Defeat, p&amp;lt;0.05), whereas those in tunica media of non-aneurysmal portion did not show any difference between the two groups. We next focused on the segregated nucleus-containing atypical monocyte (SatM), specific subtypes of monocytes/macrophages that are involved in fibrosis in injured tissues during the healing phase. We could observe SatM fraction in AAA tissue of control mice using flow cytometry. We also found that mRNA expression level of C/EBPβ, an essential regulator for SatM differentiation, was markedly decreased by 76% in BM cells of defeated mice compared with control mice (p&amp;lt;0.05). Conclusions Our findings demonstrate for the first time that RSD enhances AAA expansion by eliminating periaortic fibrosis in tissue repair phase, suggesting that the impaired resolution of acute inflammation after CaCl2 application contributes, at least in part, to the augmented expansion of AAA in defeated mice. Funding Acknowledgement Type of funding source: None

Screening for abdominal aortic aneurysm in patients with clinically manifest vascular disease.

Declining prevalence of abdominal aortic aneurysm (AAA) might force a more targeted screening approach (high-risk populations only) in order to maintain (cost-)effectiveness. We aimed to determine temporal changes in the prevalence of screening-detected AAA, to assess AAA-related surgery, and evaluate all-cause mortality in patients with manifest vascular disease. We included patients with manifest vascular disease but without a history of AAA enrolled in the ongoing single-centre prospective UCC-SMART cohort study. Patients were screened at baseline for AAA by abdominal ultrasonography. We calculated sex- and age-specific prevalence of AAA, probability of survival in relation to the presence of AAA, and the proportion of patients undergoing AAA-related surgery. Prevalence of screening-detected AAA in 5440 screened men was 2.5% [95% confidence interval (CI) 2.1-2.9%] and in 1983 screened women 0.7% (95% CI 0.4-1.1%). Prevalence declined from 1997 until 2017 in men aged 70-79 years from 8.1% to 3.2% and in men aged 60-69 years from 5.7% to 1.0%. 36% of patients with screening-detected AAA received elective AAA-related surgery during follow-up (median time until surgery = 5.3 years, interquartile range 2.5-9.1). Patients with screening-detected AAA had a lower probability of survival (sex and age adjusted) compared to patients without screening-detected AAA (51%, 95% CI 41-64% vs. 69%, 95% CI 68-71%) after 15 years of follow-up. The prevalence of screening-detected AAA has declined over the period 1997-2017 in men with vascular disease but exceeds prevalence in already established screening programs targeting 65-year-old men. Screening for AAA in patients with vascular disease may be cost-effective, but this remains to be determined.

Genetic Architecture of Abdominal Aortic Aneurysm in the Million Veteran Program.

Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability. We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease. Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24-1.66]; P=1.6×10-6), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97-1.15]; P=0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratioPRS, 1.26 [95% CI, 1.18-1.36]; PPRS=2.7×10-11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratioPRS+family history+smoking, 1.24 [95% CI, 1.14-1.35]; PPRS=1.27×10-6). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines. We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.

Screening cardiovascular patients for aortic aneurysms (SCAN) - high prevalence of abdominal aortic aneurysms in coronary heart disease patients requiring intervention.

Background: Since the prevalence of abdominal aortic aneurysms (AAA) in Europe has declined to about 2.5%, general screening programs of elderly men are being called into question. On the other hand, other vascular diseases (e.g. coronary heart disease, CHD) are associated with a higher prevalence of AAA. This might have an impact on future targeted AAA screening programs. This study aimed to reevaluate the current prevalence of AAA in male patients with CHD, in order to assess whether CHD patients should be offered a targeted AAA ultrasound screening program. Patients and methods: The SCAN (Screening Cardiovascular Patients for Aortic Aneurysms) study prospectively evaluated the AAA prevalence in 1000 consecutive male CHD patients (70.1±11.2years) requiring any coronary intervention at an university hospital. All patients received transverse and longitudinal ultrasound scans of the abdominal aorta. Aortic diameter was assessed using the outer-to-outer measurement-technique. Primary endpoint was the prevalence of AAA. Secondary outcomes included stratification in 1-, 2-, or 3-vessel CHD. Results: AAA was detected in 85 patients (median diameter 38mm, range 30-80mm), corresponding to an overall prevalence of 8.5%. AAA prevalence was significantly associated with CHD severity: 5.6% in 1-vessel, 7.1% in 2-vessel, and 10.8% in 3-vessel CHD (P=0.037). The multivariable analysis showed, that age per 10years increase (OR 1.5, 95% CI 1.2-1.9, P=0.001) and hyperlipidemia (OR 2.2, 95% CI 1.3-3.8, P=0.003) were significantly associated with an AAA. The likelihood to be diagnosed with an AAA was significantly lower in non-smokers (OR 0.24, 95% CI, P<0.001). Conclusions: This study confirms that CHD requiring any type of coronary intervention is strongly associated with AAA in male patients. AAA prevalence increases with CHD severity. Since the AAA prevalence is still significantly higher than in the general population, targeted ultrasound screening should be considered for all CHD patients.

High prevalence of abdominal aortic aneurysms in patients with lung cancer

BackgroundLung cancer and abdominal aortic aneurysms (AAAs) possess multiple shared risk factors. Whereas both have screening guidelines in place, they vary in methodology despite having significant overlap in populations of patients screened. MethodsOur hospital system's Lung Cancer Program database was used to identify patients diagnosed with primary lung cancer within the past 15 years. Demographic and risk factor data were obtained, and patients' original positron emission tomography-computed tomography scans were re-read for measurements of the abdominal aorta (aortic diameter ≥3.0 cm). A cancer-free control group was obtained for comparison. Multilinear regression modeling was used to evaluate the independent associations of multiple variables on the presence of AAA. ResultsAmong 814 patients with primary lung cancer, 90 (11.1%; 95% confidence interval [CI], 8.9%-13.3%) had AAA compared with 4 of 200 (2%; 95% CI, 0.1%-3.9%) in the control group (P = .0001). Patients who smoked were more likely than nonsmokers to have AAA (11.9% [95% CI, 9.8-14.6] vs 2.2% [95% CI, 0.1-8.1]; P = .0021). In patients with AAA, 12% (11/90) had aneurysms that required treatment, and 76.6% had early-stage lung cancer. Women in our study also had a high prevalence of AAA (4.6%). Logistic regression analysis showed male sex (odds ratio [OR], 3.70; P <.001), increasing age (OR, 1.07 per year; P <.001), smoking amount (OR, 1.01 per pack-year; P = .004), and hypertension (OR, 2.30; P = .020) to be independent risk factors for AAA. ConclusionsPatients with lung cancer have a high prevalence of AAA. If future studies can demonstrate a reduction in AAA mortality by screening for AAA and lung cancer simultaneously, it may prove worthwhile to extend the low-dose computed tomography scan through the lower abdomen in select patients.

Coprevalence and Incidence of Lung Cancer in Patients Screened for Abdominal Aortic Aneurysm.

Lung diseases are common in patients with abdominal aortic aneurysms (AAA). This study evaluates the prevalence of lung cancer (LC) in high-risk patients screened for AAA. Six hundred and one male patients (≥65 years of age, cardiovascular high-risk profile) were enrolled and followed prospectively over a median of 16.5 months. In 29 patients (4.8%) LC and in another 50 patients (8.3%) AAA were found. The prevalence of LC among patients with AAA was even higher (9 of 50, 18.0%). Twenty-one patients had an initial diagnosis of LC, with an incidence of 12.0% (6 of 50) in patients with AAA. During follow-up, 14 of 70 patients with AAA and/ or LC (20.0%) deceased. The highest mortality was found in patients with LC only (8 of 20, 40.0%), followed by patients with both AAA and LC (3 of 9, 33.3%), while patients with AAA only had the lowest mortality rate (3 of 41, 7.3%). In patients with a high cardiovascular risk profile, a high prevalence of both AAA and LC were found, whereby the prognosis is largely determined by the LC. Therefore, LC is of particular importance in the setting of screening and surveillance of AAA.

Screening of Abdominal Aortic Aneurysm Using Portable Transthoracic Echocardiography among Patients with Acute Coronary Syndrome.

Background Abdominal aortic aneurysm (AAA) and acute coronary syndrome (ACS) share common risk factors. Objectives To assess the abdominal aortic diameter (AAD) among patients with ACS using transthoracic echocardiography (TTE). Methods Patients with ACS admitted to our intensive cardiac care unit from December 2013 to June 2014 were screened prospectively for AAA via AAD measurement in the subcostal TTE view. AAA was defined as an aneurysm with a transverse diameter of ≥30 mm. Results Sixty seven patients were included. The male-to-female sex ratio was 7 : 1. The vast majority of patients were admitted due to STEMI (73%), and the rest were equally divided as NSTEMI and unstable angina. The mean patient age was 58.4 ± 10.4 years. AAD measurements were feasible in 57 patients (85%); among them, AAA was diagnosed in six patients (10.5%). The average additional time required to measure the abdominal aorta was 4 ± 1 min. All patients with AAA were men and had a higher prevalence of smoking (83.3% vs. 60.6%, p < 0.003) and a lower incidence of diabetes mellitus than those without aneurysm. The prevalence of AAA tended to be related to age (12.5% in those older than 60 years and 18.7% in those older than 65 years). Conclusions The overall prevalence of AAA is significantly high among patients with ACS and increases with age. AAA screening as a part of routine cardiac TTE can be easily, rapidly, and feasibly performed and yield accurate findings. AAD measurement in the subcostal view should be implemented as a part of routine TTE in patients with ACS.