Trends in Lower Extremity Artery Disease Repair Incidence, Comorbidity, and Mortality: A Danish Nationwide Cohort Study, 1996-2018.

Background: The prevalence of occlusive lower extremity artery disease (LEAD) is rising worldwide while European epidemiology data are scarce. We report incidence and mortality of LEAD repair in Denmark from 1996 through 2018, stratified on open aorto-iliac, open peripheral, and endovascular repair. Methods: A nationwide cohort study of prospective data from population-based Danish registers covering 1996 to 2018. Comorbidity was assessed by Charlson's Comorbidity Index (CCI). Incidence rate (IR) ratios and mortality rate ratios (MRR) were estimated by multivariable Poisson and Cox regression, respectively. Results: We identified 41,438 unique patients undergoing 46,236 incident first-time LEAD repairs by either aorto-iliac- (n=5213), peripheral surgery (n=18,665) or percutaneous transluminal angioplasty (PTA, n=22,358). From 1996 to 2018, the age- and sex-standardized IR for primary revascularization declined from 71.8 to 50.2 per 100,000 person-years (IRR, 0.70; 95% CI, 0.66-0.75). Following a 2.5-fold IR increase of PTA from 1996 to 2010, all three repair techniques showed a declining trend after 2010. The declining IR was driven by decreasing LEAD repair due to claudication, and by persons aged below 80 years, while the IR increased in persons aged above 80 years (p interaction<0.001). LEAD repair was more frequent in men (IRRfemale vs male, 0.78; 95% CI, 0.77-0.80), which was consistent over calendar time (p interaction=0.41). Crude mortality decreased following open/surgical repair, and increased following PTA, but all three techniques trended towards lower adjusted mortality comparing the start and the end of the study period (MRRaorto-iliac, 0.71; 95% CI, 0.54-0.93 vs MRRperipheral, 0.76; 95% CI, 0.69-0.83 vs MRRPTA, 0.96; 95% CI, 0.86-1.07). Increasing age and CCI, male sex, smoking, and care dependency associated with increased mortality. Conclusion: The incidence rate of LEAD repair decreased in Denmark from 1996 to 2018, especially in persons younger than 80 years, and primarily due to reduced revascularization for claudication. Adjusted mortality rates decreased following open surgery, but seemed unaltered following PTA.

Trends in Abdominal Aortic Aneurysm Repair Incidence, Comorbidity, Treatment, and Mortality: A Danish Nationwide Cohort Study, 1996-2018.

Background: Significant changes in Western populations' abdominal aortic aneurysm (AAA) epidemiology have been reported following the introduction of screening, endovascular AAA repair, and reduced tobacco consumption. We report incidence and mortality of AAA repair in Denmark from 1996 to 2018, where AAA screening was not implemented. Methods: Nationwide cohort study of prospective data from population-based Danish registries covering 1996 to 2018. We identified 15,395 patients undergoing first-time AAA repair using the Danish Vascular Registry. Comorbidity was assessed by Charlson's Comorbidity Index (CCI). Incidence rate (IR) ratios and mortality rate ratios (MRR) were estimated by multivariable Poisson and Cox regression, respectively. Results: Overall AAA repair IR decreased by 24% from 1996 through 2018, mainly reflecting a 53% IR reduction in ruptured AAA repairs in men. Overall, the IR decreased 52-63% in age groups below 70 years and increased 81% among octogenarians. The proportion of intact AAAs repaired endovascularly increased from 2% in 1996-1999 to 42% in 2015-2018. For both ruptured and intact AAAs the CCI score increased by 0.9% annually independently of age and sex. The adjusted five-year MRR in 2016-2018 vs.1996-2000 was 0.46 (95% confidence interval (CI): 0.39-0.54) following ruptured and 0.51 (95% CI: 0.44-0.59) following intact AAA repair. Conclusion: In Denmark, overall AAA repair incidence decreased between 1996 and 2018, primarily reflecting a reduction among males and a shift to an older population requiring intervention. These trends mirror changes in tobacco consumption in Denmark. Regardless of age and comorbidity, AAA repair mortality decreased markedly during the study period.

Adherence and Persistence to Antiplatelet Therapy in Lower Extremity Peripheral Arterial Disease: A Danish Population Based Cohort Study.

OBJECTIVE: Adherence to antiplatelet therapy is recommended but unexplored in patients with symptomatic lower extremity peripheral arterial disease (PAD). Therefore, this study aimed to determine adherence and persistence to antiplatelet therapy in patients with PAD, defined as intermittent claudication and chronic limb threatening ischaemia. DESIGN: Population based nationwide cohort study. METHODS: This study included all Danish citizens aged ≥ 40 years with a first inpatient or outpatient diagnosis of symptomatic PAD between 2010 - 2017, and who had at least one prescription claim for aspirin and/or clopidogrel within 90 days after diagnosis. Adherence was determined by the proportion of days covered (PDC) during the first year after diagnosis. Persistence was defined as no treatment gap ≥ 30 days between prescription renewals over three year follow up. RESULTS: A total of 39 687 patients were eligible for inclusion, of whom 23 279 (58.7%) claimed a prescription for aspirin and/or clopidogrel within 90 days of diagnosis. Among these, 12 898 (55.4%) were prevalent users, while the remainder comprised new users who initiated the therapy after the index PAD diagnosis. The mean PDC was 74.5% (SD 35.0%) for prevalent users and 60.5% (SD 30.5%) for new users. Adherence increased with age and number of concomitant drugs. The overall one year cumulative incidence treatment discontinuation was 13.0% (95% CI 12.5 - 13.4%) overall, 17.2% (CI 16.6 - 17.9%) for prevalent users, and 7.9% (CI 7.4 - 8.4%) for new users. At three year follow up, the cumulative incidence of discontinuation was 31.5% (CI 30.9 - 32.2%) overall, 44.6% (CI 43.7 - 45.4%) for prevalent users, and 14.6% (CI 13.9 - 15.3) for new users. CONCLUSION: Less than 60% of patients with newly diagnosed symptomatic PAD claimed a prescription for antiplatelet therapy within 90 days of diagnosis, and both adherence and persistence were moderate during the first year after diagnosis. These findings underscore the importance of efforts to improve the initiation and continuation of antiplatelet therapy in patients with PAD.

Prehospital point-of-care ultrasound in ruptured abdominal aortic aneurysms-a retrospective cohort study.

BACKGROUND: Patients with ruptured abdominal aortic aneurysm (rAAA) require immediate vascular treatment to survive. The use of prehospital point-of-care ultrasound (POCUS) may support clinical assessment, correct diagnosis, appropriate triage and reduce system delay. The aim was to study the process of care and outcome in patients receiving prehospital POCUS versus patients not receiving prehospital POCUS in patients with rAAA, ruptured iliac aneurysm or impending aortic rupture. METHODS: We performed a retrospective cohort study in patients diagnosed with rAAA in the Central Denmark Region treated by a prehospital critical care physician from 1 January 2017 to 31 December 2021. Performance of prehospital POCUS was extracted from the prehospital electronic health records. System delay was defined as the time from the emergency phone call to the emergency medical service dispatch centre until the start of surgery. Data on patients primary hospital admission to a centre with/without vascular treatment expertise, treatments and complications including death were extracted from electronic health records. RESULTS: We included 169 patients; prehospital POCUS was performed in 124 patients (73%). Emergency surgical treatment was performed in 71 patients. The overall survival in the POCUS group was 39% versus 16% in the NO POCUS group (hazard ratio (HR) (95% 0.60, 95% CI: 0.41-0.89, p = .011). In the POCUS group 99/124 (80%) were directly admitted to a vascular surgical centre versus 25/45 (56%) in the NO POCUS, RD 24% (95% CI: 8-40)), (p = .002). In the POCUS group, system delay was a median of 142 minutes (interquartile range (IQR) 121-189) and a median of 232 minutes (IQR 166-305) in the NO POCUS group (p = .006). In a multivariable analysis incorporating age, sex, previously known rAAA, and typical clinical symptoms of rAAA, the HR for death was 0.57, 95% CI 0.38-0.86 (p = .008) favouring prehospital POCUS. CONCLUSIONS: Prehospital POCUS was associated with reduced time to treatment, higher chance of operability and significantly higher 30-day survival in patients with rAAA, ruptured iliac aneurysm or impending rupture of an AAA in this retrospective study. Residual confounding cannot be excluded. This study supports the clinical relevance of prehospital POCUS of the abdominal aorta.

3-D Contrast-Enhanced Fusion Ultrasound for Accurate Volume Assessment of Vessel Lumen and Plaque in Carotid Artery Disease as Compared With Computed Tomography Angiography.

OBJECTIVE: Three-dimensional contrast-enhanced fusion ultrasound (CEFUS) of atherosclerotic carotid arteries provides spatial visualization of the vessel lumen, creating a lumenography. As in 3-D computed tomography angiography (CTA), 3-D CEFUS outlines the contrast-filled lumen. Plaque and vessel contours are distinguished in 3-D CEFUS, allowing plaque volume quantification as a valid estimate of carotid plaque burden. Three-dimensional CEFUS is unproven in intermodality studies, vindicating the assessment of 3-D CEFUS applicability and comparing 3-D CEFUS and 3-D CTA lumenography as a proof-of-concept study. METHODS: Using an ultrasound system with magnetic tracking, a linear array transducer and SonoVue contrast agent, 3-D CEFUS acquisitions were generated by spatial stitching of serial 2-D images. From 3-D CEFUS and 3-D CTA imaging, the atherosclerotic carotid arteries were reconstructed with lumenography in an offline software program for lumen and plaque volume quantification. Bland-Altman analysis was used for inter-image modality agreement. RESULTS: The study included 39 carotid arteries. Mean lumen and plaque volume in 3-D CEFUS were 0.63 cm3 (standard deviation [SD]: 0.26) and 0.62 cm3 (SD: 0.26), respectively. Lumen volume differences between 3-D CEFUS and 3-D CTA were non-significant, with a mean difference of 0.01 cm3 (SD: 0.02, p = 0.26) and limits of agreement (LoA) range of ±0.11 cm3. Mean plaque volume difference was -0.12 cm3 (SD: 0.19, p = 0.006) with a LoA range of ±0.39 cm3. CONCLUSION: There was strong agreement in lumenography between 3-D CEFUS and 3-D CTA. The interimage modality difference in plaque volumes was substantial because of challenging vessel wall definition in 3-D CTA. Three-dimensional CEFUS is viable in quantifying carotid plaque volume burden and can potentially monitor plaque development over time.

Proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque types.

Cardiovascular disease is the leading cause of death, with atherosclerosis the major underlying cause. While often asymptomatic for decades, atherosclerotic plaque destabilization and rupture can arise suddenly and cause acute arterial occlusion or peripheral embolization resulting in myocardial infarction, stroke and lower limb ischaemia. As extracellular matrix (ECM) remodelling is associated with plaque instability, we hypothesized that the ECM composition would differ between plaques. We analyzed atherosclerotic plaques obtained from 21 patients who underwent carotid surgery following recent symptomatic carotid artery stenosis. Plaques were solubilized using a new efficient, single-step approach. Solubilized proteins were digested to peptides, and analyzed by liquid chromatography-mass spectrometry using data-independent acquisition. Identification and quantification of 4498 plaque proteins was achieved, including 354 ECM proteins, with unprecedented coverage and high reproducibility. Multidimensional scaling analysis and hierarchical clustering indicate two distinct clusters, which correlate with macroscopic plaque morphology (soft/unstable versus hard/stable), ultrasound classification (echolucent versus echogenic) and the presence of hemorrhage/ulceration. We identified 714 proteins with differential abundances between these groups. Soft/unstable plaques were enriched in proteins involved in inflammation, ECM remodelling, and protein degradation (e.g. matrix metalloproteinases, cathepsins). In contrast, hard/stable plaques contained higher levels of ECM structural proteins (e.g. collagens, versican, nidogens, biglycan, lumican, proteoglycan 4, mineralization proteins). These data indicate that a single-step proteomics method can provide unique mechanistic insights into ECM remodelling and inflammatory mechanisms within plaques that correlate with clinical parameters, and help rationalize plaque destabilization. These data also provide an approach towards identifying biomarkers for individualized risk profiling of atherosclerosis.

External Validation of the OAC3-PAD Bleeding Score in a Nationwide Population of Patients Undergoing Invasive Treatment for Peripheral Arterial Disease.

OBJECTIVE: The OAC3-PAD score was developed to predict bleeding risk in patients with lower extremity peripheral arterial disease (PAD), but its performance in concomitant international cohorts is largely unknown. This study aimed to validate the OAC3-PAD score in an unselected nationwide population of patients undergoing invasive treatment for symptomatic PAD. METHODS: This was a nationwide cohort study including all patients who underwent a first revascularisation procedure or major amputation for symptomatic PAD in Denmark from 2000 - 2021. The study population was stratified based on OAC3-PAD score, and the one year risk of major bleeding was assessed, accounting for the competing risk of death. The score performance was evaluated using calibration plots, C statistic, Brier score, and the index of prediction accuracy (IPA). RESULTS: A total of 52 016 patients were included (mean age 71 years, 43.8% female). The one year risk of major bleeding increased with higher OAC3-PAD score, ranging from 1.6% (95% confidence interval [CI] 1.4 - 1.8%) to 2.3% (95% CI 2.0 - 2.5%), 3.5% (95% CI 3.2 - 3.8%), and 5.2% (95% CI 4.8 - 5.6%) for patients with low, low moderate, moderate high, and high score, respectively. Using patients with low risk as reference, the OAC3-PAD score effectively categorised patients, demonstrating statistically significant differences in bleeding risk across strata. However, the score showed modest discriminative performance, with a C statistic of 65% (95% CI 63 - 66%) and a Brier score of 2.6% (95% CI 2.5 - 2.7%). Nevertheless, it performed significantly better than the null model, as indicated by an IPA of 3.1%. CONCLUSION: Among patients who underwent invasive treatment for symptomatic PAD in routine care, the OAC3-PAD score was associated with greater risk of major bleeding with increasing score level. However, its discriminatory ability was modest, and the clinical utility remains to be determined.

Danish Nationwide Study on Surgical Treatment of Infective Native Abdominal Aortic Aneurysms.

OBJECTIVE: This study aimed to describe surgical trends, survival, and infection related complications (IRC) in a Danish cohort of patients with infective native aortic aneurysms (INAAs). METHODS: A retrospective nationwide cohort study including all patients in Denmark who were surgically treated for abdominal INAA between 2000 and 2020 was conducted. Patients were identified through the Danish vascular registry, Karbase, which is a database registering all patients treated with vascular surgery in Denmark. Subsequent data on clinical presentation, treatment, all cause mortality, and complications were obtained from the electronic patient charts. RESULTS: Seventy-five patients were included in the study, of whom 60 (80%) were male, with a median age of 69 (IQR 64, 75) years. Open surgical repair (OSR) was performed in 54 (72%) patients and endovascular aortic repair (EVAR) in 21 (28%). Median follow up was 52 (IQR 32, 103) months. Open repair was consistently the most frequent treatment modality throughout the study period, but EVAR became more frequent over time. The 30 day survival of the total cohort was 97% (94 - 100%). Kaplan-Meier survival estimates for the cohort were 92% (95% CI 85 - 98%), 80% (95% CI 71 - 91%), 63% (95% CI 52 - 78%), and 48% (95% CI 35 - 66%) at one, three, five and 10 years, respectively. Patients treated by EVAR had comparable long term survival to patients treated by OSR, with a hazard ratio of 0.35 (95% CI 0.10 - 1.22), but was associated with better short term survival up to five years. The most common cause of death was sepsis. Five (9%) OSR patients had IRC compared with one (5%) EVAR patient. CONCLUSION: In this nationwide study of patients treated for abdominal INAA, an increasing number of patients were surgically treated during the study period. Patients treated by EVAR demonstrated long term survival comparable to OSR. The incidence of post-operative IRC was low. These results should be interpreted with caution and prospective registries are needed.

Abdominal aortic aneurysms volume growth patterns with three-dimensional ultrasound.

BACKGROUND: Three-dimensional ultrasound (3D-US) and computed tomography (CT) have proven abdominal aortic aneurysm (AAA) volume a more sensitive measure of growth than diameter. This proof-of-concept study aimed to investigate the clinical applicability of two-dimensional ultrasound and 3D-US for AAA diameter and volume growth pattern evaluation. METHODS: AAA patients with at least three follow-ups within a minimum of 24 months were included prospectively and consecutively from the COpenhagen Aneurysms CoHort (COACH). Individual diameter and volume growth rates were categorized as rapid, slow, or no growth (>6.0, 3.8-6.0, and ≤3.7 mm/year for diameter. >17.4, 8.8-17.3, and ≤8.7 mL/year for volume). Similarly, diameter and volume growth patterns were categorized as as linear, exponential, staccato, and indeterminate growth, based from individual regressions. RESULTS: Thirty patients were included, of which 19 (63%) had no diameter growth, 10 (33%) had slow growth, and one (3%) had rapid growth. Regarding volume, 11 (37%) patients had no growth, 12 (40%) had slow growth, and seven (23%) had rapid growth. Growth patterns according to diameter showed that 18 (60%) patients had linear growth, none had staccato or exponential growth. Twelve (40%) were indeterminate. Volume growth patterns found 19 (63%) patients with linear growth, 3 (10%) with staccato, and none with exponential growth. Eight (27%) were indeterminate. CONCLUSIONS: Analysis of AAA volume growth patterns is a practical and safe modality that seems more sensitive at detecting growth patterns than AAA diameter. Volume also detects more AAA growth than diameter.

Antiplatelet Therapy in Patients With Abdominal Aortic Aneurysm Without Symptomatic Atherosclerotic Disease.

Importance: Patients with abdominal aortic aneurysm have a high risk of ischemic events associated with concomitant atherosclerotic cardiovascular disease, and current clinical practice guidelines recommend antiplatelet therapy to mitigate this risk. However, in patients with aneurysms without symptomatic atherosclerosis, the benefit of antiplatelet therapy has been sparsely investigated. Objective: To estimate the effect of antiplatelets on the risk of ischemic events and bleeding in individuals with abdominal aneurysms with no symptomatic atherosclerotic vascular disease. Design, Setting, and Participants: A comparative effectiveness research study using a target trial emulation framework was performed. Population-based, cross-linked observational data from Danish national health registries containing comprehensive, individual-level information on all Danish citizens were used to evaluate patients who were antiplatelet-naive and diagnosed with abdominal aortic aneurysms, with no record of symptomatic atherosclerotic vascular disease, from January 1, 2010, through August 21, 2021. Exposure: Prescription filled for aspirin or clopidogrel. Main Outcomes and Measures: Risk of ischemic events (myocardial infarction and/or ischemic stroke) and risk of major bleeding. For target trial emulation, trials were emulated as sequential, contingent on patient eligibility at the time of inclusion, and were evaluated by means of pooled logistic regression models to estimate the intention-to-treat and as-treated effects, expressed as hazard ratio (HR) and event-free survival. Results: A total of 6344 patients (65.2% men; age, 72 [IQR, 64-78] years) provided 131 047 trial cases; 3363 of these cases involved initiation of antiplatelet therapy and 127 684 did not. A total of 182 ischemic events occurred among initiators and 5602 ischemic events occurred among noninitiators, corresponding to an intention-to-treat HR of 0.91 (95% CI, 0.73-1.17) and an estimated absolute event-free survival difference of -0.6% (95% CI, -1.7% to 0.5%). After censoring nonadherent person-time, the treatment HR was 0.90 (95% CI, 0.68-1.20), with similar risk difference. For bleeding, the intention-to-treat HR was 1.26 (95% CI, 0.97-1.58) and the event-free survival difference was 1.0%. The treatment HR was 1.21 (95% CI, 0.82-1.72); the risk difference was similar. Conclusions and Relevance: In this study, no evidence of effectiveness of antiplatelet therapy to lower the risk of ischemic events and a trend toward higher bleeding risk was noted. The observed differences between the treatment groups were minimal, suggesting limited clinical relevance of antiplatelet treatment.

Biofilm formation on endovascular aneurysm repair (EVAR) grafts-a proof of concept in vitro model.

OBJECTIVES: An endovascular aneurysm repair (EVAR) graft is a catheter-implanted vascular prosthesis and is the preferred treatment for patients with aortic aneurysm. If an EVAR graft becomes the focus of infection, the treatment possibilities are limited because it is technically difficult to remove the graft to obtain source control. This study examines whether Pseudomonas aeruginosa and Staphylococcus aureus form biofilm on EVAR prostheses. METHODS: EVAR graft sections were exposed to bacteria at 102 or 108 colony forming units (CFU)/mL in lysogeny broth and Krebs-Ringer at 37°C, bacterial biofilm formation was evaluated by scanning electron microscopy and counting CFU on the graft sections after antibiotic exposure at × 10 minimal inhibitory concentration. Bacteria were tested for tolerance to benzylpenicillin, tobramycin, and ciprofloxacin. RESULTS: Bacterial exposure for 15 minutes established biofilms on all prosthesis fragments (6/6 replicates). After 4 hours, bacteria were firmly attached to the EVAR prostheses and resisted washing. After 18-24 hours, the median CFU/g of EVAR graft reached 5.2 × 108 (1.15 × 108-1.1 × 109) for S. aureus and 9.1 × 107 (3.5 × 107-6.25 × 108) for P. aeruginosa. Scanning electron microscopy showed bacterial attachment to the graft pieces. There was a time-dependent development of tolerance with approximately 20 (tobramycin), 560 (benzylpenicillin), and 600 (ciprofloxacin) times more S. aureus surviving antibiotic exposure in 24- compared with 0-hour-old biofilm. Five (tobramycin) and 170 times (ciprofloxacin) more P. aeruginosa survived antibiotic exposure in 24- compared with 0-hour-old biofilms. DISCUSSION: Our results show that bacteria can rapidly adhere to and subsequently form antibiotic-tolerant biofilms on EVAR graft material in concentrations equivalent to levels seen in transient bacteraemia in vivo. Potentially, the system can be used for identifying optimal treatment combinations for infected EVAR prosthesis.

Epidemiological Trends and Projections of Incidence, Prevalence, and Disease Related Mortality Associated With Peripheral Arterial Disease: Observations Using Nationwide Danish Data.

OBJECTIVE: Peripheral arterial disease (PAD) trends remain unclear because contemporary data are sparse and conflicting. This nationwide cohort study quantified changes in PAD incidence, prevalence, and all cause mortality, and projected prevalence development through to 2040. METHODS: Population based registries covering the entire Danish population aged ≥ 40 years from 2000 to 2018 were linked to assess trends in PAD incidence, prevalence, and all cause mortality, overall and by sex and age groups. Based on observed trends in incidence and mortality, and estimated future annual age distribution and population mortality, the PAD prevalence through to 2040 was projected. RESULTS: The Danish population aged 40 - 99 years in 2000 - 2018 included 4 811 281 individuals, among whom 145 870 incident PAD diagnoses were identified. The age and sex standardised PAD incidence decreased from 2.26 per 1 000 person years in 2000 to 1.65 in 2018 (incidence RR 0.74, 95% CI 0.72 - 0.77). The incidence was approximately 20% higher in men than women but declined similarly over time. Concurrently, PAD prevalence in the Danish adult population increased from 1.3% to 1.6% (prevalence ratio 1.28, 95% CI 1.26 - 1.30). Among patients aged ≥ 80 years, the prevalence reached 5.7% in women and 7.9% in men. The age and sex standardised annual mortality among patients with PAD decreased from 9.8% in 2000 to 7.2% in 2018 (mortality ratio 0.75, 95% CI 0.72 - 0.78). Projections of PAD prevalence demonstrated that the rising PAD prevalence will continue until around 2030, followed by a decline towards 2040. Among individuals aged ≥ 80 years, the prevalence was projected to plateau at 8.9% for men and 6.2% for women before declining. CONCLUSION: Within an unselected nationwide population, the incidence and all cause mortality of PAD have declined over the last two decades. Concurrently, prevalence increased and is projected to increase further over the coming decade, emphasising the growing burden of this common atherosclerotic disease in ageing populations.

Editor's Choice - Sex Related Differences in Indication and Procedural Outcomes of Carotid interventions in VASCUNET.

OBJECTIVE: It has been suggested that peri-operative complications after carotid surgery may be higher in women than in men. This assumption may affect the treatment patterns, and it is thus possible that carotid endarterectomy (CEA) is provided to women less often. The aim of the current VASCUNET study was to determine sex related differences in operative risk in routine clinical practice among non-selected patients undergoing carotid revascularisation. METHODS: Data on CEA and carotid artery stenting (CAS) from 14 vascular registries were collected and amalgamated. Comprehensive data were available for 223 626 carotid artery procedures; these were analysed overall and by country. The primary outcome was any stroke and or death within 30 days of carotid revascularisation. Secondary outcomes were stroke, death, or any major cardiac event or haemorrhage leading to re-operation. RESULTS: Of the procedures, 34.8% were done in women. The proportion of CEA for asymptomatic stenosis compared with symptomatic stenosis was significantly higher among women than men (38.4% vs. 36.9%, p < .001). The proportion of octogenarians was higher among women than men who underwent CEA in both asymptomatic (21.2% vs. 19.9%) and symptomatic patients (24.3% vs. 21.4%). In the unadjusted analysis of symptomatic and asymptomatic patients, there were no significant differences between men and women in the rate of post-operative combined stroke and or death, any major cardiac event, or combined death, stroke, and any major cardiac event after CEA. Also, after stenting for asymptomatic or symptomatic carotid stenosis, there were no significant differences between men and women in the rate of post-operative complications. In adjusted analyses, sex was not significantly associated with any of the end points. Higher age and CAS vs. CEA were independently associated with all four end points. CONCLUSION: This study confirmed that, in a large registry among non-selected patients, no significant sex related differences were found in peri-operative complication rates after interventions for carotid stenosis.

Abdominal Aortic Aneurysm Repair in Patients with Concomitant Cancer: A Literature Review.

OBJECTIVES: Abdominal aortic aneurysmal (AAA) repair in patients with concomitant cancer is controversial due to increased comorbidity and reduced life expectancy in this specific patient group. This literature review aims to investigate the evidence supporting one treatment modality over another (endovascular aortic repair (EVAR) or open repair (OR)), as well as treatment strategy (staged AAA-, cancer first or simultaneous procedures) in patients with AAA and concomitant cancer. METHODS: Literature review, including studies published from 2000 to 2021 on surgical treatment in patients with AAA and concomitant cancer and related outcomes (30-day morbidity/complications as well as 30-day and 3-year mortality). RESULTS: 24 studies comprising 560 patients undergoing surgical treatment of AAA and concomitant cancer were included. Of these, 220 cases were treated with EVAR and 340 with OR. Simultaneous procedures were performed in 190 cases, 370 received staged procedures. The 30-day mortality for EVAR versus OR was 1% and 8%, corresponding to a relative risk (RR) of 0.11 (95% CI: 0.03-0.46, p = 0.002). No difference in mortality was observed between staged versus simultaneous procedure nor between AAA-first versus cancer-first strategy, RR 0.59 (95% CI: 0.29-1.1, p = 0.13) and 0.88 (95% CI 0.34-2.31, p = 0.80), respectively. Overall, 3-year mortality was 21% for EVAR and 39% for OR from 2000-2021, while the mortality up to 3 years after EVAR within recent years (2015-2021) was 16%. CONCLUSION: This review supports EVAR treatment as first choice if suitable. No consensus was established on treating either the aneurysm or the cancer first or simultaneously. Long-term mortality after EVAR was comparable to non-cancer patients within recent years.

Artificial Intelligence Outperforms Kaplan-Meier Analyses Estimating Survival after Elective Treatment of Abdominal Aortic Aneurysms.

OBJECTIVE: Long term differences in survival after elective repair of abdominal aortic aneurysms (AAAs) between open surgical repair (OSR) and endovascular aneurysm repair (EVAR) are unclear, and hitherto artificial intelligence has not been used for this purpose. The aim was to compare the precision of survival estimates between the Kaplan-Meier (KM) method and the artificial intelligence derived method Neural Multi-Task Logistic Regression (N-MTLR), and to compare survival estimates as a function of patient age and time since surgery between OSR and EVAR using N-MTLR. METHODS: All AAAs between 2003 and 2018 in Denmark were identified in the Danish vascular registry. Survival was estimated using the KM and N-MTLR methods, and prediction performance was estimated with the Brier score. RESULTS: 7 912 patients were included in the study, n = 6 569 (83%) men, median age 72 years (range 35 - 92), with a median follow-up time of 45.7 months (range 0 - 120). The two treatment cohorts, OSR n = 5 495 (69%), and EVAR n = 2 417 (31%), differed significantly in patient characteristics. The Brier score for KM increased from 0.044 to 0.244, and for N-MTLR from 0.044 to 0.206, from 90 days to 10 years. The N-MTLR method was more accurate than KM from 90 days to 10 years after surgery, p ≤ .025. N-MTLR demonstrated significant increased probability for survival for OSR in patients aged 58 - 76 years at five years, and 65 - 73 at 10 years after surgery, and the opposite was found for the benefit of EVAR in patients aged 72 - 85 years at one year, 85 - 90 years at five years, and for 85 - 90 year olds at 10 years after surgery. CONCLUSION: N-MTLR outperforms KM for the entire post-operative follow-up time. This N-MTLR model has the potential to render more precise patient specific survival estimates and establish survival differences between subgroups of patients that KM is unable to detect, demonstrated here for different age groups.

Stroke and Myocardial Infarction in Patients with Abdominal Aortic Aneurysm and New-Onset Atrial Fibrillation.

OBJECTIVE: We investigated the association between new-onset atrial fibrillation (AF) and risk of stroke and myocardial infarction (MI) in patients with abdominal aortic aneurysmal (AAA) disease. METHODS: Observational crossover study using Danish nationwide data, including patients with AAA and incident AF between 1997 and 2018. We estimated the 1-year risk of stroke and MI and the within-individual odds ratios (ORs) of ischemic events before and after an AF diagnosis, stratified by year of AF diagnosis (1997-2010 and 2011-2018), and supplemented with analyses on changes in use of antithrombotic therapy. RESULTS: A total of 3,035 AAA patients were included: 1,040 diagnosed during 1997 to 2010, and 1,995 during 2011 to 2018 (22.2% females, median age 78 years; median CHA2DS2-VASc score 4; interquartile range: 3-5). One-year risk of ischemic events after AF was 5.9% (confidence interval [CI] 95%: 4.6-7.5%) and 4.5% (CI 95%: 3.7-5.5%) for stroke and 5.4% (CI 95%: 4.2-6.9%) and 4.0% (CI 95%: 3.2-4.9%) for MI during 1997 to 2010 and 2011 to 2018, respectively. The OR of ischemic stroke before and after incident AF was 2.8 (CI 95%: 1.6-5.2) during 1997 to 2010; and 2.4 (CI 95%: 1.5 to 3.9) during 2011 to 2018, and 3.5 (CI 95%: 1.7-7.5) and 1.5 (CI 95%: 0.9-2.4) for MI. One-year proportion of prescription claims for oral anticoagulants after AF changed from 66.1% in 1997 to 2010 to 82.6% in 2011 to 2018, while antiplatelet prescription claims changed from 80.8 to 60.9%. CONCLUSION: Cardiovascular prognosis has improved in patients with prevalent AAA disease and new-onset AF in concordance with optimization of antithrombotic therapy over time. A diagnosis of AF conferred residual risk of stroke and MI.

Anticoagulants and reduced thrombus load in abdominal aortic aneurysms assessed with three-dimensional contrast-enhanced ultrasound examination.

OBJECTIVE: The relationship between intraluminal thrombus (ILT) and abdominal aortic aneurysm (AAA) growth and rupture risk remains ambiguous. Studies have shown a limited effect of antiplatelet therapy on ILT size, whereas the impact of anticoagulant therapy on ILT is unresolved. This study aims to evaluate an association between antithrombotic therapy and ILT size assessed with three-dimensional contrast-enhanced ultrasound (3D-CEUS) examination in a cohort of patients with AAA. METHODS: In a cross-sectional study, 309 patients with small AAAs were examined with 3D-CEUS. Patients were divided into three groups based on prescribed antithrombotic therapy: anticoagulant (n = 36), antiplatelet (n = 222), and no antithrombotic therapy (n = 51). Patient ILT size was calculated in volume and thickness and compared between the three groups. RESULTS: Patients on anticoagulants had a significantly lower estimated marginal mean ILT volume of 16 mL (standard error [SE], ±3.2) compared with 28 mL (SE, ±2.7) in the no antithrombotic group and 30 mL (SE, ±1.3) in the antiplatelet group when adjusting for AAA volume (P < .001) and comorbidities (P < .001). In addition, patients on anticoagulant therapy had significantly lower estimated marginal mean ILT thickness of 10 mm (SE, ±1.1) compared with 13 mm (SE, ±0.9) in the no antithrombotic group of and 13mm (SE, ±0.4) in the antiplatelet group when adjusting for AAA diameter (P = .03) and comorbidities (P = .035). CONCLUSIONS: A 3D-CEUS examination is applicable for ILT assessment and demonstrates that patients with AAA on anticoagulant therapy have lower ILT thickness and volume than patients with AAA on antiplatelet therapy and those without antithrombotic therapy. Causality between anticoagulants and ILT size, and extrapolation to AAA growth and rupture risk, is unknown and merits further investigations, to further nuance US-based AAA surveillance strategy.