The pleiotropic benefits of statins may result from their impact on vascular inflammation. The molecular process underlying this phenomenon is not fully elucidated. In the present study, RNA-sequencing designed to investigate gene expression patterns after CD47–SIRPα inhibition identifies a link of statins, efferocytosis and vascular inflammation. In vivo and in vitro studies provide evidence that statins augment programmed cell removal by inhibiting the nuclear translocation of NF-κB1 p50 and suppressing the expression of the critical ‘don’t-eat-me’ molecule, CD47. Statins amplify the phagocytic capacity of macrophages, and thus the anti-atherosclerotic effects of CD47–SIRPα blockade, in an additive manner. Analyses of clinical biobank specimens suggest a similar link between statins and CD47 expression in humans, highlighting the potential translational implications. Taken together, our findings identify efferocytosis and CD47 as pivotal mediators of statin pleiotropy. In turn, statins amplify the anti-atherosclerotic effects of prophagocytic therapies independently of any lipid-lowering effect. Jarr and colleagues show that statins augment efferocytosis by inhibiting the nuclear translocation of NF-κB1 p50 and suppressing the expression of the key ‘don’t-eat-me’ molecule CD47, which in part explains the pleiotropic effects of statins and provides a basis for future translational efforts.

Identifying novel pathways regulating the adaptive immune response in chronic inflammatory diseases such as atherosclerosis is of particular interest in view of developing new therapeutic drugs. Here we report that the lipid receptor GPR55 is highly expressed by splenic B cells and inversely correlates with atheroma plaque size in mice. In human carotid endarterectomy specimen, GPR55 transcript levels were significantly lower in unstable compared to stable carotid plaques. To study the impact of GPR55 deficiency in atherosclerosis, we crossed Gpr55 knockout mice with apolipoprotein E ( ApoE ) knockout mice and subjected the mice to Western diet for 4 to 16 weeks. Compared to ApoE -/- controls, ApoE -/- Gpr55 -/- mice developed larger plaques with increased necrotic core size, associated with elevated circulating and aortic leukocyte counts. Flow cytometry, immunofluorescence and RNA-sequencing analysis of splenic B cells in these mice revealed a hyperactivated B cell phenotype with disturbed plasma cell maturation and immunoglobulin (Ig)G antibody overproduction. The specific contribution of B cell GPR55 in atherosclerosis was further studied in mixed Gpr55 -/- / µMT bone marrow chimeras on low density receptor deficiency ( Ldlr -/- ) background, revealing that B-cell specific depletion of Gpr55 was sufficient to promote plaque development. Conversely, adoptive transfer of wildtype B cells into ApoE -/- Gpr55 -/- mice blunted the proatherogenic phenotype. In vitro stimulation of splenocytes with the endogenous GPR55 ligand LPI promoted plasma cell proliferation and enhanced B cell activation marker expression, which was inhibited by the GPR55 antagonist CID16020046. Collectively, these discoveries provide new evidence for GPR55 as key modulator of the adaptive immune response in atherosclerosis. Targeting GPR55 could be useful to limit inflammation and plaque progression in patients suffering from atherosclerosis.

Background: With respect to the number of publications, basic research projects and clinical trials, vascular surgeons in Germany have difficulty to keep up with their international peers and with other surgical specialties in Germany. This article aims to emphasize the crucial role of vascular surgeon scientists for the academically oriented vascular surgery, particularly as a connector between (basic) research and patient care. Moreover, proposals are given for the implementation of clinician scientist programs in vascular surgery training programs. Method: A selective literature search was conducted. Furthermore, due to the co-authorship of vascular surgeons with different levels of experience, the outline of a vascular surgeon scientist is illuminated from different angles. Results and conclusion: Vascular surgeon scientists hold a pivotal position in modern vascular surgery as they mediate between (basic) research, patient care, and the development of medical devices. Thereby they act as a mainspring for progress in vascular surgery. Apart from a specific skill set, the central position requires bringing together professional and personal needs. Intensifying vascular surgical education, mentoring, and structured programs could be important starting points to fortify the vascular surgeon scientist concept and thereby strengthen the academic branch of vascular surgery in Germany.

OBJECTIVE:This is a description of the German healthcare landscape regarding carotid artery disease, assessment of hospital incidence time courses for carotid endarterectomy (CEA) and carotid artery stenting (CAS), and simulation of potential effects of minimum hospital caseload requirements for CEA and CAS.METHODS:The study is a secondary data analysis of diagnosis related group statistics data (2005-2016), provided by the German Federal Statistical Office. Cases encoded by German operation procedure codes for CEA or CAS and by International Classification of Diseases (ICD-10) codes for carotid artery disease were included. Hospitals were categorised into quartiles according to annual caseloads. Linear distances to the closest hospital fulfilling hypothetical caseload requirements were calculated.RESULTS:A total of 132 411 and 33 709 patients treated with CEA and CAS from 2012 to 2016 were included. CEA patients had lower rates of myocardial infarction (1.4% vs. 1.8%) and death (1.2% vs. 4.0%), and CAS patients were more often treated after emergency admission (38.1% vs. 27.1%). Age standardised annual hospital incidences were 67.2 per 100 000 inhabitants for CEA and 16.3 per 100 000 inhabitants for CAS. The incidence for CEA declined from 2005 to 2016, with CAS rising again until 2016 after having declined from 2010 to 2013. Regarding distance from home to hospital, centres offering CEA are distributed more homogeneously across Germany, compared with those performing CAS. Hypothetical introduction of minimum annual caseloads (> 20 for CEA; > 10 for CAS) imply that 75% of the population would reach their hospital after travelling 45 km for CEA and 70 km for CAS.CONCLUSION:Differences in spatial distribution mean that statutory minimum annual caseloads would have a greater impact on CAS accessibility than CEA in Germany. Presumably because of a decline in carotid artery disease and a transition towards individualised therapy for asymptomatic patients, hospital incidence for CEA has been declining.

Background: Declining perioperative stroke and death rates over the past 3 decades have been paralleled by an increasing use of intraoperative completion studies (ICS) following carotid endarterectomy (CEA). Techniques applied include angiography, intraoperative duplex ultrasound (IDUS), flowmetry, and angioscopy. This systematic review and meta-analysis is aiming on providing an overview of techniques and corresponding outcomes. Methods: A PubMed based systematic literature review comprising the years 1980 through 2020 was performed using predefined keywords to identify articles on different ICS techniques. Pooled analyses and meta-analyses estimating risk ratios (RR) and 95% confidence intervals (CI) were performed to compare outcomes of different ICS modes to nonapplication of any ICS. I-2 values were assessed to quantify study heterogeneities. Results: Identification of 34 studies including patients undergoing CEA with angiography (n=53,218), IDUS (n=20,030), flowmetry (n=16,812), and angioscopy (n=2,291). Corresponding rates of perioperative stroke were 1.5%, 1.8%, 3.6%, and 1.5%, perioperative stroke or death occurred in 1.7%, 1.9%, 2.2%, and 2.0%. Intraoperative surgical revision rates were 6.2%, 5.9%, and 7.9% after CEA with angiography, IDUS, and angioscopy, respectively. Compared to nonapplication of any ICS, the pooled analysis revealed angiography to be significantly associated with lower rates of stroke (RR 0.47; 95% CI, 0.36-0.62; P<0.0001) and stroke or death (RR 0.76; 95% CI, 0.70-0.83; P<0.0001). IDUS was significantly associated with lower rates of stroke (RR 0.56; 95% CI, 0.43-0.73; P<0.0001) and stroke or death (RR 0.83; 95% CI, 0.74-0.93; P=0.0018), whereas angioscopy showed a significant association with a lower stroke rate (RR 0.48; 95% CI, 0.033-0.68; P=0.0001), but no effect on the combined stroke or death rate. Angioscopy was associated with a higher intraoperative revision rate compared to angiography (RR 1.29; 95% CI, 1.07-1.54; P=0.006). The meta-analyses confirmed lower perioperative stroke or death rates for angiography (RR 0.83; 95% CI, 0.76-0.91) and IDUS (RR 0.86; 95% CI, 0.76-0.98) compared to non-application of any ICS, whereas flowmetry showed no significant association. Conclusions: This study represents the first systematic literature review and meta-analysis on usage of ICSs in CEA. Data strongly indicate a significant beneficial effect of angiography, IDUS, and angioscopy on perioperative CEA outcomes. Any carotid surgeon should consider implementation of ICSs in his routine armamentarium.

Hinsichtlich der Anzahl an Publikationen, grundlagenwissenschaftlichen Projekten und klinischen Studien bleibt die deutsche Gefäßchirurgie im internationalen Vergleich innerhalb des Fachs sowie im nationalen Vergleich mit anderen chirurgischen Fächern zurück. Ziel dieses Beitrags ist es, die zentrale Rolle des vascular surgeon scientist für die akademische Gefäßchirurgie, insbesondere als Bindeglied zwischen (Grundlagen‑)Forschung und Patientenversorgung herauszustellen. Ferner sollen Anstöße zur sinnvollen Umsetzung eines Cinician-scientist-Programms in der Gefäßchirurgie gegeben werden. Es erfolgte eine selektive Literaturrecherche. Außerdem wurde das Modell des vascular surgeon scientist durch Beiträge von Co-Autoren unterschiedlicher gefäßchirurgischer Ausbildungsstände aus verschiedenen Blickwinkeln beleuchtet. Dem vascular surgeon scientist kommt eine entscheidende Rolle in der modernen Gefäßchirurgie zu. Er vollzieht die Translation von der (Grundlagen‑)Forschung über die Patientenversorgung bis hin zur Weiterentwicklung medizinischer „devices“ und ist somit Triebfeder des gefäßchirurgischen Fortschritts. Die zentrale Stellung verlangt ausgeprägte Fähigkeiten und die Vereinigung beruflicher und persönlicher Bedürfnisse. Intensivierung der gefäßchirurgischen Lehre, Mentoring und strukturierte Programme könnten zentrale Punkte zur Vertiefung eines Vascular-surgeon-scientist-Konzepts sein und so zur Stärkung der akademischen Gefäßchirurgie in Deutschland beitragen.

OBJECTIVE:The application of intra-operative completion studies may have contributed to the ongoing improvement of peri-operative outcomes in carotid surgery. METHODS:This prospective study aimed to compare angiography and duplex ultrasound (IDUS) as intra-operative completion studies after carotid endarterectomy (CEA) with respect to differences in the rating of vessel wall defects and interobserver reliability. Patients undergoing CEA for symptomatic or asymptomatic carotid stenosis were included. After CEA, angiography and IDUS were performed. Intra-operatively obtained video footage was evaluated at a later date by three independent and blinded raters with different levels of clinical experience. Rating was done according to a four step rating scale, with higher grades representing more severe defects. Standard statistical methods (Pearson's chi square test; permutation test; Wilcoxon signed rank test; Kendall's coefficient of concordance, Wt) were applied. RESULTS:In total, 150 patients (mean ± standard deviation age 72 ± 7 years, 68.7% male, 33.3% symptomatic) were enrolled between March 2016 and September 2017. Significantly more defects requiring intra-operative revision (grades 3 and 4 on rating scale) were detected by IDUS, which, in part, remained undetected by angiography: 22 (14.7%) vs. 10 (6.7%) (p = .040). Defects were also judged to be more severe with IDUS than with angiography: median rating grade 1: 74 (49.3%) vs. 102 (68.0%); grade 2: 54 (36.0%) vs. 38 (25.3%); grade 3: 21 (14.0%) vs. 9 (6.0%); grade 4: 1 (0.7%) vs.1 (0.7%) (p < .001). Furthermore, Wt was significantly higher for IDUS compared with angiography (0.70 vs. 0.57; p = .003). CONCLUSION:IDUS revealed more defects after CEA than angiography. Despite both techniques only showing moderate interobserver reliability, IDUS is less dependent on the surgeon's subjectivity than angiography. Taking into account the absence of procedure associated risks (i.e., adverse effects of iodinated contrast media and Xray), IDUS could be considered as an alternative intra-operative morphological assessment tool in carotid surgery.

Objective: The aim of this study was to analyze the correlation of age and sex with the outcome after carotid artery stenting (CAS). We used the statutory nationwide quality assurance database in Germany, in which, among others, all endovascular procedures on the extracranial carotid artery are filed. Methods: We performed a secondary data analysis of all CAS procedures (N = 13,086) between 2012 and 2014 in Germany. The primary outcome was defined as any in-hospital stroke or death; the secondary outcomes were defined as in-hospital stroke (alone) and in-hospital death (alone). Descriptive analyses as well as multilevel multivariable analyses were applied. Results: About 70% of the patients were male, and the mean age of all patients was 69.7 6 9.3 years. Carotid stenosis was symptomatic in 36% of all patients. The primary outcome occurred in 2.4% (n = 317) of patients (2.5% of women, 2.4% in men, 1.7% of asymptomatic patients, and 3.7% of symptomatic patients). Multivariable regression analysis indicated that age (linear effect per 10-year increase) was significantly correlated with a higher risk of in-hospital stroke or death after CAS (risk ratio [RR], 1.54; 95% confidence interval [CI], 1.35-1.75). The risks of stroke alone (RR, 1.47; 95% CI, 1.26-1.72) and death alone (RR, 1.62; 95% CI, 1.01-2.58) were also significantly associated with age in CAS patients. Sex did not significantly alter the age effect and was not associated with the primary outcome rate (RR, 0.99; 95% CI, 0.78-1.26). Conclusions: Age but not sex is correlated with a higher risk of in-hospital stroke or death in asymptomatic and symptomatic patients after CAS under routine conditions. The primary outcome rate was fueled to a comparable magnitude by both components of the composite outcome.

Collecting biological tissue samples in a biobank grants a unique opportunity to validate diagnostic and therapeutic strategies for translational and clinical research. In the present work, we provide our long-standing experience in establishing and maintaining a biobank of vascular tissue samples, including the evaluation of tissue quality, especially in formalin-fixed paraffin-embedded specimens (FFPE). Our Munich Vascular Biobank includes, thus far, vascular biomaterial from patients with high-grade carotid artery stenosis (n = 1567), peripheral arterial disease (n = 703), and abdominal aortic aneurysm (n = 481) from our Department of Vascular and Endovascular Surgery (January 2004–December 2018). Vascular tissue samples are continuously processed and characterized to assess tissue morphology, histological quality, cellular composition, inflammation, calcification, neovascularization, and the content of elastin and collagen fibers. Atherosclerotic plaques are further classified in accordance with the American Heart Association (AHA), and plaque stability is determined. In order to assess the quality of RNA from FFPE tissue samples over time (2009–2018), RNA integrity number (RIN) and the extent of RNA fragmentation were evaluated. Expression analysis was performed with two housekeeping genes—glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin (ACTB)—using TaqMan-based quantitative reverse-transcription polymerase chain reaction (qRT)-PCR. FFPE biospecimens demonstrated unaltered RNA stability over time for up to 10 years. Furthermore, we provide a protocol for processing tissue samples in our Munich Vascular Biobank. In this work, we demonstrate that biobanking is an important tool not only for scientific research but also for clinical usage and personalized medicine.

Objective: We sought to analyze the association between last neurologic event and the risk of stroke or death among patients treated with carotid endarterectomy (CEA) or carotid artery stenting (CAS) under routine conditions in Germany. Methods: Secondary data analysis was performed based on the German statutory quality assurance database for carotid procedures. A total of 144,347 patients treated by CEA and 14,794 patients treated by CAS were included in the analysis. Primary outcome was any in-hospital stroke or death. To analyze the association between the last neurologic event and outcome, multilevel multivariable regression analysis was performed. Results: In patients treated by CEA, raw risk for any in-hospital stroke or death was 2.0% (2923/144,347), with a risk of 1.4% in asymptomatic and 3.0% in symptomatic patients. In patients treated by CAS, raw risk for any in-hospital stroke or death was 3.6% (538/14,794), with a risk of 1.7% in asymptomatic and 6.1% in symptomatic patients. Regression analysis revealed that increasing severity of last neurologic event was significantly associated with an increasing risk of any in-hospital stroke or death in patients treated by both CEA and CAS (P < .004). However, the risk of any stroke or death did not significantly differ between asymptomatic patients and patients with amaurosis fugax before CEA or CAS (P = .219 for CEA, P = .124 for CAS). Conclusions: Increasing severity of last neurologic event is associated with an increasing risk of any in-hospital stroke or death in patients treated by CEA and CAS. The risk of any stroke or death did not differ between asymptomatic patients and patients with amaurosis fugax.

Southmead HospitalTwo recent studies report conflicting results for carotid artery stenting (CAS) in elderly patients.1Mazzaccaro D. Modafferi A. Malacrida G. Nano G. Assessment of long-term survival and stroke after carotid endarterectomy and carotid stenting in patients older than 80 years.J Vasc Surg. 2019; 70: 522-529Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, 2Schmid S. Tsantilas P. Knappich C. Kallmayer M. Breitkreuz T. Zimmermann A. et al.Age but not sex is associated with higher risk of in-hospital stroke or death after carotid artery stenting in symptomatic and asymptomatic carotid patients.J Vasc Surg. 2019; 69: 1090-1101Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar A single-center, retrospective cohort study reported that any-stroke rate was similar between patients older than 80 years undergoing CAS (n = 295) and carotid endarterectomy (CEA; n = 178; 1% vs 0.6%, for CAS vs CEA, respectively; P = .23).1Mazzaccaro D. Modafferi A. Malacrida G. Nano G. Assessment of long-term survival and stroke after carotid endarterectomy and carotid stenting in patients older than 80 years.J Vasc Surg. 2019; 70: 522-529Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar In addition, estimated freedom from any stroke at 5 years was similar between the two procedures (97.3% ± 0.5% vs 93.2% ± 1.2%, for CEA vs CAS, respectively; P = .07).1Mazzaccaro D. Modafferi A. Malacrida G. Nano G. Assessment of long-term survival and stroke after carotid endarterectomy and carotid stenting in patients older than 80 years.J Vasc Surg. 2019; 70: 522-529Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar In contrast, a secondary data analysis of all CAS procedures (n = 13,086) in Germany between 2012 and 2014 demonstrated that increasing age (linear effect per 10-year increase) was associated with a higher risk of stroke alone (risk ratio [RR], 1.62; 95% confidence interval [CI], 1.01-2.58; P < .05), death alone (RR, 1.47; 95% CI, 1.01-2.58; P < .05), and any in-hospital stroke or death (RR, 1.54; 95% CI, 1.33-1.75; P < .05).2Schmid S. Tsantilas P. Knappich C. Kallmayer M. Breitkreuz T. Zimmermann A. et al.Age but not sex is associated with higher risk of in-hospital stroke or death after carotid artery stenting in symptomatic and asymptomatic carotid patients.J Vasc Surg. 2019; 69: 1090-1101Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Similarly, a study attempting to identify predictors of 30-day postoperative major adverse clinical events after CAS using data from the American College of Surgeons National Surgical Quality Improvement Program showed that age ≥80 years was associated with a >3-fold higher risk for 30-day death, ipsilateral stroke/transient ischemic attack or arrhythmia/myocardial infarction compared with age <70 years (adjusted odds ratio, 3.35; 95% CI, 1.20-9.37; P = .02).3Bennett K.M. Hoch J.R. Scarborough J.E. Predictors of 30-day postoperative major adverse clinical events after carotid artery stenting: an analysis of the procedure-targeted American College of Surgeons National Surgical Quality Improvement Program.J Vasc Surg. 2017; 66: 1093-1099Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar The worse outcomes of CAS with increasing age reported in the study from Germany2Schmid S. Tsantilas P. Knappich C. Kallmayer M. Breitkreuz T. Zimmermann A. et al.Age but not sex is associated with higher risk of in-hospital stroke or death after carotid artery stenting in symptomatic and asymptomatic carotid patients.J Vasc Surg. 2019; 69: 1090-1101Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar and the American College of Surgeons National Surgical Quality Improvement Program3Bennett K.M. Hoch J.R. Scarborough J.E. Predictors of 30-day postoperative major adverse clinical events after carotid artery stenting: an analysis of the procedure-targeted American College of Surgeons National Surgical Quality Improvement Program.J Vasc Surg. 2017; 66: 1093-1099Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar were also replicated in the Carotid Revascularization Endarterectomy vs Stenting Trial subgroup analysis by age.4Voeks J.H. Howard G. Roubin G.S. Malas M.B. Cohen D.J. Sternbergh 3rd, W.C. et al.CREST InvestigatorsAge and outcomes after carotid stenting and endarterectomy: the carotid revascularization endarterectomy versus stenting trial.Stroke. 2011; 42: 3484-3490Crossref PubMed Scopus (193) Google Scholar In Carotid Revascularization Endarterectomy vs Stenting Trial, the risk for the primary end-point (any stroke, myocardial infarction, or death within the periprocedural period ± postprocedural ipsilateral stroke) increased with age by 1.77 times (95% CI, 1.38-2.28; P < .0001) per 10-year increment.4Voeks J.H. Howard G. Roubin G.S. Malas M.B. Cohen D.J. Sternbergh 3rd, W.C. et al.CREST InvestigatorsAge and outcomes after carotid stenting and endarterectomy: the carotid revascularization endarterectomy versus stenting trial.Stroke. 2011; 42: 3484-3490Crossref PubMed Scopus (193) Google Scholar Strokes were the primary contributor to the overall effect modification (Pinteraction = .033). In contrast, there was no evidence of increased risk for CEA-treated patients (P = .27).4Voeks J.H. Howard G. Roubin G.S. Malas M.B. Cohen D.J. Sternbergh 3rd, W.C. et al.CREST InvestigatorsAge and outcomes after carotid stenting and endarterectomy: the carotid revascularization endarterectomy versus stenting trial.Stroke. 2011; 42: 3484-3490Crossref PubMed Scopus (193) Google Scholar Finally, a recent meta-analysis (n = 9 studies; 5955 patients) on outcomes after CEA vs CAS in the elderly population showed that elderly patients undergoing CEA had a lower risk of 30-day stroke compared with those undergoing CAS (OR, 0.38; 95% CI, 0.29-0.50; I2 = 0%).5Texakalidis P. Chaitidis N. Giannopoulos S. Giannopoulos S. Machinis T. Jabbour P. et al.Carotid revascularization in older adults: a systematic review and meta-analysis.World Neurosurg. 2019; 126: 656-663Crossref PubMed Scopus (11) Google Scholar The robust evidence demonstrating that CAS outcomes are worse with increasing age2Schmid S. Tsantilas P. Knappich C. Kallmayer M. Breitkreuz T. Zimmermann A. et al.Age but not sex is associated with higher risk of in-hospital stroke or death after carotid artery stenting in symptomatic and asymptomatic carotid patients.J Vasc Surg. 2019; 69: 1090-1101Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 3Bennett K.M. Hoch J.R. Scarborough J.E. Predictors of 30-day postoperative major adverse clinical events after carotid artery stenting: an analysis of the procedure-targeted American College of Surgeons National Surgical Quality Improvement Program.J Vasc Surg. 2017; 66: 1093-1099Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 4Voeks J.H. Howard G. Roubin G.S. Malas M.B. Cohen D.J. Sternbergh 3rd, W.C. et al.CREST InvestigatorsAge and outcomes after carotid stenting and endarterectomy: the carotid revascularization endarterectomy versus stenting trial.Stroke. 2011; 42: 3484-3490Crossref PubMed Scopus (193) Google Scholar, 5Texakalidis P. Chaitidis N. Giannopoulos S. Giannopoulos S. Machinis T. Jabbour P. et al.Carotid revascularization in older adults: a systematic review and meta-analysis.World Neurosurg. 2019; 126: 656-663Crossref PubMed Scopus (11) Google Scholar suggest that CEA should probably be preferred over CAS in elderly patients requiring a carotid revascularization procedure. Assessment of long-term survival and stroke after carotid endarterectomy and carotid stenting in patients older than 80 yearsJournal of Vascular SurgeryVol. 70Issue 2PreviewThe objective of this study was to analyze preoperative risk factors affecting long-term survival and the occurrence of stroke in patients older than 80 years undergoing either carotid endarterectomy (CEA) or carotid artery stenting (CAS) for carotid stenosis. Full-Text PDF Open ArchiveAge but not sex is associated with higher risk of in-hospital stroke or death after carotid artery stenting in symptomatic and asymptomatic carotid stenosisJournal of Vascular SurgeryVol. 69Issue 4PreviewThe aim of this study was to analyze the correlation of age and sex with the outcome after carotid artery stenting (CAS). We used the statutory nationwide quality assurance database in Germany, in which, among others, all endovascular procedures on the extracranial carotid artery are filed. Full-Text PDF Open ArchiveReplyJournal of Vascular SurgeryVol. 70Issue 5PreviewWe thank Dr Paraskevas for his Letter to the Editor concerning carotid artery stenting outcomes in elderly patients, mentioning our recently published results on higher risk for stroke and death after carotid artery stenting at higher age.1 Full-Text PDF Open Archive

Objective: The objective of this study was to describe characteristics and in-hospital outcomes of patients treated with carotid endarterectomy (CEA) and carotid artery stenting (CAS) for stroke in evolution (SIE) under routine conditions in Germany. Methods: This secondary data analysis is based on the German statutory quality assurance database for carotid revas-cularization procedures. Patients with SIE who had undergone CEA or CAS were included. The primary outcome was any new stroke or all-cause death until hospital discharge. Descriptive statistics were calculated using statistical standard methods. To identify factors that are associated with the primary or secondary outcomes, a multilevel multivariable regression analysis was performed (exploratory approach). Results: Between 2009 and 2014, a total of 5058 patients (mean age, 70 +/- 11 years; 68% male) with SIE were treated with CEA (n = 3176) or percutaneous transluminal angioplasty/CAS (n = 1882). The primary outcome occurred in 9.0% and 11.7% after CEA and CAS, respectively. The multivariable regression analysis revealed that age (per 10-year increase: risk ratio [RR], 1.30; 95% confidence interval [CI], 1.12-1.50), American Society of Anesthesiologists (ASA) class (ASA class 4 and 5 vs ASA class 3: RR, 2.34; 95% CI, 1.65-3.32), ipsilateral degree of stenosis (occlusion vs severe stenosis: RR, 1.90; 95% CI, 1.29-2.79; low grade vs severe stenosis: RR, 3.06; 95% CI, 1.55-6.02), and neurologic deficit on admission (modified Rankin scale score of 3-5 vs 0-2: RR, 1.48; 95% CI, 1.04-2.10) are significantly associated with the risk of stroke or death after emergency CEA for SIE. In patients treated with CAS, only age (per 10-year increase: RR, 1.58; 95% CI, 1.37-1.82), ASA class (ASA class 1 and 2 vs ASA class 3: RR, 0.66; 95% CI, 0.46-0.95; ASA class 4 and class 5 vs ASA class 3: RR, 1.91; 95% CI, 1.31-2.78), and ipsilateral degree of stenosis (moderate vs severe stenosis: RR, 0.19; 95% CI, 0.04-0.77; occlusion vs severe stenosis: RR, 1.63; 95% CI, 1.18-2.25) were significantly associated with the primary outcome rate. Conclusions: Emergency carotid revascularization is associated with a combined stroke or death rate of about 10% under routine conditions in Germany. Lower age, lower ASA class, moderate to high-grade stenosis, and less severe neurologic deficit preceding CEA potentially serve as protective factors.

Background Subgroup analyses from randomized trials indicate that the time interval between the neurologic index event and carotid artery stenting is associated with periprocedural stroke and death rates in patients with symptomatic carotid stenosis. The aim of this article is to analyze whether this observation holds true under routine conditions in Germany. Methods and Results Secondary data analysis was done on 4717 elective carotid artery stenting procedures that were performed for symptomatic carotid stenosis. The patient cohort was divided into 4 groups according to the time interval between the index event and intervention (group I 0‐2, II 3‐7, III 8‐14, and IV 15‐180 days). Primary outcome was any in‐hospital stroke or death. For risk‐adjusted analyses, a multilevel multivariable regression model was used. The in‐hospital stroke or death rate was 3.7% in total and 6.0%, 4.4%, 2.4%, and 3.0% in groups I, II , III , and IV , respectively. Adjusted analysis showed a decreased risk for any stroke or death in group III , a decreased risk for any major stroke or death in groups III and IV , and a decreased risk for any death in groups II and III compared to the reference group I. Conclusions A short time interval between the neurologic index event and carotid artery stenting of up to 7 days is associated with an increased risk for stroke or death under routine conditions in Germany. Although results cannot prove causal relationships, carotid artery stenting may be accompanied by an increased risk of stroke or death during the early period after the index event.

Objective: There is currently no clear consensus regarding the optimal perioperative antiplatelet therapy regimen for carotid surgery. Therefore, associations between different antiplatelet therapies and the risk of stroke or death and perioperative complications after carotid endarterectomy on a national level in Germany were analyzed. Methods: Overall, 117,973 elective carotid endarterectomies for asymptomatic or symptomatic carotid artery stenosis between 2010 and 2014 were included. Data were extracted from the statutory nationwide quality assurance database. The primary outcome was any in-hospital stroke or death until discharge from the hospital. Secondary outcomes were any major stroke or death, death alone, stroke, myocardial infarction, local bleeding, and any local complications ( cranial nerve palsy, severe bleeding, acute occlusion). Descriptive statistics and multilevel multivariable regression analyses were applied. Single-agent therapy with aspirin was used as reference. Results: Patients were predominantly male (68%), with amean age of 71 years. Carotid stenosis was symptomatic in 40%. Of all patients, 82.8% were treated perioperatively by monotherapy with aspirin alone, 2.7% received other platelet inhibitors, and 4.8% of the patients were operated on under dual antiplatelet therapy. The primary outcome occurred in 1.8% of all patients. Multilevel multivariable regression analysis revealed that the combined stroke and death rate of patients with no perioperative antiplatelet therapy was significantly higher (risk ratio [RR], 1.21; 95% confidence interval [CI], 1.04-1.42) compared with the group of patients receiving monotherapy. The same was true for the major stroke and death rate (RR, 1.23; 95% CI, 1.02-1.48). In contrast, dual antiplatelet therapy was associated with a lower risk of death alone (RR, 0.67; 95% CI, 0.51-0.88) but with a significantly higher rate of secondary bleeding requiring reoperation (RR, 2.16; 95% CI, 1.88-2.50). Conclusions: This study shows that the risk of stroke or death was significantly higher in patients without any perioperative antiplatelet therapy. In contrast, dual antiplatelet therapy vs aspirin monotherapy was associated with a lower risk only of perioperative death but with a higher risk of neck bleeding until discharge. Perioperative antiplatelet therapy was significantly associated with a decreased in-hospital stroke and death risk. Further studies are needed to evaluate the risk-benefit ratio of single vs dual antiplatelet therapy.

Objectives: The purpose of this observational study was to analyze the association between the initial neurological status and the risk of any in-hospital stroke or death in patients treated with carotid endarterectomy (CEA) or carotid artery stenting (CAS) under routine conditions in Germany. Methods: Secondary data analysis based on the German statutory quality assurance database for carotid procedures between 2009-2014. The primary outcome was any periprocedural stroke or all-cause death until discharge. To analyze the association between initial neurological status and outcome, a multilevel multivariable regression analyses adjusting for confounders was performed. Results: From a total of 182,033 patients documented between 2009 and 2014, 144,347 patients treated with CEA and 14,794 patients treated with CAS were included in the analysis. In total, there 68% were men and the mean age of the cohort was 70.5±9.1 years. The risk of any in-hospital stroke or death in patients treated with CEA was 2.0% (n=2923/144,347). The raw risk of any in-hospital stroke or death was 1.4% in asymptomatic patients and 3.0% in symptomatic patients treated with CEA. Within the group of symptomatic patients, risk of any in-hospital stroke or death after CEA increased from 1.2% (amaurosis fugax, AFX), 2.3% (TIA), 2.8% (minor stroke), 4.4% (major stroke), 4.8% (crescendo TIA, cTIA) to 9.0% (stroke in evolution, SIE). The risk of any in-hospital stroke or death in patients treated with CAS was 3.6% (n=538/14,794). The raw risk of any in-hospital stroke or death was 1.7% in asymptomatic patients and 6.1% in symptomatic patients treated with CAS. Within the group of symptomatic patients, risk of any in-hospital stroke or death increased from 1.0% (AFX), 4.1% (TIA), 4.1% (minor stroke), 5.4% (major stroke), 5.2% (cTIA) to 11.7% (SIE). Regression analysis revealed that the severity of initial neurologic symptoms was associated with an increased risk of any in-hospital stroke or death in both patients treated for CEA and CAS. Conclusion: Periprocedural risk for any stroke or death did not significantly differ between asymptomatic patients and patients with AFX but between asymptomatic patients and patients with TIA, stroke, cTIA or SIE.

Background and Purpose-In Germany, all surgical and endovascular procedures on the carotid bifurcation must be documented in a statutory nationwide quality assurance database. We aimed to analyze the association between procedural and perioperative variables and in-hospital stroke or death rates after carotid endarterectomy.Methods-Between 2009 and 2014, overall 142074 elective carotid endarterectomy procedures for asymptomatic or symptomatic carotid artery stenosis were documented in the database. The primary outcome of this secondary data analysis was in-hospital stroke or death. Major stroke or death, stroke, and death, each until discharge were secondary outcomes. Adjusted relative risks (RRs) were assessed by multivariable multilevel regression analyses.Results-The primary outcome occurred in 1.8% of patients, with a rate of 1.4% in asymptomatic and 2.5% in symptomatic patients, respectively. In the multivariable analysis, lower risks of stroke or death were independently associated with local anesthesia (versus general anesthesia: RR, 0.85; 95% confidence interval [CI], 0.75-0.95), carotid endarterectomy with patch plasty compared with primary closure (RR, 0.71; 95% CI, 0.52-0.97), intraoperative completion studies by duplex ultrasound (RR, 0.74; 95% CI, 0.63-0.88) or angiography (RR, 0.80; 95% CI, 0.71-0.90), and perioperative antiplatelet medication (RR, 0.83; 95% CI, 0.71-0.97). No shunting and a short cross-clamp time were also associated with lower risks; however, these are suspected to be confounded.Conclusions-Local anesthesia, patch plasty compared with primary closure, intraoperative completion studies by duplex ultrasound or angiography, and perioperative antiplatelet medication were independently associated with lower in-hospital stroke or death rates after carotid endarterectomy.

Objectives: Current guidelines recommend that carotid endarterectomy (CEA) should be performed within two weeks after the neurologic index event in patients with a 50-99% symptomatic carotid artery stenosis (sCS). Safety of early CEA and early carotid artery stenting (CAS) within those two weeks remains unclair. This study aims to analyze the safety of CEA and CAS in sCS in Germany. Methods: By German law all extracranial carotid procedures have to be documented prospectively in a nationwide quality assurance registry. We analysed data on 56,336 CEAs (68% male, mean age 71 years (SD ± 9.6) and 4,726 CAS (68% male, median age 70 years (SD ± 9.8) treated between 2009-2014 for sCS. The patient cohort was divided into four time interval groups (I: 0-2 days, II: 3-7 days, III: 8-14 days and IV: 14-180 days respectively). Primary endpoint was the combined in-hospital stroke and mortality rate. We excluded all emergency CEAs (stroke-in-evolution, acute occlusion) and all procedures for recurrent carotid stenosis from this analysis. We performed chi-squared tests and a multivariable multilevel Poisson-regression analysis to estimate adjusted risk ratios (RR). Results: The procedural combined stroke and mortality rate was 3.0% (157 of 5198)/6.0% (33 of 550) in group I, 2.5% (480 of 19,117)/4.4% (70 of 1579) in group II, 2.6% (427 of 16,205)/2.4% (30 of 1244) in group III and 2.3% (370 of 15,759)/3.0% (40 of 1344) in group IV respectively. In the multivariable regression analysis the time interval was no independent risk factor for patients treated by CEA. However, CAS was associated with a decreased periprocedural risk when performed 8-14 days (group III) after the index event vs. group I (0-2 days) (RR 0.47, 95% CI 0.28-0.79). No significance was found comparing time group II vs. I (RR 0.80, 95% CI0.52-1.24) and IV vs. I (RR 0.64, 95% CI 0.39-1.05). Conclusion: Time interval between neurologic event and CEA has no significant influence on the perioperative stroke and mortality rate. CAS was associated with a higher risk when performed early. In accordance with the guidelines, CEA remains to be the treatment of choice in the early period after cerebral ischemia.

Background Guideline recommendations on carotid endarterectomy are based predominantly on randomized, controlled trials, in which women or elderly patients are often under‐represented. This study analyzed the association of age and sex with the risk of in‐hospital stroke or death following carotid endarterectomy under routine conditions in Germany. Methods and Results Secondary data analysis using the Statutory German Quality Assurance Database on all carotid endarterectomy procedures (n=142 074) performed between 2009 and 2014. Primary outcome was any stroke or death until discharge; secondary outcomes were any in‐hospital stroke (alone), and death (alone). Descriptive statistics and multilevel multivariable regression analyses were applied. Patients were predominately male (68%), with mean age 71 years. Carotid stenosis was symptomatic in 40%. Primary outcome occurred in 1.8% of women and 1.9% of men. Multivariable regression analysis revealed that more‐advanced age was associated with a higher primary outcome rate (relative risk [RR] per 10‐year increase: 1.19; 95% CI , 1.14–1.24). Risk of death (alone) was associated with age ( RR , 1.68; 95% CI , 1.54–1.84). Age was associated with the risk of stroke (alone; RR , 1.05; 95% CI , 1.00–1.11). Sex was not associated with primary outcome rate (1.01; 95% CI , 0.93–1.10), nor did it significantly modify the age effect. Conclusions This study shows that increasing age, but not sex, is associated with a higher risk of in‐hospital stroke or death following carotid endarterectomy under everyday conditions in Germany. Whereas the risk of death (alone) is significantly associated with age, the association between age and the risk of stroke (alone) can be considered of minor importance.

OBJECTIVES The aim of this study was to analyze the association between intraprocedural and periprocedural variables and in-hospital stroke or death rate after carotid artery stenting.BACKGROUND In Germany, all open surgical and endovascular procedures on the extracranial carotid artery must be documented in a statutory nationwide quality assurance database.METHODS A total of 13,086 carotid artery stenting procedures for asymptomatic (63.9%) or symptomatic carotid stenosis (mean age 69.7 years, 69.7% men) between 2009 and 2014 were recorded. The following variables were analyzed: stent design, stent material, neurophysiological monitoring, periprocedural antiplatelet medication, and use of an embolic protection device. The primary outcome was in-hospital stroke or death. Major stroke or death, any stroke, and death, all until discharge, were secondary outcomes. Adjusted relative risks (RRs) were assessed using multilevel multivariable regression analyses.RESULTS The primary outcome occurred in 2.4% of the population (1.7% in asymptomatic and 3.7% in symptomatic patients). The multivariable analysis showed an independent association between the use of an embolic protection device and lower in-hospital rates of stroke or death (adjusted RR: 0.65; 95% confidence interval [CI]: 0.50 to 0.85), major stroke or death (adjusted RR: 0.60; 95% CI: 0.43 to 0.84), and stroke (adjusted RR: 0.57; 95% CI: 0.43 to 0.77). Regarding the occurrence of in-hospital death, there was no significant association (adjusted RR: 0.78; 95% CI: 0.46 to 1.35). None of the outcomes was associated with stent design, stent material, neurophysiological monitoring, or antiplatelet medication.CONCLUSIONS The use of an embolic protection device was independently associated with lower in-hospital risk for stroke or death, major stroke or death, and stroke. (J Am Coll Cardiol Intv 2017; 10: 1257-65) (C) 2017 by the American College of Cardiology Foundation.

Objective: Current guidelines recommend that carotid endarterectomy (CEA) be performed as early as possible after the neurologic index event in patients with 50% to 99% carotid artery stenosis. However, recent registry data showed that patients treated <= 48 hours had a significantly increased perioperative risk. Therefore, the aim of this single-center study was to determine the effect of the time interval between the neurologic index event and CEA on the periprocedural complication rate at our institution.Methods: Prospectively collected data for 401 CEAs performed between 2004 and 2014 for symptomatic carotid stenosis were analyzed. Patients were divided into four groups according to the interval between the last neurologic event and surgery: group I, 0 to 2 days; group II, 3 to 7 days; group III, 8 to 14 days; and group IV, 15 to 180 days. The primary end point was the combined rate of in-hospital stroke or mortality. Data were analyzed by way of chi(2) tests and multivariable regression analysis.Results: The patients (68% men) had a median age of 70 years (interquartile range, 63-76 years). The index events included transient ischemic attack in 43.4%, amaurosis fugax in 25.4%, and an ipsilateral stroke in 31.2%. CEA was performed using the eversion technique in 61.1% of patients, and 50.1% were treated under locoregional anesthesia. The perioperative combined stroke and mortality rate was 2.5% (10 of 401), representing a perioperative mortality rate of 1.0% and stroke rate of 1.5%. Overall, myocardial infarction, cranial nerve injuries, and postoperative bleeding occurred in 0.7%, 2.2%, and 1.7%, respectively. We detected no significant differences for the combined stroke and mortality rate by time interval: 3% in group I, 3% in group II, 2% in group III, and 2% in group IV. Multivariable regression analysis showed no significant effect of the time interval on the primary end point.Conclusions: The combined mortality and stroke rate was 2.5% and did not differ significantly between the four different time interval groups. CEA was safe in our cohort, even when performed as soon as possible after the index event.