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

BACKGROUND: 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. METHOD: 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. RESULTS: 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). CONCLUSION: 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.

Peak wall rupture index is associated with risk of rupture of abdominal aortic aneurysms, independent of size and sex.

BACKGROUND: Information on the predictive determinants of abdominal aortic aneurysm rupture from CT angiography are scarce. The aim of this study was to investigate biomechanical parameters in abdominal aortic aneurysms and their association with risk of subsequent rupture. METHODS: In this retrospective study, the digital radiological archive was searched for 363 patients with ruptured abdominal aortic aneurysms. All patients who underwent at least one CT angiography examination before aneurysm rupture were included. CT angiography results were analysed to determine maximum aneurysm diameter, aneurysm volume, and biomechanical parameters (peak wall stress and peak wall rupture index). In the primary survival analysis, patients with abdominal aortic aneurysms less than 70 mm were considered. Sensitivity analyses including control patients and abdominal aortic aneurysms of all sizes were performed. RESULTS: A total of 67 patients who underwent 109 CT angiography examinations before aneurysm rupture were identified. The majority were men (47, 70%) and the median age at the time of CTA examination was 77 (71-83) years. The median maximum aneurysm diameter was 56 (interquartile range 46-65) mm and the median time to rupture was 2.13 (interquartile range 0.64-4.72) years. In univariable analysis, maximum aneurysm diameter, aneurysm volume, peak wall stress, and peak wall rupture index were all associated with risk of rupture. Women had an increased HR for rupture when adjusted for maximum aneurysm diameter or aneurysm volume (HR 2.16, 95% c.i. 1.23 to 3.78 (P = 0.007) and HR 1.92, 95% c.i. 1.06 to 3.50 (P = 0.033) respectively). In multivariable analysis, the peak wall rupture index was associated with risk of rupture. The HR for peak wall rupture index was 1.05 (95% c.i. 1.03 to 1.08) per % (P < 0.001) when adjusted for maximum aneurysm diameter and 1.05 (95% c.i. 1.02 to 1.08) per % (P < 0.001) when adjusted for aneurysm volume. CONCLUSION: Biomechanical factors appear to be important in the prediction of abdominal aortic aneurysm rupture. Women are at increased risk of rupture when adjustments are made for maximum aneurysm diameter alone.

The Role of Antigranulocyte Scintigraphy in Diagnosis of Aortic Graft Infection and Evaluation of Treatment Outcome.

BACKGROUND: The aim of this study was to assess the eventual added benefit of antigranulocyte monoclonal antibodies scintigraphy for the diagnostic imaging of aortic graft infection (AGI) and its role in evaluation of treatment outcome. METHODS: A population-based, retrospective, register-based analysis was carried out of all patients with infected aortic grafts after treatment for aneurysmal or aortoiliac occlusive disease at Karolinska University Hospital, covering the greater Stockholm area during November 2012-December 2020. Cases were based on the definitions in the 2016 Management of Aortic Graft Infection Collaborations consensus. Using the in-hospital electronic patient registry (Take Care®) and the Swedish National Registry for Vascular Surgery (Swedvasc), 835 patients who had been treated for aortic aneurysms or aortoiliac occlusive disease were identified. The diagnostic arsenal of laboratory tests, computed tomography (CT), and clinical signs has been supplemented by antigranulocyte monoclonal antibodies (anti-G mAb) scintigraphy. Data were analyzed using SPSS Statistics. RESULTS: Eighteen cases of AGI out of 835 operations incorporating aortic grafts during the period were identified. Fourteen patients (78%) were categorized as diagnosed AGI (AGI-D), and the remaining 4 (22%) were classified as suspected AGI (AGI-S). In the AGI-D group (n = 14), 10 patients (71%) had positive CTs and 4 (29%) had low-probability CTs. In the group of 10 positive CTs, 9 patients also had positive scintigraphy scans with only one negative scintigraphy scan. There were no negative scintigraphy scans without ongoing antibiotic treatment at the time of investigation. In 15 of 18 cases, a culprit agent was identified, either preoperatively or perioperatively. Thirteen of the 18 patients were treated solely by antibiotics, whereas 5 underwent surgical treatment in addition to antibiotic treatment. The outcome has been divided into 3 groups: infection-free (n = 6; 33%), lifelong antibiotic treatment (n = 7; 39%), and deceased (n = 5; 28%). CONCLUSIONS: The imaging modalities in AGI diagnostics are a cornerstone of the investigative work-up, complemented by clinical signs and laboratory methods. The main advantage conveyed by anti-G mAb scintigraphy is in postoperative imaging and its ability to differentiate between infection and general postoperative changes in the areas of concern. We have identified 6 patients in our cohort in whom antibiotic therapy was discontinued after a negative anti-G mAb scintigraphy scan. Anti-G mAb scintigraphy may fulfill a unique need for diagnosis in suspected cases, evaluation of therapeutic efficacy in patients requiring long-term antibiotic treatment, and aiding in the decision to discontinue antibiotic therapy.

Women with large intact abdominal aortic aneurysms remain untreated.

OBJECTIVE: A lower elective repair rate among women with abdominal aortic aneurysms (AAAs) has been a consistent finding. Reasons behind this gender gap have not been thoroughly outlined. METHODS: This was a retrospective multicenter cohort study (ClinicalTrials.gov: NCT05346289) at three European vascular centers in Sweden, Austria and Norway. Patients in surveillance with AAAs were consecutively identified starting from January 1, 2014, until reaching a total sample size of 200 women and 200 men. All individuals were followed for 7 years through medical records. Final treatment distributions and the proportion of "truly untreated" (surgically untreated despite reaching guideline-directed thresholds: 50 mm for women and 55 mm for men) were determined. In a complementary analysis, a universal 55-mm threshold was used. Gender-specific primary reasons behind untreated statuses were clarified. Eligibility for endovascular repair among the truly untreated was assessed in a structured computed tomography analysis. RESULTS: Women and men had similar median diameters at inclusion (46 mm; P = .54) and at treatment decisions (55 mm; P = .36). After 7 years, the repair rate was lower among women (47% vs 57%). More women were truly untreated (26% vs 8%; P < .001) despite similar mean ages as for male counterparts (79.3 years; P = .16). With the 55-mm threshold, 16% women still classified as truly untreated. Similar reasons for nonintervention were captured for women and men (50% due to comorbidities alone, 36% morphology and comorbidity). The endovascular repair imaging analysis revealed no gender differences. Among truly untreated women, ruptures were common (18%), and mortality was high (86%). CONCLUSIONS: Surgical AAA management differed between women and men. Women could be underserved in terms of elective repairs: one in every four women was untreated with over-the-threshold AAAs. The lack of obvious gender differences in eligibility analyses could imply unmeasured discrepancies (eg, in disease extent or patient frailty).

Radiation therapy for cancer is potentially associated with reduced growth of concomitant abdominal aortic aneurysm.

PURPOSE: Co-prevalence of abdominal aortic aneurysm (AAA) and cancer poses a unique challenge in medical care since both diseases and their respective therapies might interact. Recently, reduced AAA growth rates were observed in cancer patients that received radiation therapy (RT). The purpose of this study was to perform a fine-grained analysis of the effects of RT on AAA growth with respect to direct (infield) and out-of-field (outfield) radiation exposure, and radiation dose-dependency. METHODS: A retrospective single-center analysis identified patients with AAA, cancer, and RT. Clinical data, radiation plans, and aneurysm diameters were analyzed. The total dose of radiation to each aneurysm was computed. AAA growth under infield and outfield exposure was compared to patients with AAA and cancer that did not receive RT (no-RT control) and to an external noncancer AAA reference cohort. RESULTS: Between 2003 and 2020, a total of 38 AAA patients who had received well-documented RT for their malignancy were identified. AAA growth was considerably reduced for infield patients (n = 18) compared to outfield patients (n = 20), albeit not significantly (0.8 ± 1.0 vs. 1.3 ± 1.6 mm/year, p = 0.28). Overall, annual AAA growth in RT patients was lower compared to no-RT control patients (1.1 ± 1.5 vs. 1.8 ± 2.2 mm/year, p = 0.06) and significantly reduced compared to the reference cohort (1.1 ± 1.5 vs. 2.7 ± 2.1 mm/year, p < 0.001). The pattern of AAA growth reduction due to RT was corroborated in linear regression analyses correcting for initial AAA diameter. A further investigation with respect to dose-dependency of radiation effects on AAA growth, however, revealed no apparent association. CONCLUSION: In this study, both infield and outfield radiation exposure were associated with reduced AAA growth. This finding warrants further investigation, both in a larger scale clinical cohort and on a molecular level.

Long Term Mortality Rate in Patients Treated with Carotid Endarterectomy.

OBJECTIVE: Carotid endarterectomy (CEA) is an effective surgical method for stroke prevention in selected patients with carotid stenosis. Few contemporary studies report on the long term mortality rate in CEA treated patients, despite continuous changes in medication, diagnostics, and patient selection. Here, the long term mortality rate is described in a well characterised cohort of asymptomatic and symptomatic CEA patients, sex differences evaluated, and mortality ratio compared with the general population. METHODS: This was a two centre, non-randomised, observational study evaluating all cause, long term mortality in CEA patients from Stockholm, Sweden between 1998 and 2017. Death and comorbidities were extracted from national registries and medical records. Cox regression was adapted to analyse associations between clinical characteristics and outcome. Sex differences and standardised mortality ratio (SMR, age and sex matched) were studied. RESULTS: A total of 1 033 patients were followed for 6.6 ± 4.8 years. Of those, 349 patients died during follow up where the overall mortality rate was similar in asymptomatic and symptomatic patients (34.2% vs. 33.7%, p = .89). Symptomatic disease did not influence the mortality risk (adjusted HR 1.14, 95% CI 0.81 - 1.62). Women had lower crude mortality rate than men in the first 10 years (20.8% vs. 27.6%, p = .019). In women, cardiac disease was associated with increased mortality (adjusted HR 3.55, 95% CI 2.18 - 5.79), while in men, lipid lowering medication was protective (adjusted HR 0.61, 95% CI 0.39 - 0.96). Within the first five years after surgery, SMR was increased for all patients (men 1.50, 95% CI 1.21 - 1.86; women 2.41, 95% CI 1.74 - 3.35), as well as in patients < 80 years (SMR 1.46, 95% CI 1.23 - 1.73). CONCLUSION: Symptomatic and asymptomatic carotid patients have similar long term mortality rates after CEA, but men had worse outcome than women. Sex, age, and time after surgery were shown to influence SMR. These results highlight the need for targeted secondary prevention, to alter the long term adverse effects in CEA patients.

Excess Mortality for Abdominal Aortic Aneurysms and the Potential of Strict Implementation of Cardiovascular Risk Management: A Multifaceted Study Integrating Meta-Analysis, National Registry, and PHAST and TEDY Trial Data.

OBJECTIVE: Previous studies imply a profound residual mortality risk following successful abdominal aorta aneurysm (AAA) repair. This excess mortality is generally attributed to increased cardiovascular risk. The aim of this study was (1) to quantify the excess residual mortality for patients with AAA, (2) to evaluate the cross sectional level of cardiovascular risk management, and (3) to estimate the potential of optimised cardiovascular risk management to reduce the excess mortality in these patients. METHODS: Excess mortality was estimated through a systematic review and meta-analysis, and through data from the Swedish National Health Registry. Cardiovascular risk profiles were individually assessed during eligibility screening of patients with AAA for two multicentre pharmaceutical AAA stabilisation trials. The potential of full implementation of cardiovascular risk management was estimated through the validated Second Manifestations of ARTerial disease (SMART) risk scores algorithm. RESULTS: The meta-analysis showed a similarly impaired survival for patients who received early repair (small AAA) or regular repair (≥ 55 mm), and a further impaired survival for patients under surveillance for a small AAA. Excess mortality was further quantified using Swedish population data. The data revealed a more than quadrupled and doubled five year mortality rate for women and men who had their AAA repaired, respectively. Evaluation of the level of risk management of 358 patients under surveillance in 16 Dutch hospitals showed that the majority of patients with AAA did not meet therapeutic targets set for risk management in high risk populations, and indicated a more pronounced prevention gap in women. Application of the SMART risk score algorithm predicted that optimal implementation of risk management guidelines would reduce the 10 year risk of major adverse cardiovascular events from 43% to 14%. CONCLUSION: Independent of the rupture risk, AAA is associated with a worryingly compromised life expectancy with a particularly poor prognosis for women. Optimal implementation of cardiovascular risk prevention guidelines is predicted to profoundly reduce cardiovascular risk.

Natural history, growth rates, and treatment of popliteal artery aneurysms.

BACKGROUND: The natural history of a cohort of patients monitored for popliteal artery aneurysms (PAAs) has not been well described. A prevailing uncertainty exists regarding the optimal surveillance strategies and timing of treatment. The primary aim of the present study was to describe the care trajectory of all patients with PAAs identified at two tertiary vascular centers, both in surveillance and eventually treated. The secondary aim was to define the PAA growth rates. METHODS: A retrospective, multicenter cohort study was performed of all patients with PAAs at two vascular centers in two countries (Sweden, 2009-2016; New Zealand, 2009-2017). Data were collected from electronic medical records regarding the comorbidities, treatment, and outcomes and analyzed on a patient- and extremity-specific level. Treatment was indicated at the occurrence of emergent symptoms or considered at a PAA threshold of >2 cm. The PAAs were divided into small (≤15 mm) and large (>15 mm) aneurysms. The mean surveillance follow-up was 5.1 years. RESULTS: Most of the 241 identified patients (397 limbs) with a diagnosis of PAAs had bilateral aneurysms (n = 156). Most patients were treated within the study period (163 of 241; 68%), and one half of the diagnosed extremities with PAA had been treated (54%; 215 of 397). Among those who had undergone elective repair, treatment had usually occurred within 1 year after the diagnosis (66%; 105 of 158). More small PAAs were detected in the group that had required emergent repair compared with elective repair (6 of 57 [11%] vs 12 of 158 [8%]; P < .001). No differences were found in the mean diameters between the elective and emergent groups (30.1 mm vs 32.2 mm; P = .39). Growth was recorded in 110 PAAs and on multivariate analysis was associated with a larger index diameter (odds ratio, 1.138; 95% confidence interval, 1.040-1.246; P = .005) and a concurrent abdominal aortic aneurysm (odds ratio, 2.553; 95% confidence interval, 1.018-6.402; P = .046). CONCLUSIONS: The present cohort of patients represented a true contemporary clinical setting of monitored PAAs and showed that most of these patients will require elective repair, usually within 1 year. The risk of emergent repair is not negligible for patients with smaller diameter PAAs. However, the optimal selection strategy for preventive early repair is still unknown. Future morphologic studies are needed to support the development of individualized surveillance protocols.

Editor's Choice - Structured Computed Tomography Analysis can Identify the Majority of Patients at Risk of Post-Endovascular Aortic Repair Rupture.

OBJECTIVE: The main objective was to report mechanisms and precursors for post-endovascular aneurysm repair (EVAR) rupture. The second was to apply a structured protocol to explore whether these factors were identifiable on follow up computed tomography (CT) prior to rupture. The third objective was to study the incidence, treatment, and outcome of post-EVAR rupture. METHODS: This was a multicentre, retrospective study of patients treated with standard EVAR at five Swedish hospitals from 2008 to 2018. Patients were identified from the Swedvasc registry. Medical records were reviewed up to 2020. Index EVAR and follow up data were recorded. The primary endpoint was post-EVAR rupture. CT at follow up and at post-EVAR rupture were studied, using a structured protocol, to determine rupture mechanisms and identifiable precursors. RESULTS: In 1 805 patients treated by EVAR, 45 post-EVAR ruptures occurred in 43 patients. The cumulative incidence was 2.5% over a mean follow up of 5.2 years. The incidence rate was 4.5/1 000 person years. Median time to post-EVAR rupture was 4.1 years. A further six cases of post-EVAR rupture in five patients found outside the main cohort were included in the analysis of rupture mechanisms only. The rupture mechanism was type IA in 20 of 51 cases (39%), IB in 20 of 51 (39%) and IIIA/B in 11 of 51 (22%). One of these had type IA + IB combined. One patient had an aortoduodenal fistula without another mechanism being identified. Precursors had been noted on CT follow up prior to post-EVAR rupture in 16 of 51 (31%). Retrospectively, using the structured protocol, precursors could be identified in 43 of 51 (84%). In 17 of 27 (63%) cases missed on follow up but retrospectively identifiable, the mechanisms were type IB/III. Overall, the 30 day mortality rate after post-EVAR rupture was 47% (n = 24/51) and the post-operative mortality rate was 21% (n = 7/33). CONCLUSIONS: Most precursors of post-EVAR rupture are underdiagnosed but identifiable before rupture using a structured follow up CT protocol. Precursors of type IB and III failures caused the majority of post-EVAR ruptures.

Radiation and Chemotherapy are Associated with Altered Aortic Aneurysm Growth in Patients with Cancer: Impact of Synchronous Cancer and Aortic Aneurysm.

OBJECTIVE: The purpose of this study was to assess the associations between malignancy, therapeutic regimens, and aorto-iliac aneurysm (i.e., abdominal aortic aneurysm [AAA]) growth rates. METHODS: A retrospective single centre analysis identified patients with an AAA plus cancer. Patients who had two or more computed tomography angiograms over six months or more and additional malignancy were included. Clinical data and aneurysm diameters were analysed. AAA growth under cancer therapy (chemotherapy or radiation) was compared with a non-cancer AAA control cohort and to meta-analysis data. Statistics included t tests and a linear regression model with correction for initial aortic diameter and type of treatment. RESULTS: From 2003 to 2020, 217 patients (median age 70 years; 92% male) with 246 aneurysms (58.8% AAA) and 238 malignancies were identified. Prostate (26.7%) and lung (15.7%) cancer were most frequently seen. One hundred and fifty-seven patients (72.3%) received chemotherapy, 105 patients (48.4%) radiation, and 79 (36.4%) both. Annual AAA growth (mean ± standard deviation) was not statistically significantly different for cancer and non-cancer patients (2.0 ± 2.3 vs. 2.8 ± 2.1 mm/year; p = .20). However, subgroup analyses revealed that radiation was associated with a statistically significantly reduced mean aneurysm growth rate compared with cancer patients without radiation (1.1 ± 1.3 vs. 1.6 ± 2.1 mm/year; p = .046) and to the non-cancer control cohort (1.7 ± 1.9 vs. 2.8 ± 2.1 mm/year; p = .007). Administration of antimetabolites resulted in statistically significantly increased AAA growth (+ 0.9 mm/year; p = .011), while topoisomerase inhibitors (- 0.8 mm/year; p = .17) and anti-androgens (- 0.5 mm/year; p = .27) showed a possible trend for reduced growth. Similar observations were noted for iliac aneurysms (n = 85). Additionally, the effects persisted for chemotherapy combinations (2.6 ± 1.4 substances/patient). CONCLUSION: Patients with cancer and concomitant aortic aneurysms may require intensified monitoring when undergoing specific therapies, such as antimetabolite treatment, as they may experience an increased aneurysm growth rate. Radiation may be associated with reduced aneurysm growth.

Sex hormones in men with abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysms (AAAs) primarily affect elderly men. The effect of sex on aneurysm development has been associated with the effects of sex hormones through mechanisms that are not fully understood. The present study examined the association between the levels of sex hormones and the occurrence of AAAs in elderly men. METHODS: A prospective case-control study was conducted of 452 men aged 65 years participating in screening for AAAs from 2013 to 2019. Of the 452 men, 230 had an AAA and 222 an aortic diameter of <30 mm (control group). Questionnaires and blood samples were collected and stored consecutively. The serum levels of total testosterone, estradiol, progesterone, luteinizing hormone, and sex hormone-binding globulin were analyzed using electrochemiluminescent immunoassays. Multivariable logistic regression analysis was used to assess the association between sex hormones and AAA. RESULTS: The median aneurysm diameter was 33 mm. Men with AAA had greater estradiol (93 pmol/L vs 84 pmol/L; P =.003) and progesterone (0.41 nmol/L vs 0.17 nmol/L; P < .001) levels compared with the controls. The testosterone levels were lower in the AAA group than in the control group (13 nmol/L vs 14 nmol/L; P = .026). AAA was associated with detectable levels of progesterone (odds ratio [OR], 6.69; 95% confidence interval [CI], 3.86-11.47), smoking (OR, 5.26; 95% CI, 3.12-8.85), coronary heart disease (OR, 4.06; 95% CI, 1.92-8.58), and a body mass index >25 kg/m2 (OR, 2.26; 95% CI, 1.34-3.82). CONCLUSIONS: The observed higher estradiol and progesterone levels in men with an AAA suggest an effect of sex hormones on aneurysm development. The association between progesterone levels and the aortic diameter stresses the importance of focusing on the potential effect of this unconsidered female sex hormone on aneurysm formation.

A population-based study of post-endovascular aortic repair rupture during 15 years.

OBJECTIVE: The devastating event of a ruptured abdominal aortic aneurysm (rAAA) in patients who have survived a previous AAA repair, either elective or urgent, is a feared and quite uncommon event. It has been suggested to partly explain the loss of the early survival benefit for endovascular aortic repair (EVAR) vs open surgical repair (OSR). The main objective of this study was to report the national incidence rate, risk factors and outcome of post-EVAR ruptures. Secondarily, the national incidence rate of ruptures after OSR (post-OSR ruptures) was investigated. METHODS: We conducted a nationwide, population-based, retrospective cohort study using the inpatient and outpatient entries for all patients >40 years of age, receiving their first (index) surgical procedure for AAA, from 2001 to 2015. Only patients surviving their index procedure were included. The primary outcome was rAAA, registered after discharge from the index procedure (EVAR or OSR), identified in the Swedish National Patient Registry and the Cause of Death Registry. RESULTS: In total, 14,859 patients survived their primary (index) AAA procedure. There were 6470 EVAR procedures, 5893 for intact AAA (iAAA) and 577 for rAAA. Of the 6470 EVAR patients, 86 cases of post-EVAR rupture were identified, corresponding with a cumulative incidence of 1.3% over a mean follow-up time of 3.9 years. The incidence rate was 3.4 (95% confidence interval [CI], 2.7-4.2)/1000 person-years. The independent risk factors identified for post-EVAR rupture were rAAA at index surgery HR 2.4 (95% CI, 1.4-4.1, p 0.002) and age (hazard ratio, 1.1; 95% CI, 1.0-1.1; P < .001). Freedom from post-EVAR rupture was 99%, 98%, and 96% at 3, 5, and 10 years, respectively. Total and postoperative mortality after post-EVAR rupture were 42% and 17% (30 days), 45% and 22% (90 days), and 53% and 33% (1 year). The incidence rate of post-OSR rupture was 0.9/1000 person-years (95% CI, 0.7-1.2). CONCLUSIONS: Post-EVAR rupture is a rare complication that can occur at any time after the index EVAR procedure. This finding may have implications for the discussion of limited follow-up programs and for the choice of procedure in patients with an AAA with a long life expectancy. An rAAA as the indication for the index surgery and age were identified as risk factors for post-EVAR rupture. The mortality associated with post-EVAR rupture is high, but lower than that of primary rAAA. The much lower risk of post-OSR rupture was confirmed, but must not be neglected as a possible late complication.

Tunica-Specific Transcriptome of Abdominal Aortic Aneurysm and the Effect of Intraluminal Thrombus, Smoking, and Diameter Growth Rate.

OBJECTIVE: There is no medical treatment to prevent abdominal aortic aneurysm (AAA) growth and rupture, both of which are linked to smoking. Our objective was to map the tunica-specific pathophysiology of AAA with consideration of the intraluminal thrombus, age, and sex, and to subsequently identify which mechanisms were linked to smoking and diameter growth rate. Approach and Results: Microarray analyses were performed on 246 samples from 76 AAA patients and 13 controls. In media and adventitia, there were 5889 and 2701 differentially expressed genes, respectively. Gene sets related to adaptive and innate immunity were upregulated in both tunicas. Media-specific gene sets included increased matrix disassembly and angiogenesis, as well as decreased muscle cell development, contraction, and differentiation. Genes implicated in previous genome-wide association studies were dysregulated in media. The intraluminal thrombus had a pro-proteolytic and proinflammatory effect on the underlying media. Active smoking resulted in increased inflammation, oxidative stress, and angiogenesis in all tissues and enriched lipid metabolism in adventitia. Processes enriched with active smoking in control aortas overlapped to a high extent with those differentially expressed between AAAs and controls. The AAA diameter growth rate (n=24) correlated with T- and B-cell expression in media, as well as lipid-related processes in the adventitia. CONCLUSIONS: This tunica-specific analysis of gene expression in a large study enabled the detection of features not previously described in AAA disease. Smoking was associated with increased expression of aneurysm-related processes, of which adaptive immunity and lipid metabolism correlated with growth rate.

Results After Open and Endovascular Repair of Popliteal Aneurysm: A Matched Comparison Within a Population Based Cohort.

OBJECTIVE: To identify factors affecting the outcome after open surgical (OSR) and endovascular (ER) repair of popliteal artery aneurysm (PA) in comparable cohorts. METHODS: A matched comparison in a national, population based cohort of 592 legs treated for PA (2008 - 2012), with long term follow up. Registry data from 899 PA patients treated in 2014 - 2018 were analysed for time trends. The 77 legs treated by ER were matched, by indication, with 154 legs treated with OSR. Medical records and imaging were collected. Analysed risk factors were anatomy, comorbidities, and medication. Elongation and angulations were examined in a core lab. The main outcome was occlusion. RESULTS: Patients in the ER group were older (73 vs. 68 years, p = .001), had more lung disease (p = .012), and were treated with dual antiplatelet therapy or anticoagulants more often (p < .001). The hazard ratio (HR with 95% confidence intervals) for occlusion was 2.69 (1.60 - 4.55, p < .001) for ER, but 3.03 (1.26 - 7.27, p = .013) for poor outflow. For permanent occlusion, the HR after ER was 2.47 (1.35 - 4.50, p = .003), but 4.68 (1.89 - 11.62, p < .001) for poor outflow. In the ER subgroup, occlusion was more common after acute ischaemia (HR 2.94 [1.45 - 5.97], p = .003; and poor outflow HR 14.39 [3.46 - 59.92], p < .001). Larger stent graft diameter reduced the risk (HR 0.71 [0.54 - 0.93], p = .014). In Cox regression analysis adjusted for indication and stent graft diameter, elongation increased the risk (HR 1.020 per degree [1.002 - 1.033], p = .030). PAs treated for acute ischaemia had a median stent graft diameter of 6.5 mm, with those for elective procedures being 8 mm (p < .001). Indications and outcomes were similar during both time periods (2008 - 2012 and 2014 - 2018). CONCLUSION: In comparable groups, ER had a 2.7 fold increased risk of any occlusion, and 2.4 fold increased risk of permanent occlusion, despite more aggressive medical therapy. Risk factors associated with occlusion in ER were poor outflow, smaller stent graft diameter, acute ischaemia, and angulation/elongation. An association between indication, acute ischaemia, and small stent graft diameter was identified.

Deep Femoral Vein Reconstruction for Abdominal Aortic Graft Infections is Associated with Low Aneurysm Related Mortality and a High Rate of Permanent Discontinuation of Antimicrobial Treatment.

OBJECTIVE: Aortic prosthesis infection is a devastating complication of aortic surgery. In situ reconstruction with the neo-aorto-iliac system (NAIS) bypass technique has become increasingly used and is recommended in recent treatment guidelines. The main aim was to evaluate NAIS procedural outcomes when undertaken after previous open or endovascular aortic repair in Sweden. METHODS: In this retrospective study, The National Quality Registry for Vascular Surgery (Swedvasc) was used to identify Swedish centres that offered the NAIS bypass procedure for aortic prosthesis infection between 2008 and 2018. Variables of special interest were procedural details, short and long term survival, renal and other complications, and the durtion of antimicrobial treatment. RESULTS: Forty patients (36 males, four females [mean age 69 years], 32 open repairs, seven endovascular aortic repairs [EVAR] and one fenestrated EVAR; 21 presented with aorto-enteric fistula) operated on with NAIS bypass were reviewed. The median time from the primary aortic intervention to the NAIS bypass procedure was 32 months (range 0 - 252 months). Mean ± standard deviation operating time was 645 ± 160 minutes, mean blood loss was 6 277 ± 6 525 mL, mean length of intensive care unit stay was 5.3 ± 3.7 days, and mean length of overall hospital stay was 21.2 ± 11.4 days. Thirty-five patients (88%) had a positive microbial culture; the most commonly isolated pathogen was Candida spp. The majority of patients survived for 30 days (n = 35 [88%]), and 33 (83%) and 32 (80%) patients survived for 90 days and one year, respectively. The number of surviving patients free from antimicrobial treatment at 90 days, six months, and one year was 19 (58%), 29 (88%), and 30 (94%). After a mean long term follow up of 69.9 ± 44.7 months, 20 patients were still alive. CONCLUSION: The NAIS bypass procedure offered reasonable survival and functional outcomes, and was associated with a high cure rate, defined as freedom from any antimicrobial treatment.

The Short-term Predictive Value of Vessel Wall Stiffness on Abdominal Aortic Aneurysm Growth.

BACKGROUND: Abdominal aortic aneurysm (AAA) surveillance programs are currently based solely on AAA diameter. The diameter criterion alone, however, seems inadequate as small AAAs comprise 5-10 % of ruptured AAAs as well as some large AAAs never rupture. Aneurysm wall stiffness has been suggested to predict rupture and growth; this study aimed to investigate the prognostic value of AAA vessel wall stiffness for growth on prospectively collected data. METHODS: Analysis was based on data from a randomised, placebo-controlled, multicentre trial investigating mast-cell-inhibitors to halt aneurysm growth (the AORTA trial). Systolic and diastolic AAA diameter was determined in 326 patients using electrocardiogram-gated ultrasound (US). Stiffness was calculated at baseline and after 1 year. RESULTS: Maximum AAA diameter increased from 44.1 mm to 46.5 mm during the study period. Aneurysm growth after 1 year was not predicted by baseline stiffness (-0.003 mm/U; 95 % CI: -0.007 to 0.001 mm/U; P = 0.15). Throughout the study period, stiffness remained unchanged (8.3 U; 95 % CI: -2.5 to 19.1 U; P = 0.13) and without significant correlation to aneurysm growth (R: 0.053; P = 0.38). CONCLUSIONS: Following a rigorous US protocol, this study could not confirm AAA vessel wall stiffness as a predictor of aneurysm growth in a 1-year follow-up design. The need for new and subtle methods to complement diameter for improved AAA risk assessment is warranted.

Sex differences and temporal trends in aortic dissection: a population-based study of incidence, treatment strategies, and outcome in Swedish patients during 15 years.

AIMS: As large population-based studies of aortic dissection are lacking, the incidence numbers and knowledge about time-trends and sex differences are uncertain. The objective was to describe incidence, temporal trends and outcome of aortic dissection with particular emphasis on sex differences. METHODS AND RESULTS: During the study period 2002-2016, 8057 patients in Sweden were diagnosed with aortic dissection, identified from the National Patient Register and the Cause of Death Register. A total of 5757 (71%) patients were hospitalized, whereas 2300 (29%) patients were deceased without concurrent hospital stay. The annual incidence was 7.2 per 100 000 (9.1 in men and 5.4 in women), decreasing over time in men (P = 0.005). Mean age in the hospitalized patients was 68 years (SD 13), 2080 (36%) were women. Within the first 14 days after onset, 1807 patients (32%) underwent surgical repair. The proportion of surgically treated increased from the 5-year period 2002-2006 to 2012-2016 [27% vs. 35%, odds ratio (OR) 1.61, 95% confidence interval (CI) 1.39-1.86; P < 0.001]. In hospitalized patients, 30-day mortality decreased between the same periods (26% vs. 21%, OR 0.68, 95% CI 0.59-0.80; P < 0.001). Long-term mortality decreased as well (hazard ratio 0.74, 95% CI 0.67-0.82; P < 0.001). Women had higher 30-day mortality than men after acute repair, a sex difference that remained after age adjustment (17% vs. 12%, OR 1.38, 95% CI 1.04-1.82; P = 0.006). CONCLUSION: This population-based study detected a higher incidence of aortic dissection than prior reports, but a decreasing incidence in men. Surgical therapy was increasingly used and with more favourable outcome but was less frequently offered to elderly patients. The sustained sex differences regarding both incidence and outcome require further attention.

Long-term Prognosis After Elective Abdominal Aortic Aneurysm Repair is Poor in Women and Men: The Challenges Remain.

OBJECTIVE: To evaluate the impact of changes in elective Abdominal Aortic Aneurysm (AAA) management on life-expectancy of AAA patients. BACKGROUND: Over the past decades AAA repair underwent substantial changes, that is, the introduction of EVAR and implementation of intensified cardiovascular risk management. The question rises to what extent these changes improved longevity of AAA patients. METHODS: National evaluation including all 12.907 (82.7% male) patients who underwent elective AAA repair between 2001 and 2015 in Sweden. The impact of changes in AAA management was established by a time-resolved analysis based on 3 timeframes: open repair dominated period (2001-2004, n = 2483), transition period (2005-2011, n = 6230), and EVAR-first strategy period (2012-2015, n = 4194). Relative survival was used to quantify AAA-associated mortality, and to adjust for changes in life-expectancy. RESULTS: Relative survival of electively treated AAA patients was stable and persistently compromised [4-year relative survival and 95% confidence interval: 0.87 (0.85-0.89), 0.87 (0.86-0.88), 0.89 (0.86-0.91) for the 3 periods, respectively]. Particularly alarming is the severely compromised survival of female patients (4-year relative survival females 0.78, 0.80, 0.70 vs males 0.89, 0.89, 0.91, respectively). Cardiovascular mortality remained the main cause of death (51.0%, 47.2%, 47.9%) and the proportion cardiovascular disease over non-cardiovascular disease death was stable over time. CONCLUSIONS: Changes in elective AAA management reduced short-term mortality, but failed to improve the profound long-term survival disadvantage of AAA patients. The persistent high (cardiovascular) mortality calls for further intensification of cardiovascular risk management, and a critical appraisal of the basis for the excess mortality of AAA patients.

Risk factors in 50-year-old men predicting development of abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a potentially lethal condition associated with several well-known risk factors including age, smoking, and male sex. The aim of this study was to identify risk factors predicting future development of AAA, which could influence future prevention strategies. METHODS: This study collected the data sets of the Westmannia Cardiovascular Risk Factors Study (WICTORY) from 1990 to 1999 and combined them with cases of individuals who have undergone ultrasound examination of the infrarenal aortic diameter as part of the Västmanland County's ongoing AAA screening program that commenced in 2007 or for other purposes. The study analyzed 5817 men aged 50 years at the time they participated in WICTORY and who underwent an ultrasound examination of the infrarenal aorta on average 15 years later. RESULTS: The prevalence of AAA in our study was 2.6%. Age, smoking status, angina pectoris treatment, prior myocardial infarction, blood pressure treatment, body mass index, waist circumference, systolic blood pressure, heart rate, and total cholesterol level were found to be associated with the development of AAA later in life in the univariate analysis. In the multivariate analysis, current smokers at age 50 years had 11 times higher risk for later development of AAA (hazard ratio [HR], 11.178; confidence interval [CI], 6.277-19.908; P < .001). Former smokers did not suffer a similar risk of AAA development. Elevated total cholesterol concentration at baseline was associated with later AAA development (HR, 1.275; CI, 1.119-1.451; P < .001), as were increasing age (HR, 1.702; CI, 1.153-2.512; P = .007) and waist circumference (HR, 1.019; CI, 1.002-1.037; P = .031). CONCLUSIONS: Both the well-known and the somewhat less established possible predictors for future development of AAA identified in this study can support improvement of strategic preventive measures toward specific risk groups and thereby possibly reduce the risk for development of AAA later in life or at least increase the possibility of an early diagnosis in patients with intact AAA.

Systematic Review and Meta-Analysis of Health Related Quality of Life and Reported Experiences in Patients With Abdominal Aortic Aneurysm Under Ultrasound Surveillance.

OBJECTIVE: Most screening and opportunistically detected abdominal aortic aneurysms (AAA) are small and kept under surveillance for several years before preventive surgery. Living with the diagnosis of an AAA may have an influence on the patient's life. Thus, it is important to study patients' experiences so that the screening process and follow up care are adapted to the patient's needs. The aim was to review systematically review the current knowledge of the effect on health related quality of life (HRQoL) and patients' experiences of living with an AAA while under surveillance. METHODS: A systematic literature review of quantitative and qualitative studies, which were quality assessed according to the GRADE system, was carried out. Pubmed, Cochrane, Embase, CINAHL, PsycINFO, and MEDLINE were searched. Narrative synthesis and meta-analysis were performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: Synthesis and meta-analyses of studies based on the Short Form-36 demonstrated that patients with an AAA consistently rated their general health (GH) lower than controls and conveyed no significant negative impact for patients with an AAA when assessed at follow up and compared with pre-screening. Synthesis and meta-analyses of HRQoL estimates encompassing mental health, anxiety, and depression demonstrated no significant differences for patients with AAA compared with controls, or within the AAA group. Qualitative studies revealed that patients with an AAA felt safe being under surveillance, and receiving a diagnosis of AAA set thoughts and feelings in motion regarding health, ageing, and mortality. Patients' lack of knowledge about the disease, its progression, and future planning can cause insecurity and worries. CONCLUSION: The current evidence does not support a negative impact on HRQoL from being under surveillance for an AAA. Qualitative data indicate that adequate patient information and professional care have the potential to reduce unnecessary worries and concerns in patients with an AAA.