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Despite the presence of only a few established risk factors, some patients will experience atherosclerotic events. Therefore, methods for improved risk stratification for atherosclerotic events are wanted. We aimed to detect changes in carotid artery atherosclerotic plaque volume and echogenicity over time in patients with an acute thromboembolic event and in patients with chronic atherosclerotic disease, both treated with statin, using a novel 3D ultrasound system.We included two cohorts of patients; 70 patients, naïve to statin treatment, admitted with acute, first-time myocardial infarction (aMI), and 69 patients who had been on statin treatment for a minimum of 6 months with chronic peripheral arterial disease (cPAD). 3D ultrasound examination was performed at baseline and after 3 and 12 months. Plaque volume was quantified in 3D ultrasound plaque acquisitions, and echogenicity was assessed using grayscale median (GSM) and normalized with adventitia as reference.The aMI group had darker plaques than the cPAD group at baseline (mean GSM: 60.98, standard deviation (SD): 24.09 vs. 71.75, SD: 21.55; P = 0.006), 3 months (63.64, SD: 20.47 vs. 73.44, SD: 20.46; P = 0.006) and at 12 months follow-up (59.25, SD: 18.07 vs. 71.02, SD: 22.31; P = 0.004). The differences were not significant after adjusting for traditional risk factors. Dividing both groups by the median GSM, the darkest half of the aMI group's had an increase in GSM mainly within the first 3 months (10.49, CI 95%: 2.45 to 18.53; P = 0.012) and hereafter remained unchanged at 12 months follow-up (-0.53, CI 95%: -7.28 to 6.22, P = 0.875). In the darkest cPAD group GSM also increased within 3 months (8.14, CI 95%: 1.85-14.32, P = 0.012) and hereafter stabilized till 12 months (-2.54, CI 95%: -9.62 to 4.53, P = 0.475). Plaque volume did not change in the aMI group from baseline (median: 55.41 mmEcholucent carotid plaque, assessed with the novel 3D matrix ultrasound system, had increasing GSM within 3 months period, indicating stabilization of the more vulnerable plaques in aMI and cPAD patients. Plaque volume decreased over 12 months follow-up in a long-term statin-treated patient with cPAD, but not during the first 12 months statin therapy in patients with aMI.

Three-dimensional ultrasound (US) of abdominal aortic aneurysms (AAAs) is limited by the field-of-view of the 3D-US transducer. To obtain an extended field-of-view (XFoV), two transducer navigation system-assisted US protocols have been developed: XFoV-2D and XFoV-3D. In this study, the XFoV US protocols were compared with the currently available 3D-US protocol with standard field-of-view (FoV-st) and the established gold standard, computed tomography angiography (CTA). A total of 65 patients with AAA were included, and AAA imaging was processed offline with prototype software. The novel XFoV-2D and XFoV-3D protocols allowed for assessment of full AAA volume in significantly more patients (45/65 [69%] and 43/65 [66%], respectively), compared with the current 3D-US standard, FoV-st (30/65 [46%] patients). The mean difference in AAA volume estimation between each XFoV US protocol and 3-D CTA differed significantly (XFoV-2D: 16.9 mL, XFoV-3D: 7.6 mL, p = 0.002), indicating that XFoV-3D agreed best with 3D-CTA. No significant difference was found in the variance of full AAA volume quantification between each XFoV US protocol and CTA (p = 0.49). It is concluded that the XFoV US protocols improved the generation of full AAA volumes compared with the currently available 3D-US technology, with AAA volume estimates comparable to CTA estimates.

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Background: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Previous lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking. Methods: The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD; rNCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan-Meier estimates, and Cox proportional hazards models were used to generate hazard ratios and associated CIs. Analyses were performed as intention-to-treat. Results: Among 6564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, previous LER, baseline ankle-brachial index P =0.0001), with benefit starting early (HR, 0.45 [95% CI, 0.24–0.85]; P =0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and intensive care unit stay, HR, 0.58 [95% CI, 0.40–0.83]; P =0.003) and regardless of LER type (surgical versus endovascular revascularization, P interaction=0.42) or clopidogrel use ( P interaction=0.59). Conclusions: After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.

Objective To examine whether a cardiac rehabilitation programme in a community based setting for patients with intermittent claudication (IC) affects walking ability, quality of life, and changes in health behaviour. The trial investigated a cross sector cardiovascular rehabilitation programme compared with usual care for patients having non-operative management. Methods The trial allocated 118 patients, with 1:1 individual randomisation to either an intervention or control group. Data were collected at a department of vascular surgery and at a healthcare centre in Denmark. The rehabilitation intervention consisted of usual care plus 12 weeks of exercise training, pedometer, health education, and text messages. The primary outcome was maximum walking distance at six months measured by treadmill walking test. The secondary outcomes were maximum walking distance at 12 months and pain free walking distance measured by treadmill walking test, healthy diet, level of physical activity, and quality of life (QoL) at six and 12 months. Results In the intervention group, 46 participants were analysed, with 47 in the control group. Following three months of rehabilitation, a 37% difference (95% CI 1.10 – 1.70; p = .005) was found between groups in maximum walking distance at six and 12 months, in favour of the intervention group. The same positive effect was found in physical activity, QoL, and healthy diet, but was not statistically significant in pain free walking distance and smoking. Conclusion A specialised community based cardiac rehabilitation programme for patients with IC showed statistically and clinically significant effects on maximum walking distance, physical activity, quality of life, and healthy diet, but not on pain free walking distance and smoking, compared with usual care without rehabilitation.

OBJECTIVE Conventional two-dimensional ultrasound (2D-US) has been the recommended and preferred modality for the diagnosis and surveillance of abdominal aortic aneurysms (AAAs). Measurement of the aneurysm diameter using three-dimensional ultrasound (3D-US) has shown promising results in a research setting, improving agreement and reproducibility. However, studies evaluating 3D-US in a clinical context are lacking, which could hinder the optimal usage of this new modality. In the present study, we investigated the clinical value of 3D-US for AAA surveillance compared with the current standard 2D-US examination. METHODS Data from 126 patients with infrarenal AAAs

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.

Aims Chronic limb-threatening ischaemia (CLTI) entails dismal outcomes and is an absolute indication to lower extremity revascularization (LER) whenever possible. Antithrombotic therapy is here crucial, but available evidence on best strategies (choice of drugs, combinations, duration) is scarce. We conducted a European internet-based survey on physicians’ use of antithrombotic therapy after revascularization for CLTI, under the aegis of the ESC Working Group on Aorta and Peripheral Vascular Disease in collaboration with other European scientific societies involved in CLTI management and agreeing to send the survey to their affiliates. Methods and results 225 respondents completed the questionnaire. Antithrombotic therapy following surgical/endovascular LER varies widely across countries and specialties, with dedicated protocols reported only by a minority (36%) of respondents. Dual antiplatelet therapy with aspirin and clopidogrel is the preferred choice for surgical (37%) and endovascular (79%) LER. Dual pathway inhibition (DPI) with aspirin and low-dose rivaroxaban is prescribed by 16% of respondents and is tightly related to the availability of reimbursement (OR 6.88; 95% CI 2.60–18.25) and to the choice of clinicians rather than of physicians performing revascularization (OR 2.69; 95% CI 1.10–6.58). A ≥ 6 months-duration of an intense (two-drug) postprocedural antithrombotic regimen is more common among surgeons than among medical specialists (OR 2.08; 95% CI 1.10–3.94). Bleeding risk assessment is not standardised and likely underestimated. Conclusion Current antithrombotic therapy of CLTI patients undergoing LER remains largely discretional, and prescription of DPI is related to reimbursement policies. An individualised assessment of thrombotic and bleeding risks is largely missing.

The aim of this collaborative document is to provide an update for clinicians on best antithrombotic strategies in patients with aortic and/or peripheral arterial diseases. Antithrombotic therapy is a pillar of optimal medical treatment for these patients at very high cardiovascular risk. While the number of trials on antithrombotic therapies in patients with aortic or peripheral arterial diseases is substantially smaller than for those with coronary artery disease, recent evidence deserves to be incorporated into clinical practice. In the absence of specific indications for chronic oral anticoagulation due to concomitant cardiovascular disease, a single antiplatelet agent is the basis for long-term antithrombotic treatment in patients with aortic or peripheral arterial diseases. Its association with another antiplatelet agent or low-dose anticoagulants will be discussed, based on patient’s ischaemic and bleeding risk as well therapeutic paths (e.g. endovascular therapy). This consensus document aims to provide a guidance for antithrombotic therapy according to arterial disease localizations and clinical presentation. However, it cannot substitute multidisciplinary team discussions, which are particularly important in patients with uncertain ischaemic/bleeding balance. Importantly, since this balance evolves over time in an individual patient, a regular reassessment of the antithrombotic therapy is of paramount importance.

Summary: Background: Peripheral artery disease (PAD) of the lower limbs is a common condition with considerable global burden. Some country-specific studies suggest low levels of public awareness. To our knowledge public awareness of PAD has never been assessed simultaneously in several countries worldwide. Patients and methods: This was an international, general public, internet-based quantitative survey assessing vascular health and disease understanding. Questionnaires included 23 closed-ended multiple-choice, Likert scale and binary choice questions. Data were collected from 9,098 survey respondents from nine countries in Europe, North and Latin America during May-June 2018. Results: Overall, familiarity with PAD was low (57% of respondents were “not at all familiar”, and 9% were “moderately” or “very familiar”). Knowledge about PAD health consequences was limited, with 55% of all respondents not being aware of limb consequences of PAD. There were disparities in PAD familiarity levels between countries; highest levels of self-reported awareness were in Germany and Poland where 13% reported to be “very” or “moderately” familiar with PAD, and lowest in Scandinavian countries (5%, 3% and 2% of respondents in Norway, Sweden and Denmark, respectively). There were disparities in awareness according to age. Respondents aged 25–34 were most familiar with PAD, with 12% stating that they were “moderately” or “very” familiar with the condition, whereas those aged 18–24 were the least familiar with PAD (7% “moderately” or “very” familiar with PAD). In the 45–54, 55–64 and 65+ age groups, 9% said they were “moderately” or “very” familiar with the term. There was no important gender-based difference in PAD familiarity. Conclusions: On an international level, public self-reported PAD awareness is low, even though PAD is a common condition with considerable burden. Campaigns to increase PAD awareness are needed to reduce delays in diagnosis and to motivate people to control PAD risk factors.

Aims To establish a set of quality indicators (QIs) for the cardiovascular (CV) assessment and management of patients undergoing non-cardiac surgery (NCS). Methods and results The Quality Indicator Committee of the European Society of Cardiology (ESC) and European Society of Anaesthesiology and Intensive Care (ESAIC) in collaboration with Task Force members of the 2022 ESC Guidelines on CV assessment and management of patients undergoing NCS followed the ESC methodology for QI development. This included (1) identification, by constructing a conceptual framework of care, of domains of the CV assessment, and management of patients with risk factors or established cardiovascular disease (CVD) who are considered for or undergoing NCS, (2) development of candidate QIs following a systematic literature review, (3) selection of the final set of QIs using a modified Delphi method, and (4) evaluation of the feasibility of the developed QIs. In total, eight main and nine secondary QIs were selected across six domains: (1) structural framework (written policy), (2) patient education and quality of life (CV risk discussion), (3) peri-operative risk assessment (indication for diagnostic tests), (4) peri-operative risk mitigation (use of hospital therapies), (5) follow-up (post-discharge assessment), and (6) outcomes (major CV events). Conclusion We present the 2022 ESC/ESAIC QIs for the CV assessment and management of patients with risk factors or established CVD who are considered for or are undergoing NCS y. These indicators are supported by evidence from the literature, underpinned by expert consensus, and align with the 2022 ESC Guidelines on CV assessment and management of patients undergoing NCS.

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To compare aortic sac changes after endovascular aneurysm repair (EVAR) assessed by three-dimensional ultrasound (3D-US), two-dimensional ultrasound (2D-US), and traditional computed tomographic angiography (CTA).Using volume assessment with three-dimensional CTA (3D-CTA-volume) as the gold standard, this study investigated aortic sac changes at three and 12 months after EVAR with three different ultrasound methods (2D-US anterior-posterior (AP) diameter, 3D-US AP centerline diameter, and 3D-US partial volume), and traditional CT multiplanar outer-to-outer diameter (CT-MPR OTO diameter). From august 1st, 2011 to January 2014, consecutive EVAR patients (n = 113) were available for analysis in two time intervals; 1) between preoperative and three-month follow-up and 2) between three and 12 month follow-up.The risk of missing true aortic sac growth (false negative finding) at three-month postoperative visit using 3D-US partial volume, 3D-US AP centerline diameter, 2D-US AP diameter, and CT-MPR OTO diameter was 19%, 21%, 22%, and 18%, respectively. Corresponding low sensitivities (0% to 21%) and kappa-values (0.50) in detecting aortic sac changes were found. The risk of missing true growth between three and 12 months were lower (6%, 5%, 6%, and 6%, respectively), and matching sensitivities 33%, 33%, 17%, and 17%, respectively.All tested methods for aortic sac changes were as good as traditional CT-MPR OTO diameter and corresponded poorly with 3D-CTA-volume at three months postoperative visit but substantially better after 12 months where the residual sac change was more profound.

Patients with peripheral artery disease (PAD) requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. VOYAGER PAD demonstrated that rivaroxaban significantly reduced this risk with an overall favorable net benefit in patients undergoing surgical revascularization; however, the efficacy and safety in those treated by surgical bypass including stratified by bypass conduit (venous or prosthetic) has not been described.In the VOYAGER PAD trial, patients with PAD after surgical and endovascular infrainguinal LER were randomized to rivaroxaban 2.5 mg twice daily or placebo and followed for a median of 28 months. The primary endpoint was a composite of acute limb ischemia (ALI), major amputation of vascular etiology, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. Index procedure details including conduit type (venous or prosthetic) were collected at baseline.Among 6564 randomized, 2185 (33%) underwent surgical LER. Of these, surgical bypass was performed in 1448 (66%), using prosthetic conduit in 773 (53%) and venous in 646 (45%). Adjusting for baseline differences and anatomic factors, the risk for unplanned limb revascularization in the placebo arm was 2.5-fold higher for those receiving prosthetic versus venous conduits (adjHR 2.53, 95% CI 1.65-3.90; p0.001) while the risk for ALI was 3 times greater (adjHR 3.07, 95% CI 1.84-5.11; p0.001). Rivaroxaban reduced the primary outcome in patients treated with bypass surgery (HR 0.78, 95% CI 0.62-0.98) with consistent benefits in those receiving venous (HR 0.66, 95% CI 0.49-0.96) and prosthetic (HR 0.87, 95% CI 0.66-1.15) conduits (pSurgical bypass with prosthetic conduit is associated with significantly higher rates of major adverse limb events relative to venous conduits even after adjusting for patient and anatomic characteristics. Adding rivaroxaban 2.5 mg twice daily to aspirin or dual antiplatelet therapy significantly reduces this risk, increases bleeding, but has a favorable benefit risk in patients treated with bypass surgery and regardless of conduit type. Rivaroxaban should be considered after lower extremity bypass for symptomatic PAD to reduce ischemic complications of the heart, limb, and brain.

Background: The VOYAGER PAD trial (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) demonstrated superiority of rivaroxaban plus aspirin versus aspirin to reduce major cardiac and ischemic limb events after lower extremity revascularization. Clopidogrel is commonly used as a short-term adjunct to aspirin after endovascular revascularization. Whether clopidogrel modifies the efficacy and safety of rivaroxaban has not been described. Methods: VOYAGER PAD was a phase 3, international, double-blind, placebo-controlled trial in patients with symptomatic PAD undergoing lower extremity revascularization randomized to rivaroxaban 2.5 mg twice daily plus 100 mg aspirin daily or rivaroxaban placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was TIMI (Thrombolysis in Myocardial Infarction) major bleeding, with International Society on Thrombosis and Haemostasis major bleeding a secondary safety outcome. Clopidogrel use was allowed at the discretion of the investigator for up to 6 months after the qualifying revascularization. Results: Of the randomized patients, 3313 (50.6%) received clopidogrel for a median duration of 29.0 days. Over 3 years, the hazard ratio for the primary outcome of rivaroxaban versus placebo was 0.85 (95% CI, 0.71–1.01) with clopidogrel and 0.86 (95% CI, 0.73–1.01) without clopidogrel without statistical heterogeneity ( P for interaction=0.92). Rivaroxaban resulted in an early apparent reduction in acute limb ischemia within 30 days (hazard ratio, 0.45 [95% CI, 0.14–1.46] with clopidogrel; hazard ratio, 0.48 [95% CI, 0.22–1.01] without clopidogrel; P for interaction=0.93). Compared with aspirin, rivaroxaban increased TIMI major bleeding similarly regardless of clopidogrel use ( P for interaction=0.71). With clopidogrel use >30 days, rivaroxaban was associated with more International Society on Thrombosis and Haemostasis major bleeding within 365 days (hazard ratio, 3.20 [95% CI, 1.44–7.13]) compared with shorter durations of clopidogrel ( P for trend=0.06). Conclusions: In the VOYAGER PAD trial, rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events with an early benefit for acute limb ischemia regardless of clopidogrel use. The safety of rivaroxaban was consistent regardless of clopidogrel use but with a trend for more International Society on Thrombosis and Haemostasis major bleeding with clopidogrel use >30 days than with a shorter duration. These data support the addition of rivaroxaban to aspirin after lower extremity revascularization regardless of concomitant clopidogrel, with a short course (≤30 days) associated with less bleeding. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02504216.

Using a novel 3-D ultrasound system, we aimed to determine differences in carotid plaque size and echogenicity in two atherosclerotic groups. Seventy patients admitted with acute myocardial infarction (aMI) and 69 patients known with chronic peripheral arterial disease (cPAD) were included. The cPAD group had larger plaque volumes (median: 70.24 mm3, interquartile range [40.12-135.61] vs. 55.41 mm3 [4.24-84.31], p = 0.004), thicker plaques (2.45 mm [1.85-3.25] vs. 1.99 mm [1.55 - 2.64], p = 0.005) and higher gray-scale medians (GSMs) (mean: 71.75, standard deviation: 21.55 vs. 60.99 [24.09], p = 0.006) than the aMI group. After adjustment for traditional risk factors, the difference persisted for thickness and volume. The difference in GSM persisted after adjustment for volume only. Patients with stable atherosclerotic disease had larger and brighter carotid plaques compared with unstable atherosclerotic patients. 3-D ultrasound may prove useful in identifying thromboembolic risk.

Atherosclerotic plaque detection by carotid ultrasound provides cardiovascular disease risk stratification. The advantages and disadvantages of two-dimensional (2D) and three-dimensional (3D) ultrasound methods for carotid arterial plaque quantification are reviewed. Advanced and emerging methods of carotid arterial plaque activity and composition analysis by ultrasound are considered. Recommendations for the standardization of focused 2D and 3D carotid arterial plaque ultrasound image acquisition and measurement for the purpose of cardiovascular disease stratification are formulated. Potential clinical application towards cardiovascular risk stratification of recommended focused carotid arterial plaque quantification approaches are summarized.

Background The objective of the study was to compare bypass surgery and endovascular revascularization of the femoropopliteal segment in patients with peripheral arterial disease and critical limb-threatening ischemia (CLTI). Methods This is a single-center study including patients undergoing first-time lower extremity intervention with peripheral bypass surgery or percutaneous transluminal angioplasty with or without stenting (PTA/S) of the femoropopliteal segment because of CLTI from 2011 to 2015. Based on prospective entered data from the Danish Vascular Registry, the primary end points were amputation-free survival, overall mortality, and reinterventions. Results A total of 679 patients with CLTI were included of which 35% (n = 239) were treated with PTA/S, 54% (n = 363) with vein bypass, and 11% (n = 77) with synthetic bypass. After 3 years, amputation-free survival was significantly better with a vein bypass (41.8% [95% CI: 35–48.4]) than both PTA/S (29.7% (95% CI: 22.7–37)) and synthetic bypass (31.7% [95% CI: 19–45.1]). Overall, the endovascular-treated patients faced more than 50% increased risk of major amputation or death than that of a vein bypass, after adjusting for comorbidity and Trans-Atlantic Inter-Society Consensus (TASC) classification (HR: 1.56 [95% CI: 1.21–2.05]). As expected, postoperative complications, length of hospital stay, and reinterventions were more frequent in the bypass groups. Conclusions In this nonrandomized study, autologous vein bypass was superior to both PTA/S and synthetic bypass in regard to amputation-free survival and overall mortality. Despite the increased frequency of surgical complications, a vein bypass appears justified in both shorter (TASC B-C) and longer (TASC D) femoropopliteal lesions.

Background In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, atorvastatin was compared with placebo in 4,731 participants with recent stroke or transient ischemic attack and no known coronary heart disease. Atorvastatin reduced the first occurrence of stroke and the first occurrence of a composite of vascular events. Objectives The aim of this post hoc analysis was to assess the occurrence of all (first and subsequent) vascular events and the effect of atorvastatin to reduce these events by vascular territory (cerebrovascular, coronary, or peripheral) in SPARCL. Methods Treatment effects on total adjudicated vascular events, overall and by vascular territory, were summarized by marginal proportional hazards models. Vascular event rates were estimated for each treatment group with cumulative incidence functions. Results The placebo group had an estimated 41.2 first and 62.7 total vascular events per 100 participants over 6 years. There were 164 fewer first and 390 fewer total vascular events in the atorvastatin group (total events hazard ratio: 0.68; 95% confidence interval: 0.60 to 0.77). The total events reduction included 177 fewer cerebrovascular, 170 fewer coronary, and 43 fewer peripheral events. Over 6 years, an estimated 20 vascular events per 100 participants were avoided with atorvastatin treatment. Conclusions In participants with recent stroke or transient ischemic attack, the total number of vascular events prevented with atorvastatin was more than twice the number of first events prevented. Total event reduction provides a comprehensive metric to capture the totality of atorvastatin clinical efficacy in reducing disease burden after stroke or transient ischemic attack. (Lipitor in the Prevention of Stroke, for Patients Who Have Had a Previous Stroke [SPARCL]; NCT00147602)

OBJECTIVE: Three-dimensional ultrasound (3D-US) examination is a relatively new modality that can be used for abdominal aortic aneurysm (AAA) surveillance, and may offer improved reproducibility over conventional two-dimensional ultrasound (2D-US) examination. The aim of this study was to evaluate the interoperator reproducibility of maximum anterior-to-posterior diameter by nonphysician ultrasound technicians in a typical vascular laboratory setting, on patients with infrarenal AAAs using 3D-US and 2D-US examination.METHODS: A total of 134 consecutive patients with asymptomatic infrarenal AAAs were screened. Of the 134 patients, 28 (21%) were screen failures. From the remaining 106 patients, 3 (2.8%) had missing data and 13 (12.3%) had technically unacceptable image quality. As a result, 90 patients were included for final analysis. Ultrasound image acquisitions were performed during the single visit. The 2D-US images were evaluated at the time of examination by the respective ultrasound technicians who acquired them. All 3D-US images were evaluated offline by both ultrasound technicians after a wash-out period of at least 6 weeks.RESULTS: Excellent interoperator reproducibility was observed for measuring maximum diameter using 3D-US (intraclass correlation coefficient, 0.97), and good agreement among ultrasound technicians (mean difference, -0.08 mm; limits of agreement, -3.17; 3.00 mm). When using 3D-US examination, 74 of the 90 patients (82%) were estimated within 2 mm of interoperator variability. Of 90 patients, 52 (58%) were estimated to be within the same variability by 2D-US examination. Estimating AAA diameter using 3D-US was superior to 2D-US with respect to interoperator reproducibility.CONCLUSIONS: Both 3D-US and 2D-US examination demonstrated good reproducibility among two vascular ultrasound technicians with superior agreement from 3D-US examination. The present results support the broader use of 3D-US in standard AAA surveillance programs.

Background "Profiling" is a new method based on three-dimensional ultrasound (3D-US) allowing for direct comparison of baseline and follow-up diameters along the AAA length. This study aimed to evaluate the feasibility of profiling to visualize AAA changes at sub-maximum diameters, and to categorize the growth profiles. Methods Retrospective analysis of prospectively and consecutively included patients under AAA surveillance at a tertiary referral centre. 3D-US images of AAAs at baseline and at one-year follow-up were segmented, generating a centerline and a mesh of the aneurysm geometry. The mesh was processed to illustrate diameter changes of a given AAA. Three growth profiles were identified: A) Peak Growth: the largest, significant (≥3.6 mm) diameter difference occurred within a 10 mm margin to either side of the maximum baseline diameter; B) Edge Growth: at least one significant diameter difference and the criteria for Peak Growth did not apply; C) No Growth: all diameter differences were nonsignificant. A centerline length of ≥60 mm was assumed to capture a comparable segment of the wall geometry at baseline and follow-up. Cohen's kappa and Kaplan Meier analysis were used to analyze data. Results In total, 186 patients had growth profiles generated. Of these, 28 (15%) were discarded, mainly based on inadequate centerline lengths (n= 21, 11.3%). The remaining patients were categorized into Edge Growth (n=83, 52%), No Growth (n=47, 30%), and Peak Growth (n=28, 18%). Conclusions Profiling interprets AAA growth at sub-maximum diameters. Half of the cohort had Edge Growth. These AAAs risk being classified as stable.

Background and aims: Urokinase-type plasminogen activator receptor (uPAR) is associated with extracellular matrix (ECM) degradation and cancer aggressiveness. Its role in arterial atherogenesis as a molecular imaging target is not well-established. The aim of this study was to non-invasively visualize uPAR expression in atherosclerosis by a novel uPAR-targeting positron emission tomography (PET) tracer [64Cu]Cu-DOTA-AE105.Methods: We used molecular biology to investigate uPAR expression by analyzing human atherosclerotic plaques and cultured cells. A retrospective analysis was performed on patients, who underwent combined PET/CT (n = 10) to measure [64Cu]Cu-DOTA-AE105 uptake in five large arteries, divided into a high and low-risk group based on coronary artery calcium score (CAC score).Results: The in vitro assay for THP-1 monocytes displayed a significantly upregulated uPAR expression upon stimulation (5.2-fold upregulation, p < 0.0001 by a one-way ANOVA followed by Tukey's test) by single-cell flowcytometric analysis. Freshly excised human atherosclerotic plaques underwent flow cytometric and microarray analyses manifesting 73.9 ± 2.9% of mononuclear phagocyte system (MPS) cells expressing uPAR and had a greater than 7-fold higher gene expression of plasminogen activator urokinase receptor (PLAUR, p = 0.002), integrin subunit alpha X (ITGAX, p = 0.0008), and cluster of differentiation 163 (CD163, p < 0.0001). The tissue-to-background ratios (TBRmax) in five large arteries showed a higher [64Cu]Cu-DOTA-AE105 uptake in the group with high CAC score compared to the group with low CAC score (2.4 ± 0.1 vs 1.7 ± 0.1, p = 0.057), significantly higher in the ascending aorta (2.7 ± 0.1 vs 2.0 ± 0.1, p = 0.038) and the abdominal aorta (3.2 ± 0.2 vs 2.0 ± 0.2, p = 0.038) by a non-parametric Mann-Whitney test.Conclusions: uPAR is abundantly expressed by MPS cells in atherosclerotic plaques and can be visualized by the novel PET tracer [64Cu]Cu-DOTA-AE105 that may non-invasively detect extracellular matrix remodeling during atherogenesis.

Aim: This study aimed to explore how qualitative data about rehabilitation for patients with intermittent claudication do provide an enhanced understanding of the quantitative experimental results.Background: The study was a randomized clinical trial comparing a rehabilitation intervention with usual care. A statistically significant difference between rehabilitation and usual care was found in walking distance, physical activity, quality of life and diet. The findings from the quantitative and qualitative analyses were analysed separately on their own tradition. In this study, mixed methods address whether the qualitative results could help explain the quantitative results and bring forward additional information.Design: Complex mixed-method intervention design with a convergent questionnaire variant.Methods: From April 2017- May 2019, patients diagnosed with intermittent claudication were included in a randomized clinical trial (N=118). In addition, qualitative interview informants from the intervention group were sampled from the quantitative study population for a survey (N=43) and focus group interviews (N=10). Interviews were conducted from April 2018-August 2019.Results: Integrated analyses identified how improvement in walking distance, physical activity, diet and quality of life was affected by team spirit, pedometer, education and fun exercise in a local setting. Quantitative and qualitative findings primarily confirmed and expanded each other; however, two discordant results were also evident.Conclusion: Our study adds empirical evidence regarding how a mixed-methods study can be used to obtain a more nuanced understanding of complex healthcare problems. The study provides new knowledge concerning how to set up a rehabilitation programme for patients with intermittent claudication.

Urokinase-type plasminogen activator receptor (uPAR) is associated with extracellular matrix (ECM) degradation and cancer aggressiveness. Its role in arterial atherogenesis as a molecular imaging target is not well-established. The aim of this study was to non-invasively visualize uPAR expression in atherosclerosis by a novel uPAR-targeting positron emission tomography (PET) tracer [We used molecular biology to investigate uPAR expression by analyzing human atherosclerotic plaques and cultured cells. A retrospective analysis was performed on patients, who underwent combined PET/CT (n = 10) to measure [The in vitro assay for THP-1 monocytes displayed a significantly upregulated uPAR expression upon stimulation (5.2-fold upregulation, p 0.0001 by a one-way ANOVA followed by Tukey's test) by single-cell flowcytometric analysis. Freshly excised human atherosclerotic plaques underwent flow cytometric and microarray analyses manifesting 73.9 ± 2.9% of mononuclear phagocyte system (MPS) cells expressing uPAR and had a greater than 7-fold higher gene expression of plasminogen activator urokinase receptor (PLAUR, p = 0.002), integrin subunit alpha X (ITGAX, p = 0.0008), and cluster of differentiation 163 (CD163, p 0.0001). The tissue-to-background ratios (TBRuPAR is abundantly expressed by MPS cells in atherosclerotic plaques and can be visualized by the novel PET tracer [

Aim: This study aimed to explore how qualitative data about rehabilitation for patients with intermittent claudication do provide an enhanced understanding of the quantitative experimental results. Background: The study was a randomized clinical trial comparing a rehabilitation intervention with usual care. A statistically significant difference between rehabilitation and usual care was found in walking distance, physical activity, quality of life and diet. The findings from the quantitative and qualitative analyses were analysed separately on their own tradition. In this study, mixed methods address whether the qualitative results could help explain the quantitative results and bring forward additional information. Design: Complex mixed-method intervention design with a convergent questionnaire variant. Methods: From April 2017- May 2019, patients diagnosed with intermittent claudication were included in a randomized clinical trial (N=118). In addition, qualitative interview informants from the intervention group were sampled from the quantitative study population for a survey (N=43) and focus group interviews (N=10). Interviews were conducted from April 2018-August 2019. Results: Integrated analyses identified how improvement in walking distance, physical activity, diet and quality of life was affected by team spirit, pedometer, education and fun exercise in a local setting. Quantitative and qualitative findings primarily confirmed and expanded each other; however, two discordant results were also evident. Conclusion: Our study adds empirical evidence regarding how a mixed-methods study can be used to obtain a more nuanced understanding of complex healthcare problems. The study provides new knowledge concerning how to set up a rehabilitation programme for patients with intermittent claudication.

Background/Introduction Lower extremity peripheral arterial disease (PAD) is a severe form of atherosclerotic cardiovascular (CV) disease. The classical symptom is intermittent claudication (IC), associated with limited walking ability and poor health-related quality of life (QoL). Type 2 diabetes (T2D) is one of the leading causes of PAD; ∼30% of patients with PAD have T2D. While anti-atherosclerotic drugs and lifestyle changes are recommended, there are no effective drugs to specifically improve functional outcomes in PAD and T2D. Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved as an adjunct to diet and exercise for glycaemic control in patients with T2D. In the T2D SUSTAIN clinical trial programme, once-weekly (OW) subcutaneous semaglutide 0.5 and 1.0 mg was superior for glycaemic control and weight loss vs placebo and a range of approved antidiabetic drugs. In SUSTAIN 6, a dedicated CV outcomes trial, OW semaglutide resulted in a 26% reduction in three-point major adverse CV events (MACE) compared with placebo in patients with T2D at high CV risk, leading to its approval for MACE risk reduction in those with T2D and CV disease in the USA. Evidence suggests this may be partly attributable to the anti-inflammatory and anti-atherosclerotic effects of semaglutide, which may also apply to PAD. Purpose The STRIDE trial will demonstrate the effect of OW semaglutide 1.0 mg vs placebo on walking ability in patients with T2D and PAD with IC. Methods STRIDE is a 52-week, randomised, double-blind, placebo-controlled, phase 3b trial. Trial design and eligibility criteria are shown in the Figure; ∼800 patients will be randomised 1:1 to OW semaglutide 1.0 mg or placebo, both added to standard of care. The primary endpoint is change in maximum walking distance on a constant load treadmill test from baseline to week 52. Secondary confirmatory endpoints include changes in pain-free walking distance and PAD-specific, health-related patient-reported outcomes (Vascular QoL Questionnaire-6) from baseline to week 52. Results The trial started in October 2020 and is currently recruiting, with ∼120 sites in ∼20 countries across Asia, Europe, and North America. Conclusion STRIDE is the first and only dedicated PAD outcomes trial with a GLP-1RA and thus presents a unique trial design. While major adverse limb events typically occur in the later stages of PAD, STRIDE instead measures the effect of OW semaglutide on functional outcomes such as walking ability and QoL, which affect everyday living in patients with PAD and IC. STRIDE data will provide important clinical insights regarding the role of OW semaglutide in patients with T2D and PAD. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novo Nordisk A/S

Objectives This study aimed to examine the frequency of cancer among patients with chronic limb-threatening ischaemia (CLTI) due to peripheral artery disease (PAD) and to determine how active cancer affected outcomes after open or endovascular revascularization. In addition, we aimed to investigate all-cause mortality and cause of death in the PAD population. Design Observational single-centre cohort study based on a retrospective analysis of prospectively entered registry data. Materials All consecutive patients treated for CLTI due to PAD at a single university centre between the 1st of January 2011 and the 31st of December 2015 were included. Data from the Danish Vascular Registry (Karbase) regarding demographics, surgical procedure, and complications were linked with data from the Danish Cancer Registry and Cause of Death Registry. Methods The primary endpoint was major amputation-free survival. Secondary endpoints were postoperative complications within 30 days, cancer-free survival, all-cause mortality and cause of death in the cohort. Major amputation-free survival, cancer-free survival and mortality were described with Kaplan–Meier (KM) survival estimates. Results We included 920 patients, of which 116 (13%) were in the active cancer group at the time of revascularization. There was no difference in amputation-free survival between those with cancer (86.8% 1-year KM estimate) and those without cancer (85.2% 1-year KM estimate) ( p = 0.50). Likewise, we found no difference in 30-day postoperative complication rate. The risk of developing cancer in the included CLTI cohort was similar to the age-matched background population (6.1% vs 6.4%) ( p = 0.69). All-cause mortality was higher in CLTI patients with cancer, mainly due to cancer, compared with CLTI patients without cancer who mainly died from cardiovascular disease. Three-year KM survival estimates were 48.3% (95% CI 40.0%–58.3%) and 64.4% (95% CI 61.2%–67.8%) ( p = 0.014) for cancer and non-cancer patients, respectively. Conclusions Although cancer in patients with CLTI is related to higher medium- to long-term mortality, active cancer per se should not contravene revascularization, as postoperative complications and risk of amputation are not overrepresented.

Background: Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. Methods: The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary end point was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding. International Society on Thrombosis and Haemostasis bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee. Results: Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared with placebo, rivaroxaban reduced the primary end point consistently regardless of LER method ( P -interaction, 0.43). After surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (hazard ratio, 0.81 [95% CI, 0.67–0.98]; P =0.026). In the overall trial, Thrombolysis in Myocardial Infarction major bleeding and International Society on Thrombosis and Haemostasis major bleeding were increased with rivaroxaban. There was no heterogeneity for Thrombolysis in Myocardial Infarction major bleeding ( P -interaction, 0.17) or International Society on Thrombosis and Haemostasis major bleeding ( P -interaction, 0.73) on the basis of the LER approach. After surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence was 1.3% and 1.4%, respectively (hazard ratio, 0.88 [95% CI, 0.39–1.95]; P =0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage ( P =0.95) and postprocedural bleeding requiring intervention ( P =0.93) was not significantly increased. Conclusions: The efficacy of rivaroxaban is associated with a benefit in patients who underwent surgical LER. Although bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention. Registration: URL: http://www.clinicaltrials.gov ; Unique Identifier: NCT02504216.

To further characterize the analysis of total events in the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial ([1][1]), we appreciate the suggestion by Dr. Spence to explore the relationship between achieved low-density lipoprotein cholesterol (LDL-C) at month 3 and risk

The aim was to assess the anatomical distribution of acute deep venous thrombosis (DVT) with a focus on iliofemoral DVT, and, in particular, to characterise thrombus in the common femoral vein (CFV) and the deep femoral vein (DFV).A one year prospective study including patients older than 18 years of age with an acute first time DVT according to ultrasound examination at one of three university hospitals in Copenhagen, Denmark. Thrombus location and extent were registered and divided into five segments: calf veins; popliteal vein; femoral and deep femoral vein; common femoral vein; and iliac veins and/or the inferior vena cava. Thrombus appearance of the CFV and the DFV (partial or occlusive) was examined in detail.Acute DVTs were identified in 203 extremities in 200 patients (58% male). The median age of the patients was 68 years (range 19-92 years), and left-sided DVT was observed in 56%. Iliofemoral DVT was present in 54 (27.0%) patients. Thrombus involving the CFV but not the iliac veins (CFV group) was seen in 28 patients; the remaining 26 had involvement of the iliac veins (iliac group). Thrombus in the CFV was more likely to be occlusive in the iliac group than in the CFV group (77% vs. 4%; p .001). Thrombus in the DFV was more often occlusive in the iliac group than in the CFV group (81% vs. 11%; p .001). The DFV was free of thrombus in 12% of patients in the iliac group and in 64% of those in the CFV group.The presence of occlusive thrombus in the CFV and/or in the DFV pointed to a DVT also involving the ipsilateral iliac veins. Thrombosis of the deep leg veins extending into the CFV below the inguinal ligament was more likely to be partial in the CFV, mainly due to inflow from the DFV.

Vascular ultrasound has proven to be a cornerstone for the management of patients with vascular disease, and is utilized by vascular surgeons in the outpatient clinic, the operating room, and for follow-up after revascularisation. Today vascular surgeons are among the most frequent users of ultrasound apart from radiologists. Mastering the skills of vascular ultrasound and interpretation is best acquired under supervision and is more easily learned as part of the daily practice of vascular surgery. Separating vascular ultrasound into basic and advanced procedures is useful, and basic vascular ultrasound skills should be a part of a vascular surgical training program curriculum. In Europe, certification of vascular surgeons in basic vascular ultrasound via a pass-fail test is in its infancy, preceded by local and national initiatives. In the area of clinical vascular research, duplex ultrasound is superior to most other diagnostic modalities due to its availability and noninvasive nature and ultrasound-based research will in addition to improving patient care generate physicians highly experienced in vascular ultrasound.

Objectives Carotid stenosis patients are at risk of vascular events despite antiplatelet therapy. Data on prescribed antiplatelet regimens have not been comprehensively collated from trials to guide optimal therapy in this population. Methods This review was conducted in line with the current Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline, Ovid, Embase, Web of Science, and Google Scholar from 1988 to 2018 were searched using the search terms “carotid stenosis”, “asymptomatic”, “symptomatic”, “antiplatelet”, and “anti-platelet” to identify randomised trials in patients with asymptomatic or symptomatic extracranial moderate–severe carotid stenosis on any form of antiplatelet therapy in which vascular events and pre specified composite outcome events were reported. Results Twenty-five studies were judged eligible for inclusion. Data from one randomised controlled trial showed no significant difference in benefit with aspirin versus placebo in asymptomatic carotid stenosis, but it is still reasonable to recommend aspirin (81–325 mg daily) for prevention of vascular events in these patients. Low to medium dose aspirin (81–325 mg daily) is superior to higher doses (>650 mg daily) at preventing recurrent vascular events in patients undergoing endarterectomy. Data from endovascular treatment (EVT) trials support peri-procedural treatment of asymptomatic and symptomatic patients with 81–325 mg of aspirin daily. The use of peri-procedural aspirin–clopidogrel in patients undergoing EVT is based on one pilot trial, but appears safe. Short-term aspirin–dipyridamole or aspirin–clopidogrel treatments are equally effective at reducing micro-embolic signals on transcranial Doppler ultrasound in patients with ≥50% symptomatic carotid stenosis. There is insufficient evidence to recommend routine aspirin–clopidogrel combination therapy to reduce the risk of recurrent clinical ischaemic events in patients with symptomatic moderate–severe carotid stenosis. Conclusions This comprehensive review outlines an evidence based approach to antiplatelet therapy in carotid stenosis patients. Future trials should randomise such patients to receive different antiplatelet regimens to assess their efficacy and safety and to optimise peri-procedural and long-term preventive treatment in this patient cohort.

Background and Aims Chronic kidney disease (CKD) accelerates both atherosclerosis and arterial calcification. The aim of the present study was to explore whether maximal carotid plaque thickness (cPT max) was increased in patients with CKD stage 3 compared to controls and associated with cardiovascular disease and severity of calcification in the carotid and coronary arteries. Method The study group consisted of 200 patients with CKD stage 3 from the Copenhagen CKD Cohort and 121 age- and sex-matched controls. cPT max was assessed by ultrasound and arterial calcification by computed tomography scanning. Results Carotid plaques were present in 58% of patients (n=115) compared with 40% of controls (n=48), P=0.002. Among participants with plaques, cPT max (median, interquartile range) was significantly higher in patients compared with controls (1.9 (1.4-2.3) versus 1.5 (1.2-1.8) mm, P=0.001. Cardiovascular disease was present in 9.4% of patients without plaques (n=85), 23.2% of patients with cPT max 1.0-1.9 mm (n=69) and 34.8% of patients with cPT max >1.9 mm (n=46), P=0.001. Carotid and coronary calcium scores >400 were present in 0.0% and 4.0%, respectively, of patients with no carotid plaques, in 19.1% and 24.2% of patients with cPT max 1.0-1.9 mm, and in 47.5% and 52.6% of patients with cPT max >1.9 mm, P Conclusion This is the first study showing that cPT max is increased in patients with CKD stage 3 compared to controls and closely associated with prevalent cardiovascular disease and severity of calcification in both the carotid and coronary arteries.

Background Atherosclerotic plaque vulnerability is comprised by plaque composition driven by inflammatory activity and these features can be depicted with 3D ultrasound and 2-[18F]FDG-PET, respectively. The study investigated timely changes in carotid artery plaque inflammation and morphology after a thromboembolic event with PET/CT and novel ultrasound volumetric grayscale median (GSM) readings. Patients with a single hemisphere-specific neurological symptom and the presence of an ipsilateral carotid artery atherosclerotic plaque were prospectively included to both 2-[18F]FDG PET/CT and 3D ultrasound scans of the plaque immediately after their event and again three months later. On PET/CT images the maximum standardized uptake value (SUVmax) was measured and the volumetric ultrasound acquisitions were analyzed using a semiautomated software measuring GSM values. Results Baseline scans were performed by a mean of 7 days (range 2–14) after the symptom and again after 98 days (range 91–176). For the entire group (n = 14), we found a decrease in average SUVmax from baseline to follow-up of − 0.18 (95% confidence interval: − 0.34 to − 0.02, P = 0.034). GSM did not increase significantly over time (mean change: + 2.21, 95% confidence interval: − 17.02 to 21.44, P = 0.808). Conclusion A decrease in culprit lesion 2-[18F]FDG-uptake 3 months after an event indicates a decrease in inflammatory activity, suggesting that carotid plaque stabilization over time. 3D ultrasound morphological quantitative differences in GSM were not detectable after 3 months.

Background Chronic kidney disease accelerates both atherosclerosis and arterial calcification. The aim of the present study was to explore whether maximal carotid plaque thickness (cPTmax) was increased in patients with chronic kidney disease compared to controls and associated with cardiovascular disease and severity of calcification in the carotid and coronary arteries. Methods The study group consisted of 200 patients with chronic kidney disease stage 3 from the Copenhagen Chronic Kidney Disease Cohort and 121 age- and sex-matched controls. cPTmax was assessed by ultrasound and arterial calcification by computed tomography scanning. Results Carotid plaques were present in 58% of patients (n = 115) compared with 40% of controls (n = 48), p = 0.002. Among participants with plaques, cPTmax (median, interquartile range) was significantly higher in patients compared with controls (1.9 (1.4–2.3) versus 1.5 (1.2–1.8) mm), p = 0.001. Cardiovascular disease was present in 9% of patients without plaques (n = 85), 23% of patients with cPTmax 1.0–1.9 mm (n = 69) and 35% of patients with cPTmax >1.9 mm (n = 46), p = 0.001. Carotid and coronary calcium scores >400 were present in 0% and 4%, respectively, of patients with no carotid plaques, in 19% and 24% of patients with cPTmax 1.0–1.9 mm, and in 48% and 53% of patients with cPTmax >1.9 mm, p Conclusions This is the first study showing that cPTmax is increased in patients with chronic kidney disease stage 3 compared to controls and closely associated with prevalent cardiovascular disease and severity of calcification in both the carotid and coronary arteries.

OBJECTIVE: The risk of ipsilateral neurological recurrence (NR) was assessed in patients awaiting carotid endarterectomy (CEA) due to symptomatic carotid artery stenosis and whether current national guidelines of performing CEA within 14 days are adequate in present day practice.METHODS: This was a retrospective multicentre observational cohort study. Patients scheduled for CEA due to symptomatic carotid artery stenosis in a five year period, 1 January 2014 to 31 December 2018, from four centres were included. Data from the Danish Vascular Registry (www.karbase.dk), operative managing systems, and electronic medical records were reviewed.RESULTS: In total, 1 125 patients scheduled for CEA were included and 1 095 (97%) underwent the planned surgery. During a median delay from index event to CEA of 11 days (interquartile range 8-16 days), 40 patients (3.6%; 95% confidence interval [CI] 2.5%-5%) experienced a NR. One third were minor strokes (n = 12, 30%); half were transient ischaemic attacks (TIA) (n = 22, 55%); and amaurosis fugax accounted for 15% (n = 6). Twenty-six (2%) CEA procedures was cancelled, of which one was due to a disabling recurrent ischaemic event (aphasia). There were no deaths or major strokes in the waiting time for CEA. Best medical treatment (BMT) with platelet inhibitory or anticoagulation drugs and a statin was initiated in nearly all patients (98%) at first assessment. The overall 30 day risk of a post-operative major event (death or stroke) was (Kaplan-Meier [KM] estimate) 2.7% (95% CI 1.8-3.8), and not significantly correlated with the timing of surgery. Most (69%) occurred within the first three days. One, two, and three year mortality rate for CEA patients was (KM estimate) 4.8%, 7.8%, and 11.5% respectively.CONCLUSION: In symptomatic carotid artery stenosis patients awaiting CEA, very few NRs occurred within 14 days. Institution of immediate BMT in specialised TIA/stroke units followed by early, but not necessarily urgent, CEA is a reasonable course of action in patients with high grade symptomatic carotid artery stenosis.

Objective Three-dimensional ultrasound (3D-US) has already demonstrated improved reproducibility with a high degree of agreement (intermodality variability), reproducibility (interoperator variability), and repeatability (intraoperator variability) compared with conventional two-dimensional ultrasound (2D-US) when estimating the maximum diameter of native abdominal aortic aneurysms (AAAs). The aim of the present study was, in a clinical, multicenter setting, to evaluate the accuracy of 3D-US with aneurysm model quantification software (3D-US abdominal aortic aneurysm [AAA] model) for endovascular aortic aneurysm repair (EVAR) sac diameter assessment vs that of computed tomography angiography (CTA) and 2D-US. Methods A total of 182 patients who had undergone EVAR from April 2016 to December 2017 and were compliant with a standardized EVAR surveillance program were enrolled from five different vascular centers (Rigshospitalet, Copenhagen, Denmark; Catharina Ziekenhuis, Eindhoven, Netherlands; L'hospital de la Timone, Paris, France; Cleveland Clinic, Cleveland, Ohio; and The Christ Hospital, Cincinnati, Ohio) in four countries. All image acquisitions were performed at the local sites (ie, 2D-US, 3D-US, CTA). Only the 2D-US and CTA readings were performed both locally and centrally. All images were read centrally by the US and CTA core laboratory. Anonymized image data were read in a randomized and blinded manner. Results The sample used to estimate the accuracy of the 3D-US AAA model and 2D-US included 164 patients and 177 patients, respectively. The Bland-Altman analysis revealed that the mean difference between CTA and 3D-US was −2.43 mm (95% confidence interval [CI], −5.20 to 0.14; P = .07) with a lower and upper limit of agreement of −8.9 mm (95% CI, −9.3 to −8.4) and 2.7 mm (95% CI, 2.3-3.2), respectively. For 2D-US and CTA, the mean difference was −3.62 mm (95% CI, −6.14 to −1.10; P = .002), with a lower and upper limit of agreement of −10.3 mm (95% CI, −10.8 to −9.8) and 2.5 mm (95% CI, 2-2.9), respectively. Conclusions The 3D-US AAA model showed no significant difference compared with CTA for measuring the anteroposterior diameter, indicating less bias for 3D-US compared with 2D-US. Thus, 3D-US with AAA model software is a viable modality for anteroposterior diameter assessment for surveillance after EVAR.

Although coronavirus disease 2019 seems to be the leading topic in research number of outstanding studies have been published in the field of aorta and peripheral vascular diseases likely affecting our clinical practice in the near future. This review article highlights key research on vascular diseases published in 2020. Some studies have shed light in the pathophysiology of aortic aneurysm and dissection suggesting a potential role for kinase inhibitors as new therapeutic options. A first proteogenomic study on fibromuscular dysplasia (FMD) revealed a promising novel disease gene and provided proof-of-concept for a protein/lipid-based FMD blood test. The role of NADPH oxidases in vascular physiology, and particularly endothelial cell differentiation, is highlighted with potential for cell therapy development. Imaging of vulnerable plaque has been an intense field of research. Features of plaque vulnerability on magnetic resonance imaging as an under-recognized cause of stroke are discussed. Major clinical trials on lower extremity peripheral artery disease have shown added benefit of dual antithrombotic (aspirin plus rivaroxaban) treatment.

Background and aims Polyvascular disease (PVD) affects approximately 20% of patients with atherosclerosis and is a strong independent risk factor for ischemic outcomes. However, guidelines do not address screening or treatment for PVD, and there have been no PVD-specific trials. We reviewed subgroup analyses of large randomized controlled trials of more intense antithrombotic therapy to determine whether increased intensity of therapy improved ischemic outcomes in patients with PVD. Methods MEDLINE, MEDLINE in-Process, EMBASE, and the Cochrane Library were queried for randomized controlled trials larger than 5000 patients evaluating secondary prevention therapies in patients with coronary artery disease or lower extremity peripheral artery disease. Results Thirteen trials were included ranging in size from 7243 to 27,395 patients. In 9 trials (CHARISMA, TRA 2°P–TIMI 50, PEGASUS—TIMI 54, VOYAGER PAD, TRACER, EUCLID, TRILOGY ACS, PLATO, and COMPASS), patients in the PVD subgroup treated with increased-intensity antithrombotic therapy had similar or greater relative risk reductions for ischemic events in comparison with the general trial cohorts. In four trials (DAPT, THEMIS, APPRAISE-2, and ATLAS ACS 2 TIMI 51), the PVD subgroup had an increased hazard of ischemic events with increased-intensity therapy compared with the general trial cohorts. Conclusions More intense antithrombotic therapy in patients with PVD was associated with a similar relative risk reduction for ischemic events compared with patients without PVD. Therefore, patients with PVD benefit from a larger absolute risk reduction because of their higher baseline risk. Future trials in patients with atherosclerotic cardiovascular disease should intentionally include PVD patients to adequately assess treatment options for this under-studied, under-treated population.